Stomach Cancer Research:
2002-2006  
     
J Thorac Cardiovasc Surg. 2006 Oct;132(4):755-62. Epub 2006 Aug 30.
Surgical treatment of tumors of the proximal stomach with involvement of the distal esophagus: a 26-year experience with Siewert type III tumors.
Shen KR, Cassivi SD, Deschamps C, Allen MS, Nichols FC 3rd, Harmsen WS, Pairolero PC.
Division of General Thoracic Surgery, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA.

OBJECTIVE: A paucity of outcome data exists regarding patients with proximal stomach cancer involving the distal esophagus (Siewert type III tumors). This is especially true with regard to long-term survival rates after surgical intervention. METHODS: Medical records were reviewed of all patients who underwent total gastrectomy and distal esophagectomy with Roux-en-Y esophagojejunostomy for Siewert type III tumors from January 1975 through December 2000. RESULTS: There were 116 patients (93 men and 23 women). The median age was 66 years (range, 22-87 years). Pathologic stage was 0 (carcinoma in situ) in 1 patient, IB in 13 patients, II in 17 patients, IIIA in 34 patients, IIIB in 10 patients, and IV in 41 patients. Complete resection was achieved in 69 (59.5%) patients. Eleven (9.5%) patients were treated with neoadjuvant therapy, 49 (42.2%) received adjuvant therapy, and 6 (5.2%) received intraoperative radiation. Follow-up was complete in 114 (98.3%) patients, ranging from 1 to 281 months (median, 14 months). Operative mortality was 5.2%. Complications occurred in 51 (43.9%) patients. Clinically significant anastomotic leaks occurred in 15 (12.9%) patients. Median hospitalization was 13 days (range, 8-70 days). Median follow-up was 14 months (range, 1-281 months). Overall median survival was 434 days, with 1-, 5-, and 10-year survivals of 56.2%, 19.0%, and 13.5%, respectively. The only factor associated with increased hospital mortality was anastomotic leakage (P = .002). Incomplete resection, increased tumor stage and grade, and splenic involvement significantly worsened long-term survival. CONCLUSIONS: Total gastrectomy and distal esophagectomy for Siewert type III tumors is associated with reasonable mortality and significant morbidity. Although often palliative, surgical intervention can provide long-term survival, especially in patients with completely resected, early-stage, low-grade tumors.

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Clin Transl Oncol. 2006 Aug;8(8):611-5.
Evaluation of the toxicity of the combined treatment of chemoradiotherapy, according to the scheme of Macdonald, after radical surgery in patients diagnosed of gastric cancer.
Tormo Ferrero V, Andreu Martinez FJ, Cardenal Macia R, Pomares Arias A.
Radiotherapy Oncology Service, Sant Joan University Hospital, Alicante, Spain.

PURPOSE: In this study we evaluated the acute toxicity of the combined treatment with chemoradiotherapy, according to the scheme of McDonald et al, in patients diagnosed with gastric cancer, after radical curative surgery. METHODS: From July 2001 to December 2005, a total of 24 patients, with diagnosis of adenocarcinoma of the stomach or adenocarcinoma of the gastroesophageal junction, who were operated with total or subtotal gastrectomy with free resection margins, were treated at our service with a combined scheme of adjuvant chemoradiotherapy. RESULTS: Grade 3 toxicity or higher appeared in three patients (12%) and grade 2 in five of the twenty-four patients (21%). Two patients (8%) needed to suspend treatment before the scheduled end date of treatment due to acute toxicity. No acute toxicity of cardiological, hepatic or renal nature was registered, and the most frequent toxicity was the gastrointestinal toxicity (detected in the 79% of the patients). CONCLUSIONS: Combined treatment with chemoradiotherapy, according to the scheme of Macdonald, in diagnosed patients with gastric cancer, after radical curative surgery is a well tolerated treatment, with a low degree of acute toxicity, thus the treatment compliance is not difficult.

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World J Gastroenterol. 2006 Aug 28;12(32):5108-12.
Endoscopic submucosal dissection for stomach neoplasms.
Fujishiro M.

Recent advances in techniques of therapeutic endoscopy for stomach neoplasms are rapidly achieved. One of the major topics in this field is endoscopic submucosal dissection (ESD). ESD is a new endoscopic technique using cutting devices to remove the tumor by the following three steps: injecting fluid into the submucosa to elevate the tumor from the muscle layer, pre-cutting the surrounding mucosa of the tumor, and dissecting the connective tissue of the submucosa beneath the tumor. So the tumors are resectable in an en bloc fashion, regardless of the size, shape, coexisting ulcer, and location. Indication for ESD is strictly confined by two aspects: the possibility of nodal metastases and technical difficulty, which depends on the operators. Although long-term outcome data are still lacking, short-term outcomes of ESD are extremely favourable and laparotomy with gastrectomy is replaced with ESD in some parts of therapeutic strategy for early gastric cancer.

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J Clin Oncol. 2006 Aug 20;24(24):3953-8.
Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response.
Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA.
Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. Jajani@mdanderson.org

PURPOSE: Preoperative therapy for localized gastric cancer has considerable appeal. We hypothesized that, in a cooperative group setting, preoperative chemoradiotherapy would induce a 20% pathologic complete response (pathCR) rate. Combined-modality therapy quality, survival, and safety were secondary end points. PATIENTS AND METHODS: Patients with localized gastric adenocarcinoma were eligible. A negative laparoscopic evaluation was required. Patients received two cycles of induction fluorouracil, leucovorin, and cisplatin followed by concurrent radiation and chemotherapy (infusional fluorouracil and weekly paclitaxel). Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed. Quality of therapy was assessed with other end points. RESULTS: Twenty institutions participated. Forty-nine patients were entered and 43 were assessable (12% stage IB; 37% stage II; and 52% stage III). The pathCR and R0 resection rates were 26% and 77%, respectively. At 1 year, more patients with pathCR (82%) are living than those with less than pathCR (69%). Grade 4 toxicity occurred in 21% of patients. Chemotherapy, radiotherapy, and surgery per protocol (including acceptable variations) occurred in 98%, 44%, and 63% of patients, respectively. A D2 dissection was performed in 50% of patients. Of 18 major radiotherapy variations, 17 were due to the lack of inclusion of the L3-4 vertebral interphase as prespecified. CONCLUSION: For localized gastric cancer, preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20% in a cooperative group setting. The quality of surgery improved (50% with D2 dissection) possibly because surgery was part of this trial. With some refinements, this preoperative chemoradiotherapy strategy is poised for a randomized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer.

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Am J Clin Oncol. 2006 Aug;29(4):376-9.
Paclitaxel poliglumex (PPX-Xyotax) and concurrent radiation for esophageal and gastric cancer: a phase I study.
Dipetrillo T, Milas L, Evans D, Akerman P, Ng T, Miner T, Cruff D, Chauhan B, Iannitti D, Harrington D, Safran H.
Brown University Oncology Group, Providence, RI, USA.

OBJECTIVES: To determine the maximal tolerated dose (MTD) and dose limiting toxicities of poly(l-glutamic acid)-paclitaxel (PPX) and concurrent radiation (PPX/RT) for patients with esophageal and gastric cancer. METHODS: Patients with esophageal or gastric cancer receiving chemoradiation for loco-regional, adjuvant, or palliative intent were eligible. The initial dose of PPX was 40 mg/m2/wk, for 6 weeks with 50.4 Gy radiation. Dose levels were increased in increments of 10 mg/m2/wk of PPX. RESULTS: Twenty-one patients were enrolled over 5 dose levels. Sixteen patients had esophageal cancer and 5 had gastric cancer. Twelve patients received PPX/RT as definitive loco-regional therapy, 4 patients had undergone resection and received adjuvant PPX/RT, and 5 patients had metastatic disease and received PPX/RT for palliation of dysphagia. Dose limiting toxicities of gastritis, esophagitis, neutropenia, and dehydration developed in 3 of 4 patients treated at the 80 mg/m2 dose level. Four of 12 patients (33%) with loco-regional disease had a complete clinical response. CONCLUSIONS: The maximally tolerated dose of PPX with concurrent radiotherapy is 70 mg/m2/wk for patients with esophageal and gastric cancer.

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Am J Clin Oncol. 2006 Aug;29(4):371-5.
Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic gastric cancer (MGC).
Cavanna L, Artioli F, Codignola C, Lazzaro A, Rizzi A, Gamboni A, Rota L, Rodino C, Boni F, Iop A, Zaniboni A.
Department of Oncology, Hospital of Piacenza, Italy.

OBJECTIVE: Treatment options for advanced or metastatic gastric cancer (A/MGC) are limited and inclusion of novel substances is necessary. Few studies have confirmed the activity and tolerability of the combination of oxaliplatin (OXA) and 5-fluorouracil (5-FU) modulated with leucovorin (LV) administrated to patients with A/MGC. The goal of current study was to evaluate the efficacy and toxicity of Folfox-4 regimen in patients with A/MGC. PATIENTS AND METHODS: Fifty-six patients were treated with Folfox-4 regimen. Treatment was continued until disease progression, unacceptable toxicity or until a patient chose to discontinue treatment. Responses to treatment and toxicity were recorded according to the WHO criteria and NCI toxicity criteria. RESULTS: All patients were assessable for toxicity and response. Patients (71.4% male, 28.6% female) had a median age of 65 years (range, 28-78). All patients had histologically confirmed metastatic (89.3%) or advanced (10.7%) gastric cancer. Response was evaluated every 6 weeks; 1 complete (1.8%) and 23 (41.1%) partial remission were observed (overall response rate 42.9%). Twenty patients (35.7%) showed stable disease and 12 (21.4%) had a progressive disease. Median overall survival, time to progression and follow up were 10 months, 6 months, and 11.5 months, respectively. WHO grade 3 or 4 hematologic toxicities included leucopenia, neutropenia, thrombocytopenia, and anemia. No patient experienced neutropenic fever. Other grade 3/4 toxicities included nausea, vomiting, diarrhea, stomatitis, and anorexia. Three patients (5.3%) experienced grade 3 peripheral neuropathy. No treatment-related deaths were recorded. CONCLUSIONS: Folfox-4 regimen is active and well tolerated in patients with advanced/metastatic gastric cancer.

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Expert Opin Pharmacother. 2006 Aug;7(12):1627-31.
Chemotherapy for advanced gastric or gastroesophageal cancer: defining the contributions of docetaxel.
Ajani JA.
Department of GI Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Box 426, Houston, TX 77030, USA. jajani@mdanderson.org

Despite continuing decline in its incidence, gastric cancer remains the fourth most commonly diagnosed malignancy and is the second leading cause of cancer death around the world. There are > 50% of patients who develop metastatic cancer, which in the majority is beyond cure and, despite many advances that have been achieved in the management of gastric cancer over the past 15 years, patient prognosis remains very poor. The need for the development of more effective therapies that are likely to further improve survival time cannot be overemphasised. A number of new active classes of agents have been identified and these include camptothecins, taxanes, platinols and oral fluoropyrimidines. This review explicitly focuses on the development of docetaxel in the treatment of advanced gastric or gastroesophageal cancer. Docetaxel, a potent taxane, is active as a single agent and in combination with other active agents. Most importantly, the final results of a pivotal randomised Phase III trial have demonstrated a higher overall response rate, longer time to progression and longer overall survival when docetaxal was added to cisplatin plus 5-fluorouracil and compared with cisplatin plus 5-fluorouracil (a reference regimen). This regimen with docetaxel, cisplatin and 5-fluorouracil is intense and proper patient selection and monitoring of the patients is recommended. Future developments will lead to the incorporation of docetaxel in regimens with improved safety profile.

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Surg Endosc. 2006 Aug;20(8):1299-304. Epub 2006 Jul 24.
Lessons learned from laparoscopic treatment of gastric and gastroesophageal junction stromal cell tumors.
Granger SR, Rollins MD, Mulvihill SJ, Glasgow RE.
Department of Surgery, University of Utah, 30 North, 1900 East, 3B110, Salt Lake City, UT 84132, USA.

BACKGROUND: Stromal cell tumors of the gastric and gastroesophageal junction are rare neoplasms that traditionally have been resected for negative margins using an open approach. This study aimed to evaluate the efficacy laparoscopic resection of gastric and gastroesophageal stromal cell tumors and the lessons learned from experience with this method. METHODS: This retrospective review evaluated all patients who underwent laparoscopic resection of gastric or esophageal stromal cell tumors at a tertiary referral center between December 2002 and March 2005. Medical records were reviewed with regard to patient demographics, preoperative evaluation, operative approach, tumor location and pathology, length of operation, complications, and length of hospital stay. RESULTS: A total of 12 consecutive patients with a mean age of 55 +/- 5.9 years were treated. Preoperative endoscopic ultrasound (EUS) was performed for 11 of 12 patients with a diagnostic accuracy of 100%, whereas EUS-guided fine-needle aspiration was performed for 10 of 12 patients with a diagnostic accuracy of 50%. Four patients with symptomatic gastroesophageal junction leiomyomas were treated with enucleation and Nissen fundoplication. Eight patients were treated with laparoscopic wedge resection of gastric lesions. Complete R0 resection was achieved for all the patients undergoing laparoscopic resection. Intraoperative endoscopy was performed for four patients and resulted in shorter operative times. The average operative time for this entire series was 169 +/- 17 min: 199 +/- 24 min for the first six cases and 138 +/- 19 min for the last six cases. The median hospital length of stay was 2 days. One patient with esophageal leiomyoma had persistent dysphagia at the 12-month follow-up assessment. There were no other complications and no deaths in this series of patients. CONCLUSIONS: Laparoscopic resection of gastric and gastroesophageal junction stromal cell tumors may be performed safely with low patient morbidity. This approach can achieve adequate surgical margins and lead to short hospital stays. Improvements in the technique have led to shorter operative times.

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Eur Rev Med Pharmacol Sci. 2006 Jul-Aug;10(4):179-82.
Palliative treatment of upper gastrointestinal obstruction using self-expansible metal stents.
Fiocca E, Ceci V, Donatelli G, Moretta MG, Santagati A, Sportelli G.
Department of Surgical Endoscopy, P Stefanini Department of General Surgery, La Sapienza University, Umberto I General Hospital, Rome, Italy. fausto.fiocca@uniroma1.it

Gastric outlet obstruction is either a late event in the natural history of bilio-pancreatic tumors or the result of recurrent gastric or pancreatic tumors. Self-expansible metal stents, inserted under endoscopic and fluoroscopic control, can be used for palliative treatment. The present study was aimed at evaluating both the feasibility and the results of stenting in patients with malignant gastric outlet obstruction; in addition, some technical suggestions are presented. A total of 33 patients, who had a metal stent positioned, were retrospectively evaluated; 20 of them were women and 13 were men, aged from 45 to 94 years, with a mean age of 75 years. Twenty-seven patients had a pancreatic adenocarcinoma, 4 had a stricture of a gastrojejunal anastomosis due to recurrent pancreatic tumor, 2 had a stricture of a gastrojejunal anastomosis secondary to gastric cancer surgery. No postoperatory complications were observed. Improvement in the quality of life was obtained in all patients. Following the stenting procedure, the median duration of hospitalization was 8 days (range: 6-20 days), and the mean survival rate was 12 weeks (range: 2-66 weeks). Endoscopic stenting for the palliation of malignant gastric outlet obstruction is feasible and is well tolerated by most patients. In some cases a period of enteral nutrition had to be necessarily carried out; nonetheless, the insertion of the stent improved the quality of life.

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Int J Palliat Nurs. 2006 Jul;12(7):306-17.
Palliative treatments for patients with inoperable gastroesophageal cancers.
Popat S, Lopez J, Chan S, Waters J, Cominos M, Rutter D, Hill ME.
Kent Oncology Centre, Maidstone Hospital, Kent ME16 9QQ, UK.

Most patients with cancers of the stomach, oesophagus or gastroesophageal junction ultimately develop metastatic or inoperable disease, rendering them incurable. They can, however, benefit from a variety of palliative interventions involving the multidisciplinary team, including chemotherapy, radiotherapy, endoluminal stenting, laser, or surgery. Often a combination of such strategies will be used to control symptoms, and maintain or improve quality of life. In this article, we review these multidisciplinary interventional approaches in patients with gastroesophageal cancers, and highlight future trends.

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Lancet Oncol. 2006 Apr;7(4):309-15. Comment in: Lancet Oncol. 2006 Apr;7(4):279-80.
Nodal dissection for patients with gastric cancer: a randomised controlled trial.
Wu CW, Hsiung CA, Lo SS, Hsieh MC, Chen JH, Li AF, Lui WY, Whang-Peng J.
Department of Surgery, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan. cwwu@vghtpe.gov.tw

BACKGROUND: The survival benefit and morbidity after nodal dissection for gastric cancer remains controversial. We aimed to do a single-institution randomised trial to compare D1 (ie, level 1) lymphadenectomy with that of D3 (ie, levels 1, 2, and 3) dissection for gastric cancer in terms of overall survival and disease-free survival. METHODS: From Oct 7, 1993, to Aug 12, 1999, 335 patients were registered. 221 patients were eligible, 110 of whom were randomly assigned D1 surgery and 111 of whom were randomly assigned D3 surgery, both with curative intent. Three participating surgeons had done at least 25 independent D3 dissections before the start of the trial, and every procedure was verified by pathological analyses. The primary endpoints were 5-year overall survival and 5-year disease-free survival. We also analysed risk of recurrence. Main analyses were done by intention to treat. This trial is registered at the US National Institute of Health website . FINDINGS: Median follow-up for the 110 (50%) survivors was 94.5 months (range 62.9-135.1). Overall 5-year survival was significantly higher in patients assigned D3 surgery than in those assigned D1 surgery (59.5% [95% CI 50.3-68.7] vs 53.6% [44.2-63.0]; difference beteween groups 5.9% [-7.3 to 19.1], log-rank p=0.041). 215 patients who had R0 resection (ie, no microscopic evidence of residual disease) had recurrence at 5 years of 50.6% [41.1-60.2] for D1 surgery and 40.3% [30.9-49.7] for D3 surgery (difference between groups 10.3% [-3.2 to 23.7], log-rank p=0.197). INTERPRETATION: D3 nodal dissection, compared with that of D1, offers a survival benefit for patients with gastric cancer when done by well trained, experienced surgeons.

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J Am Coll Surg. 2006 Apr;202(4):612-7.
Prophylactic gastrectomy for hereditary diffuse gastric cancer syndrome.
Newman EA, Mulholland MW.
Section of Gastrointestinal Surgery, Department of Surgery, The University of Michigan Medical Center, Ann Arbor, MI 48108, USA.

BACKGROUND: Germline mutations in the E-cadherin gene, CDH1, were recently identified in families with hereditary diffuse gastric cancer. The efficacy of endoscopic surveillance by current methods is largely ineffective because most tumors spread diffusely. There has been little evidence that prophylactic gastrectomy should be performed in patients with the genetic mutation, and few data are available on the outcomes of operations in patients with the CDH1 mutation undergoing prophylactic gastrectomy. We report the outcomes of patients with the CDH1 mutation who have undergone prophylactic gastrectomy in the year 2003 to 2004. STUDY DESIGN: After genetic counseling and informed consent, two patients underwent total gastrectomy with Roux-en-Y reconstruction. Demographic information, pedigree analysis, preoperative screening results, operative course, and postoperative data, including complications, were collected and reviewed for each patient. RESULTS: Pathologic examination of the stomach revealed no evidence of in situ or invasive carcinoma. There were no operative complications. Both patients reported diarrhea and moderate weight loss. There were no other postoperative complications. CONCLUSIONS: Prophylactic gastrectomy can be performed safely, without mortality or severe morbidity, in patients with CDH1 mutations, and should be curative in this population of patients.

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J Surg Oncol. 2006 Apr 1;93(5):368-72.
Presentation, treatment, and outcome of type 1 gastric carcinoid tumors.
Dakin GF, Warner RR, Pomp A, Salky B, Inabnet WB.
Department of Surgery, Weill Medical College of Cornell University, New York, NY, USA.

BACKGROUND AND OBJECTIVES: The aim of this study was to review the presentation, treatment, and outcome of patients with Type 1 gastric carcinoid tumors. METHODS: A retrospective review of 1,600 carcinoid patients was analyzed to identify patients with gastric carcinoid tumors. RESULTS: Eighteen patients were found to have biopsy-confirmed Type 1 gastric carcinoid tumors on upper endoscopy. Reasons for endoscopy included abdominal pain (n = 4), gastrointestinal bleeding (n = 4), surveillance for pernicious anemia (n = 8), and other (n = 2). The mean pre-treatment serum gastrin and chromogranin A levels were 1,436 ng/ml (+/-771 ng/ml) and 91.6 ng/ml (+/-68.6 ng/ml), respectively. Imaging revealed evidence of gastric carcinoid in 4 of 10 patients undergoing CT scanning and 3 of 10 patients undergoing octreotide scintigraphy. Of the 18 patients, 8 were treated medically (acidification or octreotide) and 10 were treated with surgery (laparoscopic antrectomy or partial gastrectomy). Mean gastrin levels decreased by 37.2% in the medically treated group (median follow-up 6 months), versus 94.0% in the surgically treated patients (median follow-up 5 months). Mean chromogranin A levels decreased by 56.2% in patients undergoing surgery. CONCLUSIONS: Gastric antrectomy is the most efficacious treatment for Type 1 gastric carcinoid, leading to a significant reduction in serum gastrin levels and regression of carcinoid tumors. (c) 2006 Wiley-Liss, Inc.

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J Surg Oncol. 2006 Apr 1;93(5):394-400. Comment in: J Surg Oncol. 2006 Apr 1;93(5):345-6.
Extended lymph node dissection without routine spleno-pancreatectomy for treatment of gastric cancer: low morbidity and mortality rates in a single center series of 250 patients.
Biffi R, Chiappa A, Luca F, Pozzi S, Lo Faso F, Cenciarelli S, Andreoni B.
Division of General Surgery, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. Roberto.Biffi@ieo.it

BACKGROUND AND OBJECTIVES: To verify the hypothesis that avoidance of routine splenectomy and distal pancreatectomy in a modified D-2 resection for gastric cancer can significantly lower the complications rate of this procedure in a population of Western patients. METHODS: A series of 250 consecutive Italian patients suffering from localized, histology-proven gastric cancer was submitted to gastrectomy and extended D-2 lymphadenectomy for treatment of their disease during an 8-year period (1994-2002) at the European Institute of Oncology in Milano, Italy. Caudal pancreas and spleen were routinely preserved, unless the tumor was not closely adjacent to or directly invading these organs. Postoperative morbidity, overall mortality, and length of hospital stay were recorded. RESULTS: One hundred forty patients underwent total gastrectomy and 110 a subtotal distal one; splenectomy was performed in 8 cases and spleno-pancreatectomy in 15. The postoperative morbidity rate was 18%, the mortality rate was 1.2% and 9 patients experienced re-operation. The median length of stay was 14.8 days. CONCLUSIONS: These results compete favorably with those reported after standard D-1 gastrectomy in Western patients series. D-2 gastrectomy with spleen and pancreas routine preservation can be considered a safe treatment for gastric cancer in Western patients, at least in experienced centers. (c) 2006 Wiley-Liss, Inc.

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Gan To Kagaku Ryoho. 2006 Mar;33(3):327-31.
[Combined chemotherapy with weekly Paclitaxel and doxifluridine for advanced and recurrent gastric cancers]
[Article in Japanese]
Mizutani S, Oyama T, Hatanaka N, Uchikoshi F, Yoshidome K, Tori M, Ueshima S, Okuma K, Hiraoka K, Yamagami Y, Takahashi H, Sueyoshi K, Taira M, Nakahara M, Nakao K.
Dept. of Surgery, Osaka Police Hospital.

We conducted combined therapy of weekly paclitaxel and doxifluridine (5'-DFUR) for 23 cases of advanced and recurrent gastric carcinomas to investigate their efficacy and safety. Subjects included 7 unresectable cases, 5 noncurative resection cases, and 11 recurrent cases. Twenty of the 23 subjects had a history of prior treatment with another anticancer drug. The treatment regime consisted of one course comprising 70 mg/m(2)of paclitaxel weekly for three consecutive weeks followed by one week rest, combined with 800 mg/day of 5'-DFUR orally. Results revealed a response rate of 17.6% (3/17), with 2 cases of CR, 1 case of PR, 10 cases of NC, and 4 cases of PD. One of the CR cases was an unresectable case involving a primary tumor, liver metastasis, and abdominal lymph node metastasis, while the other was a recurrent case involving abdominal lymph node metastasis. The median survival period was 387 days. The one-and two-year survival rates were 52% and 24%, respectively. In terms of adverse effects, there were only single cases of grade 3 leukopenia and grade 3 neutropenia, with no cases of grade 4 hemotoxicity. Both patients could be treated as outpatients. Combination therapy of weekly paclitaxel and 5'-DFUR can be an effective and safe therapy for advanced and recurrent gastric carcinomas.

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J Formos Med Assoc. 2006 Mar;105(3):194-202.
Clinical outcome of primary gastric lymphoma treated with chemotherapy alone or surgery followed by chemotherapy.
Chang MC, Huang MJ, Su YW, Chang YF, Lin J, Hsieh RK.
Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. mmhdonald@yahoo.com.tw

BACKGROUND: The role of surgical resection in the treatment of primary gastric lymphoma (PGL) remains unclear. This retrospective study evaluated the clinical outcome of PGL treated with chemotherapy alone or surgery followed by chemotherapy. METHODS: During 1986-2003, 59 patients with PGL (other than mucosa-associated lymphoid tissue type lymphoma) were identified from hospital files. The medical records, pathologic sections, radiographic images and treatment modalities of these patients were reviewed. Patients were categorized into localized (stage IE and IIE-1) and advanced (stage IIE-2 or beyond) stage groups. Survival was estimated by the Kaplan-Meier method. RESULTS: The study included 55 patients who received treatment at the same institute. Among them, 32 had localized PGL (15 stage IE, 17 stage IIE-1) and 23 had advanced disease. The median survival of the localized stage group was not reached during a mean follow-up of 168.1 +/- 16.7 months (95% confidence interval [CI], 135.4-200.8 months), while that of the advanced stage group was 33.0 +/- 6.8 months (95% CI, 19.7-46.5; p < 0.001, log-rank test). Among patients with localized PGL, the 5-year overall survival rate of those receiving chemotherapy alone (n = 19) or combination therapy (surgery followed by chemotherapy, n = 13) was 73.4% and 87.5%, respectively (p = 0.229). The 5-year disease-free survival was 68.4% and 84.6%, respectively (p = 0.540). However, post-chemotherapy life-threatening hemorrhage occurred in five of the 32 patients (15.6%) in the localized stage group: four in the chemotherapy-alone group, and one in the combination therapy group, all of whom had failed to achieve complete response. CONCLUSION: The clinical outcome of localized PGL treated by chemotherapy alone is similar to that treated by surgery followed by chemotherapy in terms of tumor response, disease-free survival and overall survival, suggesting that surgery be reserved for those with residual tumors after chemotherapy.

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Cancer. 2006 Feb 2; [Epub ahead of print]
Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion: analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique.
Kusamura S, Younan R, Baratti D, Costanzo P, Favaro M, Gavazzi C, Deraco M.
Department of Surgery, National Cancer Institute of Milan, Milan, Italy.

BACKGROUND: The purpose of this prospective Phase II study was to analyze morbidity and mortality of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP) in the treatment of peritoneal surface malignancies. METHODS: A total of 205 patients (50 with peritoneal mesothelioma, 49 with pseudomyxoma peritonei, 41 with ovarian cancer, 32 with abdominal sarcomatosis, 13 with colon cancer, 12 with gastric cancer, and 8 with carcinomatosis from other origins) underwent 209 consecutive procedures. Four patients underwent the intervention twice because of disease relapse. There were 70 men and 135 women. Mean age was 52 years (range, 22-76 yrs). CRS was performed by using peritonectomy procedures. IPHP through the closed abdomen technique was conducted with a preheated (42.5 degrees C) perfusate containing cisplatin + mitomycin C or cisplatin + doxorubicin. RESULTS: Major morbidity rate was 12%. The most significant complications were 23 anastomotic leaks or bowel perforations, 4 abdominal bleeds, and 4 sepses. Operative mortality rate was 0.9%. On logistic regression model multivariate analysis, extent of cytoreduction (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.29-6.40) and dose of cisplatin for IPHP >/= 240 mg (OR, 3.13; 95% CI, 1.24-7.90) were independent risk factors for major morbidity. Ten patients presented with Grade 3 to 4 toxicity. CONCLUSIONS: CRS + IPHP presented acceptable morbidity, toxicity, and mortality rates, all of which support prospective Phase III clinical trials. Cancer 2006. (c) 2006 American Cancer Society.

