Diagnosis and localization of intestinal metaplasia and early gastric cancer is problematic because of the lack of any telltale gross endoscopic signs.

To compare the efficacy of chromoendoscopy with conventional endoscopy for the detection of gastric premalignant lesions (intestinal metaplasia).

Thirty-three patients in whom previous routine endoscopic biopsies showed intestinal metaplasia were enrolled in a prospective study. Each patient underwent a two-step endoscopy procedure: conventional endoscopy and chromoendoscopy using methylene blue. Biopsies were taken during each step and were studied by an expert pathologist. Presence of intestinal metaplasia was considered a positive result.

Considering the presence of intestinal metaplasia anywhere in the stomach as a positive result, 13 patients were diagnosed with intestinal metaplasia using both endoscopic methods, while eight patients had positive results using chromoendoscopy without any metaplastic changes detected with the conventional method (P=0.003). One patient showed positive biopsies with the conventional method while the pathology report showed no positive biopsies using the chromoendoscopy method. The number of positive biopsies from the antrum, body and fundus were 18, 15 and seven, respectively, using chromoendoscopy, and 10, four and two, respectively, from the same sites using conventional endoscopy.

The present study demonstrated that chromoendoscopy is superior to conventional endoscopy for the detection of metaplastic changes and its use can be suggested for the screening of early malignancies of the stomach.

The incidence of gastric carcinoma has declined worldwide during the past several decades, and yet this cancer remains the most common malignancy in several countries around the world, particularly Japan, Chile, and Costa Rica. Gastric carcinoma, although not as common in the United States as it was in the past, is still the eighth most frequent cause of cancer death. For patients with localized gastric carcinoma, surgery remains the most effective therapy, resulting in a consistent but low rate of cure. Unresectable gastric carcinoma is an incurable disease with the exception of a small fraction of patients who are salvaged with chemoradiotherapy. In Western countries curative resection rates have been dismal because of the lack of early diagnosis. Additionally, postoperative adjuvant strategies in the United States and Europe have been ineffective. Even patients with curative resection frequently develop intraperitoneal and systemic carcinoma in addition to locoregional relapses. Many investigators have therefore embarked on the therapeutic strategies of preoperative chemotherapy and postoperative intraperitoneal chemotherapy. The preoperative chemotherapy strategy has particular appeal because of its potential to reduce the size of the primary tumor, thereby allowing a higher rate of curative resection; early systemic therapy of micrometastases might prove biologically more effective. To date, several studies using preoperative chemotherapy have demonstrated its feasibility. The effectiveness of repeated courses of postoperative intraperitoneal chemotherapy remains unsettled mainly owing to the inadequacy of peritoneal drug distribution and the associated toxic effects. Additional investigations are necessary to improve preoperative staging with the use of endoscopic ultrasonography and laparoscopy (peritoneal staging).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinomas of the esophagus and the stomach are highly virulent and remain a major health problem worldwide; 5-year survival rates have not changed in the past 30 years. Recently, preoperative chemotherapy has been used to treat these adenocarcinomas. The authors evaluated the usefulness of serial serum carcinoembryonic antigen (CEA) levels in diagnosing these patients and compared the prognosis of patients with high or normal CEA levels.

Ninety consecutive patients with potentially resectable adenocarcinoma of the esophagus or stomach treated with preoperative chemotherapy were evaluated. Serum CEA levels were determined before registration, after each chemotherapy course, every 3 months for the first year after completion of all therapy, and every 6 months thereafter for 5 years.

The CEA positivity rate before chemotherapy was 22.2% (20/90); after chemotherapy, it dropped to 10.9% (9/82). An increasing CEA level predicted relapse and correlated well with liver, lung, or pleural involvement in some patients. Most patients with peritoneal involvement did not show elevated levels of CEA. Clinical responses correlated with declining levels of CEA in the patients who showed a negative conversion in CEA level after chemotherapy.

An elevated serum CEA level enabled early detection of relapse in the absence of clinical symptoms in patients with adenocarcinoma of the esophagus or the stomach. The level of CEA was also useful in monitoring the response to chemotherapy in patients who had a high CEA level before treatment. Although the pre- and postchemotherapy CEA-positive group had a higher relapse rate than that of other group, the CEA level did not predict resectability or survival. Future research with labeled monoclonal anti-CEA antibodies may prove useful for certain groups of patients.

