Combined splenectomy does not improve survival in radical total gastrectomy for advanced gastric cardia cancer.

BACKGROUND/AIMS: Splenectomy is the most common combined organ resection in the surgical management for gastric cardia cancer. The role of combined splenectomy is still controversial. METHODOLOGY: From January 1998 to December 2006, a total of 174 patients received radical total gastrectomy for advanced adenocarcinoma of cardia. Patients with previous gastric surgery or tumor invasion of pancreas or spleen were excluded. Among them, 115 patients were enrolled in this study. Patients were divided into group 1 (splenectomy, n=47) and group 2 (spleen preservation, n=68). Their clinicopathological characteristics were compared. RESULTS: Multivariate analysis showed that only tumor size and lymphovascular invasion were two independent indicators of survival. The surgically-related morbidity and mortality rates were similar between the two groups. Among the 3 patients with splenic hilar lymph nodes metastasis, all of them had large tumor size (=4cm), advanced stage (stage III and IV) and tumor center located at the posterior wall of stomach. The 5-year overall survival for advanced cancer was similar (57.1% vs. 60.2%, p=0.681). CONCLUSIONS: Splenectomy does not improve overall survival in the management of advanced gastric cardia cancer. Splenectomy has limited clinical benefits except for large advanced tumors located at the posterior wall of stomach.

Factors associated with recurrence within 2 years after curative surgery for gastric adenocarcinoma.

BACKGROUND: Despite curative surgery for gastric cancer, many patients die of recurrent cancer. Few studies have investigated the time to recurrence after curative resection for gastric cancer. METHODS: Data were collected prospectively between December 1987 and December 2006. A total of 1,549 patients underwent curative resection of adenocarcinoma of the stomach at Taipei Veterans General Hospital. Among them, 419 patients had recurrence; they were divided into early recurrence (<2 years) and late recurrence (≥2 years). The clinicopathological characteristics, survival time after recurrence, and recurrence patterns were compared between the two groups. RESULTS: Multivariate analysis showed that stage III gastric cancer patients with early recurrence had larger tumors and more lymph node metastasis than patients with late recurrence, while no difference between early and late recurrence was observed in stage I and II patients. Early recurrence was associated with more distant metastasis than was late recurrence. Patients with advanced TNM stage tended to die within 2 years after recurrence. CONCLUSIONS: Gastric cancer patients with larger tumors and more lymph node metastasis tended to have early recurrence, especially stage III patients. Advanced TNM stage was associated with early cancer death after recurrence.

Comparison of the survival difference between AJCC 6th and 7th editions for gastric cancer patients.

BACKGROUND: The AJCC 7th edition changes the classification of T- and N-factors and the TNM stage of gastric cancer. We evaluated its prognostic impact. METHODS: From December 1987 to December 2006, a total of 1,380 patients underwent curative surgery for gastric cancer at the Department of Surgery, Taipei Veterans General Hospital, with a retrieved lymph node number ≥ 15. Survival was compared for disease classified according to the AJCC 6th and 7th editions. RESULTS: There is a significant difference in 5-year survival between T2 and T3 gastric cancer classified according to the AJCC 7th edition (75.2 vs. 54.9%, p < 0.001), as well as between N1 and N2 (71.4 vs. 44.1%, p < 0.001). Although patients with N3a had a better 5-year survival than did those with N3b (27.6 vs. 11.3%, p < 0.001), the N3 categories were combined and not applied in the TNM stage in the 7th edition. Multivariate analysis using Cox's proportional hazards model with a forward logistics regression stepwise procedure demonstrates that age, N category of 6th edition, and T and N categories of 7th edition are independent prognostic factors; however, T category of 6th edition is no longer significant. Furthermore, the discriminative power of survival difference between each TNM stage seems to be comparable between the 6th and 7th editions. CONCLUSIONS: The AJCC 7th edition provides a more stratified survival difference in staging of gastric cancer. Future division of N3a and N3b in the classification of the TNM stage is recommended.

Risk factors and management of anastomotic leakage after radical gastrectomy for gastric cancer.