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J Clin Oncol. 2006 Feb 1;24(4):663-7.
Multicenter phase II trial of S-1 plus cisplatin in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma.
Ajani JA, Lee FC, Singh DA, Haller DG, Lenz HJ, Benson AB 3rd, Yanagihara R, Phan AT, Yao JC, Strumberg D.
Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. jajani@mdanderson.org

PURPOSE: S-1 plus cisplatin is considered highly active in Japanese gastric cancer patients. We conducted a phase II multi-institutional trial, in the West, in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma to evaluate activity and safety of this combination. METHODS: Patients received cisplatin intravenously at 75 mg/m2 on day 1 and S-1 orally at 25 mg/m2/dose bid (50 mg/m2/d) on days 1 to 21, repeated every 28 days. Patients with histologic proof of gastric or gastroesophageal junction adenocarcinoma with a Karnofsky performance status (KPS) of > or = 70% and near-normal organ function were eligible. All patients provided a written informed consent. To observe a 45% confirmed overall response rate (ORR), 41 assessable patients were needed. RESULTS: All 47 patients were assessed for safety and survival, and 41 patients were assessed for ORR. The median age was 56 years and median KPS was 80%. The median number of chemotherapy cycles was four. The confirmed ORR was 51% (95% CI, 35% to 67%) and it was 49% by an independent review. At the 6-month interval, 71% of patients were alive, with a median survival time of 10.9 months. Frequent grade 3 or 4 toxicities included fatigue (26%), neutropenia (26%), vomiting (17%), diarrhea (15%), and nausea (15%); however, stomatitis (2%) and febrile neutropenia (2%) were uncommon. There was one (2%) treatment-related death. CONCLUSION: S-1 plus cisplatin is active against gastric cancer and has a favorable toxicity profile. A global phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin currently is accruing patients.

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Anticancer Drugs. 2006 Feb;17(2):231-236.
Phase II study of a 4-week capecitabine regimen in advanced or recurrent gastric cancer.
Sakamoto J, Chin K, Kondo K, Kojima H, Terashima M, Yamamura Y, Tsujinaka T, Hyodo I, Koizumi W; on behalf of the Clinical Study Group of Capecitabine.
aKyoto University Graduate School of Medicine, Kyoto, Japan bCancer Institute Hospital, Tokyo, Japan cNagoya National Hospital, Nagoya, Japan dAichi Cancer Center Aichi Hospital, Okazaki, Japan eFukushima Medical University, Fukushima, Japan fAichi Cancer Center, Nagoya, Japan gOsaka National Hospital, Osaka, Japan hNHO Shikoku Cancer Center, Matsuyama, Japan iKitasato University School of Medicine, Sagamihara, Japan.

Our objective was to evaluate the efficacy and safety of capecitabine in chemotherapy-naive patients with unresectable advanced or metastatic gastric cancer. An open-label multicenter phase II study was conducted for previously untreated patients with advanced or metastatic gastric cancer. Oral capecitabine 828 mg/m twice daily was given on days 1-21 every 4 weeks. Baseline characteristics of 60 enrolled patients were: male/female 49/11, median age 64 years (range 28-74), good performance status (ECOG 0-1) in 98% of patients and 27 patients had prior gastrectomy (45%). A median of 4 treatment cycles were administered (range 1-37). Five patients were excluded from the efficacy analysis because they did not meet eligibility criteria. The overall response rate (RR) in the evaluable patient population (n=55) was 26% [95% confidence interval (95% CI) 15-39%] and a further 29% of patients had stable disease. The overall RR in the intent-to-treat population (n=60) was 23% (95% CI 13-36.0%). Median time to progression in the evaluable patient population was 3.4 months (95% CI 1.8-6.1) and overall survival time in the intent-to-treat population was 10.0 months (95% CI 6.4-13.6). The most frequent grade 3/4 drug-related adverse event was hand-foot syndrome (13%), but this was readily managed by treatment interruption and dose reduction. No patients developed grade 3/4 drug-related diarrhea, vomiting, leukopenia or thrombocytopenia. We conclude that this 4-week regimen of capecitabine showed promising activity and was well tolerated as first-line therapy for advanced/metastatic gastric cancer. Further investigation of this regimen is warranted.

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Crit Rev Oncol Hematol. 2006 Feb;57(2):123-31.
Gastric cancer: Standards for the 21st century.
Archie V, Kauh J, Jones DV Jr, Cruz V, Karpeh MS Jr, Thomas CR Jr.
Department of Radiation Oncology, The David Geffen U.C.L.A. School of Medicine, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.

Although the incidence of gastric cancer has been decreasing in the United States, it remains a leading cause of cancer death in the world, only lung cancer causes more deaths worldwide. The combination of relatively low prevalence, lack of pathognomonic symptoms, and lack of defined risk factors are associated with a delay in diagnosis leading to a dismal prognosis. For localized disease, surgery remains a cornerstone of treatment but much controversy remains regarding optimal peri-operative therapy. For advanced disease, several new agents and new combination chemotherapies have offered encouraging results. This paper seeks to review the major topics surrounding gastric cancer and cover the results of recently reported and ongoing trials.

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Acta Biomed Ateneo Parmense. 2005;76 Suppl 1:49-51.
Palliative surgery for gastric cancer in elderly patients.
Martella B, Militello C, Spirch S, Bruttocao A, Nistri R, De Rossi A, Barbon B, Terranova O.
Department of Geriatric Surgery, University of Padua, Padua, Italy.

Poor survival rate of elderly patients affected by locally advanced or metastatic gastric cancer is related to primary tumour complications. Bleeding is the most important adverse event, other major complications are gastric outlet obstruction and nutritional deprivation. Rarely the patients will perforate the stomach cancer and there is a sudden end to their life; contamination of the ascites result in a rapid death. Thus, an aggressive approach toward palliation of this condition is resection: in this manner the expected survival is approximately one year. Derivation techniques or endoscopic treatments are applied in those patients whose operative risk is inacceptable; in these cases poor median survival is expected. The aim of this report in to refer about the experience in palliative surgery for gastric cancer in the Department of Geriatric Surgery of the University of Padua.

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Bull Cancer. 2006 Jan 1;93(1):E1-6.
Epirubicin-docetaxel in advanced gastric cancer: two phase II studies as second and first line treatment.
Nguyen S, Rebischung C, Van Ongeval J, Flesch M, Bennamoun M, Andre T, Ychou M, Gamelin E, Carola E, Louvet C.
Service d'oncologie, Centre hospitalier, 40 avenue Leon-Blum, 60021 Beauvais Cedex, France. s.nguyen@ch-beauvais.fr

METHODS: We evaluated the Epitax combination (epirubicin 60 mg/m2 and docetaxel 75 mg/m2, every 3 weeks) in advanced gastric cancer (AGC) as second-line treatment after fluorouracil and platinum in 50 patients, then as first-line treatment in 36 patients. We report here the results of these two phase II studies. RESULTS: In the second-line treatment, the response rate (RR) was 15.5%. Grade 3-4 neutropenia was observed in 68% (febrile neutropenia in 40%, one treatment-related death). Median time to progression (TTP) and overall survival (OS) were 2.4 and 5.0 months, respectively. In the first-line treatment, the RR was 19.4%. With prophylactic granulocyte colony-stimulating factor, grade 3-4 neutropenia was reported in 38.9%. Then 22 patients received a second-line and 11 patients a third-line treatment. Median TTP and OS were 4.5 and 12 months, respectively. CONCLUSION: Epitax showed moderate activity in AGC. RR in both trials suggests a non-cross resistance with fluorouracil/platinum combination. The 12-month OS in the first-line treatment could be partly explained by early evaluation and active non-cross resistant second-line therapy.

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Cochrane Database Syst Rev. 2006 Jan 25;(1):CD004276.
Endoscopic mucosal resection for early gastric cancer.
YP W, C B, T P.

BACKGROUND: The treatment of early gastric cancer (EGC) using an endoscopy, namely, endoscopic mucosal resection (EMR), has been adopted for about 20 years, but the effectiveness and the safety of the modality are still controversial. The quality of these trials has not been assessed systematically. OBJECTIVES: The purpose of this review was to compare the effectiveness and the safety of EMR with gastrectomy for the treatment of EGC. SEARCH STRATEGY: Searches were conducted on the Cochrane Central Register of Controlled Trials - CENTRAL (which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register) on The Cochrane Library (Issue 1 2005) MEDLINE (1966 to March 2005) and EMBASE (1980 to March 2005), CINAHL (1985-March 2005) and CBM (Chinese BioMedical Database 1982 -2002). Reference lists from trials selected by electronic searching were handsearched to identify further relevant trials. Published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) were handsearched. Members of the Cochrane UGPD Group, and experts in the field were contacted and asked to provide details of outstanding clinical trials and any relevant unpublished materials SELECTION CRITERIA: All randomised controlled trials of EGC patients involving a treatment arm of EMR and a comparison arm of gastrectomy were to be included, but no RCTs were found. DATA COLLECTION AND ANALYSIS: Three reviewers (YP Wang, C Bennett and T Pan) independently assessed the eligibility of potential trials and extracted the data. MAIN RESULTS: There are no included randomised control trials for the systematic review. Available evidence derived from non-randomised controlled trials is discussed in the main text of this review. AUTHORS' CONCLUSIONS: There is a lack of randomised controlled trials in which EMR is compared with gastrectomy for EGC. There is a need for well designed randomised controlled trials to determine the effects of EMR compared to gastrectomy.

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J Chemother. 2005 Dec;17(6):656-62.
The emerging role of oxaliplatin in the treatment of gastric cancer.
Zaniboni A, Meriggi F.
Fondazione Poliambulanza, Brescia, Italy. zanib@numerica.it

Gastric cancer is often diagnosed in locally advanced or metastatic stages and, therefore, of poor prognosis. Many controversies exist about surgery, neoadjuvant, adjuvant and palliative treatments of gastric cancer. So we need to explore a variety of novel management options including the use of new agents and new combinations. Some of these agents include oral fluoropyrimidine, irinotecan, docetaxel and oxaliplatin. Oxaliplatin is a diaminocyclohexane-platinum compound that is significantly different from cisplatin and carboplatin with respect to its activity and toxicity. Oxaliplatin is an alkylating agent inhibiting DNA replication by forming adducts between two adjacent guanines or guanine and adenine molecules. However, the adducts of oxaliplatin appear to be more effective than cisplatin adducts in regard to the inhibition of DNA synthesis. In contrast to cisplatin, oxaliplatin has demonstrated efficacy alone and in combination with 5-fluorouracil in advanced colorectal cancer. Many studies are ongoing to test the combination in noncolorectal gastrointestinal tumors and other malignancies. This review focuses on the increasing amount of data concerning the clinical activity of oxaliplatin-based regimens in advanced gastric cancer.

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Dig Dis Sci. 2005 Dec;50(12):2218-23.
A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma.
Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. Peter_Enzinger@dfci.harvard.edu

Chemotherapy options for esophagogastric adenocarcinoma remain limited. Irinotecan has demonstrated broad activity in a variety of epithelial malignancies. Forty-six patients with previously untreated, measurable, unresectable, or metastatic esophagogastric adenocarcinoma were enrolled. Patients received irinotecan (125 mg/m2 intravenously over 90 min weekly) for 4 consecutive weeks followed by a 2-week rest. Forty-three patients received at least one treatment and were evaluable for response and toxicity. One complete and five partial responses were observed, for an overall response rate of 14% (95% CI, 4-24%). Median survival for all 43 patients was 6.4 months (95% CI, 4.6-8.2 months). Grade 3 to 4 toxicity included 10 patients (23%) with neutropenia, 13 patients (30%) with late diarrhea, 6 patients (14%) with vomiting, and 6 patients (14%) with fatigue. We conclude that although single-agent irinotecan is an active agent for esophagogastric adenocarcinoma, the schedule utilized in this trial is associated with moderate toxicity. When used as a single-agent, a tri-weekly schedule may be preferable for this patient population.

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World J Gastroenterol. 2005 Nov 28;11(44):7014-7.
Treatment for isolated loco-regional recurrence of gastric adenocarcinoma: Does surgery play a role?
Carboni F, Lepiane P, Santoro R, Lorusso R, Mancini P, Carlini M, Santoro E.
Department of Digestive Surgery and Liver Transplantation, Regina Elena Cancer Institute, via Elio Chianesi 53, 00144, Rome, Italy. fabiocarb@tiscali.it.

AIM:To evaluate the role of surgical treatment for isolated loco-regional recurrences of operated gastric adenocarcinoma.METHODS:Among the 837 patients operated for gastric adenocarcinoma between December 1979 and April 2004, 713 (85%) underwent resection with curative intent. A retrospective review of a prospectively collected gastric cancer database was carried out. Overall recurrence rate was 44% (315 cases), with 75% occurring within the first 2 years from the operation. Isolated L-R recurrences were observed in 38 (12%) patients. Symptomatic lesions were observed in 27 (71%).RESULTS:Six (16%) patients were macroscopically resected with curative intent. The recurrence was located in the gastric stump after a STG in three patients, in the esophagojejunal anastomosis after a TG in two patients and in the gastric bed after a TG in one patient. Surgical procedures consisted of three secondary TG, two esophagojejunal resection and one excision of an extraluminal recurrence. Postoperative complications occurred in two patients (33%), including one anastomotic leakage and one hemorrhage. The latter patient died of sepsis 35 d after the surgery (mortality rate 17%). All patients died of recurrent gastric cancer: 2 within 1 year from surgery (8 and 11 mo, respectively), 2 after 16 and 17 mo respectively and 1 after 28 mo from the second operation.CONCLUSION:Surgery plays a very limited role in the treatment for isolated loco-regional recurrence of gastric adenocarcinoma.

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J Clin Oncol. 2005 Oct 1;23(28):6957-65. Epub 2005 Sep 6.
Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma.
Ajani JA, Faust J, Ikeda K, Yao JC, Anbe H, Carr KL, Houghton M, Urrea P.
Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. jajani@mdanderson.org

PURPOSE: The conversion rate of tegafur (a component of S-1) to fluorouracil (FU) differs in Asians and whites because of polymorphic differences in the CYP2A6 gene. S-1 with cisplatin is considered highly active in Japanese gastric cancer patients. Therefore, we initiated a phase I pharmacokinetic study of this combination in our gastric cancer patients. PATIENTS AND METHODS: Patients received cisplatin intravenously on day 1 and S-1 orally, twice daily, on days 1 to 21 every 28 days. At level 1, the S-1 dose was 25 mg/m2/dose (50 mg/m2/d), but it was increased by 5 mg/m2/dose for the next level. Cisplatin was administered at 75 mg/m2 (for levels 1 and 2) but was then reduced to 60 mg/m2 (level 1A). At every level, a cohort of three patients, which could be expanded to six patients, was studied. Maximum-tolerated dose (MTD) was determined based on the dose-limiting toxicity (DLT) in the first cycle. Patients with histologic proof of gastric adenocarcinoma and near-normal organ function were studied. RESULTS: Sixteen patients were enrolled. No DLTs occurred at level 1. However, DLTs occurred at levels 2 and 1A. The area under the curve for FU correlated significantly with DLT (P = .006) and grade 3 to 4 diarrhea (P = .004). Six partial responses were confirmed, including three at the MTD. CONCLUSION: At the established MTD of S-1 plus cisplatin, the S-1 dose (50 mg/m2/d for 21 days) is lower in our study than in the Japanese study (80 mg/m2/d for 21 days). A multi-institutional phase II study of this active combination is currently accruing patients.

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Anticancer Res. 2005 Sep-Oct;25(5):3513-6.
The efficacy of endoscopic mucosal resection in the diagnosis and treatment of group III gastric lesions.
Katsube T, Konnno S, Hamaguchi K, Shimakawa T, Naritaka Y, Ogawa K, Aiba M.
Department of Surgery and Surgical Pathology, Tokyo Women's Medical University Daini Hospital, 2-2-10 Nishiogu, Arakawa-ku Tokyo 116-8567, Japan.

BACKGROUND: The efficacy of endoscopic mucosal resection (EMR) in diagnosing and treating group III lesions was analyzed. PATIENTS AND METHODS: Forty-three patients, with group III lesions confirmed by histopathological examination of the biopsy specimens, were included. All of these patients underwent EMR. The final diagnosis after EMR broadly classified the lesions as adenocarcinoma or adenoma. The clinicopathological features and therapeutic results were analyzed. RESULTS: Adenocarcinoma was identified in 16 patients (37.2%) and adenoma in 27 patients (62.8%). There were no differences in gender, age, lesion site, macroscopic type, or maximum diameter between the two groups. A significant difference in the maximum diameter of elevated lesions (p<0.05) was found between adenocarcinomas and adenomas, with the elevated lesions of adenocarcinomas measuring more than 10 mm. No residual focus recurrence was found among the adenomas. CONCLUSION: We conclude that EMR is effective and useful in diagnosing and treating group III lesions.

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Ugeskr Laeger. 2005 Sep 26;167(39):3678-81.
[Self-expanding metal stents as palliative treatment of a malign obstruction in the distal part of the ventricle or duodenum]
[Article in Danish]
Olsen E, Kiil J, Petersen JB.
Viborg Sygehus, Organkirurgisk Afdeling og Billeddiagnostisk Afdeling. eyo@dadlnet.dk

INTRODUCTION: Self-expanding metal stents (SEMS) have emerged as a simple therapeutic option for the palliation of patients with non-resectable malignant gastric outlet obstruction. We present our results from a three-year period. MATERIALS AND METHODS: Twenty-nine patients with obstruction from tumors in the pancreas (15), bile ducts (3), stomach (9) or transverse colon (2) underwent palliative stenting with a 9-cm-long, 22 mm Wallstent under general anaesthesia. Insertion of the SEMS was done under endoscopic and fluoroscopic control. Biliary stents were implanted prior to or simultaneously with the duodenal stent in eight patients. Seven were covered 6-cm-long, 10 mm Wallstents. Two patients had biliary stents implanted 12 and 262 days, respectively, after the duodenal stent by "rendezvous" technique. RESULTS: The stent deployment was successful in all patients. There were no procedure-related complications, but one patient died of cardiac arrest 12 hours after the operation. Obstruction was relieved in all patients, and an exclusively oral diet was possible for 23 of them. Seven patients with rapid progression of the disease stayed in hospital and died 0-16 days after the procedure. The median length of stay in hospital after the procedure was 2 days (1-32 days), after which the patients stayed at home for 40 days (2-270 days). The overall median survival time was 47 days (median, 0-274 days). There were no late complications (stent migration or perforation), but two patients needed an overlapping stent due to tumor overgrowth. DISCUSSION: Duodenal stents effectively resolve the obstructive symptoms of gastric outlet obstruction. There are few procedure-related complications, and the vast majority of patients can leave hospital and spend the short time left to them at home.

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Gan To Kagaku Ryoho. 2005 Sep;32(9):1319-22.
[A pilot study of TS-1+CDDP therapy for highly advanced stage IV gastric cancer]
[Article in Japanese]
Sakai Y, Saotome T, Fujimori M, Shimizu S, Inkyo T, Yugeta H, Ohbu M, Koma Y, Sato T, Nagashima F, Hayasaka A, Fukuyama Y, Tsuchiya S, Tsuyuguchi T, Saisho H.
Division of Gasttroenterlogy. Chiba University.

We performed a pilot study of combination chemotherapy with TS-1 and cisplatin for highly advanced gastric cancer. From June 2002, 12 patients with multiple liver metastases, carcinomatous lymphangitis or peritoneal dissemination, were enrolled in the study. TS-1 was administered at a daily dose on day 1-21 and an intermediate-dose of cisplatin (60 mg/m2) was administered on day 8. The combination was repeated in a 5-week cycle. The median administered cycles were three (one to eight). An objective response was obtained in 9 cases (75.0%) of primary sites and 6 cases of metastatic sites. No severe hematological toxicity occurred, and grade 3 stomatitis (in one case) and vomiting (in two cases) occurred as non-hematological toxicities. The improvement of clinical symptoms such as appetite loss and abdominal discomfort was obtained in 9 of 10 cases. The median survival time is 244 days. The TS-1/CDDP regimen had almost no survival benefits, but may induce relief of symptoms due to cancer and better quality of life.

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J Clin Oncol. 2005 Sep 1;23(25):6220-32.
Adjuvant therapy in gastric cancer.
Lim L, Michael M, Mann GB, Leong T.
Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.

Gastric cancer has a poor prognosis. The majority of patients will relapse after definitive surgery, and 5-year survival after surgery remains poor. The role of adjuvant therapy in gastric cancer has been controversial given the lack of significant survival benefit in many randomized studies so far. The results of a large North American study (Gastrointestinal Cancer Intergroup Trial INT 0116) reported that postoperative chemoradiotherapy conferred a survival advantage compared with surgery alone, which has led to the regimen being adopted as a new standard of care. However, controversies still remain regarding surgical technique, the place of more effective and less toxic chemotherapy regimens, and the use of more modern radiation planning techniques to improve treatment delivery and outcome in the adjuvant and neoadjuvant setting. This article reviews the current status of the adjuvant treatment for gastric cancer including discussion on the research directions aimed at optimizing treatment efficacy. Issues such as the identification of patients who are more likely to benefit from adjuvant therapy are also addressed. Further clinical trials are needed to move towards better consensus and standardization of care.

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Oncology. 2005;69(3):261-8. Epub 2005 Sep 1.
Phase I study of a combination of s-1 and weekly paclitaxel in patients with advanced or recurrent gastric cancer.
Ueda Y, Yamagishi H, Ichikawa D, Morii J, Koizumi K, Kakihara N, Shimotsuma M, Takenaka A, Yamashita T, Kurioka H, Nishiyama M, Morita S, Nakamura K, Sakamoto J.
Department of Surgery, Division of Digestive Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan. yueda@koto.kpu-m.ac.jp

OBJECTIVE: A phase I study of weekly intravenous paclitaxel combined with a fixed dose of S-1, a dihydropyrimidine-dehydrogenase-inhibitory oral fluoropyrimidine, was conducted for patients with advanced or recurrent gastric cancer (ARGC). Endpoints of this study were to examine the toxicity profile OF this regimen and to determine the recommended dose (rd) of paclitaxel. METHODS: S-1 was fixed at a dose of 80 mg/m(2) per day and was administered for 2 weeks (days 1--14) followed by a 2-week rest. Two dose levels of paclitaxel (level 1: 60 mg/m(2), level 0: 50 mg/m(2)) were studied. Paclitaxel was infused over 1 h on days 1, 8, and 15. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of paclitaxel in some patients. Fifteen patients were enrolled (6 patients in level 1, and 9 patients in level 0). Dose-limiting toxicities were defined as grade 4 hematological (including grade 3 febrile neutropenia) and grade 3 non-hematological (except anorexia, nausea, vomiting and depilation) toxicities. RESULTS: Three of 6 patients in level 1 developed grade 4 neutropenia or grade 3 febrile neutropenia, and 1 of them also showed grade 3 diarrhea, which settled the maximum-tolerated dose at this level. At level 0, 2 of 9 patients developed grade 4 neutropenia or grade 3 febrile neutropenia, and the RD of paclitaxel for this protocol was set at this level. Pharmacologic studies demonstrated the persistence of significant serum paclitaxel levels over 24 h after drug administration at both levels. Objective responses according to Response Evaluation Criteria in Solid Tumors were observed in 3 of 6 patients who had measurable disease. CONCLUSION: A combination of S-1 and weekly paclitaxel was feasible and well tolerated, and is suggested to produce a worthwhile response in ARGC. These results warrant further investigation, and a phase II study has already been started. Copyright (c) 2005 S. Karger AG, Basel.

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J Surg Oncol. 2005 Sep 15;91(4):232-6.
Results of total gastrectomy with extended lymphadenectomy for gastric cancer in elderly patients.
Otsuji E, Fujiyama J, Takagi T, Ito T, Kuriu Y, Toma A, Okamoto K, Hagiwara A, Yamagishi H.
Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji Kamigyo-ku, Kyoto, Japan. otsuji@koto.kpu-m.ac.jp

BACKGROUND AND OBJECTIVES: The incidence of gastric cancer, in people over 70 years of age, has increased remarkably. Aggressive lymphadenectomy with gastrectomy has been reported to improve survival in patients with gastric cancer. Because complication rates following gastrectomy increase with advancing age, we sought to determine whether this procedure was merited in elderly patients with gastric cancer. METHODS: We performed a retrospective analysis of 202 patients who underwent total gastrectomy with extended lymphadenectomy for gastric carcinoma. Postoperative complication rates were compared between patients over and under 70 years of age. RESULTS: The 10-year survival rates of patients under and over 70 years of age following total gastrectomy with extended lymphadenectomy were not significantly different. Although medical comorbidities in each group were similar, pulmonary dysfunction was significantly more common following total gastrectomy in patients over 70 years than in patients under 70 years. Moreover, logistic regression analysis revealed that patient's age was the only variable that independently correlated with the presence of postoperative complications. CONCLUSIONS: The prognosis of the gastric cancer patients over 70 years of age was similar to that of younger patients after total gastrectomy with extensive lymphadenectomy. However, pulmonary dysfunction was significantly more common in patients over 70 years old. Copyright 2005 Wiley-Liss, Inc.

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J Surg Oncol. 2005 Sep 15;91(4):276-9.
Needle catheter jejunostomy at esophagectomy for cancer.
Sica GS, Sujendran V, Wheeler J, Soin B, Maynard N.
Department of Surgery, Upper G.I. Unit, The John Radcliffe Hospital, Headington Oxford, United Kingdom. sica.giuseppe@fastwebnet.it

Important physiological changes occur after major abdominal surgery. Cellular and morphological changes follow a period of malnutrition. Enteral feeding is an important strategy for maintaining gut integrity and function. Controversies remain on the use of feeding jejunostomy after major abdominal surgery and its use had not gained widespread acceptance. The records of 262 consecutive patients who underwent esophagectomy for cancer were reviewed retrospectively to assess whether the placement of a needle catheter jejunostomy (NCJ) at the time of surgery is a safe and useful procedure. All the patients had a 9 Fr. NCJ place in a standardized fashion at the time of the esophagectomy. The technique of placement, the utilisation, and the complications of the NCJ were examined. The enteral nutrition was started in the first post-operative day. Sixty-three percent of our patients required enteral nutrition for 10 or more days. In 19%, this requirement was prolonged for more then 20 days, upto 68 days. The complications related to NCJ were four (1.5%). The use of the NCJ as described is safe, with an extremely low rate of complications. It may provide adequate nutritional support for a prolonged period of time at low costs. Its routine use in patients undergoing esophagectomy is recommended. Copyright 2005 Wiley-Liss, Inc.

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J Clin Oncol. 2005 Aug 20;23(24):5660-7.
Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma.
Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E.
Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Box 426, 1515 Holcombe Blvd, Houston, TX 77030, USA. jajani@mdanderson.org

PURPOSE: The purpose of this study was to define the contribution of docetaxel to combination chemotherapy in the outcome of patients with advanced gastric or gastroesophageal adenocarcinoma. We compared the overall response rate (ORR) and safety of docetaxel plus cisplatin (DC) with DC plus fluorouracil (DCF) to select either DC or DCF as the experimental treatment in the ensuing phase III part of trial V-325. PATIENTS AND METHODS: In this phase II randomized study, untreated patients with confirmed advanced gastric or gastroesophageal adenocarcinoma received either DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2 on day 1, and fluorouracil 750 mg/m2/d as continuous infusion on days 1 to 5) or DC (docetaxel 85 mg/m2 and cisplatin 75 mg/m2 on day 1) every 3 weeks. An independent data monitoring committee (IDMC) was to select one of the two regimens based primarily on ORR and safety profile. RESULTS: Of 158 randomly assigned patients, 155 (DCF, n = 79; DC, n = 76) received treatment. The confirmed ORR was 43% for DCF (n = 79) and 26% for DC (n = 76). Median time to progression was 5.9 months for DCF and 5.0 months for DC. Median overall survival time was 9.6 months for DCF and 10.5 months for DC. The most frequent grade 3 and 4 events per patient included neutropenia (DCF = 86%; DC = 87%) and GI (DCF = 56%; DC = 30%). CONCLUSION: Both regimens were active, but DCF produced a higher confirmed ORR than DC. Toxicity profiles of DCF were considered manageable. The IDMC chose DCF for the phase III part of V-325, which compares DCF with cisplatin plus fluorouracil.

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Gan To Kagaku Ryoho. 2005 Aug;32(8):1145-8.
[Clinical study of TS-1 for inoperative and recurrent gastric cancer and evaluation of long survival cases]
[Article in Japanese]
Tanabe K, Yoshida K, Hamai Y, Ukon K, Ohta K, Hihara J, Toge T.
Dept. of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University.

