D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer.

BACKGROUND: Gastrectomy with D2 lymphadenectomy is the standard treatment for curable gastric cancer in eastern Asia. Whether the addition of para-aortic nodal dissection (PAND) to D2 lymphadenectomy for stage T2, T3, or T4 tumors improves survival is controversial. We conducted a randomized, controlled trial at 24 hospitals in Japan to compare D2 lymphadenectomy alone with D2 lymphadenectomy plus PAND in patients undergoing gastrectomy for curable gastric cancer. METHODS: Between July 1995 and April 2001, 523 patients with curable stage T2b, T3, or T4 gastric cancer were randomly assigned during surgery to D2 lymphadenectomy alone (263 patients) or to D2 lymphadenectomy plus PAND (260 patients). We did not permit any adjuvant therapy before the recurrence of cancer. The primary end point was overall survival. RESULTS: The rates of surgery-related complications among patients assigned to D2 lymphadenectomy alone and those assigned to D2 lymphadenectomy plus PAND were 20.9% and 28.1%, respectively (P=0.07). There were no significant differences between the two groups in the frequencies of anastomotic leakage, pancreatic fistula, abdominal abscess, pneumonia, or death from any cause within 30 days after surgery (the rate of death was 0.8% in each group). The median operation time was 63 minutes longer and the median blood loss was 230 ml greater in the group assigned to D2 lymphadenectomy plus PAND. The 5-year overall survival rate was 69.2% for the group assigned to D2 lymphadenectomy alone and 70.3% for the group assigned to D2 lymphadenectomy plus PAND; the hazard ratio for death was 1.03 (95% confidence interval [CI], 0.77 to 1.37; P=0.85). There were no significant differences in recurrence-free survival between the two groups; the hazard ratio for recurrence was 1.08 (95% CI, 0.83 to 1.42; P=0.56). CONCLUSIONS: As compared with D2 lymphadenectomy alone, treatment with D2 lymphadenectomy plus PAND does not improve the survival rate in curable gastric cancer. (ClinicalTrials.gov number, NCT00149279.)

Function-preserving gastrectomy for gastric cancer in Japan.

Surgery used to be the only therapy for gastric cancer, and since its ability to cure gastric cancer was the focus of attention, less attention was paid to function-preserving surgery in gastric cancer, though it was studied for gastroduodenal ulcer. Maki et al developed pylorus-preserving gastrectomy for gastric ulcer in 1967. At the same time, the definition of early gastric cancer (EGC) was being considered, histopathological investigations of EGC were carried out, and the validity of modified surgery was sustained. After the development of H2-blockers, the number of operations for gastroduodenal ulcers decreased, and the number of EGC patients increased simultaneously. As a result, the indications for pylorus-preserving gastrectomy for EGC in the middle third of the stomach extended, and various alterations were added. Since then, many kinds of function-preserving gastrectomies have been performed and studied in other fields of gastric cancer, and proximal gastrectomy, jejunal pouch interposition, segmental gastrectomy, and local resection have been performed. On the other hand, from the overall perspective, it can be said that endoscopic resection, which was launched at almost the same time, is the ultimate function-preserving surgery under the current circumstances. The current function-preserving gastrectomies that are often performed and studied are pylorus-preserving gastrectomy and proximal gastrectomy. The reasons for this are that these procedures that can be performed with systemic lymph node dissection, and they include three important elements: (1) reduction of the extent of gastrectomy; (2) preservation of the pylorus; and (3) preservation of the vagal nerve. In addition, these operations are more likely to be performed with a laparoscopic approach as minimally invasive surgery. Of the above-mentioned three elements, reduction of the extent of gastrectomy is the most important in our view. Therefore, we should try to reduce the extent of gastrectomy if curability of the gastric cancer can still be achieved. However, if we preserve a wider residual stomach in function-preserving gastrectomy, we should pay attention to the development of metachronous gastric cancer.

Gastric cancer surgery: morbidity and mortality results from a prospective randomized controlled trial comparing D2 and extended para-aortic lymphadenectomy--Japan Clinical Oncology Group study 9501.

PURPOSE: Radical gastrectomy with regional lymphadenectomy is the only curative treatment option for gastric cancer. The extent of lymphadenectomy, however, is controversial. The two European randomized trials only reported an increase in operative morbidity and mortality, but failed to show survival benefit, in the D2 lymphadenectomy group. We conducted a randomized controlled trial to compare the Japanese standard D2 and D2 + para-aortic nodal dissection. PATIENTS AND METHODS: Only experienced surgeons in both procedures from 24 Japanese institutions participated in the study. Patients with potentially curable gastric adenocarcinoma (T2-subserosa, T3, or T4) who were surgically fit were intraoperatively randomized. Postoperative morbidity and hospital mortality were recorded prospectively in a fixed format and were compared between the two groups in this study. RESULTS: A total of 523 patients were randomized between July 1995 and April 2001. Postoperative complications were reported in 24.5% of all patients. Although the morbidity for the extended surgery group (28.1%) was slightly higher than the standard group (20.9%), there was no difference in the incidence of four major complications (anastomotic leak, pancreatic fistula, abdominal abscess, pneumonia) between the two groups. Hospital mortality was reported at 0.80%: one patient in each group died of operative complications, while one from each group died of rapid progressive cancer while inpatient. CONCLUSION: Specialized surgeons could safely perform gastrectomy with D2 lymphadenectomy in patients with low operative risks. Para-aortic lymphadenectomy could be added without increasing major surgical complications in this setting.