Locally advanced gastric adenocarcinomas (LAGC) have a poor prognosis, particularly when tumours are bulky, located in the cardia or in the event of locoregional lymph node involvement. Patients bearing these tumours were entered in a phase II trial of neoadjuvant chemotherapy, combining continuous intravenous 5-fluorouracil (5FU) (1000 mg/m2 for 5 days) and cisplatinum (CDDP) (100 mg/m2 on day 2) repeated every 4 weeks, for one to six cycles according to response and tolerance. 30 patients have been entered, 26 after clinical evaluation (CAT scan and upper gastrointestinal endoscopy) and 4 with unresectable tumours at prior laparotomy. Median age was 60 years, 15/30 patients had a tumour of the cardia, 15/30 had enlarged lymph nodes and 7/30 had linitis plastica (diffuse type). A mean number of three cycles was administered (range 1-6). 27 of the 30 patients were evaluable for response. One patient achieved a complete response (CR) and 14 a partial response (56%; 95% confidence interval 38-74%). No patient had tumour progression, and only 1/6 with linitis plastica responded. 28 patients underwent surgery, and 23 had a macroscopically complete resection (77% of the 30 entered patients); RO resections were performed in 60% of the cases, mainly after an objective response (13/15 versus 4/12 in nonresponders). No pathological CR were seen. Grade 4 neutropenia was observed in eight cycles (5 patients), with five septic complications and one death due to toxicity. Four postoperative complications were observed: 2 cases of severe pneumonia and 2 subphrenic abscesses. One postoperative death, due to intravascular disseminated coagulation, was observed at day 30. Median survival was 16 months and the 1-, 2- and 3-year survival was 67, 42 and 38%, respectively. Patients with linitis plastica had a significantly shorter survival (P < 0.002). We conclude that neodjuvant chemotherapy is feasible in LAGC, although randomised trials are warranted to demonstrate its efficacy on survival and resection rates.

Gastric adenocarcinomas, even in the absence of distant metastases, have a poor prognosis which is particularly dismal when tumors are located in the cardia, in the event of locoregional lymph node involvement and/or bulky tumors. Postoperative adjuvant chemotherapy has never clearly demonstrated its efficacy on survival. Besides ongoing trials using new and more active regimens, preoperative chemotherapy has been used for unresectable cancer due to loco-regional extension and when locally advanced cancer is potentially resectable but with poor prognosis such as bulkiness, when tumors are located in the cardia and when there is tumor in the coeliac area at CAT-scan with suspected metastatic lymph nodes. In case of unresectable tumor at initial surgery five publications have reported the ability of chemotherapy to reduce the tumor volume and to allow subsequent resection of the gastric tumor in 40% to 60% of the cases. In these cases there is a clear survival advantage as the median survival reported in 2 of these studies was 12 and 18 months compared to the 4 to 6 months median survival reported in historical studies in case of unresectable cancer [17, 18]. In case of locally advanced gastric tumors some Japanese case reports have demonstrated the ability of preoperative chemotherapy to concentrate in the tumor tissue and to downstage the tumors. Four North American and European studies have demonstrated that preoperative chemotherapy is feasible, and will probably increase the resection rate. J. Ajani has reported 2 studies in which tolerance was acceptable: a major response (R) observed in 24% and 31%, the resectability rates were 72% and 77% and the median survival 15 and 16 months, respectively. Our experience is based on 30 patients treated with a combination of continuous i.v. 5-FU and CDDP. Fifteen had a tumor of the cardia, 15/30 had enlarged lymph nodes and 7/30 a linitis plastica (diffuse type). After a mean number of 3 cycles, 27/30 patients were evaluable for response. One patient achieved a CR and 14 a PR (OR rate 56%, 95% CI: 38% to 74%) but only one of those with linitis plastica responded. Twenty-eight patients underwent surgery and 23 had a macroscopically complete resection (82%). Resectability rate was higher after OR (13/15) than in nonresponding patients (4/12). Toxicity was acceptable, however grade 4 leucopenia in 5 patients and one toxicity-related death were observed. There was no increase in postoperative complications. Nine patients received postoperative chemotherapy and 3 patients with positive margins received postoperative external radiotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

At present, only radical surgical resection of gastric cancer offers a chance for cure. The objective of an operation for patients with disease that is confined locally is to maximize the potential for cure. The objective for patients with advanced incurable disease, obstruction, hemorrhage, and intractable pain is to provide the best palliation. The evaluation, staging, and surgical management of gastric cancer are described.

In this review of English language publications from 1970, 5-year survival rates after surgery for gastric cancer have been analysed. While the proportion of patients coming to operation has fallen from 92 per cent before 1970 to 71 per cent by 1990, the proportion of operated patients undergoing resection has increased from 37 per cent before 1970 to 48 per cent before 1990. This change suggests improved preoperative staging leading to better patient selection for operation. The 5-year survival rate following all resections has increased significantly from 20.7 per cent before 1970 to 28.4 per cent before 1990, an increase of 7.7 per cent (95 per cent confidence interval 7.1-8.3 per cent). The 5-year survival rate following curative or radical resection has risen from 37.6 to 55.4 per cent over the same period, an increase of 17.8 per cent (95 per cent confidence interval 17.1-18.5 per cent). It is likely that this improvement has contributed to the decrease in the mortality rate from gastric cancer. Comparison of Japanese series with others suggests that diagnosis and treatment of the disease at an earlier stage will result in an even greater increase in 5-year survival rates outside Japan. Of the papers studied, 56 per cent were excluded from analysis, the majority because the data provided about 5-year survival rates were insufficient or the survival calculations inappropriate. Results of survival after operations for gastric cancer should be calculated and presented in a standardized manner.