The clinical efficacy and safety of TS-1 therapy were studied retrospectively in patients with inoperable and recurrent gastric cancer. The subjects were 67 patients who were treated with TS-1 in our department between June 1999 and September 2004. The objective overall response rate was 41.0% (16/39; 95% confidence interval, CI, 25.3-56.7). By location, the response rate of peritoneal dissemination was high (57.1%), as were those of primary lesion (53.3%) and lymph nodes (42.9%). The prevalence of adverse reactions with a grade of 3 or 4 was 12.8%. The median survival rate (MST) was 276 days with 1-year and 2-year survival rates of 48.9% and 27.8%, respectively. This resulted in 6 long-term survival cases (over 2.5 years) after TS-1 therapy, and the longest survival time was 3y 5m after TS-1 therapy. PRs or long-term NCs after TS-1 therapy were likely to be important factors for long-term survival. In conclusion, TS-1 is safe and effective for patients with inoperable and recurrent gastric cancer, and is promising as a first-line treatment.

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Aliment Pharmacol Ther. 2005 Aug 1;22(3):233-41.
Trends in the management and survival of digestive tract cancers among patients aged over 80 years.
Bouvier AM, Launoy G, Lepage C, Faivre J.
Registre des cancers digestifs de la Cote-d'Or, EMI INSERM 0106, Dijon Cedex, France.

Summary Background: Advances have occurred in the management of digestive tract cancers, but it is not known how much they have benefited the elderly. Aims: To determine trends in treatment, stage at diagnosis and prognosis of digestive tract cancers among patients aged >/=80 years in two well-defined French populations. Design: Time trends were studied in three age classes and in 5 four-year time intervals. A multivariate relative survival analysis was performed to estimate the independent effect of both age and period on prognosis. Results: Five-year relative survival rates were 1.9% for oesophageal cancer, 12% for stomach cancer, 41% for colon cancer and 37% for rectal cancer. The survival rates improved between the first and the fifth period for all cancer sites except for oesophageal cancer. This improvement remained significant after adjustment for age, sex, site and treatment. It was associated with an increase in the proportion of patients who underwent curative resection. Very few patients received adjuvant chemotherapy. The use of adjuvant radiotherapy for rectal and oesophageal cancers did not significantly increase over time. Conclusions: Except for oesophageal cancers, substantial advances in the care of digestive tract cancers in the elderly have been achieved. Surgery should not be restricted on the basis of age alone. Further improvements can be made in particular to enhance adjuvant therapy whenever possible.

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J Clin Oncol. 2005 Jul 10;23(20):4509-17.
Optimal locoregional treatment in gastric cancer.
Jansen EP, Boot H, Verheij M, van de Velde CJ.
Department of Radiotherapy and Gastroenterology of the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.

Worldwide, gastric cancer is one of the leading causes of cancer-related death. The mainstay of curative treatment is radical surgery. But even with optimal surgical resection, the prognosis remains modest in the Western world. Numerous attempts have been undertaken to improve clinical outcome. More extensive lymph node dissection, adjuvant radiotherapy and adjuvant chemotherapy did not result in a survival benefit in randomized trials. Only postoperative chemoradiotherapy has proven to be valuable in prospective randomized trials. Questions are to be answered about optimization of surgery, radiotherapy and chemotherapy, and fine tuning of the three modalities. One of the key issues that should be addressed is whether pre- or postoperative chemoradiotherapy will benefit survival or locoregional control in the case of optimal surgery with an "over-D1" lymphadenectomy and without splenectomy. In this article the most relevant literature on locoregional treatment in operable gastric cancer will be reviewed and future strategies will be discussed.

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J Surg Oncol. 2005 Jul 1;91(1):26-32.
Laparoscopy-assisted distal gastrectomy with systemic lymph node dissection: a phase II study following the learning curve.
Fujiwara M, Kodera Y, Miura S, Kanyama Y, Yokoyama H, Ohashi N, Hibi K, Ito K, Akiyama S, Nakao A.
Department of Surgery II, Nagoya University School of Medicine, Nagoya/Aichi, Japan.

BACKGROUND AND OBJECTIVES: A preliminary study on the use of laparoscopy-assisted approach to treat gastric carcinoma resulted in higher morbidity. STUDY DESIGN: A prospective phase II study of laparoscopy-assisted distal gastrectomy (LADG) was performed for patients with preoperative diagnosis of T1 N0 stage cancer located in the lower or middle-third stomach. Bleeding amount, operating time, mortality, morbidity, and the number of lymph node retrieval were recorded and compared with the preliminary series reported previously by the same authors. RESULTS: Between 2000 and 2002, 47 patients were accrued. The mean blood loss and postoperative hospital stay were significantly decreased compared with the previous series, whereas the operating time was not. There were no in-hospital deaths, with the incidence of anastomotic leakage significantly decreased. All patients remain disease-free to date. CONCLUSIONS: LADG can be performed safely and morbidity, no longer, is a drawback by experienced hands that have reached plateau of the learning curve, although it remains a time-consuming procedure. Its application to gastric cancer surgery is feasible for early stage cancer, and its applicability to the treatment of T2 stage cancer will be the next issue to be explored.

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J Surg Oncol. 2005 Jun 1;90(3):134-8; discussion 138.
New strategies for the prevention of gastric cancer: Helicobacter pylori and genetic susceptibility.
Correa P.
Department of Pathology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA. correa@lsuhsc.edu

Recently acquired knowledge points to the potential of markedly improved strategies for the prevention of gastric cancer. The International Agency for Cancer Research has reached the conclusion that infection with Helicobacter pylori (H. pylori) is carcinogenic to humans (Group I). The bacterium displays marked genetic heterogeneity. Virulence related genes, especially cag A and vac A s1 m1 are associated with an increased cancer risk. Genetic susceptibility, especially polymorphisms of the cytokine genes may increase cancer risk. Highly susceptible individuals infected with high virulence bacterial genotypes have a markedly increased gastric cancer risk. They should be targeted for endoscopic monitoring to detect advanced precancerous lesions. The state of the art is briefly reviewed and the needed research identified. Copyright 2005 Wiley-Liss, Inc

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J Surg Oncol. 2005 Jun 1;90(3):166-70.
Role of post-operative chemoradiation in resected gastric cancer.
Macdonald JS.
Saint Vincent's Comprehensive Cancer Center, New York, New York 10011, USA. jmacdonald@aptiumoncology.com

The curative management of gastric adenocarcinoma depends upon complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are at least 70%-80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared to less extensive operations. Until recently, attempts at preventing recurrence have employed adjuvant chemotherapy and have been ineffective. A large U.S. Intergroup study (INT-0116) demonstrated that combined chemoradiation following complete gastric resection improves median time to relapse (30 vs. 19 months, P < 0.0001) and overall survival (35 vs. 28 months, P = 0.01). The improvements in disease-free and overall survival resulting from post-operative chemoradiation have defined a new standard of care. An update of the results of INT-0116 analysis performed in 2004 with 7 years median follow-up, not only confirms the benefits from post-operative chemoradiation but also shows that chemoradiation does not produce significant long-term toxicity. The recent publication of the first large adequately powered III neoadjuvant chemotherapy trial suggested this technique might down-stage tumors and increase resectability. Future advances in the therapy of resectable gastric cancer may come from studies of pre-operative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and anti-angiogenesis agents. Copyright 2005 Wiley-Liss, Inc

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J Surg Oncol. 2005 Jun 1;90(3):153-65.
Status of extended lymph node dissection: locoregional control is the only way to survive gastric cancer.
Hartgrink HH, van de Velde CJ.
Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands. H.H.Hartgrink@lumc.nl

There are many factors that are of influence on gastric cancer treatment. The only way to survive is complete locoregional control. More extended dissections should lead to better outcome, but increased morbidity and mortality probably offset its long-term effect in survival in randomised studies. In this article the factors of influence on outcome of gastric cancer treatment such as the extent of lymph node dissection, splenectomy, pancreatectomy, age, volume and additional treatments are discussed. A literature review of these factors in relation to the latest results of the Dutch Gastric Cancer Trials are presented. If morbidity and mortality can be reduced there might be an advantage of extended lymph node dissection. Splenectomy and pancreatectomy should be performed only in case of direct in growth from the tumour into these organs. Centralisation of gastric cancer treatment should be achieved in order to improve results and to facilitate research. By refining selection criteria in the treatment of gastric cancer further improvements are to be expected. Copyright 2005 Wiley-Liss, Inc

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J Surg Oncol. 2005 Jun 1;90(3):174-86; discussion 186-7.
Perioperative adjunctive treatment in the management of operable gastric cancer.
Silberman H.
Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. hsilber777@aol.com

Outcome in the management of clinically resectable gastric carcinoma has been disappointing, at least in Western populations, despite increasingly radical surgery and extensive experience with adjunctive perioperative treatment with innumerable single and combined modality regimens. The United States Intergroup Study, a prospective, randomized, controlled trial of adjuvant chemoradiation, demonstrated significant improvement in disease-free and overall survival. Consequently, this regimen of postoperative fluoruracil plus leucovorin and locoregional radiation has been incorporated into current clinical practice. In hopes of further improving cure rates, many other regimens are under investigation, including the efficacy of neoadjuvant therapy alone, combined neoadjuvant and adjuvant therapy, and adjuvant therapy alone. In these clinical trials, therapeutic agents are prescribed alone or in multimodal regimens and include systemic chemotherapy, intraperitoneal (IP) chemotherapy with or without hyperthermia, intraoperative radiotherapy (IORT), and postoperative external beam irradiation. Several molecular markers have been identified, which seem to predict that a given tumor may be effective or resistant to a drug, raising the possibility of customized chemotherapy regimens. Preclinical studies suggest potential efficacy of angiogenesis inhibitors, monoclonal antibodies, and antisense agents. Copyright 2005 Wiley-Liss, Inc

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J Surg Oncol. 2005 Jun 1;90(3):195-207; discussion 207.
Gastric GI stromal tumors (GISTs): the role of surgery in the era of targeted therapy.
Heinrich MC, Corless CL.
OHSU Cancer Institute, Oregon Health and Science University and VA Medical Center, Portland, Oregon 97239, USA. heinrich@ohsu.edu

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm arising in the stomach. These tumors were previously classified as smooth muscle tumors, but in recent years it has become clear that they are clinically, pathologically, and molecularly distinct from other tumors and are much more common than previously appreciated. Historically, patients with primary localized or advanced GIST have been managed surgically, as there was no proven role of other treatment modalities such as radiation or chemotherapy. However, the field of GIST was revolutionized with the 1998 discovery that the vast majority of these tumors have oncogenic gain-of-function mutations of the KIT receptor tyrosine kinase. Follow-up studies have confirmed that KIT is both a useful diagnostic marker and an excellent therapeutic target. Imatinib, an inhibitor of KIT kinase activity, is now the standard front-line therapy for patients with advanced GIST. In this review, we discuss pathological and molecular features of gastric GISTs and review the historic and current roles of surgery in the treatment of patients with primary or metastatic GIST. The importance of a multi-disciplinary approach using both surgery and imatinib therapy is emphasized. Copyright 2005 Wiley-Liss, Inc

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Gut. 2005 Jun;54(6):735-8.
The time to eradicate gastric cancer is now.
Graham DY, Shiotani A.
Michael E DeBakey Veterans Affairs Medical Center, RM 3A-320 (111D), 2002 Holcombe Boulevard, Houston, TX 77030, USA. dgraham@bcm.tmc.edu

Worldwide gastric cancer remains one of the most common cancers, killing upwards of one million people each year. While the molecular pathogenesis remains unclear, infection with the bacterium Helicobacter pylori is considered a "necessary but not sufficient" cause, not surprisingly as gastric cancer has long been known to be associated with atrophic gastritis. Eradication of H pylori is expected to virtually eliminate gastric cancer and H pylori associated peptic ulcer within approximately 40 years and thus reduce overall mortality. In the USA, the incidence of gastric cancer in the general population is low, reflecting the change in the pattern of gastritis from atrophic to non-atrophic and in the low and decreasing prevalence of H pylori infection in the middle and upper classes. However, the plan for eradication of this important pathogen must be considered within the context of the prevalence and outcome within specific populations.Anticancer Res. 2005 Mar-Apr;25(2B):1297-301.

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A phase II multicentric trial of S-1 combined with 24 h-infusion of cisplatin in patients with advanced gastric cancer.
Iwase H, Shimada M, Tsuzuki T, Horiuchi Y, Kumada S, Haruta J, Yamaguchi T, Sugihara M, Ina K, Kusugami K, Goto S.
Department of Gastroenterology, Nagoya Medical Center, Japan. iwaseh@nnh.hosp.go.jp

BACKGROUND: The aim of this multicentric trial was to determine the clinical toxicities and antitumor effects of a chemotherapy regimen of S-1 combined with cisplatin in patients with inoperable locally or metastatic advanced gastric cancer. PATIENTS AND METHODS: Forty-two patients were entered into the study. S-1 (80 mg/m2) was administered orally daily for 14 consecutive days and 24-h infusion of cisplatin (70 mg/m2) was administered on day 8 of every 28-day cycle. RESULTS: The overall response rate was 50% and complete response rate was 5%. The most common adverse event was leucopenia, which occurred with grade 3 in 7 patients (16.6%) and grade 4 in 2 patients (4.8%). Non-hematological adverse events were generally mild. The median survival time was 342 days. The 2-year survival rate was 22.9%. CONCLUSION: This combination chemotherapy is active, convenient and well tolerated in patients with high-grade advanced gastric cancer.

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Gan To Kagaku Ryoho. 2005 Mar;32(3):405-10.
[Limited surgery for early gastric cancer using lymphatic basin dissection--a sure method of sentinel node biopsy for gastric cancer]
[Article in Japanese]
Kinami S, Miwa K, Ishii K, Miyashita T, Fushida S, Fujimura T, Ohta T.
Dept. of Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medicine, Kanazawa University, Japan.

The results of our sentinel node biopsy for early-stage gastric cancer had a high predictive value for nodal metastasis, with a sensitivity of 85% (34/40) and an accuracy of 98% (259/265). Therefore, sentinel node biopsy is expected to be decided as an adaptation of limited surgery for early gastric cancer. However, there were two serious problems in sentinel node biopsy for gastric cancer; one was the great difficulty of sentinel node detection and biopsy in the operative field, and the other was the possibility of false negative cases in the frozen section diagnosis. To solve these problems, we developed lymphatic basin dissection, a new technique suitable for sentinel node biopsy of gastric cancer. The lymphatic basin is an own lymphatic components dyed in blue in the dye method. In the lymphatic basin dissection method, sentinel nodes are detected and harvested at the back table after en bloc dissection of the lymphatic basins. Lymphatic basin dissection is an excellent method because of the certainty in sentinel node biopsy, and the sure back-up dissection. Lymphatic basin dissection and following limited surgery was performed on 143 patients for early-stage gastric cancer in our hospital. No patient had a recurrence of gastric cancer; 9 patients died of other diseases, and the other 134 survived.

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Surgery. 2005 Mar;137(3):317-22.
Laparoscopic assisted distal gastrectomy for early gastric cancer: Five years' experience.
Mochiki E, Kamiyama Y, Aihara R, Nakabayashi T, Asao T, Kuwano H.
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Japan. emochiki@showa.gunma-u.ac.jp

BACKGROUND: Laparoscopic assisted gastrectomy is being reported increasingly as the treatment of choice for early gastric cancer. However, no reports concerning the prognosis of patients who have undergone laparoscopic assisted distal gastrectomy (LADG) for early gastric cancer or data comparing the results to those obtained after open gastric surgery are yet available. METHODS: A retrospective study was performed comparing laparoscopic assisted and open distal gastrectomies for early gastric cancer. Eighty-nine patients who underwent LADG were compared to 60 who underwent conventional open distal gastrectomy (DG) in terms of pathologic findings, operative outcome, complications, and survival. RESULTS: There were no significant differences between LADG and DG in operation time (209 vs 200 minutes), complication rate (9% vs 18%), and 5-year survival rate (98% vs 95%). There were differences between LADG and DG with regard to blood loss (237 vs 412 mL), number of lymph nodes (19 vs 25), postoperative stay (17 vs 25 days), and the duration of epidural analgesia (2 vs 4 days) ( P < .05 each). CONCLUSIONS: For properly selected patients, LADG can be a curative and minimally invasive treatment for early gastric cancer.

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Br J Surg. 2005 Mar;92(3):370-5.
Treatment of peritoneal dissemination from gastric cancer by peritonectomy and chemohyperthermic peritoneal perfusion.
Yonemura Y, Kawamura T, Bandou E, Takahashi S, Sawa T, Matsuki N.
Peritoneal Dissemination Programme, Shizuoka Cancer Centre, 1007 Shimo-nagakubo, Nagaizumi-machi, Suntougun, Shizuoka 411-8777, Japan. y.yonemura@scchr.p

BACKGROUND: There is no standard treatment for peritoneal dissemination from gastric cancer. A novel treatment consisting of peritonectomy and intraoperative chemohyperthermic peritoneal perfusion (CHPP) was compared with conventional surgery and CHPP. METHODS: Records of all patients who underwent CHPP after cytoreductive surgery between 1992 and 2002 were reviewed. RESULTS: Data for 107 patients with peritoneal dissemination were available. Complete cytoreduction was achieved in 47 (43.9 per cent) of the 107 patients: 18 of 65 who underwent conventional surgery and 29 of 42 who had peritonectomy. Twenty-three patients (21.5 per cent) suffered from complications. The overall operative mortality rate was 2.8 per cent. Seventeen patients (15.9 per cent) were disease free and 87 subsequent deaths were related to disease progression. The median survival for all patients was 11.5 months, with a 5-year survival rate of 6.7 per cent. Median survival after complete cytoreduction was 15.5 months and that after incomplete cytoreduction was 7.9 months, with 5-year survival rates of 13 and 2 per cent respectively. Completeness of cytoreduction and peritonectomy were independent prognostic factors. The 5-year survival rate after complete cytoreduction by peritonectomy with CHPP was 27 per cent. CONCLUSION: Complete cytoreduction after peritonectomy and CHPP may improve the survival of patients with peritoneal dissemination from gastric cancer.

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Onkologie. 2005 Mar;28(3):128-32.
Infusional 5-fluorouracil and mitomycin C: an effective regimen in the treatment of advanced gastric cancer.
Rudi J, Werle S, Bergtholdt D, Hofheinz RD.
Abteilung Innere Medizin I, Theresienkrankenhaus und St. Hedwig-Klinik GmbH, Mannheim, Germany.

BACKGROUND: Weekly infusional 5-fluorouracil (5-FU) and folinic acid (FA) as part of multi-drug chemotherapy regimens in advanced gastric cancer (AGC) has shown to be effective with low toxicity. The present analysis was carried out to evaluate the safety and efficacy of 5-FU/FA in combination with 3-weekly mitomycin C (MMC) in patients with advanced gastric cancer. PATIENTS AND METHODS: A total of 28 patients with AGC were analysed (first line n=23). They received weekly 24-h 5-FU 2,600 mg/m2 preceded by 2-h FA 500 mg/m2 for 6 weeks followed by a two week rest period. Bolus MMC 10 mg/m2 was applied on days 1 and 22. Patient characteristics were: m/f 17/11; median age 67 years (43-79). The most common metastatic sites were liver and peritoneum (n=12, respectively). RESULTS: A median of 3 and a total of 91 cycles were administered. Mean dose intensity in cycle I was: 5-FU 86%, MMC 87%. Responses were observed in 43%, no change was seen in 29% of the patients. Median overall survival was 9.7 months (10.7 months for patients treated first line). Non-haematological toxicities (NCI CTC grades 3 and 4) were observed in 2 patients, leukopenia and thrombocytopenia grades 3/4 were observed in 50 and 25% of the patients, respectively. CONCLUSIONS: Infusional 5-FU/FA plus MMC may safely be used in patients with AGC in the routine clinical setting. This regimen yields response rates and survival data comparable to platinum-based regimen.

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Gan To Kagaku Ryoho. 2005 Feb;32(2):195-9.
[Results of treatment of far advanced and recurrent stomach cancer with TS-1]
[Article in Japanese]
Johira H, Yunoki S, Kawata N, Watanabe N, Hachisuka Y, Kimura M, Uomoto M, Hatano H, Sanada E, Watanabe R, Ohmori K, Miyata N.
Dept of Surgery, Matsuyama Shimin Hospital.

We used TS-1 as first-line therapy to treat 44 patients with far advanced or recurrent gastric cancer, and assessed the results and safety. One treatment cycle consisted of TS-1, 80 mg/m2/day, for 28 days followed by a 14-day rest period. The efficacy rate in the cases capable of being evaluated was 30.1% (11/36), and 25.0%, (7/28) when TS-1 was used as monotherapy. The efficacy rate was lower than in a phase II study, however, the median survival time (MST) of 10.7 months for the patients as a whole, the 1-year survival rate of 43.2%, and the 2-year survival rate of 20.5% were favorable. There were many NC cases in which long-term therapy was possible, and they contributed to the long-term survival. The incidence of adverse events was 84.1%, but the incidence of grade 3 or more events was low at 13.6%. Since TS-1 is highly efficacious and safe, as well as convenient because of being an oral preparation, it appears that it can be ranked as the drug of first choice for chemotherapy of far advanced or recurrent gastric cancer.

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Cancer J. 2005 Jan-Feb;11(1):18-25.
Minimally invasive treatment of stomach cancer.
Otsuka K, Murakami M, Aoki T, Tajima Y, Kaetsu T, Lefor AT.
Department of Surgery, Division of General & Gastroenterological Surgery, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.

The rate of detection of early gastric cancer has increased because of the development of diagnostic techniques, such as endoscopy, biopsy, and endoscopic ultrasonography. Recently, minimally invasive surgical procedures for benign gastric conditions have been advocated, and the laparoscopic approach is noted as a technique that increases the quality of life. However, the development of laparoscopic gastric resections and laparoscopically assisted gastric operations for malignancy still deserve a word of caution. Laparoscopic local resection of the stomach is used to treat mucosal cancer without lymph node metastasis, and laparoscopy-assisted distal gastrectomy is used to treat early gastric cancer with lymph node metastasis in the perigastric portion. According to short-term results reported by a small group of surgeons, laparoscopic approaches for gastric cancer result in a minimally invasive approach, early recovery, and decreased morbidity and mortality. However, the longterm results of these less invasive treatments are not known in advanced gastric cancer. If the results of randomized controlled studies for advanced gastric cancer are confirmed, the use of these techniques will spread worldwide and may become a standard technique for the resection of gastric cancer.

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Ned Tijdschr Geneeskd. 2004 Dec 18;148(51):2529-34.
[New insights in the adjuvant treatment of gastric cancer]
[Article in Dutch]
Jansen EP, Boot H, Cats A, van Coevorden F, Zoetmulder FA, Verheij M.
Afd. Radiotherapie, Het Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis, Plesmanlaan 121, 1066 CX Amsterdam. epm.jansen@nki.nl

The current standard treatment of patients with gastric cancer is partial or total stomach resection and dissection of the draining lymph nodes. This approach, however, results in a rather low survival rate, partly because the diagnosis is often established in an advanced stage. Various strategies, including adjuvant radiotherapy, chemotherapy or more extensive surgical procedures, have resulted mainly in increased morbidity without improving survival. In a recent randomised trial, concurrent postoperative radiotherapy and chemotherapy prolonged survival and reduced the chance of a local recurrence at an acceptable toxicity. Although several aspects of combined radiochemotherapy require further study, this new treatment concept appears to be a promising addition to the therapeutic arsenal for gastric cancer.

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Gan To Kagaku Ryoho. 2004 Dec;31(13):2183-6.
[Low-dose paclitaxel therapy as second-line chemotherapy for patients who previously received TS-1 therapy]
[Article in Japanese]
Takemura M, Osugi H, Lee S, Kaneko M, Tanaka Y, Fujiwara Y, Nishizawa S, Iwasaki H.
Dept. of Gastroenterological Surgery, Osaka City University Graduate School of Medicine.

TS-1 is often used as first-line chemotherapy for treatment of advanced or recurrent gastric cancer, but there is no definite therapeutic policy for patients for whom TS-1 is not effective, or to whom it cannot be administered. We have treated 6 patients with low-dose weekly paclitaxel therapy as second-line chemotherapy after initial treatment with TS-1. These patients consisted of 3 males and 3 females with a mean age of 56 years. Four patients had recurrent gastric cancer and two had unresectable advanced gastric cancer. Paclitaxel was administered in doses of 80 or 100 mg weekly. Adverse events more severe than grade 3 were not observed, but there were 2 cases of leukopenia (grade 1) and 2 cases of decreased hemoglobin (grade 2). Mean survival time after the administration of paclitaxel was 139 days. Five patients died of their cancer, and one is still alive 382 days after the paclitaxel administration. The one-year survival rate after administration was 16.7%. Low-dose weekly paclitaxel therapy is therefore safe and effective for patients with advanced and recurrent gastric cancer who previously received TS-1 therapy.

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J Surg Oncol. 2004 Dec 15;88(4):201-5.
Surgical treatment for gastric carcinoma in the elderly.
Coniglio A, Tiberio GA, Busti M, Gaverini G, Baiocchi L, Piardi T, Ronconi M, Giulini SM.
Surgical Clinic, Department of Medical and Surgical Sciences, Brescia University, Brescia, Italy.

BACKGROUND AND OBJECTIVES: The incidence of gastric cancer is increasing in the elderly. The aim of this study is to evaluate the impact of advanced age (> or =80 years) on morbidity, mortality and late outcome after curative surgery for gastric cancer. METHODS: The cases of 30 octogenarians (Group A) with gastric cancer who underwent surgical treatment in our Institution from 1990 to 2003 were reviewed and compared to a simultaneous group of 228 younger patients (Group B). RESULTS: The rate of resective and curative procedures was not different in the two groups, although the American Society of Anaesthesiologists (ASA) risk was significantly higher in the elderly (P < 0.001) and the lymphatic dissection was less extended in group A. In the two groups, the curability was directly correlated to the cancer stage, but not affected by the ASA risk. The postoperative morbidity and mortality rates were similar in the two groups and were not related to the ASA risk. Considering the mortality for gastric cancer alone, the two groups showed a similar survival rate, only correlated to the cancer stage. CONCLUSIONS: In the elderly, an oncologically correct surgical procedure can safely be prosecuted with satisfactory immediate and late results.

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World J Gastroenterol. 2004 Dec 1;10(23):3405-8.
Surgical treatment and prognosis of gastric cancer in 2,613 patients.
Zhang XF, Huang CM, Lu HS, Wu XY, Wang C, Guang GX, Zhang JZ, Zheng CH.
Department of Oncology, Affiliated Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China. zjzchina@vipsina.com

AIM: To analyze the factors influencing the prognosis of patients with gastric cancer after surgical treatment, in order to optimize the surgical procedures. METHODS: A retrospective study of 2 613 consecutive patients with gastric cancer was performed. Of these patients, 2,301 (88.1%) received operations; 196 explorative laparotomy (EL), 130 by-pass procedure (BPP), and 1 975 surgical resection of the tumors (891 palliative resection and 1 084 curative resection). The survival rate was calculated by the actuarial life table method, and the prognostic factors were evaluated using the Cox regression proportional hazard model. RESULTS: Of the patients, 2,450 (93.8%) were followed-up. The median survival period was 4.6 mo for patients without operation, 5.2 mo for EL, 6.4 mo for BPP, and 15.2 mo for palliative resection (P = 0.0001). Of the patients with surgical resection of the tumors, the overall 1, 3 and 5-year survival rates after were 82.7%, 46.3% and 31.1%, respectively, with the 5-year survival rate being 51.2% in patients with curative resection, and 7.8% for those with palliative resection. The 5-year survival rate was 32.5% for patients with total gastrectomy, and 28.3% for those with total gastrectomy plus resection of the adjacent organs. The factors that independently correlated with poor survival included advanced stage, upper third location, palliative resection, poor differentiation, type IV of Borrmann classification, tumor metastasis (N3), tumor invasion into the serosa and contiguous structure, proximal subtotal gastrectomy for upper third carcinoma and D1 lymphadenectomy after curative treatment. CONCLUSION: The primary lesion should be resected as long as the local condition permitted for stage III and IV tumors, in order to prolong the patients' survival and improve their quality of life after operation. Total gastrectomy is indicated for carcinomas in the cardia and fundus, and gastric cancer involving the adjacent organs without distant metastasis requires gastrectomy with resection of the involved organs.