BACKGROUND/AIMS: Radical gastrectomy remains the primary treatment for gastric cancer without distant metastasis. However, anastomotic leakage and extended lymph node dissection might cause additional morbidity and related mortality. METHODOLOGY: From January 1988 to December 2004, 2076 patients with gastric cancer underwent radical gastrectomy at Taipei Veterans General Hospital. The risk factors for anastomotic leakage, including clinicopathological factors, operative procedures, combined organ resection, operating time, blood loss, and associated disease, were analyzed. The various methods used to measure anastomotic leakage and the clinical courses of different sites of anastomotic leakage were compared. RESULTS: The overall complication rate was 18.7% and the incidence of anastomotic leakage was 2.7% (n=57). The anastomotic leakage-related mortality rate was 21.1% (n=12). Older age (> or =65 years), longer operating time, more blood loss, and co-morbidities were the precipitating factors. Adequate drainage was the treatment approach used for anastomotic leakage. The incidence of anastomotic leakage was reduced during the later period of the study (3.4% vs. 1.8%). CONCLUSION: Only in an institute with a well-established training program and high volume of gastric cancer patients can we improve the surgical skills and accumulate the experiences with management of anastomotic leakage that make radical gastrectomy safer.

Peritoneal recurrence in serosa-negative gastric adenocarcinoma after curative surgery.

BACKGROUND/AIMS: The rate of recurrence increases in proportion to the degree of tumor depth, even after curative resection for gastric adenocarcinoma. Serosal exposure is considered as an important risk factor of peritoneal recurrence. However, some patients with serosa-negative cancer were found to have peritoneal recurrence. There are few reports concerning risk factors of peritoneal recurrence in serosa-negative gastric adenocarcinoma. The aim of this study is to evaluate the incidence and risk factors of peritoneal recurrence in serosa-negative gastric adenocarcinoma after curative resection. METHODOLOGY: Total 1128 serosa-negative gastric cancer patients (574 pT1, 251 pT2, 303 pT3) diagnosed as gastric adenocarcinoma that underwent R0 resection from 1988 to 2005 were enrolled. RESULTS: Peritoneal recurrence was observed in 50 (4.4%) patients, including 3 pT1, 3 pT2 and 44 pT3 patients. The incidence of peritoneal recurrence increased significantly with tumor invading subserosa (pT3). Multivariate analysis showed that the independent risk factor of peritoneal recurrence was tumor depth. CONCLUSIONS: The incidence of peritoneal recurrence in serosa-negative cancer is low, and tumor depth is a significant risk factor. We should be aware of peritoneal recurrence during follow-up, especially for patients with subserosal tumor invasion.

Esophagogastric junction adenocarcinoma according to Siewert classification in Taiwan.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is rapidly increasing. We evaluated the clinicopathological difference and outcomes of Taiwanese patients with AEG according to the Siewert classification. METHODS: Data were prospectively collected between December 1987 and July 2007. Two hundred thirty-one patients underwent curative resection of AEG at Taipei Veterans General Hospital and were divided into different Siewert types. The clinicopathological characteristics, operative morbidity, survival, and initial recurrence pattern were compared between the different types. RESULTS: Fifty-one type II and 180 type III cancer patients were studied. Subtotal esophagectomy via a left thoracotomy (19.6% vs 2.8%), smaller tumor size (4.43 +/- 2.04 vs. 5.35 +/- 2.03 cm), and more combined organ resection (60% vs. 43.1%) were more common in type II than type III cancer. Multivariate analysis showed that three independent risk factors for death were gender, tumor size, and lymphovascular invasion. There were long-term survivors among the patients with lesser curvature site lymph node metastasis, whereas metastasis to the lymph nodes of the distal stomach and along the greater curvature site was associated with poor prognosis. The 5-year survival was similar between type II and type III cancer (59.6% vs. 63.5%, P = 0.947). CONCLUSIONS: Lymphovascular invasion, tumor size, and gender were determined to be three independent factors of survival after curative resection for AEG, and Siewert type was not associated with differences in survival.

Mucin-producing gastric cancer: clinicopathological difference between signet ring cell carcinoma and mucinous carcinoma.