A prospective gastroscopic-bioptic study of 533 patients was performed to assess the prevalence and distribution of intestinal metaplasia (IM) and its subtypes in the antral mucosa of patients with various upper intestinal disorders and to assess whether the presence of certain IM subtypes might be of help in selecting patients for careful endoscopic-bioptic surveillance in the screening for gastric carcinoma. IM was found in 135 patients (25.3%). Its prevalence increased with age (P < 0.001) and was strongly associated with intestinal-type carcinoma as compared to diffuse-type carcinoma (P < 0.001), gastritis (P < 0.001), and gastric ulcer (P < 0.05). Type I IM was predominant (98.5%), whereas types II and III IM, respectively, were found in 77.8% and 15.6% of the patients with IM. No difference in the prevalence of type I and II IM was found among the various gastric disease states. Type III IM was strongly associated with intestinal-type carcinoma as compared to either benign lesions (P < 0.01) or diffuse-type carcinoma. These results suggest that type III IM may play a special role in the histogenesis of intestinal-type carcinoma and suggest that the finding of this IM subtype in gastric biopsies may possibly be of help in identifying patients at greater risk of developing carcinoma.

Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5-fluorouracil, and cisplatin (EFP). Ninety-eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow-up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP-induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted.

In this review of English language publications from 1970, operative mortality following surgery for gastric cancer has been analysed. Operative mortality has declined in series reporting operations in successive decades to 1970, 1980 and 1990. Series reporting patients having surgery for gastric cancer in the decade to 1990 show a mean operative mortality rate of 7.8 per cent (median 4.6 per cent). This improvement may have contributed to the declining mortality rates for gastric cancer in the face of unchanging surgical workload. Results of operations for gastric cancer should be reported in a standard manner.

A retrospective study of early gastric cancer (60 patients) was performed to evaluate its diagnosis and treatment. Ninety-five per cent of patients presented with nonspecific gastrointestinal symptoms and 53.3% had been treated for presumed benign disease for up to 48 months before diagnosis. Fiberoptic endoscopy detected these lesions more accurately than radiologic examination. The disease-free 5-year survival rate after resection was 76.4%. Survival showed no significant correlation with sex, tumor site, macroscopic appearance, extent of gastric resection, or histopathologic type. Tumors larger than 1.5 cm in diameter, invasion of submucosa, or lymph node metastasis resulted in significantly lower survival rates. Three of eight patients with nodal metastasis survived 5 or more years, including one who had second-echelon deposits. A high index of suspicion may permit more frequent detection. Extended lymphadenectomy (R2) is recommended to achieve the highest possible cure rate.

Gastric carcinoma remains a significant cause of death worldwide. A patient's prognosis depends on the degree of gastric wall penetration, presence of lymph node metastases, and location of the primary site. Metastatic gastric carcinoma is currently incurable. However, chemotherapy continues to evolve at a rapid pace. Active agents include 5-fluorouracil (5-FU), doxorubicin, cisplatin, methotrexate, mitomycin, and etoposide. Combination etoposide, doxorubicin, and cisplatin (EAP) has been reported to result in encouragingly high response rates, including a 10% complete response rate in patients with metastatic gastric carcinoma. Trials are now under way to confirm these results. Similarly, another etoposide-based combination, etoposide, leucovorin, and 5-FU (ELF), has resulted in an equally good response rate but less toxicity than EAP. The 5-FU, doxorubicin, and methotrexate (FAMTX) regimen, previously reported to have an excellent response rate, is also being investigated further. For patients with locoregional carcinoma, curative resection rate is often unsatisfactorily low; however, curative resection is consistently associated with improved survival (between 23 and 26 months). In patients with potentially resectable carcinoma, two significant problems must be recognized: (1) a low rate of curative resection and (2) the development of widespread carcinoma despite curative resection. Despite many attempts, the postoperative strategies of adjuvant chemotherapy have been ineffective. New strategies must be investigated aggressively. Combination etoposide, 5-FU, and cisplatin (EFP) has been administered preoperatively and postoperatively to patients with resectable gastric carcinoma, resulting in an encouraging curative resection rate (greater than 70%) and manageable toxicity. Based on promising results reported with EAP in patients with unresectable locoregional carcinoma of the stomach, a trial of preoperative and postoperative EAP in potentially resectable carcinoma of the stomach is now under way.

The overall cure rate for gastric cancer has changed relatively little in the United States over the past 30 years, largely because patients continue to present for treatment in advanced stages. The paucity of symptoms in early gastric cancer, the low incidence in the general United States population, and the lack of cost-effective screening methods suggest that improvements in early detection are unlikely. Hope for improved survival in late stage cases lies mostly in a better understanding of the pathophysiology and patterns of spread, in evolving techniques for more accurate perioperative staging, and in the gradually improving results of multimodality therapy for local-regional and systemic disease. A proposal is made for a new staging system integrating newer approaches to staging and for controlled trials of multimodality therapy in patients unlikely to be cured by surgery alone.