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Hepatogastroenterology. 2004 Nov-Dec;51(60):1872-6.
Phase-II randomized study of preoperative IL-2 administration in radically operable gastric cancer patients.
Romano F, Piacentini MG, Franciosi C, Caprotti R, De Fina S, Cesana G, Uggeri F, Conti M, Uggeri F.
Department of Surgery, San Gerardo Hospital, II University of Milan, Bicocca, Italy. fabriziorom@hotmail.com

BACKGROUND/AIMS: Surgery has appeared to induce lymphocytopenia and this decrease in host defenses during postoperative period could promote both the proliferation of possible micrometastases and the implantation of surgically disseminated tumor cells. The aim of this study is to evaluate if the preoperative subcutaneous injection of IL-2 (interleukin-2) may be able to abrogate surgery-induced immunosuppression in radically operable gastric cancer and to assess its toxicity. METHODOLOGY: This phase II study included 39 consecutive patients with histologically proven gastric adenocarcinoma (M/F 26/13; mean age 68; range 48-82) who underwent radical surgery from October 1999 to December 2000. Patients were randomized to be treated with surgery alone as controls (20 patients) or surgery plus preoperative treatment with recombinant human IL-2 (19 patients). IL-2 was administered subcutaneously, at a dose of 9,000,000 IU, for three consecutive days, followed by surgery within 36 hours from IL-2 withdrawal. We considered the total lymphocyte count and lymphocyte subset (CD4, CD4/CD8) during the preoperative period, before IL-2 administration, and on the 14th and 50th day. RESULTS: Two groups were well matched for type of surgery and extent of disease. All the patients underwent radical surgery plus D2 lymphadenectomy. At baseline, there were no significant differences in total lymphocyte and lymphocyte subsets between groups. The control group showed a significant decrease of total lymphocytes, CD4 cells, and CD4/CD8 ratio at the 14th postoperative day relative to the baseline value. Among the 22 patients evaluated in the control group 13 had a decreased of CD4 under 500 cells/mm3 (65%). Instead in the IL-2 group a significant increase was observed over the control group values of total lymphocytes and CD4 cells (14th ly total and CD4: IL-2 vs. control p<0.05). Moreover in this group only 3 patients had CD4 under 500 cells/mm3 (15%). This difference in CD4 count, is significant at the 50th postoperative day too (p=0.006). No anesthesiologic or surgical complication was seen in IL-2 treated group, with low grade of toxicity (WHO grade:1): the main effect was fever (14/19) easily manageable, with no cardiovascular complications. Furthermore, IL-2 group showed lower postoperative complications (p<0.05) and higher lymphocyte/eosinophil infiltration into the tumor (p<0.002). CONCLUSIONS: This phase II study would suggest that a preoperative immunotherapy with IL-2 is a well tolerated treatment able to prevent surgery induced lymphocytopenia. IL-2 seems to neutralize the immunosuppression induced by operation and so to stimulate the host reaction against tumor tissue (lymphocytes/eosinophils infiltration). Next randomized clinical trials could investigate the prognostic impact of IL-2 on the clinical course.

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Gan To Kagaku Ryoho. 2004 Nov;31(12):1982-6.
[Combination chemotherapy of TS-1 and docetaxel on advanced and recurrent gastric cancer]
[Article in Japanese]
Yoshida K, Toge T.
Dept. of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan.

In the present article, we have summarized the clinical trials on docetaxel and the phase I study of docetaxel and combination therapy. Patients with a performance status (PS) of 0 to 2 received docetaxel at the starting dose of 40 mg/m2 by iv infusion over 1 hour on day 1 and TS-1 at the full dose of 80 mg/m2 daily for two weeks every three weeks. Nine patients were treated with increasing dose levels of docetaxel as follows: (docetaxel/TS-1, mg/m2): 40/80 (level 1), 50/80 (level 2) and 60/80 (level 3), and all the cases were found to be assessable for drug safety, while 7 were assessable for response. The MTD was reached at the 50/80 mg/m2 dose level in three patients out of six, who experienced a dose limiting toxicity (DLT). On the other hand, partial response was achieved in 5 (71.4%) of the 7 patients with evaluable lesions. The drug combination showed a good safety profile, and the responses observed in the study suggest that the drug combination shows a high degree of efficacy in patients with advanced and or recurrent gastric cancer.

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Gan To Kagaku Ryoho. 2004 Nov;31(12):1978-81.
[Current combination chemotherapy containing paclitaxel for advanced, recurrent gastric cancer]
[Article in Japanese]
Emi Y, Kakeji Y, Baba H, Ishida T, Maehara Y.
Department of Surgery, Hiroshima Red Cross Hospital, 1-9-6 Senda-machi, Naka-ku, Hiroshima 730-8619, Japan.

5-FU has been a key chemotherapeutic agent in the treatment of advanced or recurrent gastric cancer. In order to enhance the effect of 5-FU, biochemical modulation or combination chemotherapy has been developed. Although several phase III studies were reported in the 1990s, a standard chemotherapeutic regimen has not been established worldwide. Recently, a newly developed anticancer agent, Paclitaxel, can be clinically used for advanced gastric cancer either as a single agent or in combination with such as 5-FU, cisplatin, and TS-1. It may well further improve the quality of life and prolong the survival of patients with gastric cancer. Further assessment for the well design phase III clinical trials will be necessary to establish the availability of such combination modalities for the treatment of advanced, recurrent gastric cancer.

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Gan To Kagaku Ryoho. 2004 Nov;31(12):1952-6.
[Combination chemotherapy for gastric cancer including LV/5-FU]
[Article in Japanese]
Sasaki T, Maeda Y, Kandaba-shi K, Ono M.
Dept of Chemotherapy, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.

LV (l-LV)/5-FU therapy has been used broadly and is considered to be a standard treatment for large bowel cancer due to an enhancing therapeutic effect of 5-FU. According to recent clinical study reports on large bowel cancer in Europe and the United States, various administration methods of LV/5-FU with a combination of other drugs have been devised. It appeared that 5-FU used together in bolus and continuous infusions have yielded outstanding results. Although the basis of combination therapy for gastric cancer seemed to be LV/5-FU, there were many reports on TS-1 combined with other drugs because the oral medicine TS-1 was domestically available for the past one or two years. Currently, controlled randomized trials of LV/5-FU therapy and TS-1 have been ongoing. However, when patients cannot take oral intakes, LV/5-FU therapy is important. It seems that LV/5-FU therapy in combination with other drugs, in particular, CDDP, CPT-11, paclitaxel, docetaxel, oxaliplatin, and ETP will be given as candidates for the standard treatment of gastric cancer.

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Gan To Kagaku Ryoho. 2004 Oct;31(11):1723-6.
[Treatment results of peritoneal dissemination from gastric cancer by neoadjuvant intraperitoneal-systemic chemotherapy]
[Article in Japanese]
Yonemura Y, Kawamura T, Bando E, Takahashi S, Sawa T, Yoshimitsu Y, Obata T, Endo Y, Sasaki T, Sugarbaker PH.
Peritoneal Dissemination Program, Shizuoka Cancer Center.

No standard treatment exists for peritoneal dissemination from gastric cancer. We reviewed our experience using a novel treatment consisting of peritonectomy and intraoperative chemo-hyperthermic peritoneal perfusion (CHPP). Records of all patients who underwent CHPP and cytoreductive surgery from 1992 to 2001 were reviewed. RESULTS: Data from 107 patients (average age, 52 years) were available. P3 dissemination was found in 72 patients, and 8 and 27 patients showed P1 or P2 dissemination, respectively. Peritoneal metastasis was synchronous in 75 and metachronous in 32 patients. All patients received CHPP after cytoreductive surgery. Peritonectomy was performed in 42 patients. Complete cytoreduction (CC-0) was achieved in 47 patients (44%). Peritonectomy, resulted in CC-0 in 69% (29/42), but CC-0 was achieved in 18 of 65 (28%) patients by ordinary surgical techniques. There were 23 postoperative complications (21%) after operation. The overall operative mortality was 2.8% (3/107). Median follow-up for the entire study group was 46 months. Seventeen patients (15%) were disease-free, and 90 patients were dead at the time of analysis. Eighty-seven deaths were related to progression of disease. The median survival of all patients was 16.2 months, with an actual 5-year survival of 6%. Median survival of CHPP plus ordinary cyoreduction was 12.0 months and that after CHPP and peritonectomy was 22.8 months. Completeness of cytoreduction and peritonectomy were significant prognostic factors on univariate analysis and 5-year survival rate was 27%. Lymph node status, grade of peritoneal dissemination (P1-2 vs P3), age (>60 years vs <60 years), tumor volume of dissemination (>2.5 cm vs <2.5 cm in diameter), and histologic type (differentiated vs. poorly differentiated type) did not affect survival. The cox proportional model demonstrated that completeness of cytoreduction was the strongest prognostic factor. Patients who had an incomplete resection had 2.8-fold higher risk of dying from disease than patients who underwent complete cytoreduction. The 5-year survival after complete cytoreduction was 12%, compared with 2% for incomplete resection. Four patients lived more than 5 years. Cytoreduction was incomplete in one 5-year survivor who showed complete response to CHPP. CONCLUSION: Complete cytoreduction using peritonectomy and CHPP may improve survival of patients with peritoneal dissemination from gastric cancer. This procedure is most appropriate for highly motivated patients who are committed to survive as long as possible.

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Oncology. 2004;67(1):48-53.
Long-term follow-up of a pilot phase II study with neoadjuvant epidoxorubicin, etoposide and cisplatin in gastric cancer.
Barone C, Cassano A, Pozzo C, D'Ugo D, Schinzari G, Persiani R, Basso M, Brunetti IM, Longo R, Picciocchi A.
Unit of Medical Oncology, Department of Internal Medicine, Universita Cattolica del S. Cuore, Roma, Italy. carlobarone@rm.unicatt.it

OBJECTIVE: The prognosis in T3-T4 or N+ gastric cancer is dismal, and the role of adjuvant therapy remains uncertain. Neoadjuvant chemotherapy could improve both resectability and survival. Here, we report the results of the long-term follow-up of a pilot study aimed at evaluating a neoadjuvant treatment in a group of patients carefully staged by computed tomography (CT), endoscopic ultrasound and laparoscopy. METHODS: Twenty-five stage II-III patients with histologically proven gastric adenocarcinoma were enrolled in the study. All patients gave informed consent and were thoroughly staged. Patients were treated with epidoxorubicin (40 mg/m2 i.v.) on days 1 and 4, etoposide (VP-16; 100 mg/m2) on days 1, 3 and 4 and cisplatinum (80 mg/m2) on day 2, every 21-28 days for 3 pre-operative cycles before CT clinical restaging followed by laparotomy and D2 gastrectomy. Three further cycles of chemotherapy were planned after radical surgery. RESULTS: Twenty-four patients received the planned pre-operative chemotherapy and underwent surgical resection; total (13 patients) or subtotal (7 patients) R0 D2 gastrectomy was possible in 20 patients. One patient died as a result of gastric bleeding. Perioperative complications occurred in 5 patients (failure of anastomosis in 1 patient and wound infection in the other 4). The pathologic response rate included 7 partial responses (29.1%) and 10 patients with stable disease (41.7%). The main toxicity was grade 3/4 neutropenia (68%), which occurred more frequently during the postoperative chemotherapy, and fatigue (68%). Fever or infection, however, were never observed. The median disease-free survival was 37 months, and median survival has not been reached after 40 months of median follow-up. One-, 2- and 3-year survival rates were 80, 64 and 60%, respectively. CONCLUSION: The notable long-term survival in the present study suggests a comparison between the neoadjuvant approach, including new drug combinations, and adjuvant chemo- or chemoradio-therapy in locally advanced gastric cancer. Copyright 2004 S. Karger AG, Basel

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Gut. 2004 Sep;53(9):1217-9.
Is gastric cancer preventable?
Correa P.
Louisiana State University, Department of Pathology, LSU Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA. correa@lsuhsc.edu

Gastric cancer is a major health burden worldwide and prevention is the most promising strategy to control the disease. The available scientific evidence indicates that curing Helicobacter pylori infection results in a modest retardation of the precancerous process but does not prevent all cancers. Individuals at the highest risk should be cured of their infection and monitored endoscopically to detect dysplasia and "early" cancer, amenable to successful treatment.

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Oncology. 2004;66(6):445-9.
FLEP chemotherapy for alpha-fetoprotein-producing gastric cancer.
Kochi M, Fujii M, Kaiga T, Takahashi T, Morishita Y, Kobayashi M, Kasakura Y, Takayama T.
Department of Digestive Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan. gann@med.nihon-u.ac.jp

OBJECTIVE: This study aimed at comparing the efficacy of FLEP chemotherapy in the treatment of stage IV AFP-producing gastric cancer and stage IV non-AFP-producing gastric cancer. METHODS: Between 1989 and 2002, 57 patients with stage IV inoperable gastric cancer were given a combination of chemotherapy with 5-fluorouracil (5-FU), leucovorin (LV), etoposide (VP-16) and cis-diamminedichloroplatinum (CDDP) (designated as FLEP). In the two groups classified histologically according to AFP positivity, the rate of response and conversion to surgery, disease-free and overall survival were compared. The disease-free and overall survival in the two groups was compared by a log-rank test. RESULTS: Patients of the AFP-producing group had a significantly better response rate (70 vs. 31.9%, p = 0.03) and a better conversion rate (40 vs. 12.8%, p = 0.04) than those of the non-AFP-producing group. Patients of the AFP-producing group also had a significantly better disease-free and overall survival (p = 0.02) than those of the non-AFP-producing group. AFP-producing gastric cancer was identified as an independent prognostic factor. CONCLUSION: FLEP chemotherapy was more effective for stage IV AFP-producing gastric cancer than in stage IV non-AFP-producing gastric cancer. Preoperative FLEP chemotherapy improved the prognosis of AFP-producing gastric cancer because of downstaging. Copyright 2004 S. Karger AG, Basel

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Asian Pac J Cancer Prev. 2004 Jul-Sep;5(3):246-52.
Helicobacter pylori eradication as a preventive tool against gastric cancer.
Hamajima N, Goto Y, Nishio K, Tanaka D, Kawai S, Sakakibara H, Kondo T.
Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya, Japan. nhamajim@med.nagoya-u.ac.jp

Helicobacter pylori (H. pylori), which increases the risk of gastric diseases, including digestive ulcers and gastric cancer, is highly prevalent in Asian countries. There is no doubt that eradication of the bacterium is effective as a treatment of digestive ulcer, but eradication aiming to reduce the gastric cancer risk is still controversial. Observational studies in Japan demonstrated that the eradication decreased the gastric cancer risk among 132 stomach cancer patients undergoing endoscopical resection (65 treated with omeprazol and antibiotics and 67 untreated). In Columbia, 976 participants were randomized into eight groups in a three-treatment factorial design including H. pylori eradication, resulting in significant regression in the H. pylori eradication group. A recent randomized study in China also showed a significant reduction of gastric cancer risk among those without any gastric atrophy, intestinal metaplasia, and dysplasia. Efficacy of eradication may vary in extent among countries with different incidence rates of gastric cancer. Since the lifetime cumulative risk (0 to 84 years old) of gastric cancer in Japan is reported to be 12.7% for males and 4.8% for females (Inoue and Tominaga, 2003), the corresponding values for H. pylori infected Japanese can be estimated at 21.2% in males and 8.0% in females under the assumptions that the relative risk for infected relative to uninfected is 5 and the proportion of those infected is 0.5. Both the fact that not all individuals are infected among those exposed and the knowledge that only a small percentage of individuals infected with the bacterium develop gastric cancer, indicate the importance of gene-environment interactions. Studies on such interactions should provide useful information for anti-H. pylori preventive strategies.

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Gan To Kagaku Ryoho. 2004 Aug;31(8):1147-51.
[COX and study of cancer therapy]
[Article in Japanese]
Yamada N, Ohira M, Hirakawa K.
Dept of Surgical Oncology, Osaka City University Graduate School of Medicine.

The increased expression of COX-2 in carcinoma tissue is found in gastric cancer, lung cancer and breast cancer as well as colon cancer. It was shown that COX-2 played an important role in carcinogenesis by an experiment using a cultured cell and an animal experiment using a knockout mouse. The inhibitory effect of COX-2 inhibitor on polyps in familial adenomatous polyposis (FAP) patients was reported from the clinical aspect, and the U. S. Food and Drug Administration (FDA) approved administration of a COX-2 inhibitor to FAP patients. COX-2 plays an important role in proliferation, invasion and metastasis of cancer. COX-2 expression was reportedly enhanced in lung cancer by an anticancer agent and radiotherapy, and clinical application of a COX-2 inhibitor is attempted. In addition, the experimental examination showed the inhibitory effect of a COX-2 inhibitor on hematogenous metastasis of colon cancer. The mechanism of the COX-2 inhibitor remains unclear. Clinical application of the COX-2 inhibitor to an effective anti-tumor agent is expected after more studies have been conducted on its molecular biologic function.

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Cancer Chemother Pharmacol. 2004 Aug 7 [Epub ahead of print]
Clinical overview: adjuvant therapy of gastrointestinal cancer.
Macdonald JS.
St. Vincent's Comprehensive Cancer Center, 325 West 15th Street, NY 10011, New York, USA.

Adjuvant therapy has been tested widely in the treatment of cancers of the stomach, pancreas, and large bowel. In the USA, the use of postoperative chemoradiation in stomach cancer is considered a standard of care after the publication of the Intergroup Study 0116 in September 2001. This study demonstrated significant benefit in overall and disease-free survival for patients receiving postoperative treatment with fluorouracil (5-FU)/leucovorin chemotherapy and radiation after gastric resection. Adjuvant chemotherapy is not considered to be of significant benefit, and such therapy for patients with resected gastric cancer is investigational. There is interest in the use of neoadjuvant chemotherapy strategies as preoperative treatment followed by surgical resection. This approach has been tested in a randomized study of over 500 patients carried out by the Medical Research Council in the UK. This study demonstrated that patients receiving preoperative and postoperative epirubicin, cisplatin, 5-FU (ECF) chemotherapy, had a downstaging of tumor size, an increase in rates of curative resection, and an increase in disease-free but not overall survival. With pancreatic cancer, there is a controversy over postoperative chemoradiation after pancreatic resection. A recently completed Intergroup Study compared gemcitabine to 5-FU chemotherapy given before and after radiation in resected pancreatic cancer. Over 500 patients have been accrued to this study, which recently closed. In Western Europe, the results of a large clinical trial (ESPAC) have suggested that chemoradiation is not beneficial in patients with resected pancreatic cancer. In large bowel cancer, 5-FU-based adjuvant chemotherapy regimens are superior to surgery alone, particularly in node-positive patients. The use of newer combinations including 5-FU/leucovorin plus irinotecan and 5-FU/leucovorin plus oxaliplatin are also of interest as chemotherapy in resected colon cancer patients. The recent publication of the MOSAIC trial demonstrated that 5-FU/leucovorin/oxaliplatin (FOLFOX 4) improves progression-free survival in node-positive patients over 5-FU/leucovorin alone. The results of studies of 5-FU/leucovorin and irinotecan both in Europe (PETACC) and the USA (IFL vs 5-FU/leucovorin) are awaited with interest. Another area of interest in resected colon cancer is the use of molecular genetic monitoring to assess the likelihood of patient relapse. The data over the past several years have demonstrated that patients whose tumors do not have deletion of the deleted in colon cancer (DCC) gene on chromosome 18 have an improved outcome. Recent data are available with tumors that demonstrate microsatellite instability (MSI). Such tumors represent about 15% of all colon cancers and have an improved outcome when compared to those not expressing MSI, and may not benefit from adjuvant chemotherapy.

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Semin Oncol. 2004 Aug;31(4):566-73.
Treatment of localized gastric cancer.
Macdonald JS.
Gastrointestinal Oncology Service, Saint Vincent's Comprehensive Cancer Center, New York, NY 10011, USA.

The curative management of gastric adenocarcinoma depends upon complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are at least 70% to 80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared to less extensive operations. Until recently, attempts at preventing recurrence have employed adjuvant chemotherapy and have been ineffective. A large US Intergroup study (INT-0116) demonstrated that combined chemoradiation following complete gastric resection improves median time to relapse (30 v 19 months, P <.0001) and overall survival (35 months v 28 months, P =.01). The improvements in disease-free and overall survival created by postoperative chemoradiation have defined a new standard of care. Also the publication of a large phase III neoadjuvant chemotherapy clinical trial using epirubicin, cisplatin, and 5-fluorouracil (5-FU) suggested that this technique may downstage tumors and increase resectability. Future advances in the therapy of resectable gastric cancer may come from studies of preoperative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and antiangiogenesis agents.

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Br J Surg. 2004 Aug;91(8):1061-5.
Laparoscopically assisted distal gastrectomy for early gastric cancer in the elderly.
Yasuda K, Sonoda K, Shiroshita H, Inomata M, Shiraishi N, Kitano S.
Department of Surgery I, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan. kyasuda@med.oita-u.ac.jp

BACKGROUND: Open gastrectomy is associated with increased morbidity and a longer hospital stay than laparoscopically assisted gastrectomy. The aim of this study was to clarify the value of laparoscopically assisted distal gastrectomy (LDG) in the elderly, in whom co-morbid disease is generally more common. METHODS: Forty-five elderly patients (aged 70 years or more) and 57 younger patients who underwent LDG, and 28 elderly patients who underwent open distal gastrectomy (ODG) for early gastric cancer between January 1994 and April 2003 were studied. Demographics and postoperative outcomes were compared. RESULTS:: Co-morbidity was more common in elderly patients than in younger patients who underwent LDG (25 of 45 versus 16 of 57; P = 0.004). The postoperative complication rate, time to solid diet and postoperative hospital stay were similar in these two groups. Elderly patients who underwent LDG had a significantly reduced medical complication rate (two of 45 versus six of 28; P = 0.023), time to first flatus (3.7 versus 4.2 days; P = 0.042), time to solid diet (4.6 versus 5.5 days; P = 0.011) and postoperative hospital stay (16.3 versus 23.9 days; P = 0.011) than elderly patients who had ODG. CONCLUSION: LDG offers particular advantages to elderly patients with early gastric cancer, including rapid return of gastrointestinal function, fewer complications and a shorter hospital stay. Copyright 2004 British Journal of Surgery Society Ltd.

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Anticancer Res. 2004 Jul-Aug;24(4):2465-70.
Randomized phase II study comparing mitomycin, cisplatin plus doxifluridine with cisplatin plus doxifluridine in advanced unresectable gastric cancer.
Koizumi W, Fukuyama Y, Fukuda T, Akiya T, Hasegawa K, Kojima Y, Ohno N, Kurihara M.
The Tokyo Cooperative Oncology Group, Department of Internal Medicine, Kitasato University School of Medicine, 2-1-1 Asamozodai Sagamihara-shi, Kanagawa 228-8520, Japan. Koizumi@med.kitasato-u.ac.jp

Various chemotherapies have been used to treat inoperable gastric cancer. Most combination therapies include cisplatin (CDDP) and fluoropyrimidine (5-FUs), which are thought of as key drugs. In the present study, we randomly compared mitomycin (MMC) and CDDP plus doxifluridine (5'-DFUR), which is an oral 5-FU and an intermediate metabolite of capecitabine (Xeloda), with CDDP plus 5'-DFUR in advanced unresectable gastric cancer. Regimen A was CDDP (70 mg/m2, by 2-hour intravenous drip infusion on day 1), MMC (7 mg/m2, injected intravenously on day 2), and oral 5'-DFUR (1200 mg/m2, on days 4 to 7, 11 to 14, 18 to 21 and 25 to 28; 3 days rest and 4 days administration). Regimen B was identical to regimen A without MMC. RESULTS: The response rate was 25.0% (8/32 patients) in Regimen A, 17.2% (5/29) in Regimen B (p=0.541). The median survival time was 241 days in Regimen A and 179 days in Regimen B (p=0.498). In Regimen A, although no significant difference was observed, end points such as response rate and suvival improved. Thus, we concluded that a randomized controlled phase III study with more subjects should be conducted.

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Br J Cancer. 2004 Jul 5;91(1):18-22.
Combination chemotherapy with epirubicin, docetaxel and cisplatin (EDP) in metastatic or recurrent, unresectable gastric cancer.
Lee SH, Kang WK, Park J, Kim HY, Kim JH, Lee SI, Park JO, Kim K, Jung CW, Park YS, Im YH, Lee MH, Park K.
Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, Korea.

Based on single agent activities and the additive or synergistic effects of three individual drugs in gastric cancer, we performed a phase II study of a new regimen combining epirubicin, docetaxel and cisplatin (EDP) for unresectable gastric cancer. The patients with histologically confirmed metastatic or recurrent, unresectable gastric cancer and no history of palliative chemotherapy were eligible for this trial. In total, 40 mg m(-2) epirubicin (reduced to 30 mg m(-2) due to high incidence of febrile neutropaenia; 75%) intravenously (i.v.) over 30 min, followed by 60 mg m(-2) docetaxel i.v. over 1 h, then 75 mg m(-2) cisplatin i.v. over 1 h was administered every 3 weeks. Between January 2002 and February 2003, 30 patients (epirubicin 40 mg m(-2), eight; 30 mg m(-2), 22) were enrolled. The median age was 52 years (range, 33-68). The patients received a median of four cycles (range, 1-8). One patient (3%) achieved a complete response, 13 (43%) showed partial responses, 13 (43%) had stable diseases and three (10%) progressed. The overall response rate was 47% (95% CI, 28-66%), and the median duration of response was 5.0 months (95% CI, 3.0-7.0). The median time to progression was 4.1 months (95% CI, 2.4-5.9), and the median overall survival was 11.0 months (95% CI, 9.5-12.4). Grade 4 neutropaenia were observed in 41%, and febrile neutropaenia in 32%, out of the patients receiving 30 mg m(-2) of epirubicin. Grade 3 nonhaematological toxicities included nausea, vomiting, anorexia and peripheral neuropathy. In conclusion, EDP is active in gastric cancer, with a manageable and predictable toxicity profile.

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Ann Surg. 2004 Jul;240(1):44-50.
The role of surgery in primary gastric lymphoma: results of a controlled clinical trial.
Aviles A, Nambo MJ, Neri N, Huerta-Guzman J, Cuadra I, Alvarado I, Castaneda C, Fernandez R, Gonzalez M.
Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico. agaviles@avantel.net

OBJECTIVE: We began a controlled clinical trial to assess efficacy and toxicity of surgery (S), surgery + radiotherapy (SRT), surgery + chemotherapy (SCT), and chemotherapy (CT) in the treatment of primary gastric diffuse large cell lymphoma in early stages: IE and II1. SUMMARY BACKGROUND DATA: Management of primary gastric lymphoma remains controversial. No controlled clinical trials have evaluated the different therapeutic schedules, and prognostic factors have not been identified in a uniform population. PATIENTS AND METHODS: Five hundred eighty-nine patients were randomized to be treated with S (148 patients), SR (138 patients), SCT (153 patients), and CT (150 patients). Radiotherapy was delivered at doses of 40 Gy; chemotherapy was CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) at standard doses. International Prognostic Index (IPI) and modified IPI (MIPI) were assessed to determine outcome. RESULTS: Complete response rates were similar in the 4 arms. Actuarial curves at 10 years of event-free survival (EFS) were as follows: S: 28% (95% confidence interval [CI], 22% to 41%); SRT: 23% (95% CI, 16% to 29%); that were statistically significant when compared with SCT: 82% (95% CI, 73% to 89%); and CT: 92% (95% CI, 84% to 99%) (P < 0.001). Actuarial curves at 10 years showed that overall survivals (OS) were as follows: S: 54% (95% CI, 46% to 64%); SRT: 53% (95% CI, 45% to 68%); that were statistically significant to SCT: 91% (95% CI, 85% to 99%); CT: 96% (95% CI, 90% to 103%)(P < 0.001). Late toxicity was more frequent and severe in patients who undergoing surgery. IPI and MIPI were not useful in determining outcome and multivariate analysis failed to identify other prognostic factors. CONCLUSION: In patients with primary gastric diffuse large cell lymphoma and aggressive histology, diffuse large cell lymphoma in early stage SCT achieved good results, but surgery was associated with some cases of lethal complications. Thus it appears that CT should be considered the treatment of choice in this patient setting. Current clinical classifications of risk are not useful in defining treatment.

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Gan To Kagaku Ryoho. 2004 Jul;31(7):1047-50.
[Examination of second-line therapies following administration of low-dose TS-1+CDDP for highly-advanced gastric cancer]
[Article in Japanese]
Kamata T, Furukawa H, Ishii K, Senda K, Yoshimoto K, Tajima H, Takeda T, Kanno M.
Dept of Surgery and Gastroenterology, Keiju Medical Center.

Sixteen patients with highly-advanced gastric cancer were administered low-dose TS-1 and CDDP as a first-line treatment, followed by either paclitaxel or CPT-11/CDDP as a second-line treatment. The results of the 2 second-line treatments are reported herein. Overall response rate for the first-line treatment was 55.6%. For the second-line treatments, responses were noted in both the paclitaxel group and the CPT-11/CDDP group. Overall MST was 16.3 months and 1-year survival was 60%. The paclitaxel group, however, showed significantly better prognoses than the CPT-11/CDDP group. Adverse reactions to the first-line treatment were grade 3 leukopenia in 1 patient, with no other reactions over grade 2 observed. No adverse reaction greater than grade 2 was noted during administration of the second-line treatments. These results appear to present ample data that a first-line treatment of low-dose TS-1/CDDP followed by a second-line treatment of paclitaxel at 1/week in the outpatient setting yields improved prognoses and minimal adverse reactions.