BACKGROUND/AIMS: Signet ring cell carcinoma and mucinous carcinoma are mucin-producing gastric cancers. Their clinicopathological difference was obscure. METHODOLOGY: From December 1987 to July 2005, a total of 1612 gastric cancer patients received curative surgery, 128 patients with signet ring cell carcinoma and 48 with mucinous carcinoma were enrolled in this study. Clinicopathological data were compared between the two groups. RESULTS: Early stage (stage I and II) patients with mucinous carcinoma were associated with more male predominant (p = 0.002), larger tumor size (p = 0.020), deeper cancer invasion (p < 0.001), and a worse 5-year overall survival (63.6% vs 88.2%, p = 0.012) than those with signet ring cell carcinoma. There was no significant difference between the two groups with advanced stage in 5-year overall survival. There is no significant difference in the initial recurrence pattern between the two groups. CONCLUSIONS: Patients with mucinous carcinoma had different biological behaviors with those with signet ring cell carcinoma, in particular early stage, hence had a worse survival.

Lymph node metastasis as a single predictor in patients with Borrmann type I gastric cancer.

BACKGROUND/AIMS: Borrmann type I gastric cancers are rare. Its clinicopathological features have never been reported. METHODOLOGY: A total of 33 patients with Borrmann type I gastric cancer was evaluated. 570 patients with Borrmann type II, III and IV were used as references. RESULTS: Borrmann type I gastric cancer occurred preferably in upper stomach, and had more T1 and T2 cancer invasion and early TNM stages, but less lymph node metastasis. Histologically, it had more intestinal type and less scirrhous stromal reaction. Five-year disease-free and overall survival rates in patients with Borrmann type I tumors were significantly higher than that of other types (73.3% vs. 45.8%; P = 0.02, and 72.6% vs. 47.8%; P = 0.01, respectively). Analysis of the relation between clinicopathological factors and survival showed that only lymph node metastasis significantly affected on disease-free survival with a relative risk of 8.4. Lymph node metastasis also affected overall survival rate at a marginal level (p = 0.05). CONCLUSIONS: Borrmann type I gastric cancer has higher survival rate. Lymph node metastasis is a single prognostic indicator for survival.

Survival of gastric cancer with concomitant liver metastases.

BACKGROUND/AIMS: Prognosis of gastric cancer with concomitant liver metastasis is poor. Gastrectomy and chemotherapy had been reported to be beneficial to this group of patients. Whether all the patients can benefit from that treatment modality and whether the clinical characteristics can give some information about survival have not been evaluated. METHODOLOGY: Eighty-three gastric cancer patients with concomitant liver metastases who had received treatment in the past 10 years were retrospectively studied with special reference to different extent of liver metastases. Clinical characteristics (peritoneal tumor dissemination, tumor markers, clinicopathological factors), treatment modalities (gastrectomy or chemotherapy) and survival were analyzed for their possible relationship with the extent of liver metastases. RESULTS: There were 33 patients with liver metastases limited to one lobe and 50 patients had metastases in both lobes. The clinicopathological characteristics show no difference between uni- and bilobar liver metastases except higher percentage of concomitant peritoneal dissemination in patients with bilobar disease. More unilobar involvement patients underwent gastrectomy (70% vs. 48%, p=0.018). Higher frequency of abnormal CEA level in bilobar metastases (38% vs. 60%, p=0.045). Median survival of unilobar metastasis is 7.8 months and 4.3 months for the bilobar involvement (p=0.001). Gastrectomy might prolong the survival in patients with unilobar metastasis (p=0.005), but not in patients with bilobar diseases (p=0.074). Chemotherapy could prolong the survival in patients without gastrectomy, but not the survival after gastrectomy. CONCLUSIONS: The clinicopathological characteristics and tumor markers have no role in predicting the survival among patients with liver metastases. Both gastrectomy and chemotherapy for the patients without gastrectomy could prolong survival, but chemotherapy could not prolong the survival after gastrectomy, the benefit of resection and chemotherapy are probably caused by selection bias.

Peritoneal carcinomatosis and lymph node metastasis are prognostic indicators in patients with Borrmann type IV gastric carcinoma.

