In a prospective multicentre study of 2394 patients with gastric carcinoma the prognostic relevance of systematic lymph node dissection was evaluated. Of 1654 patients undergoing resection, 558 had a standard lymph node dissection, defined as fewer than 26 nodes in the specimen, and 1096 underwent radical lymphadenectomy, i.e. 26 or more nodes in the specimen. Radical dissection significantly improved the survival rate in patients with Union Internacional Contra la Cancrum (UICC) stages II and IIIA tumours. Multivariate analysis identified radical dissection as an independent prognostic factor in the subgroups of patients with UICC tumour stages II and IIA. Radical dissection conferred no survival advantage in patients with pN2 tumours. There was no significant difference in morbidity and mortality rates between radical and standard lymph node dissection. Radical lymphadenectomy improves survival in patients with UICC gastric cancer stages II and IIIA, and should be the recommended treatment for such patients.
The expression of the Her2/neu gene product p185 was retrospectively analyzed in 58 patients with gastric carcinoma. The results were correlated to various clinicopathological and prognostic factors. Positive membrane staining for p185 could be detected in 38% of the patients (22/58). Membrane staining was significantly greater in well and moderately differentiated tumors of the intestinal type when compared with poorly differentiated lesions and carcinomas of the diffuse type (P less than 0.01). Positive membrane staining did not correlate with site and tumor stage, but T1 lesions had less membrane staining than more advanced primary tumors. Overall survival showed no difference between p185-positive and negative cases. Multivariate analysis defined a subgroup of curatively resected patients with stage III and IV disease that had a statistically significant poorer survival when p185 was overexpressed (P = 0.005). Overexpression of the Her2/neu product p185 appears to be associated with intestinal-type gastric carcinoma and may help in identifying a subset of patients at increased risk for shorter survival.
Thirty-four consecutive patients with measurable advanced gastric cancer were treated in a disease oriented Phase II study with high-dose folinic acid (HDFA) 300 mg/m2 10 min. inf., followed immediately by etoposide 120 mg/m2 50 min. inf., followed immediately by 5-fluorouracil (5-FU) 500 mg/m2 10 min. inf., given on day 1,2,3 (ELF). Courses were repeated every 22-28 days. All patients who entered this study were older than 65 years or had underlying cardiac disease. Thirty-three patients were evaluable for response and toxicity (greater than or equal to 1 course). One patient was lost to follow up. The overall response rate was 48% (16/23) including 12% (4/33) complete remissions. Eight patients had minor responses or no change and 9 had progressive disease. Five of six patients with locally advanced and non-resectable disease had an objective response (1 CR, 4 PR's). The response rate in patients with metastatic disease was 41% (11/27). After a median observation time of 6.5 months, the median survival time was 10.5 months, with a median remission (CR + PR) duration of 8 months. Toxicity was manageable and included mild to moderate myelosuppression and gastrointestinal toxicities. One episode of life-threatening (Grade IV) leukopenia, and two episodes of severe diarrhea requiring hydration were noted. No treatment related death occurred. ELF is an effective combination in advanced gastric cancer and can be safely administered to elderly patients and patients with cardiac risk.
Surgery still represents the therapy of choice for patients with primary gastric adenocarcinoma. The best survival results can be achieved if a potentially curative (R0) resection can be performed whatever the extent of resection of the primary tumor (total versus subtotal distal gastrectomy). Either procedure should be accompanied by systematic lymph node dissection since lymphadenectomy has relevant diagnostic (i.e. staging) and therapeutic implications (i.e. improved survival in stage II/IIIA disease). Since most gastric carcinomas are diagnosed in advanced tumor stages, the number of patients to be treated curatively by surgery alone remains limited. Multimodality treatment, consisting of chemotherapy and surgery, may be an encouraging alternative strategy. With actual chemotherapy protocols (i.e. 5-FU/doxorubicin/methotrexate, etoposide/doxorubicin/cisplatin) high remission rates in locally advanced irresectable lesions without distant metastases can be induced. Survival in these patients has been significantly improved after chemotherapy and second-look surgery. The effectiveness of these protocols in an adjuvant setting seems a worthwhile study for the future. In addition, immunological and somatic gene therapy may be of therapeutic impact in the next decade.
Peritoneal lavage was performed in 66 patients with gastric carcinoma to assess the amount of free tumor cells. 12/66 patients (18 %) proved to have free cancer cells. The intestinal type of carcinoma showed more frequently free tumor cells (8/12). There was no correlation between free cancer cells and the number of invaded lymph nodes. Patients with curative surgery but free cancer cells belong to the risk groups for early recurrences. Whether surgery on its own causes an increase in free tumor cells needs to be studied as well as the potential benefit of adjuvant chemotherapy in these patients.
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