CONTEXT Despite potentially curative resection of stomach cancer, 50% to 90% of patients die of disease relapse. Numerous randomized clinical trials (RCTs) have compared surgery alone with adjuvant chemotherapy, but definitive evidence is lacking. OBJECTIVES To perform an individual patient-level meta-analysis of all RCTs to quantify the potential benefit of chemotherapy after complete resection over surgery alone in terms of overall survival and disease-free survival, and to further study the role of regimens, including monochemotherapy; combined chemotherapy with fluorouracil derivatives, mitomycin C, and other therapies but no anthracyclines; combined chemotherapy with fluorouracil derivatives, mitomycin C, and anthracyclines; and other treatments. DATA SOURCES Data from all RCTs comparing adjuvant chemotherapy with surgery alone in patients with resectable gastric cancer. We searched MEDLINE (up to 2009), the Cochrane Central Register of Controlled Trials, the National Institutes of Health trial registry, and published proceedings from major oncologic and gastrointestinal cancer meetings. STUDY SELECTION All RCTs closed to patient recruitment before 2004 were eligible. Trials testing radiotherapy; neoadjuvant, perioperative, or intraperitoneal chemotherapy; or immunotherapy were excluded. Thirty-one eligible trials (6390 patients) were identified. DATA EXTRACTION As of 2010, individual patient data were available from 17 trials (3838 patients representing 60% of the targeted data) with a median follow-up exceeding 7 years. RESULTS There were 1000 deaths among 1924 patients assigned to chemotherapy groups and 1067 deaths among 1857 patients assigned to surgery-only groups. Adjuvant chemotherapy was associated with a statistically significant benefit in terms of overall survival (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.76-0.90; P < .001) and disease-free survival (HR, 0.82; 95% CI, 0.75-0.90; P < .001). There was no significant heterogeneity for overall survival across RCTs (P = .52) or the 4 regimen groups (P = .13). Five-year overall survival increased from 49.6% to 55.3% with chemotherapy. CONCLUSION Among the RCTs included, postoperative adjuvant chemotherapy based on fluorouracil regimens was associated with reduced risk of death in gastric cancer compared with surgery alone.

Benefit of Adjuvant Chemotherapy for Resectable Gastric Cancer A Meta-analysis

Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease.

Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies.

A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis

The value of extended organ resection for advanced gastric cancer has been debated for many years. This debate has been escalated recently by the results of both the United Kingdom Medical Research Council and the Dutch trials evaluating the survival benefit of extended lymphadenectomy. Both of these large prospective randomized control trials have reported a significant survival disadvantage in patients who have undergone gastrectomy with splenectomy or pancreaticosplenectomy. 1,2 The Medical Research Council study and the Dutch trial found a higher mortality, higher complication rate, and longer hospital stay associated with extended organ resection.

Some reports have argued that clearance of regional lymphadenopathy is improved by removing adjacent organs. The potential advantage of extended resection for clinical T4N0 gastric adenocarcinoma is necessary to improve the R0 resection rate of these lesions. Arguments against this approach are based on the observed increase in the morbidity and mortality rates, with little objective benefit in survival.

A large retrospective study from Japan found no survival difference when patients undergoing gastrectomy alone were compared to patients with additional organ resection, but again complication rate were greater. 3 This lack of survival disadvantage for gastrectomy with additional organ resection has been demonstrated in other retrospective studies when evaluating outcomes of patients undergoing total gastrectomy alone, with splenectomy, and with pancreaticosplenectomy. 4

The complication rates of additional organ resection with gastrectomy have consistently been reported to be higher when compared to patients undergoing gastrectomy alone. 1–3 In patients undergoing splenectomy, both overall complications and infectious complications have been more common. 5 The increase in overall complications and infectious complications has been implicated as a reason for the decrease in overall survival. For these reasons there has been an unwillingness to perform additional organ resection in patients with T4 disease.

The aim of this study was to report our experience with gastrectomy with additional organ resection in patients with T4 gastric carcinoma and to identify factors predictive of improved outcome.

Extended local resection for advanced gastric cancer: increased survival versus increased morbidity.