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Gan To Kagaku Ryoho. 2004 Jun;31(6):877-81.
[Usefulness of weekly administration of paclitaxel for advanced or recurrent gastric cancer]
[Article in Japanese]
Egawa T, Kubota T, Nagashima A, Doi M, Kitano M, Hayashi S, Yoshii H, Saikawa Y, Kitajima M.
Dept. of Surgery, Saiseikai Kanagawa-ken Hospital.

We report herein the efficacy and feasibility of weekly administration of paclitaxel for advanced/recurrent gastric cancer retrospectively. Eleven patients with advanced or recurrent gastric cancer who had received prior chemotherapy were treated with this regimen. Seventy mg of paclitaxel per m2 dissolved in 250 ml 5% glucose was administered by 1-hour intravenous infusion once a week for 3 weeks followed by 1 week rest. To avoid hypersensitivity reactions, the following short premedication was given to all the patients 1 hour before paclitaxel treatment: Dexamethasone 20 mg intravenously (i.v.), diphenhydramine 50 mg i.v., and ranitidine 50 mg i.v. Treatment cycle was 1 to 23 with an average cycle of 5.4. The response rate was 33% (2/6 with measurable lesions), the median time to progression was 104 days, and the median survival time was 160 days. Grade 3 neutropenia occurred in 27.2% of the patients. Weekly paclitaxel may be a promising regimen as a second-line chemotherapy for advanced/recurrent gastric cancer. However, special attention needs to be paid to the neutropenic adverse effect in gastric cancer patients with poor performance status than 2 (greater).

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Jpn J Clin Oncol. 2004 May;34(5):255-61.
A preliminary study of preoperative chemotherapy combining irinotecan and cisplatin in patients with gastric cancer with unresectable para-aortic lymph node metastases.
Yamao T, Ohta K, Ohyama S, Ishihara S, Chin K, Maruyama M, Takahashi T, Nakajima T.
Department of Internal Medicine, Cancer Institute Hospital, Tokyo, Japan. tyamao-gi@umin.ac.jp

BACKGROUND: A high response rate has been reported for chemotherapy combining irinotecan (CPT-11) and cisplatin (CDDP) against advanced gastric cancer. The strong anti-tumor activity of this regimen makes it very attractive as a preoperative chemotherapy. We conducted a preliminary study on preoperative chemotherapy with this regimen in patients with unresectable gastric cancer with para-aortic lymph node metastases to evaluate the feasibility of it as a treatment strategy. METHODS: Patients with unresectable para-aortic lymph node metastasis without distant hematogenous metastasis (H0, M0 and M1 LYM) and peritoneal dissemination (P0) were eligible for entry. The preoperative chemotherapy consisted of at least three cycles of CPT-11 (70 mg/m(2)) on days 1 and 15 and CDDP (80 mg/m(2)) on day 15, repeated every 4-6 weeks. Chemotherapy was followed by surgery with extended lymph node dissection in patients who achieved complete or partial responses and whose cancers were judged to be resectable. RESULTS: Six patients were entered into the study. In total, 18 cycles of chemotherapy were performed and five patients received at least three cycles. Objective partial responses were achieved in four patients. The major toxicities in the chemotherapy were neutropenia and diarrhea, but these were clinically acceptable. Four patients underwent surgery after the chemotherapy, and macroscopically complete resections with extended lymph node dissection were achieved in two patients. There were no therapy-related deaths. We found no pathological complete responses, but observed a definite histopathological effect caused by the chemotherapy in surgical specimens. The median survival time of all patients was 12 months. The longest survival without relapse is >6 years from the start of therapy. CONCLUSIONS: We conclude that preoperative chemotherapy with CPT-11/CDDP therapy is feasible in patients with advanced gastric cancer and that the regimen is safe when followed by surgery. Further clinical studies with larger numbers of patients are warranted to evaluate the efficacy of this strategy.

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Can J Gastroenterol. 2004 May;18(5):295-302.
Helicobacter pylori and the prevention of gastric cancer.
Sullivan T, Ashbury FD, Fallone CA, Naja F, Schabas R, Hebert PC, Hunt R, Jones N.
Division of Research and Cancer Control, Cancer Care Ontario, 620 University Avenue, Toronto, Ontario, Canada M5G 2L7. terry.sullivan@cancercare.on.ca

BACKGROUND: Helicobacter pylori is an important cause of stomach cancer that infects a substantial proportion of the Canadian adult population. H pylori can be detected by noninvasive tests and effectively eradicated by medical treatment. Screening for and treatment of H pylori may represent a significant opportunity for preventive oncology. METHODS: Cancer Care Ontario organized a workshop held in Toronto, Ontario, on October 24 and 25, 2002, to: review the current state of knowledge regarding H pylori treatment and cancer prevention; determine if there is currently sufficient evidence to consider the promotion of H pylori treatment for the purpose of cancer prevention; identify critical areas for research; and advise Cancer Care Ontario on H pylori and cancer prevention. RESULTS: Workshop participants developed a number of recommendations for research into the relationship between H pylori and stomach cancer, including determining the prevalence of infection in different regions of Canada, the pathogenetic sequence of carcinogenesis from H pylori infection, and the implementation of a prospective observational study. INTERPRETATION: Although the rate of H pylori infection is declining in Canada and the treatment of H pylori is generally accepted to be safe, the evidence to date may not warrant the implementation of population screening for H pylori infection to prevent gastric carcinoma in average-risk populations. Rather, a demonstration project is needed to estimate prevalence, evaluate the merits of screening, measure patient compliance and physician participation, develop education materials, establish a registry for monitoring and evaluation, and develop a quality assurance framework.

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Br J Cancer. 2004 May 4;90(9):1727-32.
Survival results of a multicentre phase II study to evaluate D2 gastrectomy for gastric cancer.
Degiuli M, Sasako M, Ponti A, Calvo F.
Department of Oncology, Division of Surgery, Via Cavour 31, 10123 Turin, Italy. mdegiuli@hotmail.com

Curative resection is the treatment of choice for potentially curable gastric cancer. Two major Western studies in the 1990s failed to show a benefit from D2 dissection. They showed extremely high postoperative mortality after D2 dissection, and were criticised for the potential inadequacy of the pretrial training in the new technique of D2 dissection, prior to the phase III studies being initiated. The inclusion of pancreatectomy and splenectomy in D2 dissection was associated with increased morbidity and mortality. Following these results, we started a phase II trial to evaluate the safety and efficacy of pancreas-preserving D2 dissection. The results of this trial regarding the safety of pancreas preserving D2 dissection were published in 1998. In this paper, we present the survival results of this phase II trial to confirm the rationale of carrying out a phase III study comparing D1 vs D2 dissection for curable gastric cancer.Italian patients with histologically proven gastric adenocarcinoma were registered in the Italian Gastric Cancer Study Group Multicenter trial. The study was carried out based on the General Rules of the Japanese Research Society for Gastric Cancer. A strict quality control system was achieved by a supervising surgeon of the reference centre who had stayed at the National Cancer Center Hospital, Tokyo, to learn the standard D2 gastrectomy and the postoperative management. The standard procedure entailed removal of the first and second tier lymph nodes. During total gastrectomy, the pancreas was preserved according to the Maruyama technique. Complete follow-up was available to death or 5 years in 100% of patients and the median follow-up time was 4.38 years.Out of 297 consecutive patients registered, 191 patients were enrolled in the study between May 1994 and December 1996. The overall morbidity rate was 20.9%. The postoperative in-hospital mortality was 3.1%. The overall 5-year survival rate among all eligible patients was 55%. Survival was strictly related to stage, depth of wall invasion, lymph node involvement and type of gastrectomy (distal vs total).Our results suggest a survival benefit for pancreas-preserving D2 dissection in Italian patients with gastric cancer if performed in experienced centres. A phase III trial among exclusively experienced centres is urgently needed.

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Oncology. 2004;66(4):269-74.
Chemotherapy is more active against proximal than distal gastric carcinoma.
Higuchi K, Koizumi W, Tanabe S, Saigenji K, Ajani JA.
Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Japan. khigu@aol.com

OBJECTIVE: Patients with localized proximal gastric carcinoma (PGC) have a poorer outcome than those with distal gastric carcinoma (DGC) following curative resection. However, it remains uncertain whether the location of the primary tumor influences the effect of chemotherapy in advanced gastric carcinoma. METHODS: We assessed 270 eligible patients with unresectable, advanced gastric carcinoma who had received first-line chemotherapy between 1989 and 2001. We defined PGC as carcinoma located in the upper one third, and DGC as carcinoma located in the lower two thirds of the stomach. RESULTS: Of the 270 patients, 91 (33.7%) had PGC, and 179 (66.3%) had DGC. The response rate of the primary lesion was 58.6% (51/87) in the PGC group and 35.1% (59/168) in the DGC group (p < 0.01). The overall response rate for all sites was 55.6% (50/90) in the PGC group and 39.0% (69/177) in the DGC group (p = 0.01). The median survival time was 318 days in the PGC group and 251 days in the DGC group (p = 0.0336). A multivariate analysis revealed that performance status, extent of disease, and location of the primary lesion were significantly related to survival. CONCLUSIONS: Our data suggest that the response rate and survival time after first-line chemotherapy in advanced gastric carcinoma are better in patients with PGC than in those with DGC. Copyright 2004 S. Karger AG, Basel

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Bull Cancer. 2004 Mar;91(3):257-61.
[Docetaxel and gastric cancer]
[Article in French]
Ducreux M, Boige V, Roth A.
Unite de gastroenterologie, Institut Gustave-Roussy, rue Camille-Desmoulins, 94805 Villejuif. ducreux@igr.fr

There are very few active drugs in the treatment of metastatic gastric carcinoma. Among new drugs, docetaxel has shown one of the most important activity. With precise evaluation of objective response, this drug has demonstrated a 20% response rate in monotherapy. The favorable toxicity profile of this compound allowed combination therapy with other active drugs in this disease: 5-fluorouracil (5FU), cisplatin and epiadriamycin. Two of the most interesting combinations are: bitherapy with docetaxel cisplatin and three therapy with docetaxel, continuous infusion of 5FU and cisplatin (TCF). Several large phase III trials are on-going to compare these new schedules to classical combination chemotherapies of this disease (5FU cisplatin or ECF). The potential place of docetaxel in gastric cancer is not restricted to metastatic disease and the same three-therapy with TCF is currently under evaluation as a neoadjuvant or adjuvant treatment in resectable lesions. With a high activity in terms of radiosensitization, docetaxel could also become a major drug in the design of new radiochemotherapy protocols for neoadjuvant or adjuvant disease.

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Gan To Kagaku Ryoho. 2004 Mar;31(3):361-5.
[A phase I study of combination chemotherapy using TS-1 and pirarubicin (THP) for advanced gastric cancer]
[Article in Japanese]
Yamamura Y, Kodera Y, Tanemura H, Oshita H, Miyashita K, Fujimura T; Tokai Hokuriku THP Study Group.
Dept. of Gastroenterological Surgery, Aichi Cancer Center Hospital.

The safety of chemotherapy combining TS-1 and pirarubicin (THP) for treatment of recurrent or locally advanced gastric cancer was evaluated. THP was administered by intravenous drip infusion at a dose of 14 mg/m2 every other week. TS-1 was administered orally at a dose of 40 mg/m2 twice a day for 2 weeks followed by 2 weeks of rest (level 1), for 3 weeks followed by 2 weeks of rest (level 2), and for 4 weeks followed by 2 weeks of rest (level 3). Three patients were treated with the level 1 schedule. One patient with peritoneal dissemination received 22 courses of the treatment, and benefited from a long-term NC. However the remaining 2 cases were diagnosed as PD after 4 courses and were withdrawn from further treatment. Two patients in this group suffered from grade 2 adverse events according to the NCI-CTC. Only 1 patient who had liver metastasis was treated at level 2. Fourteen courses were administered, and a PR was achieved while grade 2 adverse events were observed. One of 3 patients who were treated with level 3 had grade 3 adverse events. Consequently, 3 more cases were added to this dose level, and no additional grade 3 adverse events were observed, while grade 2 adverse events were seen in 4 cases. Urinary urgency had completely disappeared in 1 patient with peritoneal recurrence. Myelosuppression, which was the main observed adverse event, was well controlled and of brief duration. The response, including alleviation of clinical symptoms, was confirmed in 3 of 5 chemo-naive patients.

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An Med Interna. 2004 Mar;21(3):138-142.
Olive oil: influence and benefits on some pathologies.
[Article in Spanish, English]
Zamora Ardoy M, Banez Sanchez F, Banez Sanchez C, Alaminos Garcia P.
Servicio de Farmacia Hospitalaria. Hospital La Inmaculada. Huercal-Overa. Almeria, Spain.

The olive tree has been one of the agriculture bases in Mediterranean countries with a great economic and social significance. The oil derivative from it fruit can be clasified in diferents kinds acording with their quality, being the highest exponent the so-called pure olive oil that contribute in unquestionables benefits for the maintenance of health, illness prevention as well as a better evolution when the illness is present. There are some studies that prove these benefits in pathologies like cancer specially breast and stomach cancer (colon, endometrium and ovary cancer too). Gastrointestinal pathology like peptic ulcer, cholelithiasis and gastric mobility. Rheumatoid arthritis decreasing it development risk and improving it evolution. Diabetes mellitus increasing insulin sensibility and decreasing blood pressure and atherogenic lipoprotein.

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Nippon Rinsho. 2004 Mar;62(3):571-6.
[The trend of the research on H. pylori eradication and gastric cancer prevention]
[Article in Japanese]
Uemura N.
Department of Gastroenterology, International Medical Center of Japan.

The strongest evidence for the association between H. pylori infection and gastric cancer(GC) development in the current is provided by the prospective study that a large number of patients with H. pylori infection were followed with serial endoscopic examinations. Over time, GC was not diagnosed in negative patients. In contrast, the risk for GC was highly increased in positive patients. It was also revealed that in patients with early GC subjected to endoscopic mucosal resection but without eradication therapy, new GC was found in 13% as opposed to only 1% on GC relapse during 8 years in patients with eradication. These studies indicate that some positive patients should be eradicated to reduce the progression of ongoing gastric carcinogenesis.

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Am Fam Physician. 2004 Mar 1;69(5):1133-40.
Gastric cancer: diagnosis and treatment options.
Layke JC, Lopez PP.
University of Illinois Metropolitan Group Hospitals, Chicago, Illinois, USA. jlayke@yahoo.com

Although the overall incidence of gastric cancer has steadily declined in the United States, it is estimated that more than 12,000 persons died from gastric cancer in 2003. The incidence of distal stomach tumors has greatly declined, but reported cases of proximal gastric carcinomas, including tumors at the gastroesophageal junction, have increased. Early diagnosis of gastric cancer is difficult because most patients are asymptomatic in the early stage. Weight loss and abdominal pain often are late signs of tumor progression. Chronic atrophic gastritis, Helicobacter pylori infection, smoking, heavy alcohol use, and several dietary factors have been linked to increased risks for gastric cancer. Esophagogastroduodenoscopy is the preferred diagnostic modality for evaluation of patients in whom stomach cancer is suspected. Accurate staging of gastric wall invasion and lymph node involvement is important for determining prognosis and appropriate treatment. Endoscopic ultrasonography, in combination with computed tomographic scanning and operative lymph node dissection, may be involved in staging the tumor. Treatment with surgery alone offers a high rate of failure. Chemotherapy and radiotherapy have not improved survival rates when used as single modalities, but combined therapy has shown some promise. Primary prevention, by control of modifiable risk factors and increased surveillance of persons at increased risk, is important in decreasing morbidity and mortality.

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Am J Gastroenterol. 2004 Jan;99(1):23-32.
A 50-year analysis of 562 gastric carcinoids: small tumor or larger problem?
Modlin IM, Lye KD, Kidd M.
Gastrointestinal Surgical Pathobiology Research Group, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8062, USA.

OBJECTIVES: Interest in gastric carcinoid tumors has amplified considerably given the biological establishment of their relationship to gastrin and advances in the elucidation of the pathobiology of such lesions. The recognized propensity of acid-suppressing agents such as the proton pump inhibitor class of drugs to increase plasma gastrin levels has been proposed as a causal relationship in the apparent increase in the identification of such lesions although the increased prevalence of endoscopy and the enhanced awareness of pathologists have also been considered as contributory factors. We sought to examine if there has been an increase in gastric carcinoid incidence time correlative with these parameters. METHODS: Carcinoid tumor cases from the End Results Group (1950-1969) and the Third National Cancer Survey (TNCS) (1969-1971) databases were combined with the most recent release of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry (1973-1999); these three datasets revealed 13715 carcinoid cases, of which 562 were gastric in origin. Age-adjusted analyses as well as population-based gender and race correction ratios were completed in conjunction with United States decennial census data. To allow a finer granularity in incidence trends, the SEER database was divided into early (1973-1991) and late (1991-1999) subsets. RESULTS Since 1950, the percentage of gastric carcinoids among all gastric malignancies has increased from 0.3% to 1.77%. Since 1969, the proportion of gastric carcinoids among all enteric carcinoid lesions has increased from 2.4% to 8.7%. Age-adjusted incidence rates among male, female, black, and white population subsets have all increased since the TNCS time period, with the greatest increase (800%) noted in white females. The male:female ratio has fallen from 0.90 to 0.54. The occurrence of synchronous or metachronous noncarcinoid tumors with gastric carcinoid tumors has decreased by 26% during the course of SEER data collection. The 5-yr survival rate for gastric carcinoids overall has risen from 51% to 63% during the same time period. CONCLUSIONS: Gastric carcinoids have increased in incidence over the last 50 yr. Differential increases in predominance across gender and race subdivisions may reflect genetic-based propensities (or protection) for gastric carcinoid tumors among certain ethnic populations. Increased endoscopic surveillance and associated sophisticated pathological evaluation of gastric biopsies undoubtedly are responsible for some of the observed increase in the incidence of gastric carcinoid tumors. These data allow no specific role to be assigned to the effects of acid-suppressive medications. Nevertheless the role of such agents cannot be discounted at this time since the time frame of the increased incidence is somewhat comparable to the introduction of these agents as is the known biological effect of gastrin on ECL cell proliferation.

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Acta Oncol. 2003;42(7):693-700.
Docetaxel in advanced gastric cancer--review of the main clinical trials.
Di Cosimo S, Ferretti G, Fazio N, Silvestris N, Carlini P, Alimonti A, Gelibter A, Felici A, Papaldo P, Cognetti F.
Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy.

The aim was to investigate the activity of docetaxel in advanced gastric cancer either as single agent or in combination with other drugs. A systematic review was carried out using the databases of Medline, Embase and CancerLit. Results from ASCO and ESMO meetings during 2002 were also included. Eight phase II trials focused on docetaxel as a single agent. Considering collectively the 262 evaluable patients enrolled in these studies, the mean response rate (RR) was 19% (CI 95% 14-24%). Docetaxel was well tolerated with a dose-limiting myelosuppression (grade 3-4 neutropenia in 36-95% of cases). Adding fluorouracil, an RR ranging from 22% to 86% was registered, due to differences in populations studied (young vs elderly) and modalities of drug administration (continuous vs. bolus infusion). RRs for docetaxel-cisplatin combination were 56%, 37% and 36% in three phase II trials and 35% in a phase III trial. The addition of both cisplatin and fluorouracil to docetaxel did not increase toxicity. Randomized trials comparing docetaxel-cisplatin-fluorouracil with ciplatin-fluorouoracil or epirubicin-cisplatin-fluorouracil, the most commonly used regimens, are ongoing. The future results of the above phase III studies could indicate docetaxel as a key drug to improve treatment of patients with advanced gastric cancer.

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Cancer Invest. 2003;21(6):887-96.
Paclitaxel and concurrent radiation in upper gastrointestinal cancers.
Constantinou M, Tsai JY, Safran H.
Brown University Oncology Group, Providence, Rhode Island, USA.

Effective locoregional treatments are needed for adenocarcinomas of the esophagus, stomach, and pancreas. Paclitaxel has been investigated as a radiation sensitizer for upper gastrointestinal malignancies. In esophageal cancer, the combination of low-dose weekly paclitaxel, platinum, and concurrent radiation therapy (RT) has substantial activity and is well tolerated. Regimens that add fluorouracil (5-FU) to paclitaxel and platinum or incorporate hyperfractionation radiation have a higher incidence of severe esophagitis. In gastric cancer, adjuvant concurrent paclitaxel, 5-FU, and radiation is being investigated in the cooperative group setting. In pancreatic cancer, paclitaxel may be a radiation sensitizer even to tumor cells that are resistant to paclitaxel as a single agent. The Radiation Therapy Oncology Group (RTOG) demonstrated a 43% 1-year survival with paclitaxel/RT for patients with locally advanced pancreatic cancer. This represented a 40% improvement in survival compared to the previous RTOG 92-09 study of 5-FU-based chemoradiation. Ongoing trials in pancreatic cancer are investigating the addition of gemcitabine to paclitaxel and radiation and incorporating molecular targeting agents.

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Gan To Kagaku Ryoho. 2003 Dec;30(13):2107-13.
[Concurrent chemoradiation experience of recurrent gastric cancers resistant to TS-1]
[Article in Japanese]
Akagi Y, Hashimoto Y, Murakami Y, Ito K.
Dept. of Radiology, Hiroshima Asa City Hospital.

We report our experience with concurrent chemoradiation for recurrent gastric cancers resistant to TS-1. From April 2000 to March 2003, we treated 10 consecutive patients with radiation and the concurrent single chemotherapy agent of TS-1 or CPT-11. Of the 10 patients, 3 (30%) had a complete response, 4 (40%) a partial response, and 3 (30%) stable disease, yielding an overall response rate of 70% (7/10). Three patients are alive and cancer-free, 5 patients died with cancers, and 2 patients are living with cancers as outpatients. The clinical benefit response was 90% (9/10). No patient has had either acute or late complication. Concurrent chemoradiation is feasible and seems to offer good results for recurrent gastric cancers resistant to TS-1.

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Gan To Kagaku Ryoho. 2003 Nov;30(12):1933-40.
[Evaluation of TS-1 combined with cisplatin for neoadjuvant chemotherapy in patients with advanced gastric cancer]
[Article in Japanese]
Yabusaki H, Nashimoto A, Tanaka O.
Division of Surgery, Niigata Cancer Center Hospital.

We performed a critical evaluation of neoadjuvant chemotherapy (NAC) with TS-1 and cisplatin (CDDP) for advanced gastric cancer patients. Since October 2000, 37 patients with far advanced or non-curative resectable gastric cancer received NAC, together with TS-1 and CDDP after informed consent was obtained. TS-1 (80 mg/m2/day) was administrated for 21 consecutive days followed by 14 days rest as one course, and CDDP (50 mg/m2) was infused over 2 hours on day 8. After at least 2 courses of treatment, the patients underwent gastrectomy with lymphadenectomy. The median number of courses administered was 3 (range 2-7), and 6 cases were treated on an outpatient basis only. The overall response rate was 62.2% (no CR, but 23 PR), and the individual response rates were 67.6% for the primary lesion, 90.5% for lymph node metastasis including para-aortic region, 50.0% for liver metastasis and 14.3% for peritoneal dissemination, respectively. Toxicities were generally mild, no treatment-related death and no serious adverse reactions were observed. There were only 2 grade 4 anemia (5.4%), and leucopenia, neutropenia, anemia, thrombocytopenia of grade 3 were observed in one (2.7%), 3 (8.1%), 6 (16.2%), and 2 (5.4%) patients respectively at hematological toxicity. Appetite loss and diarrhea of grade 3 were observed in only one (2.7%) patient at nonhematological toxicity. Twenty-four cases had undergone surgical treatment, and resection was performed in all cases. Seventeen of the 24 (70.8%) patients underwent curative resection. There was no major morbidity following surgery. The patients were favorable both for operation time (229 min) and bleeding volume (365 ml). The mean duration of hospitalization after surgery was 23.5 days and the only complications were one leakage, ileus and 2 pancreatitis. Two-year survival rate was 46.8% and MST was 523 days. In conclusion, a combination of TS-1 and CDDP for NAC appears to be an effective treatment modality for far advanced gastric cancer patients in view of toxicities, antitumor effects and QOL of the patients.

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Gan To Kagaku Ryoho. 2003 Nov;30(12):1927-32.
[Weekly docetaxel therapy is useful for gastric carcinoma as a second-line chemotherapy]
[Article in Japanese]
Yoshida K, Ohta K, Hihara J, Tanabe K, Minami K, Yamaguchi Y, Toge T.
Dept. of Surgical Oncology Research Institute for Radiation Biology and Medicine, Hiroshima University.

In the present study, we demonstrate the results of weekly administered docetaxel treatments as a second-line chemotherapy after TS-1 treatment in 4 gastric cancer patients. Twenty-five mg/m2 of docetaxel was administered once a week for 3 weeks followed by a 1-week rest period as one cycle. The treatment was continued for 2 to 16 weeks. In case 1, a 60% reduction of the primary tumor was observed for 20 weeks. In cases 2 and 3, the decrease of tumor marker was observed. In one case, progression of the tumor was observed and the treatment was not performed. As for adverse effects, no hematological toxicity was observed; however, in one case, grade 2 hair loss, pleural effusion and grade 2 nail changes were observed. These results indicate that the weekly docetaxel therapy is useful for gastric carcinoma patients, as it reduces the hematologic toxicities and improves the quality of life of the patients in the outpatient setting.

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Gan To Kagaku Ryoho. 2003 Nov;30(12):1881-8.
[Chemotherapy for gastric cancer]
[Article in Japanese]
Baba H, Kakeji Y, Oki E, Tokunaga E, Ushiro S, Watanabe M, Maehara Y.
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

5-FU has been a key chemotherapeutic agent in the treatment of advanced or recurrent gastric cancer. In order to enhance the effect of 5-FU, biochemical modulation or combined chemotherapy has been developed. Although several phase III studies have been reported in 1990's, a standard chemotherapeutic regimen has not been established worldwide. Recently, newly developed anticancer agents such as CPT-11, TS-1, Paclitaxel, or Docetaxel can be clinically used for advanced gastric cancer either single agent or in combination that may further improve the quality of life and prolong the survival of patients with gastric cancer. In Japan, postoperative adjuvant chemotherapy has been actively developed to enhance survival benefit of surgery for patients with gastric cancer. There were a few positive single randomized controlled study showing benefit of adjuvant chemotherapy with a high evidence level. However, all reports of meta-analysis of adjuvant chemotherapy for gastric cancer indicated the survival benefit of adjuvant chemotherapy. At present, a nation-wide randomized controlled study in the postoperative adjuvant setting for gastric cancer using TS-1 (ACTS-GC) is under way that may clarify the effect of postoperative adjuvant chemotherapy in gastric cancer.

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Oncology. 2003;65(3):211-7.
Effective combination chemotherapy with bimonthly docetaxel and cisplatin with or without hematopoietic growth factor support in patients with advanced gastroesophageal cancer.
Schull B, Kornek GV, Schmid K, Raderer M, Hejna M, Lenauer A, Depisch D, Lang F, Scheithauer W.
Department of Internal Medicine I, Vienna University Medical School, Vienna, Austria.

PURPOSE: A phase II trial was performed to determine the antitumor efficacy and tolerance of combined docetaxel and cisplatin with or without hematopoietic growth factor support in patients with advanced gastroesophageal cancer. PATIENTS AND METHODS: Thirty-seven patients with histologically confirmed metastatic gastroesophageal cancer were entered in this trial. Treatment consisted of 4-weekly courses of docetaxel 50 mg/m(2) and cisplatin 50 mg/m(2) both given on day 1 and 15. Depending on absolute neutrophil counts on the days of scheduled chemotherapeutic drug administration (1,000-2,000/microl), a 5-day course of human granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/day was given subcutaneously; in addition, if hemoglobin was <12.0 mg/dl, erythropoietin 10,000 IU was administered subcutaneously 3 times per week. RESULTS: The confirmed overall response rate (intent-to-treat) was 46%, including 4 complete responses (11%) and 13 partial responses (35%). Eleven patients (30%) had stable disease and 9 (24%) progressed while on treatment. The median time to response was 3 months, the median time to progression was 7 months and the median overall survival time was 11.5 months with 16 (43%) patients currently alive. Hematologic toxicity was common, though WHO grade 4 neutropenia occurred only in 3 patients. Nonhematologic adverse reaction were usually mild to moderate; grade 3 toxicities included alopecia in 5 patients (14%), infection in 1 (3%), neutrotoxicity in 2 (5%) and anaphylaxis in 1 patient. CONCLUSION: Our data suggest that the combination of docetaxel and cisplatin with or without G-CSF and/or erythropoietin has a promising therapeutic index in patients with advanced gastroesophageal cancer. Copyright 2003 S. Karger AG, Basel

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Anticancer Res. 2003 Sep-Oct;23(5b):4219-22.
Docetaxel as salvage therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico Italia Meridionale (G.O.I.M.).
Giuliani F, Gebbia V, De Vita F, Maiello E, Di Bisceglie M, Catalano G, Gebbia N, Colucci G.
Medical and Experimental Oncology Unit, Oncology Institute, Bari, Italy.