BACKGROUND/AIMS: Having observed a lower survival rate of patients with Borrmann type IV gastric cancer, we attempted to determine its prognostic indicators. METHODOLOGY: A total of 103 patients with Borrmann type IV gastric cancer were evaluated; 604 patients with Borrmann types I, II and III were used as references. RESULTS: The results showed that Borrmann type IV gastric cancer were larger, had deeper invasion, more lymphatic and vascular invasions, predominant diffuse type and scirrhous stromal reaction, extensive lymph node metastases and peritoneal carcinomatosis. The 5-year survival rate (11.3%) was significantly lower than that of others (44.7%, P < 0.001). Univariate and multivariate analyses of survival showed that peritoneal carcinomatosis and lymph node metastasis were independently associated with a relative risk of 1.8 and 1.4, respectively. The survival rates of 46 patients with potential curative disease were similar, regardless of various extents of resection. CONCLUSIONS: Peritoneal carcinomatosis and lymph node metastases are prognostic indicators in patients with Borrmann type IV gastric cancer. Optimal surgical strategy for Borrmann type IV gastric cancer remains unclear.

Peritoneal recurrence of gastric adenocarcinoma after curative resection.

BACKGROUND/AIMS: Death from gastric carcinoma after curative resection is mostly due to recurrence. The most common recurrence is peritoneal dissemination, which represents 33 to 50% of total recurrence after curative gastrectomy. Since survival after peritoneal dissemination is very poor, selection of high-risk patients for further management after resection may contribute to better survival. METHODOLOGY: Based on a prospective database, a total of 1,092 patients with gastric carcinoma who underwent curative resection were included in this study. The incidence of peritoneal recurrence, disease-free interval and survival after peritoneal recurrence were determined. The clinicopathological factors including sex, age, tumor location, size, gross appearance, histological findings, depth of tumor invasion, lymph node status, tumor cell infiltration pattern were analyzed to see if there is any relationship with peritoneal dissemination. RESULTS: The incidence of peritoneal recurrence after curative resection was 13.46%. The mean disease-free interval was 14.2 months and the survival after peritoneal recurrence was 4.9 months in average. Almost all the clinicopathological factors were related with peritoneal recurrence, but only depth of tumor invasion, gross appearance and tumor infiltration pattern are closely associated with peritoneal tumor dissemination after multivariate analyses. CONCLUSIONS: Since the prognosis after peritoneal recurrence is so poor, selection of high-risk patients for further management after gastrectomy may be based on these three factors.

Survival predictors in patients with node-negative gastric carcinoma.

BACKGROUND: Presence or absence of nodal metastasis influences outcome of gastric cancer patients. This study gives insight into survival predictors and clinicopathological features of node-negative gastric adenocarcinoma. METHODS: Between 1988 and 1999, 689 gastric cancer patients without other cancer or gastrectomy for benign disease who underwent curative resection were enrolled in this study. Clinicopathological data in patients with node metastasis were compared with those without. RESULTS: The survival rate at 5 and 10 years for node-negative cases was 91.7% and 89.7%, respectively. On univariate analysis, node-negative patients were characterized by frequent location in the lower two-thirds of the stomach (84.9%), tumor size less than 4 cm (63.5%), grossly superficial type (71.6%), more medullary stromal reaction (50.5%) and intestinal type (67.7%), tumor invasion confined to serosa (78.4%), less poorly differentiated cell type (43.2%), and less lymphovascular invasion (33.4%). Multivariate analysis demonstrated that lymphovascular invasion (relative risk: 5.036) and depth of cancer invasion (relative risk: 4.404) were independent poor prognostic factors. However, lymphovascular invasion and serosal invasion were also correlated (P < 0.001). CONCLUSION: Patients with node-negative gastric adenocarcinoma had less disease progression and a favorable survival. Lymphovascular invasion and depth of cancer invasion were two independent but correlated survival predictors.

Surgical results of early gastric cancer and proposing a treatment strategy.

BACKGROUND: Prognosis for patients with early gastric cancer after surgical resection is excellent. The 5-year or even 10-year survival is more than 90%. In the present study, we investigated the result of treating early gastric cancer surgically in our hospital, with special reference to the risk factor(s) for tumor recurrence and the relationship between age and survival. PATIENTS AND METHODS: From January 1988 to December 2002, a total of 479 patients with early gastric cancer underwent resection by our surgeons. Results of preoperative studies, operative findings, histopathology and postoperative follow-up were recorded respectively, and the postoperative disease-related survival, overall survival, tumor recurrence and recurrent patterns were analyzed. The clinicopathological factors were also analyzed to identify the risk factor(s) related to tumor recurrence. RESULTS: Older patients (>75 years old) had a poorer overall survival than younger patients. However, the disease-related survival was not significantly different between the two. Recurrence was observed in 21 patients, the most important factor of which was lymph node status. Lymph node metastases occurred in 54 patients (11.3%)-coming from mucosal tumors in 12 patients (4.4%) and from submucosal tumors in 42 (20.3%). When the size of the mucosal tumor was smaller than 1 cm, no lymph node metastasis was found in our patients. CONCLUSIONS: The most important risk factor of recurrence in early gastric cancer is lymph node status. Given the low probability of lymph node metastasis and recurrence in tumors less than 1 cm in diameter limited to the mucosa, more limited surgery maybe appropriate in these carefully selected instances.