The diagnostic and prognostic significance of carcinoembryonic antigen (CEA), carbohydrate associated antigen 19–9 (CA19–9), alpha-fetoprotein (AFP) and cancer antigen 125 (CA125) in early gastric cancer have not been investigated yet. Thus, the present study aimed to explore the diagnostic and prognostic significance of the four tumor markers for early gastric cancer. From September 2008 to March 2015, 587 early gastric cancer patients were given radical gastrectomy in our center. The clinicopathological characteristics were recorded. The association between levels of CEA and CA19–9 and clinicopathological characteristics and prognosis of patients were analyzed. There were 444 men (75.6%) and 143 women (24.4%). The median age was 57 years (ranged 21–85). The 1-, 3- and 5-year overall survival rate was 99.1%, 96.8% and 93.1%, respectively. The positive rate of CEA, CA19–9, AFP and CA125 was 4.3%, 4.8%, 1.5% and 1.9%, respectively. The positive rate of all markers combined was 10.4%. The associations between the clinicopathological features and levels of CEA and CA19–9 were analyzed. No significant association was found between CEA level and clinicopathological features. However, elevated CA19–9 level was correlated with female gender and presence of lymph node metastasis. Age > 60 years old, presence of lymph node metastasis and elevation of CEA level were independent risk factors for poor prognosis of early gastric cancer. The positive rates of CEA, CA19–9, APF and CA125 were relatively low for early gastric cancer. Elevation of CA19–9 level was associated with female gender and presence of lymph node metastasis. Elevation of CEA level was an independent risk factor for the poor prognosis of early gastric cancer.

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Diagnostic and prognostic value of CEA, CA19–9, AFP and CA125 for early gastric cancer

BACKGROUND: This clinicopathological study evaluated the utility of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 as predictors of locoregional recurrence and long-term disease-free survival in patients with gastric cancer.METHODS: During the period January 1989 to December 1994, 485 patients with primary gastric cancer were evaluated. Gastrectomies were performed in 434 patients. Prognostic factors were analyzed by the Kaplan-Meier method and multivariate analysis, using Cox regression.RESULTS: Elevated serum CEA and CA19-9 levels were observed in 92 of the 485 patients (19.0%), and in 95 of the 435 patients (21.8%), respectively, and both markers were elevated in 29 of these 435 patients (6.7%). Elevated serum CEA and CA19-9 levels correlated well with lymph node metastasis, lymphatic invasion, vessel invasion, stage grouping, depth of invasion, and curability. Patients with elevated serum CEA levels were at significantly higher risk of having all recurrence factors than were those with normal serum CEA levels. Patients with elevated serum CA19-9 levels were at significantly higher risk of having peritoneal metastases and distant metastases than were those with normal serum CA19-9 levels. A significant difference in the cumulative survival curves of patients was demonstrated between those with elevated and those with normal serum CEA or CA19-9 levels, even for patients at the same disease stage (stage III). Patients with elevated levels of both markers had a significantly worse prognosis than patients in whom the levels of both markers were normal. In patients who underwent gastrectomy, elevated serum CEA levels either preoperatively or within 3 weeks after gastrectomy were associated with significantly worse prognosis than were normal levels. When the cutoff level of serum CEA was increased to 10 ng/ml, serum CEA, age, lymph node metastasis, and surgical stage grouping were selected as independent prognostic factors by multivariate analysis of 14 prognostic factors, using Cox regression.CONCLUSION: Serum CEA and CA19-9 levels provide additional prognostic information in patients with primary gastric cancer. In particular, an elevated serum CEA level provides additional prognostic information and is a useful indicator of curability in patients who undergo gastrectomy. Serum CEA level is an independent prognostic factor in patients with primary gastric cancer.

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Evaluation of serum CEA and CA19-9 levels as prognostic factors in patients with gastric cancer.

Background: In Japan, wide resection with extended lymph node dissection has been performed for advanced cancer with good prognosis. Pancreaticosplenectomy with gastrectomy is performed to facilitate dissection of the lymph nodes around the splenic artery. We attempted to evaluate the effects of pancreaticosplenectomy and splenectomy with gastrectomy for advanced gastric cancer. Methods: Gastric cancer patients underwent splenectomy with gastrectomy (78 cases), pancreaticosplenectomy with gastrectomy (105 cases), or gastrectomy alone (1,755 cases). Survival rates were compared among the three groups for each factor of the depth of invasion, stage, and curability. Results: There were no significant differences among the three groups. Pancreaticosplenectomy or splenectomy with gastrectomy to dissect lymph nodes does not improve survival but is associated with severe complications. Conclusions: The spleen should be resected when a patient has clearly positive node metastasis around the splenic hilus and artery, and pancreaticosplenectomy be performed when the cancer lesion invades the pancreas.