BACKGROUND: Docetaxel (DCT), a semisynthetic taxoid, has demonstrated cytotoxic activity against gastric cancer in early phase II studies producing an overall response rate of 17-24%. The Gruppo Oncologico Italia Meridionale (G.O.I.M.) started a confirmatory multicenter phase II trial to evaluate the clinical activity and toxicity of single agent TXT in the treatment of advanced gastric cancer patients who had failed a first-line chemotherapy. MATERIALS AND METHODS: Thirty patients with advanced gastric carcinoma refractory to first-line ECF or PELF chemotherapy were treated with DCT administered at the dosage of 100 mg/mq given as a 1-hour i.v. infusion every three weeks. All patients received a premedication with dexamethasone 8 mg i.v. 12 hours and 1 hour before, and 12 hours after DCT administration. Granulocyte colony stimulating factor was employed in case of febrile neutropenia as needed. The first evaluation of disease status was planned after three cycles. RESULTS: We observed 5 partial responses without any complete response for an overall response rate of 17% (95% CI = 6-36%, intent-to-treat analysis). Nine patients showed stable disease and 14 patients progressed. The duration of objective partial responses were 5, 6, 6, 9 and 12 months, respectively. The median overall survival was 6 months and the 1-year survival rate was 20.6%. No chemotherapy-related toxic death was observed. Haematological grade 3-4 side-effects were respectively: anemia (7%), leucopenia (7%) and neutropenia (18%); in 13 patients (45%) G-CSF was employed to avoid severe leukopenia. CONCLUSION: This multinstitutional single-step phase II study confirms that single-agent docetaxel is active in advanced gastric cancer progressing after first-line chemotherapy. The most frequent toxicity is neutropenia, which may be managed by G-CSF and/or dose adjustments. Docetaxel is therefore worthy of further study in combination with other active drugs.

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Suppl Tumori. 2003 Sep-Oct;2(5):S58-62.
Combined modality treatment for locally advanced gastric cancer.
De Paoli A, Buonadonna A, Boz G, Lombardi D, Innocente R, Tumolo S, Tosolini G, Rossi C, Trovo MG, Frustaci S.
Radiation Oncology Department, Centro di Riferimento Oncologico (CRO), Istituto Nazionale Tumori, Via Pedemontana Occidentale 12, 33081 Aviano, PN, Italy. adepaoli@cro.it

The positive results recently reported by the Intergroup 0116 Study with adjuvant chemoradiation have stimulated an increasing interest in the combined modality treatment of gastric cancer. The significant improvement in disease-free and overall survival reported in this study was related mainly to an improvement in local control rather than to a decrease in the incidence of metastatic disease. Therefore, new and potentially more effective chemotherapy regimens could be considered and the feasibility of their integration with radiation therapy needs to be explored to further improve the treatment in gastric cancer. Our experience with combined radiation therapy and 5-FU-with or without 5-FU based chemotherapy--in unresectable and in partially or radically resected gastric cancer is retrospectively reviewed. In addition, an initial prospective evaluation of the feasibility and toxicity of radiation and 5-FU following adjuvant chemotherapy with modern platinum containing regimens is reported. Our data and the current available experiences with investigational approaches in gastric cancer involving preoperative chemotherapy and intraoperative radiotherapy will be considered in exploring a new combined modality treatment program.

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Suppl Tumori. 2003 Sep-Oct;2(5):S45-7.
Adjuvant chemotherapy in gastric cancer. The Italian experience and review of the literature.
Berardi R, Scartozzi M, Galizia E, Cascinu S.
Medical Oncology Department, University of Ancona, Azienda Ospedaliera Umberto I, Ancona, Italy.

AIMS AND BACKGROUND: Surgery is the treatment of choice for locally advanced gastric cancer, but the 5-year survival rate is still disappointing. The aim of the present review is to summarize the results of previously performed randomized trials to evaluate the effects of adjuvant therapy in gastric cancer. METHODS: We searched the Medline database for the following items: randomized trial, adjuvant therapy for gastric cancer, stomach neoplasms and adjuvant chemotherapy, meta-analysis of adjuvant chemotherapy for gastric cancer. We also searched the bibliographies of all papers, as well as review articles, to identify other studies. RESULTS: The results of chemotherapy in the adjuvant setting are disappointing and, although some randomized controlled trials have reported positive results, none of them provides strong evidence that adjuvant chemotherapy really works. Therefore, surgery remains the mainstay of therapy of gastric cancer. CONCLUSIONS: Further studies are warranted to identify more satisfactory strategies as well as to identify patients who are more likely to benefit from an adjuvant treatment.

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Suppl Tumori. 2003 Sep-Oct;2(5):S39-44.
Combined treatments in gastric cancer: radiotherapy.
Valentini V, Cellini F, D'Angelillo RM.
Cattedra Radioterapia, Istituto di Radiologia, Policlinico Universita A Gemelli Universita Cattolica S Cuore, Largo F Vito 1, 00168 Roma, Italy. vvalentini@rm.unicatt.it

In the past decades radiation oncologists have not had a major interest in the treatment of gastric cancer. The concern on major toxicity related to an extended irradiation of the upper abdomen limited the experience in the treatment of this disease; therefore few data were available to evaluate any advantage of the use of radiation therapy. The results of the Gastrointestinal Intergroup Study promoted a new interest in the irradiation of gastric cancer. The analysis of the outcomes of the Intergroup Study supported the role of locoregional control in promoting better survival for patients treated with adjuvant chemoradiation vs resected patients (81% vs 71%). The studies reported in the last years on the use of radiotherapy in gastric carcinoma are reviewed.

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Suppl Tumori. 2003 Sep-Oct;2(5):S35-8.
Lymphadenectomy in patients with gastric cancer. A critical review.
Nitti D, Marchet A, Olivieri M, Ambrosi A, Mencarelli R, Farinati F, Belluco C, Lise M.
Department of Oncological and Surgical Sciences, Clinica Chirurgica II, University of Padua, Italy. donato.nitti@unipd.it

BACKGROUND: Surgical resection is still the main treatment for patients with gastric cancer. However, while surgical procedures for the treatment of the primary tumor have been standardized, there has been no worldwide consensus as yet on the extent of lymphadenectomy. The aim of the present study was therefore to evaluate the outcome following extended lymphadenectomy, and the prognostic significance of lymph node status, in a group of patients who underwent radical resection for gastric cancer. METHODS: Among 445 consecutive patients operated on for gastric adenocarcinoma between 1980 and 2000 at Clinica Chirurgica II of the Padua University, 314 underwent radical resection (R0). A D2 lymphadenectomy was performed in 293/314 cases (93.3%), and a D1 in 21/314 (6.7%). The rate of postoperative morbidity was 22% (69/314 patients), and the postoperative mortality (within 30 days of surgery), 4.1% (13/314 patients). Survival was determined using the Kaplan Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression. RESULTS: Of 301 valuable patients, a total of 7991 lymph nodes were examined (mean, 27.18; range, 9-62) and the total number of metastatic lymph nodes was 1343 (mean, 4.5; range, 1-47). After a median follow-up of 49 months (range, 2-251), the overall 5-year survival was 57%. At multivariate analysis of all 301 patients, factors retained were depth of invasion (P < 0.001), age (P = 0.027), number of lymph node metastasis (P = 0.029), and metastatic/examined lymph node ratio (P < 0.0001). CONCLUSIONS: D2 dissection can be performed without incurring high mortality and morbidity rates. At least 15 lymph nodes must be removed to achieve an accurate disease staging. As confirmed at multivariate analysis, a metastatic/examined lymph node ratio greater than 25% is an independent negative prognostic factor.

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Suppl Tumori. 2003 Sep-Oct;2(5):S27-30.
Blood transfusions and results after curative resection for gastric cancer.
Bortul M, Calligaris L, Roseano M, Leggeri A.
Surgical Science Department, Clinica Chirurgica Generale, University of Trieste, Italy. m.bortul@fmc.units.it

On the basis of an analysis of our experience and a review of the literature, this report discusses the effects of perioperative blood transfusions on postoperative morbidity, mortality and 5-year survival in a series of patients who underwent curative surgical treatment of gastric cancer. The authors analyze a consecutive series of 137 patients who underwent curative total or subtotal gastrectomy D2 or D3. Ninety-nine patients (72.2%) received perioperative transfusions. The data examined included the number and timing of transfusions (pre-, intra-, or postoperative), the type of operation (total or subtotal gastrectomy with or without splenectomy), tumor stage (pTNM), and the correlation between transfusions, mortality, morbidity and survival. Advanced T-stage (P = 0.01) and total gastrectomy (P = 0.009) were associated with a higher transfusion rate. No cases of operative mortality were recorded after 1988. Specific morbidity was 10.5% in non-transfused patients and 20.1% in transfused. Five-year survival rate in the transfused patients (28.3%) was significantly lower than in the non-transfused group (53.5%) (P = 0.03). Univariate analysis showed that T-stage (P = 0.001) and N-stage (P = 0.04) were associated with a lower survival. By multivariate analysis (Cox regression model) only T-stage (P = 0.001) and N-stage (P = 0.04) were independent prognostic factors, whereas transfusions were not an independent variable (P = 0.27). To conclude, the issue of the real impact of transfusions on the prognosis of gastric cancer is far from being settled, although the T and N parameters are known to be strictly correlated to prognosis. This study further confirms the importance of limiting homologous transfusions as well as of transfusing, whenever possible, autologous or leukodepleted blood; this, however, without losing sight of the primary goal of minimizing operative blood loss.

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Suppl Tumori. 2003 Sep-Oct;2(5):S23-6.
Early gastric cancer: a single-institution experience on 60 cases.
Sigon R, Canzonieri V, Rossi C.
Surgical Oncology Department, Centro di Riferimento Oncologico (CRO), Istituto Nazionale Tumori, Via Pedemontana Occidentale 12, 33081 Aviano PN, Italy. rsigon.@cro.it

AIMS AND BACKGROUND: The 5-year survival rate of early gastric cancer (EGC) is 85-100% after "curative" resection, as compared to 20-30% in advanced gastric cancer (AGC). Because of this relatively high cure rate, the interest in the diagnosis and therapy of EGC has been steadily increasing. The present study, based on 60 EGCs, in a single-institution, is aimed at critical evaluating the diagnostic procedures and surgical options. METHODS AND RESULTS: Sixty patients with early gastric cancer (36 men and 24 women; median age, 61 years; range, 28-84) were diagnosed and operated on. They represented 21% of all patients with gastric cancer (281) treated in the period January 1987 to December 2001. The most frequent symptom was epigastric pain (84%). Barium upper gastrointestinal radiography findings were strongly suggestive of malignancy in 56 cases (93%). Preoperative histopathological diagnosis of adenocarcinoma was performed in 57 cases (95%). In 3 cases (5%) severe epithelial dysplasia (associated with ulcer) was the first diagnosis, but the final diagnosis, on the basis of resected specimens, was well differentiated adenocarcinoma. The primary surgical procedure included: a) subtotal distal resection (49 cases); b) total gastrectomy (6) for proximal neoplastic extension; c) proximal gastric resection (2) for cardial cancer; d) degastro-total gastrectomy (3) for cancer of the stump. Two patients, previously treated with conservative surgery, underwent degastro-total gastrectomy for neoplastic microfocal extension to the resection margin and for early anastomotic recurrence, respectively. Mural infiltration was limited to the mucosa and submucosa in 36 and 24 cases, respectively. Lymph node metastases were found in 3 mucosal and 9 submucosal tumor cases, involving either the first and second echelon. No operative deaths or postsurgical complications occurred in this series. In the follow-up period (median, 63 months; range, 3-178) 7 patients died due to other causes; 1 developed liver metastases, another developed oropharyngeal cancer and 2 died of biopsy-proven lung cancer without evidence of recurrent or metastatic gastric cancer. CONCLUSIONS: The clinical presentation of EGC is aspecific. Preoperative endoscopy with multiple biopsies remains the most sensitive diagnostic procedure. For treatment, subtotal distal gastric resection with lymphadenectomy is the gold standard, but in some instances total gastrectomy may be indicated. Accurate pathological examination establishes the depth of infiltration, as well as the superficial extension of tumors and lymph node status. Although the prognosis of EGC is favorable, a medium-term follow-up should be planned.

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J Am Coll Surg. 2003 Sep;197(3):372-8.
Laparoscopic gastric surgery in a Japanese institution: analysis of the initial 100 procedures.
Shimizu S, Noshiro H, Nagai E, Uchiyama A, Tanaka M.
Department of Endoscopic Diagnostics and Therapeutics, Kyushu University Faculty of Medicine, Fukuoka, Japan.

BACKGROUND: Although endoscopic surgical procedures are popular in various fields, reports on its use in gastric surgical procedures are limited. This study was designed to review our initial experience with laparoscopic gastric surgical techniques to evaluate indications and surgical results. STUDY DESIGN: We undertook a retrospective analysis of 100 patients (66 men and 34 women, mean age 63 years) who underwent laparoscopic gastric surgical procedures between 1995 and 2001. Procedures performed were distal gastrectomy (n = 76), wedge resection (n = 20), and intragastric surgical procedures (n = 4). Patients were divided into two groups according to the date of the procedure, from the earliest to the most recent. RESULTS: There were 85 patients with gastric cancers, 14 submucosal tumors, and 1 duodenal ulcer. In 8 cases conversion was made to an open surgical procedure. Operation times required for distal gastrectomy, wedge resection, and intragastric surgical procedures were 330 +/- 69, 144 +/- 34, and 298 +/- 106 min, and blood loss was 354 +/- 251, 56 +/- 94, and 33 +/- 58 g, respectively. Complications included transient anastomotic stenosis (n = 5), leakage (n = 4), and bleeding (n = 1) after distal gastrectomy, and bleeding (n = 1) after intragastric surgical procedures. There were no complications after wedge resection. Comparing the first and second halves of the series, the percentage of distal gastrectomy significantly increased from 66% to 86% (p = 0.02) and the number of dissected lymph nodes at this procedure increased from 20 +/- 13 to 33 +/- 17 (p < 0.01). CONCLUSIONS: Laparoscopic gastric surgical procedures are safe and feasible for early gastric cancers and submucosal tumors. Technical advances in lymph node dissection have made distal gastrectomy a leading and increasingly popular laparoscopic procedure for early gastric cancer.

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Gan To Kagaku Ryoho. 2003 Sep;30(9):1297-301.
[Efficacy and safety of novel oral fluoropyrimidine anticancer drug, TS-1 for advanced and recurrent gastric cancer patients]
[Article in Japanese]
Arai K, Iwasaki Y, Kimura Y, Takahashi K, Yamaguchi T, Honma S, Takahashi T.
Dept. of Surgery, Tokyo Metropolitan Komagome Hospital.

The efficacy and safety of the oral fluoropyrimidine TS-1, which contains a dihydropyrimidine dehydrogenase (DPD) inhibitor, were examined in fifty-five patients with gastric cancer. The patients were divided into 28 with measurable cancer lesions (TUM group) and 27 without them (ADJ group). The total number of courses was 164 (mean: 5.9 courses) in the TUM group and 146 (mean; 5.4 courses) in the ADJ group. The response rate in the TUM group, excluding three patients who could not be evaluated because of incomplete administration, was 40% (CR: 4, PR: 6, NC: 6, PD: 9). Among responders, the mean number of courses to response was 2.2 and the median survival time (MST) was 21.7 months. In terms of safety, adverse reactions appeared in forty-five patients (82%) and the incidence was higher in the ADJ group. Major toxicities were leukopenia (38%), anorexia (27%), increased total bilirubin concentration (25%) and diarrhea (24%). Adverse reaction of grade 3 was found in only three patients (5.5%) and there were no drug-related deaths. In conclusion, TS-1 is safe and effective if attention is given to biweekly examinations for the development of adverse reactions.

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Gan To Kagaku Ryoho. 2003 Sep;30(9):1289-96.
[Pilot study of TS-1 combined with lentinan in patients with unresectable or recurrent
advanced gastric cancer]
[Article in Japanese]
Nimura H, Mitsumori N, Tsukagoshi S, Nakajima M, Atomi Y, Suzuki S, Kusano M, Yoshiyuki T, Tokunaga A.
Dept. of Surgery, Jikei University School of Medicine.

TS-1, an anticancer, antimetabolis agent, has shown clinically superior antitumor activity against unresectable advanced or recurrent gastric cancer (UARG). A biological response modifier, lentinan (LNT) prolonged the survival period of patients with UARG when combined with tegafur (FT). To assess the efficacy, the safety and prognostic factors of chemo-immunotherapy using TS-1, a FT derivative, and LNT, we conducted a multi-institutional pilot study in patients with UARG. Patients were treated with TS-1 at 80 mg/m2/day (bid) for 4-weeks, and LNT was given at 2 mg/body (i.v.) in a week, followed by a 2-week rest for 4 cycles. Twenty-two patients were entered from 4 institutes and 19 patients were eligible. The median survival time in eligible patients was 400 days. The incidence of hematological toxicity (grade 2 leukopenia), and non-hematological toxicity (grade 3 nausea or fatigue) was 5.3% (1/19) and no grade 4 toxicity was observed. The response ratio was 37.5% in 8 patients who had been administered the planned dose of TS-1. In subset analyses, the survival period of the patients with normal (< 500 micrograms/ml) serum immunosuppressive acidic protein level was significantly (p < 0.0001) better than that of the higher one. The survival period for those patients whose granulocytes/lymphocytes ratio was not more than 2 tended to be better. From the prolonged survival periods, chemo-immunotherapy using TS-1 combined with LNT would seem to have a benefit against UARG, and reduced toxicity. Future clinical trials are warranted to confirm its potency.

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Gan To Kagaku Ryoho. 2003 Sep;30(9):1238-48.
[Controversies in surgical treatment of gastric cancer]
[Article in Japanese]
Yonemura Y.
Dept. of Gastric Surgery, Periotoneal Dissemination, Shizuoka Cancer Center.

Conservative surgery is performed for patients with early gastric cancer, according to the guideline proposed from Japanese Gastric Cancer Society. There are many kinds of operations, such as ordinary open surgery, laparoscopic-assisted gastrectomy, laparoscopic intragastric surgery, pyrolus preserving gastrectomy, hand-assisted laparoscopic surgery. Indications of the operations are various, but it is necessary to have standard indication for each procedure. Standard operation for advanced gastric cancer in Japan is D2 gastrectomy. Surgeons in Eastern world believed that D1 + alpha or D1 + adjuvant radio-chemotherapy are the standard treatments, because of high incidence of mortality and morbidity after D2 dissection. In Japan, D4 dissection has been performed for patients with nodal involvement, and the validity of D4 dissection is now studied by two randomized trials. Combined resection for T4 tumor is believed to be mandatory. However, the validity of pancreato-splenectomy to yield a complete clearance of No. 10 or No. 11 lymph node station is in controversial, because of high incidence of the postoperative development of pancreatic fistula, anastomotic insufficiency and abscess. There was no prospective study to confirm the effect of omentectomy. Patients with advanced gastric cancer showing a serosal invasion-diameter less than 2.5 cm have less risk of peritoneal recurrence. It may be valuable to perform randomized controlled study consisting of omentum-preserving gastrectomy and gastrectomy with omentectomy. Prognosis of patients with peritoneal dissemination was improved by intraperitoneal chomo hyporthormia and peritonectomy, and prospective studies should be done to compare the effects of systemic chemotherapy and regional chemotherapy combined with peritonectomy. Furthermore, effects of neoadjuvant chemotherapy with cytoreduction with R0 resection should be confirmed by prospective studies.

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Semin Oncol. 2003 Aug;30(4 Suppl 11):19-25.
Adjuvant therapy for gastric cancer.
Macdonald JS.
Department of Gastrointestinal Oncology, St. Vincent's Comprehensive Cancer Center, New York, NY, USA.

The curative management of gastric adenocarcinoma depends on complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are 70% to 80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared with less extensive operations. Until recently, attempts at preventing recurrence, usually using adjuvant chemotherapy, have been ineffective. A large United States Intergroup study (INT-0116) showed that combined chemoradiation following gastric resection improves median time to relapse (30 months v 19 months, P <.0001) and overall survival (35 months v 28 months, P =.01). This treatment has become a standard of care. Future advances in the therapy for resectable gastric cancer may come from studies of preoperative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and anti-angiogenesis agents.

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Gan To Kagaku Ryoho. 2003 Aug;30(8):1125-30.
[Usefulness of TS-1 and lentinan combination immunochemotherapy in advanced or recurrent gastric cancer--pilot study aiming at a randomized trial]
[Article in Japanese]
Kimura Y, Iijima S, Kato T, Tsujie M, Naoi Y, Hayashi T, Tanigawa T, Yamamoto H, Kurokawa E, Kikkawa N, Matsuura N.
Gastrointestinal Research Center, Dept. of Surgery, Minoh City Hospital.

The quality of life (QOL) of patients with advanced or recurrent gastric cancer is poor and their immunocompetence is low, making it important to conduct chemotherapy while at the same time improving their QOL and maintaining their immunocompetence. To improve QOL and increase compliance by reducing the side effects but not the antitumor effect of TS-1, a 2-week regime with 2-week administration of TS-1, and a 1-week drug-free interval in combination with the immunotherapeutic agent lentinan (LNT) was started in 5 patients with advanced or recurrent gastric cancer. Toxicity, efficacy, QOL, and immunological parameters were investigated preliminarily to examine whether or not usefulness of lentinan could be evaluated. QOL scores for appetite, nausea/vomiting, and abdominal pain/diarrhea showed improvement, although not in statistically significant values. The Th2 (CD4-positive, IL4-positive T cells) response in peripheral blood decreased significantly. TS-1 and lentinan combination immunotherapy was carried out safely with advanced recurrent gastric cancer. In order to examine the usefulness of LNT combined use, it was thought that a randomised trial using toxicity with not only efficacy but QOL and immunological parameters as indicators would be beneficial.

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Eur J Surg Oncol. 2003 Aug;29(6):511-4.
Treatment and prognosis of early multiple gastric cancer.
Borie F, Plaisant N, Millat B, Hay JM, Fagniez PL, De Saxce B; French Associations for Surgical Research.
Service Chirurgie A, Hopital St Eloi, 34295, Montpellier, France. fborie@yahoo.com

AIM: Early gastric cancer (EGC) may have a 5-year survival rate of over 90% following surgery. Early multifocal gastric cancer (EMGC) accounts for between 8.3 and 17% of all EGCs. A multicenter retrospective study is reported of prevalence, characteristics, prognosis and type of resection for EMGC patients. METHOD: 333 patients with EGC were operated on, between January 1979 and December 1988, and followed to June 1996. RESULTS: 33 EGC patients had EMGC. There was no significant difference in clinico-pathological features between EGC and EMGC. 21 cases of EMGC underwent a subtotal gastrectomy and 12 underwent a total gastrectomy. Recurrences after subtotal gastrectomy were, respectively, 10 and 18% for EGC and EMGC patients (p=0.2). The cumulative 5 years specific survival rate for 298 EGC and 34 EMGC were 94 and 90%, respectively (p=0.9). Five-year survival rates after subtotal gastrectomy were 92 and 90% for EGC and EMGC patients, respectively (p=0.8). CONCLUSION: EGC and EMGC had the same clinico-pathological features and prognosis. A careful follow up of the stomach remnant is essential.

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Lancet Oncol. 2003 Aug;4(8):498-505.
Chemoradiation for resectable gastric cancer.
Xiong HQ, Gunderson LL, Yao J, Ajani JA.
Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, TX 77030, USA.

The incidence of gastric cancer has been declining in recent years, however, the disease continues to be a worldwide public health problem. About two thirds of patients with gastric cancer undergo surgical resection with curative intent. R0 resection--complete local-regional tumour removal with negative resection margins--is the only curative modality. The optimum extent of lymph-node dissection (D1 vs D2) is controversial. Disease relapse, both local and distant, is common and the 5-year survival rate is disappointing. Adjuvant chemotherapy has been studied extensively in this setting but an effective regimen has not yet been identified. A recent intergroup study has shown that postoperative chemoradiation is effective in improving both disease-free survival (3-year, 48% vs 31%, p<0.001) and overall survival (3-year, 50% vs 41%, p=0.005) compared with surgery alone. Preoperative radiation as a single adjuvant therapy has also yielded improvements in local-regional control, disease-free survival, and overall survival compared with surgery alone. Preoperative chemotherapy or chemoradiation has been accepted to have a theoretical advantage over postoperative therapy and has now been shown to be a feasible option. Its efficacy, however, remains to be tested.

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Expert Rev Anticancer Ther. 2003 Aug;3(4):457-70.
Individualizing therapy in gastric cancer.
Sendler A, Siewert JR.
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Munchen, Germany. sendler@nt1.chir.med.tu-muenchen.de

Although its incidence in developed countries has declined, gastric cancer remains one of the most common human malignancies. In western countries a shift from distal to proximal tumors has been noted during the past 15 years. Today, surgery is no longer the only treatment modality of gastric cancer, with the help of modern and sophisticated staging procedures it becomes increasingly possible to individually tailor therapy. Operative morbidity and mortality has markedly decreased. The importance of surgical expertise for short- as well as long-term outcome is emphasized. The knowledge of adequate surgery together with the use of combined modalities opens the door to the amelioration of the still dismal prognosis for patients with gastric cancer. This paper reviews the modern approach to gastric cancer using an individualized treatment concept.

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Br J Cancer. 2003 Sep 15;89(6):997-1001.
Irinotecan is active in chemonaive patients with metastatic gastric cancer: a phase II multicentric trial.
Kohne CH, Catane R, Klein B, Ducreux M, Thuss-Patience P, Niederle N, Gips M, Preusser P, Knuth A, Clemens M, Bugat R, Figer I, Shani A, Fages B, Di Betta D, Jacques C, Wilke HJ.
Robert Rossle Klinik, Charite University Hospital, Berlin, Germany. Claus-Henning.KOEHNE@UMKLIMKUM-DRESDEN.DE

To assess the response rate and the tolerance of irinotecan as first-line therapy, 40 patients with metastatic gastric cancer received irinotecan 350 mg m(-2) every 3 weeks administered as a 30 min infusion. Among the 35 patients evaluable for response, two complete and five partial responses were recorded (response rate: 20.0% (95% CI:8.4-36.9%)). In total, 16 patients achieved stable disease and 12 progressive disease. In all, 66 percent of the patients benefited from tumour growth control. The median time to progression was 3.0 months (95% CI: 2.3-4.4%). The median overall survival was 7.1 months (95% CI: 5.2-9.0%). The probability of being alive at 6 months and 9 months was 61.0 and 32.4%, respectively. The median number of cycles per patient was 3 (range 1-14), and the relative dose intensity was 0.98. The most common grade 3-4 toxicities by patients were diarrhoea 20%, asthenia 10%, nausea 7.5%, vomiting 5.0%, abdominal pain 5%, neutropenia 38.5%, leucopenia 28.2%, anaemia 12.8% and thrombocytopenia 5.1%. Febrile neutropenia occurred in 12.5% of patients. These findings indicate that irinotecan is active and well tolerated in patients with metastatic gastric adenocarcinoma and warrants further evaluation in this clinical setting.

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Lancet. 2003 Jul 26;362(9380):305-15.
Gastric cancer.
Hohenberger P, Gretschel S.
Division of Surgery and Surgical Oncology, Robert Roessle Hospital at the Max Delbruck Center for Molecular Medicine, Charite, Humboldt University at Berlin, Germany. hohenberger@rrk-berlin.de <hohenberger@rrk-berlin.de>

The past decade has seen many advances in knowledge about gastric cancer. Notably, tumour biology and lymphatic spread are now better understood, and treatment by surgical and medical oncologists has become more standardised. Since refrigerators have replaced other methods of food conservation, Helicobacter pylori has become a factor in the cause of gastric cancer. Cancers that arise at the oesophagogastric junction might be further examples of wealth-associated disease. To tailor treatment better, the western hemisphere needs to borrow from the East by establishing screening programmes for early diagnosis, through careful surgical resection, and through detailed analysis of tumour spread. In Europe and the USA, most patients reach treatment with cancers already at an advanced stage. For these patients, three important randomised trials are underway that evaluate combined therapy. Cytostatic drugs, especially angiogenesis inhibitors have proved disappointing; however, basic research efforts to detect familial gastric cancers and to assess minimally residual disease look more hopeful.