Prognostic factors in patients with advanced gastric cancer with macroscopic invasion to adjacent organs treated with radical surgery.

BACKGROUND: The prognosis of patients with gastric cancer with invasion to adjacent organs is poor. The prognostic factors of patients with advanced gastric cancer with macroscopic invasion to adjacent organs (T4) who were treated with radical surgery was determined in the present study.METHODS: A total of 86 consecutive patients with advanced gastric cancer who underwent radical (potentially curable) gastrectomy with combined resection of other organs for macroscopic invasion to adjacent organs during surgery, were investigated. The organs invaded macroscopically were the pancreas in 43 patients, mesocolon in 29, liver in 7, transverse colon in 5, adrenal gland in 3, spleen in 1, diaphragm in 1, and other organs in 5. The prognostic factors were evaluated by univariate and multivariate analysis.RESULTS: The cumulative 5-year survival rate of the patients treated by radical surgery with the combined resection of invaded organs was 35.0%. Multivariate analysis demonstrated that location of the tumor, lymph node metastasis, histological depth of invasion, and extent of lymph node dissection were significant prognostic factors in advanced gastric cancer patients treated by radical surgery with combined resection of adjacent organs for macroscopic invasion.CONCLUSION: For patients with macroscopic T4 gastric cancer located in the middle- or lower-third of the stomach, aggressive resection of invaded adjacent organs with extended lymph node dissection should be performed to improve long-term outcome.

Usefulness of preoperative FDG-PET for detection of gastric cancer.

BACKGROUND: Positron emission tomography (PET), using 18F-fluoro-2-deoxy-D-glucose (FDG) as a tracer, can detect malignant neoplasms with altered glucose metabolism. To clarify the usefulness of FDG-PET for detecting gastric cancer, we evaluated preoperative PET imaging in gastric cancer patients. METHODS: Sixty-two gastric cancer patients who underwent FDG-PET imaging and gastric resection with lymphadenectomy were evaluated. RESULTS: For primary tumor assessment by PET, detection rates were significantly different in the following order: tumor size 30 mm or more (76.7%) > tumor size less than 30 mm (16.8%); advanced gastric cancer (AGC, 82.9%) > early gastric cancer (EGC; 25.9%); with nodal involvement (79.3%) > without nodal involvement (39.4%). In EGCs, the detection rate of the intestinal type, according to Lauren's classification (43.8%) was significantly higher than that of the diffuse type (0%). Two of the 7 EGC patients who were PET-positive had nodal involvement and their tumors were the intestinal type. For the assessment of nodal involvement, the accuracy of nodal involvement detection was 67.7% with PET and 75.8% with computed tomography (CT). Preoperative FDG-PET revealed colon cancer in 2 patients, adrenal tumor in 1 patient, lung cancer in 1 patient, and lung metastasis in 1 patient. CONCLUSION: Larger or more advanced tumors with nodal involvement had a higher detection rate by PET. In EGCs, only the intestinal type was detectable by PET. PET-positive EGC may be aggressive, and an adequate lymphadenectomy must be done. Preoperative PET was useful for the detection of other malignancies and distant metastasis.

The usefulness of CEA and/or CA19-9 in monitoring for recurrence in gastric cancer patients: a prospective clinical study.

BACKGROUND: Many studies on postoperative carcinoembryonic antigen (CEA) and/or carbohydrate antigen (CA)19-9 monitoring after operation for gastric cancer have been reported, but most have been retrospective. METHODS: A nationwide observational study was implemented in 135 leading institutions in Japan to evaluate the significance of CEA and/or CA19-9 in postoperative monitoring for recurrence in patients with advanced gastric cancer. Three hundred and twenty-one patients examined in this analysis underwent radical gastrectomy at one of Japan's leading institutions between November 1993 and March 1996 and had been followed up for at least 5 years. Serum levels of CEA and CA19-9 were examined preoperatively and every 3 months postoperatively, with diagnostic imagings, such as chest X-ray, computed tomography (CT), and ultrasonography also being performed every 3 months. RESULTS: Recurrence was observed in 120 patients (peritoneum, 48; liver 16; lymph node, 16; multiple sites, 25; and others, 12). Sensitivities of CEA and either CEA or CA19-9, or both, for recurrence were 65.8% and 85.0%, respectively, both of which values were significantly higher than the preoperative positivities (28.3% and 45.0%, respectively). In most patients with high preoperative levels CEA and/or CA19-9, these tumor markers increased again at recurrence. Recurrent diseases were detected between 5 months after detection by diagnostic imagings and 12 months before detection by diagnostic imagings (mean of 3.1 +/- 3.6 months before detection by diagnostic imagings) and between 10 months after detection by diagnostic imagings and 13 months before detection by diagnostic imagings (mean of 2.2 +/- 3.9 months before detection by diagnostic imagings) by CEA and CA19-9 monitorings, respectively. CONCLUSION: These results suggest that CEA and/or CA19-9 monitoring after operation was useful to predict the recurrence of gastric cancer, especially in almost all the patients with high preoperative levels of these markers.