Is there a benefit of pancreaticosplenectomy with gastrectomy for advanced gastric cancer

Brain metastasis from cancers of the gastrointestinal tract is uncommon; brain metastasis from gastric cancer is rare and its incidence is low. Brain metastasis of gastric cancer is often difficult to treat and is resectable in only a few cases. We have treated three patients who had a solitary brain metastasis after a gastrectomy. These three cases are reviewed along with eight other previously reported cases of brain metastasis to clarify the clinicopathological features and to suggest guidelines for patients with metastatic brain tumors. The clinicopathological features of 11 cases of brain metastasis were analyzed. For comparison purposes, the 11 cases were classified into three groups as follows: a resection group, a chemoradiotherapy group, and a nontreatment group. All the patients had advanced gastric cancer of stage III or more. The resection group had the most survivors, and survival rates decreased in the order of the resection group, the chemoradiotherapy group, and the nontreatment group. There was a statistically significant difference between the resection group and the nontreatment group (P 5 0.0177). Aggressive multidisciplinary treatment, including a resection, for brain metastasis should improve the quality of life and prolong life expectancy.

Clinicopathological study of brain metastasis in gastric cancer patients

Background and Objectives
Free perforation and major bleeding in patients with gastric cancer are rare but serious conditions with potentially dangerous effects. To clarify the clinicopathologic characteristics of patients with these conditions and to determine the optimum management, we reviewed 16 cases of perforation and 13 cases of major bleeding in patients with gastric cancer who required emergency surgery.

Methods
We compared the clinical and histologic features of the patients with perforation and those with bleeding. Cox's multivariate regression analysis was used to compare survival rates between patients who underwent single-step surgery or a two-step radical procedure, between patients with stage I or II and stage III or IV cancer, between patients who underwent complete (R0) and incomplete (R1 or R2) resection, and between patients with bleeding and those with perforation.

Results
Many of the patients had advanced disease. There were no significant differences in clinicopathologic findings or survival between patients with gastric perforation and those with major bleeding. Patients who had major bleeding tended to have larger cancers. In the univariate analysis, gastrectomy (vs. no gastrectomy), R0 (vs. R1 or R2) resection, and lower stage (vs. higher stage) were highly correlated with improved survival time.

Conclusions
Overall, patients with gastric cancers who underwent emergency gastrectomy had a poor prognosis, but it was better than that of patients who could not have gastrectomy because of the prXesence of advanced cancer. However, the survival rate was excellent in patients with early-stage cancer who underwent complete (R0) resection. We recommend complete resection when possible. J. Surg. Oncol. 2002;80:181–185. © 2002 Wiley–Liss, Inc.

Outcomes after emergency surgery for gastric perforation or severe bleeding in patients with gastric cancer.

Perforated gastric carcinoma is rare; however, it is a serious condition associated with complications. To understand the proper management of this disease and to characterize its clinical course we reviewed available data on 16 patients with perforated gastric carcinoma. We collected data on the age and sex of the patients as well as operative findings and histological features of the primary tumor. The depth of invasion and presence of lymph node metastasis were also recorded. The Union Internationale Contre Cancer stage, extent of resection, and surgical method used were reviewed. We also reviewed published information on the management of perforated gastric carcinoma. The carcinoma was stage I in three cases, stage II in one case, stage III in three cases, and stage IV in nine cases. Many patients had distant metastases. Fourteen patients underwent gastrectomy. Two patients whose preoperative condition was poor died of surgery-related complications, but patients with early-stage carcinoma underwent an R0 resection (resection of the primary tumor with negative margins) and had minimal complications. We conclude that the outcome of patients who were able to undergo radical surgery was good and correlated with the stage of cancer. It is important to perform gastrectomy rather than repair the perforation first, and a proper lymphadenectomy should follow--thus a two-step surgery when necessary.

Fumiro Mochizuki

Papers

Evaluation of serum CEA and CA19-9 levels as prognostic factors in patients with gastric cancer.

Is there a benefit of pancreaticosplenectomy with gastrectomy for advanced gastric cancer

Clinicopathological study of brain metastasis in gastric cancer patients

Outcomes after emergency surgery for gastric perforation or severe bleeding in patients with gastric cancer.

Management of perforated gastric carcinoma: a report of 16 cases and review of world literature.