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Expert Opin Pharmacother. 2003 Jul;4(7):1083-96.
Pathological staging and therapy of oesophageal and gastric cancer.
Debruyne PR, Waldman SA, Schulz S.
Division of Clinical Pharmacology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Oesophageal and gastric cancers are a significant cause of morbidity and mortality worldwide. Despite improvements in surgical techniques, radiation and chemotherapy, the prognosis of both cancers remains poor. Immunohistochemical and experimental studies indicate that the concept of micrometastasis is applicable to oesophageal and gastric cancer. New staging approaches, including immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of various markers, have been proposed for a more accurate staging of oesophageal and gastric cancer. Preliminary results suggest that real-time RT-PCR of markers for intestinal differentiation, such as guanylyl cyclase C (GC-C), might be useful for both the detection of premalignant conditions, such as intestinal metaplasia and the detection of micrometastasis from adenocarcinoma of the upper intestinal tract. Standard curative treatment options for oesophageal cancer include surgery or chemoradiotherapy. Chemotherapy is an option for the treatment of advanced and recurrent oesophageal cancer. Standard curative treatment for gastro-oesophageal junction and gastric cancer includes surgery and adjuvant chemoradiotherapy. Chemotherapy is an option for the treatment of advanced and recurrent gastric cancer.

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Gan To Kagaku Ryoho. 2003 Jul;30(7):963-70.
[A clinical results of TS-1 in advanced and recurrent gastric cancer in our hospital]
[Article in Japanese]
Abe S, Kojima M, Tamura H, Kurihara H, Kitago M, Kobayashi T, Nakamura T, Ogihara T.
Dept. of Surgery, Haga Red Cross Hospital.

A total of 40 patients with advanced and recurrent gastric cancer in our hospital were treated with TS-1 alone, and the efficacy of treatment, survival time, and adverse effects were examined. TS-1 was administered with the usual dosage and dose regimen. Response to treatment included a complete response (CR) in 3 cases, partial response (PR) in 8 cases, no change (NC) in 10 cases, and progressive disease (PD) in 7 cases. The response rate was 39.3%, and among the 28 patients with evaluable lesions TS-1 produced a high response rate of 56.3% in 16 patients who had undergone prior therapy. The median survival time (MST) was 478 days in the 28 patients with evaluable lesions, excluding patients with peritoneal dissemination, and 283 days in the 12 patients with peritoneal dissemination. The outcome was markedly poorer in the patients with peritoneal dissemination than in the patients with evaluable lesions. The incidence of grade 3 or higher adverse effects was 20%, including two cases in which decreased dihydropyrimidine dehydrogenase (DPD) activity was suspected, and one case in which decreased dihydropyrimidinase (DHP) was suspected. Although the effect of TS-1 alone on gastric cancer is significantly superior to that of any conventional cancer drugs, the results of this study suggest that the antitumor effect varies with the site of the target lesions and according to whether the lesion is a remnant or recurrence.

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Chang Gung Med J. 2003 Jun;26(6):433-9.
Mitomycin C (MMC) with weekly 24-hour infusions of high-dose 5-fluorouracil and leucovorin in patients with advanced gastric cancer.
Chen JS, Lin YC, Liau CT, Wang CH, Liaw CC.
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei. fong0301@ms18.hinet.net

BACKGROUND: We have reported a 33% response rate with 5-fluorouracil/leucovorin (5-FU/LV) treatment along with a median survival of 7 months in patients with advanced gastric cancer. Subsequently, mitomycin C (MMC) became our target agent for the combination because of its activity towards gastric cancer. METHODS: From May 1998 to December 2000, a total of 37 chemo-naive patients with advanced gastric cancer were included. There were 20 men and 17 women with a median age of 58 (range, 21-73) years. The regimen consisted of 2600 mg/m2 5-FU and 100 mg/m2 LV admixed in an outpatient infusion pump administered for 24 hours every week for 6 weeks, followed by a 2-week break; then 10 mg/m2 MMC was given once every 8 weeks. The treatment continued until disease progression or unacceptable toxicity was noted, or the patient refused. RESULTS: In total, 404 treatments of 5-FU/LV were given. The mean number of treatments was 10 (range, 1 to 24). The intent to treat response rate was 40.5% (15/37) with 5.4% (2/37) showing a complete response. The median time to disease progression was 4.5 months. The median survival time was 8.0 months. All of the patients were evaluated for toxicity. Less than 10% of the patients developed grade III/IV toxicity. CONCLUSION: MMC with weekly 24-hour infusions of high-dose 5-FU and LV produced moderate activity in patients with advanced gastric cancer, and patients showed acceptable toxicity.

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Gan To Kagaku Ryoho. 2003 Jun;30(6):809-15.
[Clinical study of weekly administration of paclitaxel for advanced and metastatic gastric cancer]
[Article in Japanese]
Emoto T, Yoshikawa K, Fujii M, Nezu R, Dousei T, Fujikawa M, Yoshioka Y, Naka Y, Komaki T.
Dept. of Surgery, Osaka Prefectural Habikino Hospital.

Ten cases of advanced and metastatic gastric cancer treated by weekly administration of paclitaxel were studied. The patients were 50-72 years of age, including 9 men and 1 woman. In this study, paclitaxel was administered by 1 hour intravenous infusion at a dose of 50-80 mg/m2 every week. Administration was continued for 3 weeks with 1 week rest. One to four cycles were performed at minimum. Paclitaxel was administered in 5 cases as 1st line treatment, 4 cases as 2nd line treatment and 1 case as 3rd line treatment. There were 2 partial responders and no complete responders, and the overall response rate was 20%. The response rate was 100% in liver, 100% in lung, 16% in lymphnodes, and 0% in peritonial dissemination. The clinical symptoms of pain and jaundice abated in one case, the size of the tumor decreased in one case, and a temporary decrease of ascites due to peritonial dissemination was seen in two cases. The level of tumor marker was decreased in 3 out of 10 cases. Side effects included grade 3/4 leukopenia in 10% of patients, and alopecia in 50%, but peripheral neuropathy was not observed. Weekly administration of paclitaxel appears to be well-tolerated and effective against advanced and metastatic gastric cancer.

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J Chemother. 2003 Jun;15(3):275-81.
Phase II study of irinotecan and mitomycin C in 5-fluorouracil-pretreated patients with advanced colorectal and gastric cancer.
Bamias A, Papamichael D, Syrigos K, Pavlidis N.
Oncology Dept, Ioannina University Hospital, Ioannina, Greece. abamias@med.uoa.gr

The aim of this phase II study was to investigate the tolerance and efficacy of a second-line irinotecan/mitomycin C combination in patients with advanced gastric or colorectal cancer, pretreated with 5-fluorouracil. Forty patients who had received 5-fluorouracil-based chemotherapy for advanced disease or adjuvant 5-fluorouracil treatment were enrolled. Chemotherapy consisted of irinotecan 125 mg/m2 and mitomycin C 5 mg/m2, given every 2 weeks. Treatment was continued until progression or limiting toxicity occurred. Five partial responses (12.5%), 22 cases of stable disease (55%) and 13 of progression (32.5%) were registered, giving an overall response rate of 12.5% [95% confidence interval (CI), 4.2-26.8%] and an overall control of tumor growth in 67.5% (95% CI, 50.8-81.4%) of patients. Median progression-free survival was 5 months, median survival time 8 months, and 1-year probability of survival was 21.6%. Diarrhea and neutropenia affected 25% and 12.5% of patients respectively, with only 7.5% experiencing grade 3-4 toxicity. There were no chemotherapy-related deaths or hospitalizations. This combination regimen was shown to be moderately effective with substantially lower toxicity than irinotecan monotherapy in 5-fluorouracil-pretreated patients with advanced gastric or colorectal cancer. It may represent an attractive option in patients at high risk for developing specific irinotecan toxicity.

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Hepatogastroenterology. 2003 May-Jun;50(51):883-5.
Minilaparotomy for early gastric cancer.
Onitsuka A, Katagiri Y, Miyauchi T, Yasunaga H, Mimoto H, Ozeki Y.
Department of Surgery, Gifu Red Cross Hospital, 3-36, Iwakura-cho, Gifu 502-8511, Japan. oni-ak@ocn.aitia.ne.jp

BACKGROUND/AIMS: From the experience of laparoscopic-assisted distal gastrectomy, it was considered that a gastrectomy with lymph node dissection could be performed through a minilaparotomy, placed as for gastroduodenostomy in laparoscopic-assisted distal gastrectomy. METHODOLOGY: Ten patients with early gastric cancer underwent gastrectomy with lymph node dissection via minilaparotomy. Minilaparotomy was performed via a seven-centimeter midline incision placed at the mid-upper abdomen. Two six-centimeter-wide Kent retractors were used to suspend the abdominal wall on each side, and a multipurpose surgical arm to retract the liver. The abdominal wound could be moved horizontally by pulling these retractors to the right or left. This movable wound allowed direct visualization of almost all the operative field for gastrectomy. RESULTS: No operation was converted to a standard open gastrectomy. The patients who had a tumor in the lower third of the stomach underwent complete D2 lymph node dissection. In the patients who underwent pylorus-preserving gastrectomy, near complete D2 lymph node dissection was performed. Mean operation time was 175 minutes. No significant complication was encountered. CONCLUSIONS: It was concluded that minilaparotomy could be used as an alteration to the standard open gastrectomy.

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Clin Oncol (R Coll Radiol). 2003 May;15(3):92-7.
Mitomycin C, carboplatin and protracted venous infusion 5-fluorouracil in advanced oesophago-gastric and pancreatic cancer: results of two phase II studies.
Kelleher M, Tebbutt NC, Cunningham D, Andreyev J, Allen M, Hill M, Norman A.
Royal Marsden Hospital, London, UK.

Cisplatin is an active palliative chemotherapy agent in advanced upper gastrointestinal cancer, but it is associated with significant non-haematological toxicity. Substitution of cisplatin by carboplatin in combination chemotherapy regimens may reduce these adverse effects. These two phase II studies evaluated the efficacy and toxicity of the combination of mitomycin C (MMC) 7 mg/m2 q 6 weekly, carboplatin area under the concentration-time curve 5 mg/ml/min q 3 weekly and protracted venous infusion 5-fluorouracil (5FU) 300 mg/m2/day (McarboF) in advanced upper gastrointestinal cancer. Between October 1998 and June 2000, 31 patients were enrolled in the studies, 23 patients in the oesophago-gastric study and eight patients in the pancreatic study. Although non-haematological toxicity was modest, both protocols were closed prematurely because of excessive haematological toxicity and frequent treatment delays. The overall incidence of grade 3/4 neutropenia and thrombocytopenia was 39 and 52%, respectively. The McarboF combination showed significant activity with an overall response rate of 52% in advanced oesophago-gastric cancer. Palliative benefit was also evident with improvement in symptoms of pain and weight loss in over 79 and 50% of patients in the oesophago-gastric study and pancreatic study, respectively. Median overall survival times were 10.6 and 6.6 months for patients with oesophago-gastric and pancreatic cancer, respectively. The McarboF regimen showed promising activity in advanced upper gastrointestinal cancer, with modest non-haematological side-effects. This combination merits further evaluation with modification of the dose and schedule of carboplatin and MMC in order to reduce the severity of haematological toxicity.

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Oncology (Huntingt). 2003 May;17(5):714-21, 728; discussion 728-9, 732-3.
Adjuvant therapy in gastric cancer: can we prevent recurrences?
Meyerhardt JA, Fuchs CS.
Dana-Farber Cancer Institute, Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts, USA. jeffrey_meyerhardt@dfci.harvard.edu

Despite a dramatic decline in the incidence of gastric carcinoma in the United States during the past century, treatment remains a challenging problem for oncologists. Surgery continues to be the primary modality for managing early-stage gastric cancer, but up to 80% of patients who undergo a "curative" resection develop locoregional or distant recurrence. Given these sobering statistics, there has been great interest in developing strategies to prevent recurrences after surgery and improve overall mortality. In this article, we review data on adjuvant treatment modalities for this disease, including radiotherapy, chemotherapy, combination chemotherapy and radiation, intraperitoneal treatment, and immunotherapy. We focus attention on the recent widespread acceptance of adjuvant chemoradiotherapy, based on the results of Intergroup trial 0116. Future strategies incorporating different modalities of treatment will be outlined.

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Jpn J Clin Oncol. 2003 May;33(5):238-40.
A phase II clinical trial to evaluate the effect of paclitaxel in patients with ascites caused by advanced or recurrent gastric carcinoma: a new concept of clinical benefit response for non-measurable type of gastric cancer.
Sakamoto J, Morita S, Yumiba T, Narahara H, Kinoshita K, Nakane Y, Imamoto H, Shiozaki H; Ascitic Gastric Cancer Study Group of the Japan South West Oncology Group.
Department of Epidemiological and Clinical Research Information Management, Kyoto University, Kyoto, Japan. sakamoto@pbh.med.kyoto-u.ac.jp

A phase II clinical trial has started in the South West region of Japan to investigate the efficacy and safety of weekly paclitaxel chemotherapy for the treatment of patients with ascites-forming advanced gastric cancer. A novel trial design was created to assess more effectively prospective changes in symptomatology. The study design focuses on the typical features seen in patients with ascites-forming advanced gastric cancer, including girth of the abdomen and impaired performance status, which is evaluated in the endpoint of 'Clinical Benefit Response - Gastric Cancer'. The more traditional endpoints, objective tumor response and survival, are also included. As nearly 40% of patients with this disease are excluded from traditional phase II trials owing to the absence of 'measurable' disease, this study should more precisely illustrate the disease entity affecting patients with advanced gastric cancer.

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Rozhl Chir. 2003 May;82(5):278-84.
[Lymphadenectomy in gastric carcinoma--present status, new trends and personal experience]
[Article in Czech]
Simsa J, Leffler J, Hoch J, Schwarz J, Pospisil R, Bavor P.
Chirurgicka klinika 2. LF UK a FN Motol, Praha.

The only hope for long time survival in gastric cancer is radical surgery with complete tumour removal. Lymphadenectomy as a part of surgical procedure helps to remove tumour completely. The value of lymphadenectomy for staging is clear and surgeons have no doubt about it. Therapeutic effect of lymphadenectomy with improvement of the prognosis remains uncertain. In this work we would like to discuss current trends in lymphadenectomy in gastric cancer, especially evaluating the value and extent of the procedure.

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Cas Lek Cesk. 2003;142 Suppl 1:26-8.
[Role of adjuvant chemoradiotherapy in the treatment of gastric carcinoma]
[Article in Czech]
Kocakova I, Vetcha H, Soumarova R, Vyzula R.
Klinika komplexni onkologicke pece-oddeleni radiacni onkologie, Masarykuv onkologicky ustav, Brno. kocakova@mou.cz

Gastric carcinoma is often diagnosed at the advanced stage. Approximately 50% of patients with locoregional disease cannot undergo any curative resection. 5-year survival rate in patients who undergo a curative resection (R0) ranges from 30-40%. In patients with curatively resected gastric carcinoma who are at high risk of relapse the adjuvant postoperative chemotherapy with 5-FU/leucovorin is recommended. It should be followed by radiotherapy with concomitant 5-FU/leucovorin, and then two more courses of 5-FU/leukovorin (INT-0116 trial) should be added. For the surgery alone group, the overall survival was 27 months; in the chemoradiotherapy group it was 36 months. The recommended therapy for inoperable or medically unsuitable patients with locoregional carcinoma is the combined radiation therapy (45 to 50.4 Gy) with concurrent 5-fluorouracil or cisplatin based chemotherapy.

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J Am Coll Surg 2003 Jan;196(1):75-81
Laparoscopy-assisted distal gastrectomy with systemic lymph node dissection for early gastric carcinoma: a review of 43 cases.
Fujiwara M, Kodera Y, Kasai Y, Kanyama Y, Hibi K, Ito K, Akiyama S, Nakao A.
Department of Surgery II, Nagoya University School of Medicine, Nagoya/Aichi, Japan.

BACKGROUND: Recently, laparoscopy and laparoscopy-assisted surgery have been used increasingly as less-invasive alternatives to conventional open surgery. But the use of this approach in gastric carcinoma has received little attention, possibly from the low incidence of early-stage disease in the West and the relative complexity of the surgical procedure. STUDY DESIGN: A prospective feasibility study of laparoscopy-assisted distal gastrectomy was performed in patients with histologically confirmed gastric carcinoma located in the lower or middle third of the stomach. Patients whose preoperative evaluations, including endoscopic ultrasonography and computerized tomography, led to a diagnosis of T1 N0 stage disease, and who had no advanced disease discovered during laparoscopy, were eligible. Intraoperative blood loss, time of operation, mortality, and morbidity were assessed, along with the number of lymph nodes retrieved and shortterm survival. RESULTS: Between 1998 and 1999, 43 patients were enrolled. Laparoscopy-assisted distal gastrectomy was converted to an open procedure in one patient. There were no operative or in-hospital deaths, but the incidence of anastomotic leakage was 14% (6 of 43). The mean blood loss was 239 mL, the time of operation was 225 minutes, and lymph node retrieval was 20.2 nodes. These results are comparable with a series of conventional open operations. One patient died of recurrent disease, and all other patients remain disease-free to date. Port-site recurrence was not observed. CONCLUSIONS: Although laparoscopy-assisted distal gastrectomy was equivalent to open surgery in several clinical parameters, the relatively high morbidity was a drawback. Its appropriateness to gastric cancer surgery must be verified by further studies. Copyright 2003 by the American College of Surgeons

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Am J Surg 2003 Mar;185(3):285-7
Endoscopic mucosal resection for early cardia cancer by minimum laparotomy.
Endo K, Kawamoto K, Baba H, Yamamoto M, Ikeda Y, Toh Y, Kohnoe S, Okamura T.
Department of Gastroenterologic Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan. kendo@nk-cc.go.jp

Endoscopic mucosal resection (EMR) has been widely accepted as a minimally invasive and standard treatment for early gastric cancers without ulceration or signs of submucosal invasion and meeting the criteria for diameter, macroscopic appearance, and well- or moderately differentiated histology. However, EMR cannot be applied to some cases owing to technical difficulties relating to the intragastric location of the cancers even when the above criteria are satisfied. We report here a new approach to EMR for early cancers of the cardia located close to the esophagocardia junction that are outside the indications for ordinary EMR.

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Gan To Kagaku Ryoho 2003 Feb;30(2):283-7
Am J Clin Oncol 2003 Feb;26(1):37-41
Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer.
Gadgeel SM, Shields AF, Heilbrun LK, Labadidi S, Zalupski M, Chaplen R, Philip PA.
Division of Hematology/Oncology, Barbara Ann Karmanos Cancer Institute and Wayne State University, Detroit, MI 48201, USA.

5-Fluorouracil-based combination chemotherapy is commonly used in patients with advanced gastric cancer, but results with such therapy are fairly modest. Evaluation of newer agents is therefore required in this disease. Paclitaxel has shown promising activity as a single agent in gastric cancer. In vitro, paclitaxel exhibits sequence-dependent synergy with platinum compounds against gastric cancer. This study was conducted to evaluate the efficacy and toxicity of combination carboplatin and paclitaxel in patients with advanced gastric cancer. Twenty-seven patients with measurable or evaluable advanced gastric cancer were enrolled on the study from April 1996 to July 2000. Patients were treated with paclitaxel 200 mg/m intravenously during 3 hours followed by carboplatin at projected area under the curve 5 mg x h x ml (as per the Calvert formula). Twenty-six patients were assessable for toxicity, and 25 patients were assessable for objective response. Nine of the 27 enrolled patients had a major response for an objective response rate of 33% (95% CI 0.17-0.54) by intention-to-treat analysis. The median response duration was 4.9 months (95% CI 2.8-7.3), and median survival was 7.5 months. The 1-year survival rate was 23%. One hundred seventeen courses were administered with a median of four courses per patient administered. The major toxicity was neutropenia, with grade III to IV neutropenia observed in 9 patients (33%) and neutropenic fever in only 1 patient. Grade III peripheral neuropathy developed in two patients, and grade III myalgia and grade III fatigue developed in one patient each. There were no treatment-related deaths. The combination of carboplatin and paclitaxel is a highly tolerable, regimen with activity comparable to that of other regimens in advanced gastric cancer. This regimen needs to be further evaluated in combination with other agents and as a component of multimodality therapy in gastric cancer.

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Oncology 2003;64(2):111-5
Pharmacokinetic study of two infusion schedules of irinotecan combined with cisplatin in patients with advanced gastric cancer.
Fujitani K, Tsujinaka T, Hirao M.
Department of Surgery, Osaka National Hospital, Osaka, Japan. fujitani@onh.go.jp

OBJECTIVE: Irinotecan (CPT-11) in combination with cisplatin (CDDP) has shown promising antitumor activity for advanced gastric cancer, but the optimal administration schedule of CPT-11 is still controversial. To clarify the pharmacokinetic effects of different CPT-11 administration schedules, we compared two different regimens (continuous infusion of CPT-11 for 24 h and CPT-11 infusion for 90 min) combined with CDDP in patients with advanced gastric cancer. PATIENTS AND METHODS: Five patients were treated with CPT-11 at a dose of 60 mg/m(2) delivered by continuous infusion for 24 h on day 1 and by a 90-min infusion on day 15, together with CDDP daily administered at a dose of 10 mg/m(2) on days 1-3 and days 15-17 for 4 weeks. The pharmacokinetics of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were investigated, as well as the toxicity of therapy. RESULTS: Grade 3 leukopenia was observed in 1 patient after 24-hour infusion and in 1 patient after 90-min infusion of CPT-11. In addition, grade 3 thrombocytopenia was observed in 1 patient after the 90-min infusion. Other adverse reactions were mild, and the planned dose was delivered to all patients. The area under the plasma concentration-time curve of SN-38, the active metabolite from CPT-11, was increased by 24-hour infusion when compared with the 90-min infusion, and there was no increase in toxicity. CONCLUSION: Protracted infusional CPT-11 combined with CDDP is a practical regimen, and may be appropriate for a future phase II trial. Copyright 2003 S. Karger AG, Basel

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Surgery 2003 Jan;133(1):68-73
Feasibility of central gastrectomy for gastric cancer.
Iseki J, Takagi M, Touyama K, Sano K, Nakagami K, Ori T, Ooba N, Kin H, Kojima H, Kojima K.

BACKGROUND: Central gastrectomy (CG) for gastric cancer was developed to preserve pyloric function and maintain a large gastric volume. Whether this procedure is feasible for limited cases of gastric cancer is unclear. METHODS: On the basis of Union Internationale Contre le Cancer TNM classification, pathologic characteristics, perioperative parameters, and long-term results, we analyzed 100 patients who underwent CG. RESULTS: Pathologic findings included T1 (tumor depth, mucosal or submucosal) in 82 patients and T2 (muscularis propria or subserosal) in 18 patients. Mean number of dissected lymph nodes was 17.3, and pathologic N1 (node metastasis, 6 or less) was found in 14 patients. There were no operative deaths, but 5 patients had postoperative complications: anastomotic leakage in 1, severe gastric stasis in 2, ischemic gastric ulcer in 1, and intra-abdominal bleeding in 1. No patient had a cancer recurrence in a mean follow-up of 49 months. New early gastric cancer was detected in 3 patients during follow-up endoscopic examination. The 5-year cumulative survival was 0.97. One year after CG, 63 patients had early satiety after food intake. Mean ratio of 1-year postoperative/preoperative body weight was 95%. CONCLUSIONS: Central gastrectomy with sufficient node dissection resulted in good long-term survival and minimal postoperative weight loss. CG is a safe and useful procedure for selected patients with gastric cancer, although close follow-up for recurrence and a more precise analysis on physiologic states is needed.

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Am J Surg 2003 Feb;185(2):150-4
Improved quality of life with jejunal pouch reconstruction after total gastrectomy.
Kono K, Iizuka H, Sekikawa T, Sugai H, Takahashi A, Fujii H, Matsumoto Y.
First Department of Surgery, Yamanashi Medical University, 1110 Tamaho, 409-3898, Yamanashi, Japan. kojikono@res.yamanashi-med.ac.jp

BACKGROUND: There is increasing evidence that the effect of jejunal pouch reconstruction is satisfactory for reservoir function in several randomized control studies. However, these studies were performed in patients with advanced gastric cancer, where significant numbers of the patients died of disease recurrence. In order to exclude the influence of disease recurrence, we performed jejunal pouch reconstruction after total gastrectomy in patients with early gastric cancer in a randomized controlled study and investigated whether or not an improved quality of life (QOL) was observed with jejunal pouch reconstruction. METHODS: Fifty consecutive patients receiving total gastrectomy for early gastric cancer were prospectively divided into the Roux-en-Y reconstruction group without pouch (RY group) or the jejunal pouch reconstruction group (pouch group). Body weight, eating capacity, QOL assessment by gastrointestinal symptom rating scale (GSRS), nutritional parameters, endoscopical examination, 24-hour pH monitoring and Bilitec monitoring were evaluated at 3, 12, and 48 months after surgery. RESULTS: Jejunal pouch reconstruction provided the better QOL than Roux-en-Y reconstruction without pouch both at short-term and long-term periods in a randomized control study. Moreover, as a new finding, pouch reconstruction provided less bile reflux into the esophagus compared with Roux-en-Y reconstruction. CONCLUSIONS: Jejunal pouch reconstruction provided improvement of QOL in patients receiving total gastrectomy.

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Gan To Kagaku Ryoho 2003 Jan;30(1):133-9
[Treatment outcomes with paclitaxel for advanced gastric cancer patients previously treated with TS-1]
[Article in Japanese]
Suzuki T, Iwabuchi M, Matsuda Y, Imai G, Yokoyama H, Mochida A, Takahashi H, Shiina M, Yamada K, Ishibashi J, Suzuki S, Chida N, Tadokoro K.
Dept. of Gastroenterology, Sendai National Hospital.

In the present report, we describe the treatment results of paclitaxel in patients with metastatic gastric cancer previously treated with TS-1 or combination chemotherapy of TS-1 and CDDP. Paclitaxel was administered to 4 patients at a weekly dose of 80 mg/m2/day for three weeks followed by a one week interval. Remarkable tumor reduction was observed in 2 patients. Case 1: A 52-year-old male patient with gastric cancer and multiple liver metastases was treated by weekly infusion of paclitaxel as a 2nd line chemotherapy. After 1 course, the tumor was remarkably reduced, and the reduction was judged PR. Case 2: A 31-year-old male patient presented with lymphoangitis carcinomatosa and obstructive jaundice resulting from cancerous lymphoadenopathy. After 1 course, chest radiographs and abdominal CT scan showed remarkable reduction of these lesions. The adverse effects observed with this drug were leucocytopenia and liver dysfunction, both of which improved soon. These results indicate paclitaxel is effective for advanced gastric cancer pretreated with TS-1.

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Gan To Kagaku Ryoho 2003 Jan;30(1):67-71
[Weekly administration of paclitaxel with a short course of premedication for advanced or recurrent gastric cancer]
[Article in Japanese]
Yamamoto S, Tanaka Y, Ito T, Nakai S, Morimoto Y, Kitagawa T, Kurihara Y, Nishimura J.
Dept. of Surgery, Osaka Prefectural General Hospital.

Weekly administration of paclitaxel with a short course of premedication was performed for 8 patients with advanced or recurrent gastric cancer. In this regimen, 500 ml of physiological saline with vitamins was administered in a 3-hour infusion. After 30 minutes of infusion, dexamethasone 10 mg, chlorpheniramine maleate 5 mg, famotidine 20 mg and ramosetron hydrochloride 0.3 mg were administered intravenously. After 30 more minutes of infusion, paclitaxel at a dose of 65 mg/m2 was admixed in the residual normal physiological saline and administered over 2 hours. Administration was continued for 3 weeks with a 1 week rest. Though the partial response rate was 25%, clinical symptoms improved in all patients. Moreover, both hematological and non-hematological toxicities were mild. Weekly administration of paclitaxel with a short course of premedication is an effective and well-tolerated method for patients with advanced or recurrent gastric cancer.

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Nippon Rinsho 2003 Jan;61(1):97-101
[Indication of H. pylori eradication therapy]
[Article in Japanese]
Ohtaka K, Miwa H, Sato N.
Department of Gastroenterology, Juntendo University, School of Medicine.

In the guideline, for H. pylori the Japanese Society of Helicobacter published diagnosis and treatment in July 2000. Only peptic ulcers and low grade MALT lymphomas are recommended as an indication of H. pylori eradication and other diseases such as atrophic gastritis, post EMR state for early gastric cancer and post-operated stomach due to gastric cancer, hyperplastic polyps and non-ulcer dyspepsia, were not included. In addition, Japanese social security foundation approves only peptic ulcers for indication of H. pylori eradication treatment. However, eradication therapy for atrophic gastritis should be considered in aspect of decreasing gastric cancer risk. Since accumulated epidemiological, experimental and clinical data strongly support its positive correlation with cancer risk, patients in high risk group for gastric cancer should be included for a target eradication therapy. Indication of the treatment should be expanded to histological gastritis caused by H. pylori in our country, where prevalence of gastric cancer is very high.