Higher morbidity and mortality after combined total gastrectomy and pancreaticosplenectomy for gastric cancer.

Total gastrectomy with pancreaticosplenectomy for gastric cancer has been proposed for facilitating lymph node dissection or for resection of direct tumor invasion to the pancreas, especially for T4 lesions. Its effectiveness in improving patient survival is still controversial, and higher morbidity and mortality with this procedure have been reported in several series. Such risks to patient survival were not observed in the Japanese series. Based on a prospective gastric cancer database maintained from 1987 to 1999 in our institution, the morbidity and mortality were analyzed in our series of pancreaticosplenectomies. A total of 1,278 patients with gastric cancer received gastrectomy in our surgical unit. Of these, 127 patients underwent curative total gastrectomy with pancreaticosplenectomy in order to facilitate lymph node dissection or removal of direct tumor invasion. Operative time, postoperative hospital stay, postoperative complications, and surgical mortality were analyzed. Compared to another 201 total gastrectomies, longer mean operative time (7.91 +/- 2.16 hours vs. 6.67 +/- 2.01, p <0.001) and postoperative hospital stay (median, 24.5 days vs. 17, p <0.001) for combined organ resection (pancreaticosplenectomy) were shown in this series. The major complication rate, including intraabdominal abscess, anastomotic leak, postoperative bleeding, pancreatitis/fistula, chylous leak, and general complications causing unstable vital signs (26.8% vs. 11.9%, p = 0.001), but not the mortality rate (6.3% vs. 4.8%, p = 0.608), was also shown to be higher in pancreaticosplenectomy patients. The most frequent fatal complication was intraabdominal abscess. However, more than 50% of complications occurred in the first 40 pancreaticosplenectomies (1987-1991); after adequate accumulation of experience, the total complication rate (57.5% vs. 35.6%, p = 0.021), major complication rate (40% vs. 20.7%, p = 0.022), and mortality rate (17.5% vs. 1.1%, p = 0.001) improved significantly in the remaining 87 patients (1991-1999). We therefore conclude that total gastrectomy with pancreaticosplenectomy can be performed by experienced surgeons with acceptable risk of morbidity and mortality.

Incidence and factors associated with recurrence patterns after intended curative surgery for gastric cancer.

Recurrence after curative resection for gastric cancer remains high. We examined its incidence and factors related to recurrence pattern, while trying to avoid the interaction of various factors. A total of 611 gastric cancer patients after resection for curative intent (1988-1995) were analyzed. The result showed that 245 patients had recurrence (40.1%). Cumulative recurrence rates were 53.5%, 80%, 89.0%, 94.7%, 96.3%, 98%, and 99.5% at 1, 2, 3, 4, 5, 6, and 7 years, respectively. Over half of patients with recurrence (123; 50.2%) had an initial single recurrence. Taking single and multiple recurrence together, most recurrences (213; 86.9%) were distant metastases, 110 recurrences (44.9%) were local relapses, and 78 recurrences (49.8%) were both local and distant. Among the distant metastases, 131 patients (53.5%) had peritoneal dissemination, 106 patients (43.3%) had hematogenous metastases, and 70 patients (28.6%) had distant lymphatic spread. Scirrhous-type stromal reaction, serosa invasion, and female gender were factors negatively related to peritoneal recurrence. Medullary-type stromal reaction and male gender showed a preference for locoregional recurrence, and expanding growth tumor commonly led to hematogenous metastasis. Patients who had paraaortic lymph node metastasis were at high risk of developing distant lymphatic recurrence. It is conceivable that the patterns of recurrence and the times to recurrence provide a biological basis for clinical monitoring of patients with the aim of modifying therapeutic modalities.