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Chang Gung Med J 2002 Dec;25(12):792-802
Benefits of palliative surgery for far-advanced gastric cancer.
Wang CS, Chao TC, Jan YY, Jeng LB, Hwang TL, Chen MF.
Department of General Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan, ROC. wangcs@cgmh.org.tw

BACKGROUND: The optimum strategy for palliative surgery in gastric cancer patients remains undetermined. METHODS: In total, 525 patients who had undergone palliative surgery between 1994 and 2000 were evaluated in terms of operative mortality, survival, and palliative effect. Patients were grouped according to the UICC's classification of residual tumors (R) after the operation: microscopic residual tumor (R1) (N = 104) and macroscopic residual tumor (R2) (N = 421). Gastric resection was performed in all R1 patients and in 257 of the R2 patients. Non-resection procedures were performed in 164 of the R2 patients, including gastrojejunostomies in 64, gastrostomies in 17, jejunostomies in 60, and laparotomies only in 23. RESULTS: The operative mortality did not significantly differ among R1 distal gastrectomies (4.5%), R2 distal gastrectomies (3.3%), and R1 total gastrectomies (2.9%) (p = 0.919). R2 total gastrectomies showed a particularly higher operative mortality (10.9%) than did the other resection procedures. The survival time and palliative duration were significantly longer in patients after palliative resection than after non-resection operations. Postoperative chemotherapy prolonged the survival time of patients after palliative surgery. CONCLUSION: R1 or R2 distal gastrectomies and R1 total gastrectomies have benefits of survival prolongation and symptomatic palliation. However, the use of a total gastrectomy in R2 patients must be selectively reserved for far-advanced cases, otherwise it should be replaced with less-invasive procedures to avoid a high operative mortality rate. Postoperative chemotherapy is useful for prolonging survival time.

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Trop Gastroenterol 2002 Apr-Jun;23(2):94-6
Neoadjuvant chemotherapy in advanced gastric cancer—results of a pilot study.
Shukla NK, Deo SV, Asthana S, Raina V, Dronamaraju SS.
Institute Rotary Cancer Hospital (IRCH), All India Institute of Medical Sciences (AIIMS), New Delhi-110 029, India. nkshukla2@yahoo.com

INTRODUCTION: Adenocarcinoma of the stomach is usually advanced at presentation, and local or distant spread may preclude the option of primary curative resection. Neoadjuvant chemotherapy (NAC) has shown promise in downstaging initially unresectable disease. This pilot study was planned to assess the utility of NAC using Cisplatin and 5-Fluoro uracil in the management of initially unresectable gastric cancer. PATIENTS AND METHODS: Ten patients with unresectable gastric adnocarcinoma were included. They received two cycles of cisplatin, 30 mg/m2 intravenously in combination with 5-Fluoro Uracil, 1000 mg/m2. They were restaged using Endoscopy and CT scan and taken up for exploratory laparotomy. RESULTS: Eight of 10 patients (80%) had an objective response to chemotherapy. Six patients (60%) with initially unresectable disease could be offered curative surgery. The median survival was 10 months (range 1-60 months). There were two long term survivors (48 and 60 months respectively). CONCLUSION: Neoadjuvant chemotherapy (NAC) is an effective option in downstaging initially unresectable gastric carcinoma. Complete response to chemotherapy also predicts long term survival.

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Cancer Radiother 2002 Nov;6 Suppl 1:13s-23s
[Chemoradiotherapy in the adjuvant treatment of gastric adenocarcinomas: real progress?]
[Article in French]
Mineur L, Lacaine F, Ychou M, Bosset JF, Daban A.
Institut Sainte-Catherine, chemin du Lavarin, 84082 Avignon, France. laurent.mineur@caramail.com

Frequency of local and distant failures after gastrectomy has led to extended lymph nodes dissection to obtain a better locoregional control. However, five year survival rates were not significantly different between patients undergoing D2 and D1 lymphadenectomy, and higher morbidity and post operative deaths were reported in large randomised trials (respectively 25% vs 48% and 4 vs 13%). Additionally, several metanalysis failed to demonstrate a significant survival advantage with adjuvant chemotherapy. The results of the first trial demonstrating one advantage to adjuvant post-operative chemoradiotherapy should modify the standard care. Disease free and overall survival after surgery alone and after surgery and concurrent chemoradiotherapy were respectively 31% vs 48% and 41% vs 50%. The intergroup trial demonstrate that better local control improve survival if radiation fields include stamps, tumour bed, proximal nodal chains and nodes corresponding to D2 extended lymph nodes dissection. Treatment was feasible with few severe toxic effects (1%). Of the 281 patients, 17% stopped treatment because toxic effects. Technical modalities of radiotherapy and post-operative nutrition support, which are critical points of interest for this treatment, are also discussed.

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Bratisl Lek Listy 2002;103(11):424-7
Radical D2 surgery for patients with gastric cancer.
Palaj J, Konecny J, Petras L, Babiak L, Kukla K, Ciganak J, Moravekova E.
Surgical Department, Hospital Bojnice, Slovakia. bll@fmed.uniba.sk

The authors analyzed and prepared a report concerning 18 radical surgeries for gastric cancer that were performed between 1999-2001. Overall, 55 operation were performed, 32 radical, 18 palliative and 5 explorative laparatomies. D2 resections were performed 18 times, while D1 type 14 times. The group undergoing D2 surgery comprised of 10 men and 8 women with average age of 64.3. D2 resection included partial (8 times), or total (10) gastrectomy and lymfadenectomy of perigastric nodes, supra and infrapyloric nodes and nodes along common hepatic artery, truncus coeliacus, lienal artery, left paracardial nodes and removing capsula of pancreas. Splenectomy was performed twice. On average, 37.5 lymphnodes were removed for every operation (25-69). Operative mortality was none (0%) and morbidity was 22%. As of January 1, 2002 relaps was noted in six patients, and 5 patients died. CONCLUSION: D2 resection surgeries performed by an experienced surgeon show low morbidity as well as better outcome and higher perspective for long-term survival in patients with gastric cancer. (Tab. 1, Ref. 19.).

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Semin Oncol 2002 Dec;29(6 Suppl 18):63-8
Pemetrexed in gastric cancer: clinical experience and future perspectives.
Celio L, Buzzoni R, Longarini R, Marchiano A, Bajetta E.
Medical Oncology Unit B and Department of Radiology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.

The development of more effective and convenient chemotherapy regimens for the treatment of gastric cancer that incorporate novel agents remains an exciting area of research. A phase II study was conducted to assess the response rate and toxicity profile of pemetrexed, a novel multitargeted antifolate, in previously untreated patients with measurable, advanced, or metastatic adenocarcinoma of the stomach or gastroesophageal junction. In this study, pemetrexed-induced toxicity at the starting dose of 500 mg/m(2) intravenously once every 21 days was considerable with each of the first six patients who experienced at least one episode of grade 3/4 toxicity. Two patients discontinued from study, and two patients died. All deaths were caused by drug-related toxicity. No responses were seen in this briefly treated group. These observations led to an amended study protocol designed to improve tolerability of pemetrexed with folic acid supplementation. Supplementation with folic acid 5 mg was given orally once daily for 2 days before pemetrexed on the day of treatment, and for 2 days following treatment. Tumor evaluation was performed after every two cycles of therapy. The trial was recently closed to accrual and preliminary clinical results are reported here. Thirty-two patients were enrolled and 30 patients were evaluable for efficacy. A total of 129 courses of pemetrexed were administered, and the median number of courses received per patient was four (range, one to eight courses). Two complete and five partial responses were observed, with four patients experiencing stable disease. In an intent-to-treat analysis, the overall response rate was 22%, and 23% for the evaluable patients. Median duration of response was 4.4 months (range, 3 to 11 months) and median time to treatment failure was 2.6 months (range, 0.5 to 12 months). Of the 32 patients treated, eight experienced grade 4 neutropenia and one had grade 4 thrombocytopenia. The most common nonhematologic toxicities were diarrhea, fatigue, mucositis, nausea and vomiting, skin rash, and reversible abnormalities in liver function. There was no case of nonhematologic grade 4 toxicity. Although the clinical experience with pemetrexed in advanced gastric cancer remains limited, the promising activity observed in this study indicates that combination studies are warranted. In addition, high-dose intermittent oral folic acid given in this study allowed administration of pemetrexed at the dose and schedule explored with a highly satisfactory safety profile and with no apparent compromise in efficacy. This article discusses how pemetrexed may be investigated in future clinical trials in gastric cancer. Copyright 2002, Elsevier Science (USA). All rights reserved.

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Anticancer Res 2002 Nov-Dec;22(6B):3633-6
Phase II study of mitomycin C, cisplatin and 5-fluorouracil for advanced and recurrent gastric cancer.
Kikuyama S, Inada T, Oyama R, Ogata Y.
Department of Surgery, Saiseikai Central Hospital, 1-4-17, Mita, Tokyo 108-0073, Japan. kikuyama@hh.iij4u.or.jp

In this study, we assessed the efficacy and feasibility of a 5-FU, MMC and cisplatin combination in patients with advanced or recurrent gastric cancer. 5-FU was administered at a dose of 360 mg/m2 on days 1 through 5 and days 8 through 12. CDDP was administered at a dose of 7 mg/m2 on days 1 through 5 and days 8 through 12. MMC was given at a dose of 13 mg/m2 on day 1. Twenty-seven patients with non-resectable or recurrent gastric cancer were entered. The most common toxicity was leukopenia. Nausea/vomiting was generally mild and no patient suffered severe diarrhea, mucositis or renal insufficiency. While a complete response was not observed, 13 patients showed a PR giving an overall response rate of 48.1% (95%CI, 28.0 to 68.3%). Our regimen may have advantages in terms of reduced toxicity with moderate efficacy that is comparable with results using the ECF regimen.

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Anticancer Res 2002 Nov-Dec;22(6B):3605-10
Independent antitumor spectrum of UCN-01 (7-hydroxystaurosporine) against gastric and colorectal cancers as detected by MTT assay.
Abe S, Kubota T, Saikawa Y, Otani Y, Furukawa T, Watanabe M, Kumai K, Kitajima M.
Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shihjuku-ku, Tokyo 160-8582, Japan.

To evaluate the clinical usefulness of 7-hydroxystaurosporine (UCN-01), we compared the antitumor spectrum of UCN-01 with those of conventional antitumor agents against 40 fresh gastric and 40 fresh colorectal cancer specimens using the MTT assay. At a cut-off concentration of 30 micrograms/ml, UCN-01 showed a higher efficacy rate than mitomycin C (MMC), cisplatin, and 5-fluorouracil (5-FU) against both gastric and colorectal cancers. With respect to the gastric cancer specimens, the antitumor spectrum of UCN-01 was independent from those of the other agents, while the patterns of antitumor effects of the conventional agents all correlated significantly with each other. For the colorectal cancer specimens, the pattern of UCN-01-sensitivity did not correlate with the patterns for 5-FU or MMC. In conclusion, UCN-01 may be useful for clinical application against gastric and colorectal cancer due to its different antitumor spectrum from conventionally available agents.

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Anticancer Res 2002 Nov-Dec;22(6B):3513-7
Which patients with advanced, proximal gastric cancer benefit from complete clearance of spleno-pancreatic lymph nodes?
Kikuchi S, Nemoto Y, Natsuya K, Sakuramoto S, Kobayashi N, Shimao H, Sakakibara Y, Kakita A.
Department of Surgery, School of Medicine, Kitasato University, 1-15-1, Kitasato, Sagamihara-shi, Kanagawa 228, Japan.

BACKGROUND: The prognostic significance of dissecting spleno-pancreatic nodes remains unclear in patients with advanced proximal gastric cancer. MATERIALS AND METHODS: Data from a total of 104 patients (74 males and 30 females; age range, 21 to 76 years; mean, 56.0 years), who had undergone curative total gastrectomy combined with spleno-pancreatectomy for advanced proximal gastric cancer, were analyzed with respect to clinicopathological features and patient survival. RESULTS: Metastases to spleno-pancreatic nodes were found in 24 patients (23.1%). Tumor size > 40 mm (p = 0.0218), histologically-undifferentiated type (p = 0.0346) and both Japanese and TNM node-stages (p < 0.0001) were associated with metastases to these nodes. The 5-year survival rate of patients with a T2 tumor was 65.4% in patients with no metastases to the spleno-pancreatic nodes and 45.5% in patients with metastases to these nodes (p = 0.0699). No patients with a T3 tumor and metastases to the spleno-pancreatic nodes survived more than 4 years. CONCLUSION: Complete clearance of SP-nodes for patients with advanced proximal gastric cancer is beneficial for patients with a T2 tumor but not for patients with a T3 tumor. Metastases to these nodes appear to be rare in tumors less than 40 mm. Thus, this treatment should not be routinely performed in patients with proximal advanced gastric cancer. It should not be considered in patients with T3 tumors or with tumors < or = 40 mm.

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Anticancer Res 2002 Nov-Dec;22(6A):3245-52
A potential important role for thymidylate synthetase inhibition on antitumor activity of fluoropyrimidine and raltitexed.
Kabeshima Y, Kubota T, Watanabe M, Saikawa Y, Nishibori H, Hasegawa H, Kitajima M.
Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

BACKGROUND: Because thymidylate synthetase (TS) is a key enzyme in DNA synthesis, it has been used as a target for cancer chemotherapy. MATERIALS AND METHODS: We investigated the combined antitumor activity of raltitexed, 5-FU and UFT on human tumor xenografts in nude mice and examined changes in TS activity and 5-FU-bound RNA (F-RNA) levels. Human gastric (SC-1-NU) or colon (HT-29) carcinoma xenografts were transplanted subcutaneously into nude mice, and drugs administered intraperitoneally (raltitexed and 5-FU) or perorally (UFT) daily for 5 days, and repeated once after a 2-day interval. RESULTS: The antitumor effects were mostly equivalent between the treatment groups despite the different drugs and sequence orders. TS inhibition rates correlated with the tumor inhibition rate, which was statistically significant, while F-RNA levels did not correlate with antitumor activity. CONCLUSION: Our results indicated that the combination of fluoropyrimidine-related agents should be directed towards increased TS inhibition rather than increased F-RNA levels.

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Gan To Kagaku Ryoho 2002 Dec;29(13):2499-507
[Interim report of JFMC study no. 23—phase III randomized clinical trial on the effectiveness of low-dose cisplatin plus 5-FU as a postoperative adjuvant chemotherapy for advanced gastric cancer]
[Article in Japanese]
Saji S, Toge T, Kurosu Y, Hirata K, Gochi A, Tominaga S, Inokuchi K.
Second Dept. of Surgery, Gifu University School of Medicine.

The interim analysis of the JFMC study as of May, 2001 covers 190 gastrectomized patients with advanced gastric cancer from 82 institutions between May, 1996 and March, 2000. Patients were randomly assigned to the following two regimens. Group-CD: cisplatin (CDDP) 5 mg/body/day (i.v.) plus 5-FU 300 mg/body/day (cvi) day 1-5, given for 6 weeks, followed by UFT 200 mg (as tegafur) x 2/day for as long as possible. Group-UF: UFT only was administered after surgery as long as possible. The primary endpoint was survival and the secondary endpoint was disease-free survival. The 4-year survival rates were 47.6% in CD and 41.3% in UF, and the hazard ratio of CD versus UF was 0.74 (95% CL: 0.47-1.16, p = 0.189) according to a stratified (with stage) logrank analysis. The 4-year disease-free survival rates were 50.1% in CD and 39.3% in UF, and the hazard ratio of CD versus UF was 0.65 (95% CL: 0.42-1.00, p = 0.049). Cox's regression analysis using time-dependent dummy variables, revealed that the effect on the survival was accentuated within 9 months, that on disease-free survival within 6 months. The quality of life (QOL) of patients for one year after surgery in CD was significantly lower than that of patient in UF, as assessed using a QOL questionnaire. Although the present interim analysis does not statistically confirm the efficacy of the "low-dose CDDP plus 5-FU" regimen, an expectation for better results is suggested if this regimen is administered for a longer period of time. The JFMC Clinical Trial Committee permitted the release of this report on the condition that further study to verify the present study will be conducted.

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Can J Surg 2002 Dec;45(6):438-46
Comment in: Can J Surg. 2002 Dec;45(6):410.
Neoadjuvant or adjuvant therapy for resectable gastric cancer? A practice guideline.
Earle CC, Maroun J, Zuraw L; Cancer Care Ontario Practice Guidelines Initiative Gastrointestinal Cancer Disease Site Group.
Dana-Farber Cancer Institute, Boston, Mass, USA.

OBJECTIVE: To make recommendations on the use of neoadjuvant or adjuvant therapy in addition to surgery in patients with resectable gastric cancer (T1-4, N1-2, M0). OPTIONS: Neoadjuvant or adjuvant treatments compared with "curative" surgery alone. OUTCOMES: Overall survival, disease-free survival, and adverse effects. EVIDENCE: The MEDLINE, CANCERLIT and Cochrane Library databases and relevant conference proceedings were searched to identify randomized trials. VALUES: Evidence was selected and reviewed by one member of the Cancer Care Ontario Practice Guidelines Initiative (CCOPGI) Gastrointestinal Cancer Disease Site Group and methodologists. A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. This report has been reviewed and approved by the Gastrointestinal Cancer Disease Site Group, comprising medical oncologists, radiation oncologists, surgeons, a pathologist and 2 community representatives. BENEFITS, HARMS AND COSTS: When compared with surgery alone, at 3 years adjuvant chemoradiotherapy has been shown to increase overall survival by 9% (50% v. 41%, p = 0.005) and to improve relapse-free survival from 31% to 48% (p = 0.001). At 5 years, it has been shown to increase overall survival by 11.6% (40% v. 28.4%) and to improve relapse-free survival from 25% to 38% (p < 0.001). Treatment has been associated with toxic deaths in 1% of patients. The most frequent adverse effects (> grade 3 [Southwest Oncology Group toxicity scale] are hematologic (54%), gastrointestinal (33%), influenza-like (9%), infectious (6%) and neurologic (4%). The radiation fields used can possibly damage the left kidney, resulting in hypertension and other renal problems. Furthermore, this therapy could increase the demand on radiation resources. Physicians and patients should understand the tradeoffs between survival benefit and toxicity and cost before making treatment decisions. RECOMMENDATIONS: After surgical resection, patients whose tumours have penetrated the muscularis propria or involve regional lymph nodes should be considered for adjuvant combined chemoradiotherapy. The current standard protocol consists of 1 cycle of 5-fluorouracil (5-FU) (425 mg/m2 daily) and leucovorin (20 mg/m2 daily) administered daily for 5 days, followed 1 month later by 45 Gy (1.8 Gy/d) of radiation given with 5-FU (400 mg/m2 daily) and leucovorin (20 mg/m2 daily) on days 1 through 4 and the last 3 days of radiation.One month after completion of radiation, 2 cycles of 5-FU (425 mg/m2 daily) and leucovorin (20 mg/m2 daily) in a daily regimen for 5 days are given at monthly intervals. There is no evidence on which to make a recommendation for patients with node-negative tumours that have not penetrated the muscularis propria. For patients unable to undergo radiation, adjuvant chemotherapy alone may be of benefit, particularly for those with lymph-node metastases. The optimal regimen remains to be defined. There is insufficient evidence from randomized trials to recommend neoadjuvant chemotherapy, or neoadjuvant or adjuvant radiotherapy or immunotherapy, either alone or in combination, outside a clinical trial. VALIDATION: A draft version of this document was circulated to 166 clinicians using a 21-item feedback questionnaire. Ninety-nine (63%) returned the questionnaire, and 74 of these indicated that the guideline was relevant to their clinical practice and completed the survey. Of the 74 clinicians, 52 (70%) agreed that the document should be approved as a practice guideline. SPONSORS: The CCOPGI is supported by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

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Gan To Kagaku Ryoho 2002 Nov;29(12):2342-5
[Combination chemotherapy with intra-perioneal infusion of CDDP and continuous intravenous infusion of 5-FU for peritoneal metastasis in gastric cancer—analysis of long-term survivors]
[Article in Japanese]
Fujiwara H, Terashima M, Takagane A, Abe K, Irinoda T, Yonezawa H, Nakaya T, Oyama K, Takahashi M, Saito K.
Dept. of Surgery 1, Iwate Medical University.

In order to evaluate the utility of combination chemotherapy with intra-peritoneal infusion of CDDP and continuous intravenous infusion of 5-FU, we performed this therapy in 23 primary gastric cancer patients with peritoneal metastasis. CDDP was administered intraperitoneally at a dose of 70 mg/m2 over 2 hours on day 1, and 5-FU was continuously administered intravenously at a dose of 700 mg/m2 for 5 consecutive days from day 1, respectively. This treatment was given twice. Median survival time with this treatment was 343 days, and the depth of invasion was selected as an independent prognostic factor according to multivariate analysis. Five patients (21.7%) have survived more than 3 years. Major toxicities were less than Grade 2 except for two patients with each anemia (Grade 3) and venous thrombosis (Grade 3), respectively. This regimen appears to be feasible and effective for gastric cancer patients with peritoneal metastases. Long term survival may be obtained in patients without adjacent organ invasion.

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Am J Clin Oncol 2002 Dec;25(6):619-24
Adjuvant intraperitoneal chemotherapy with cisplatinum, mitoxantrone, 5-fluorouracil, and calcium folinate in patients with gastric cancer: a phase II study.
Topuz E, Basaran M, Saip P, Aydiner A, Argon A, Sakar B, Tas F, Uygun K, Bugra D, Aykan NF.
Medical Oncology Department, Institute of Oncology, Istanbul Medical Faculty, Istanbul, Turkey.

Gastric carcinoma remains one of the leading causes of cancer-related death in the world. Clinical studies have revealed that approximately two thirds of the patients seek treatment for early recurrence within the abdominal cavity. The aim of this phase II study was to evaluate the toxicity, feasibility, and efficacy of adjuvant intraperitoneal chemotherapy (IPCT) with cisplatin, mitoxantrone, 5-fluorouracil (5-FU), and folinic acid in patients with stage II-III gastric cancer. Patients with stage II and III gastric cancer aged between 15 and 70 years, after curative resection, with adequate liver, renal, and cardiac function were included in the study. The chemotherapy regimen consisted of cisplatin 60 mg/m2, mitoxantrone 12 mg/m2, 5-FU 600 mg/m2, and folinic acid 60 mg/m2, delivered intraperitoneally, diluted in 2 l normal saline. Intraperitoneal fluid was not drained. Each course of IPCT was repeated every 4 weeks for a total 6 cycles. Thirty-nine patients were enrolled in the study. Twenty-eight of the 39 patients (71.8%) completed six courses of the planned schedule. One patient (2.6%) died after a fourth cycle of IPCT from an undetermined reason. The major nonhematologic toxicity from IPCT was grade I-III nausea and/or vomiting experienced by 27 patients (69.2%). Twenty-four (61.5%) patients reported abdominal discomfort. Median follow-up was 23 (range: 3-105) months. Twenty-five patients (64.1%) were dead. Median disease-free survival and overall survival were 12 (CI 95%; 8.3-15.7 months) and 19 months (CI 95%; 10.5-27.5 months), respectively. The cumulative 5-year disease-free survival and overall survival were 24.7% and 30.7%, respectively. The regimen was generally associated with acceptable toxicity. However, adjuvant IPCT has similar survival rates in comparison to no adjuvant treatment; thus, it cannot be currently recommended outside the context of a clinical trial.

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J Clin Oncol 2002 Dec 1;20(23):4543-8
Phase II study of oxaliplatin, fluorouracil, and folinic acid in locally advanced or metastatic gastric
cancer patients.
Louvet C, Andre T, Tigaud JM, Gamelin E, Douillard JY, Brunet R, Francois E, Jacob JH, Levoir D, Taamma A, Rougier P, Cvitkovic E, de Gramont A.
Service d' Oncologie-Medecine Interne, Hopital Saint-Antoine, Paris, France. christophe.louvet@sat.ap-hop-paris.fr

PURPOSE: To evaluate the efficacy and safety of an oxaliplatin, fluorouracil (5-FU), and folinic acid (FA) combination in patients with metastatic or advanced gastric cancer (M/AGC). PATIENTS AND METHODS: Of the 54 eligible patients with measurable or assessable M/AGC, 53 received oxaliplatin 100 mg/m(2) and FA 400 mg/m(2) (2-hour intravenous infusion) followed by 5-FU bolus 400 mg/m(2) (10-minute infusion) and then 5-FU 3,000 mg/m(2) (46-hour continuous infusion) every 14 days. RESULTS: Patients (69% male, 31% female) had a median age of 61 years (range, 31 to 75 years), 89% had a performance status of 0 or 1, 70% had newly diagnosed disease, and 87% had metastatic disease. All had histologically confirmed adenocarcinoma. With a median of three involved organs, disease sites included the lymph nodes (67%), stomach (65%), and liver (61%). A median of 10 cycles per patient and 468 complete cycles were administered. Best responses in the 49 assessable patients were two complete responses and 20 partial responses, giving an overall best response rate of 44.9%. Eight patients underwent complementary treatment with curative intent (six with surgery and two with chemoradiotherapy). Median follow-up, time to progression, and overall survival were 18.6 months, 6.2 months, and 8.6 months, respectively. Grade 3/4 neutropenia, leukopenia, thrombocytopenia, and anemia occurred in 38%, 19%, 4%, and 11% of patients, respectively, and febrile neutropenia occurred in six patients (one episode each). Grade 3 peripheral neuropathy occurred in 21% of patients (oxaliplatin-specific scale). Seven patients withdrew because of treatment-related toxicity. CONCLUSION: This oxaliplatin/5-FU/FA regimen shows good efficacy and an acceptable safety profile in M/AGC patients, and may prove to be a suitable alternative regimen in this indication.

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Surg Oncol Clin N Am 2002 Apr;11(2):387-403
Is there a role for nontraditional resection of early gastric cancer?
Noguchi Y, Morinaga S, Yamamoto Y, Yoshikawa T.
Department of Surgery, Yokohama City Kowan Hospital, 3-2-3 Shinyamashita, Naka-ku, Yokohama 232-0801, Japan. yn831522@city.yokohama.jp

Current trends in the treatment of gastric cancer indicate the emergence of a more sophisticated approach, with tailored therapy applied to individual cases. Treatment includes a broader spectrum of therapeutic options (Fig. 3), including EMR, laparoscopic or laparoscopy-assisted surgery, modified radical surgery, and typical radical surgery with lymph node dissections. Precise characterization of the lesions, especially the depth of invasion in the gastric wall, its size, histology and whether there is ulceration, is the key to successful treatment of N0 mucosal cancer. Micrometastasis and metastasis at the molecular level are issues that require further investigation. Laparoscopic surgery may be more widely accepted. The limitations of nodal dissection based on the concept of a sentinel node should be carefully evaluated in future studies. [figure: see text] Many treatment options, ranging from minimally invasive surgery to D2 node dissection, are available to the surgical oncologist who is treating EGC. As more information is gathered, surgeons will be better able to select patients who are good candidates for minimal surgical procedures.

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Int J Radiat Oncol Biol Phys 2002 Nov 15;54(4):1069-75
Postoperative adjuvant chemoradiation in completely resected locally advanced gastric cancer.
Arcangeli G, Saracino B, Arcangeli G, Angelini F, Marchetti P, Tirindelli Danesi D.
Division of Radiation Oncology, Regina Elena National Cancer Institute, Via E. Chianesi 53, 00144 Rome, Italy. arcangeli@ifo.it

BACKGROUND: The 5-year survival of patients with completely resected node-positive gastric cancer ranges from 15% to 25%. We explored the feasibility of a chemoradiation regime consisting of concomitant hyperfractionated radiotherapy and 5-fluorouracil protracted venous infusion (5-FU PVI). MATERIALS AND METHODS: Forty patients received a total or partial gastrectomy operation and D2 nodal resection for Stage III gastric cancer; they were then irradiated by linac with 6-15-MV photons. The target included the gastric bed, the anastomosis, stumps, and regional nodes. A total dose of 55 Gy was given in 50 fractions using 1.1 Gy b.i.d. All patients received a concomitant 200 mg/m2/day 5-FU PVI. Patients were examined during the follow-up period as programmed. Toxicity was recorded according to RTOG criteria. RESULTS: After a median follow-up of 75.6 months (range: 22-136 months), 24 (60%) patients had died, and 16 (40%) were alive and free of disease. The 5-year actuarial incidence of relapse was 39%, 22%, and 2% for distant metastases, out-field peritoneal seeding, and in-field local regional recurrences, respectively. The 5-year actuarial cause-specific survival was 43%. Three patients survived more than 11 years. Acute > or = Grade 3 toxicity consisted of hematologic (22.5%) and gastrointestinal toxicity (nausea and vomiting 22.5%, diarrhea 2.8%, and abdominal pain 2.6%). No late toxicity was observed. CONCLUSION: This regime of concomitant 5-FU PVI and hyperfractionated radiotherapy was well tolerated and resulted in successful locoregional control and satisfactory survival.

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