Ryo Takagawa

Learning curve for laparoscopy-assisted distal gastrectomy with regional lymph node dissection for early gastric cancer.

An assessment of the learning curve of laparoscopy-assisted distal gastrectomy (LADG) might encourage its worldwide spread among inexperienced surgeons. One hundred sixty-seven patients with early gastric cancer were enrolled in this study: 67 underwent conventional open distal gastrectomy and 100 underwent LADG after classification into 5 groups of 20 according to the surgeons level of experience. Patient characteristics and operative findings were compared between groups. Operation time was significantly longer, time to first flatus earlier, and blood loss reduced in the LADG groups compared with the open distal gastrectomy group. Surgeons with experience of 60 cases performed operations of similar times in both groups, and blood loss decreased with experience of 20 cases. There was no operative conversion, the frequency of nonsteroidal anti-inflammatory drugs administered were significantly less, and length of hospital stay were shorter by surgeons with experience of 60 cases. LADG is a technically feasible surgical procedure, depending on the surgeons technical proficiency. Experience of at least 60 cases of LADG seems to result in satisfactory patient outcomes.

Predictive factors for surgical complications of laparoscopy- assisted distal gastrectomy for gastric cancer

BackgroundSome studies have found high incidences of intraoperative and postoperative complications for patients with gastric cancer. To determine the predictive factors for the surgical complications of laparoscopic gastric surgery, surgical outcomes were evaluated.MethodsBetween April 2002 and December 2007, 152 patients with preoperatively diagnosed early gastric cancer who underwent laparoscopy-assisted distal gastrectomy (LADG) were enrolled. Visceral (VFA) and subcutaneous fat areas (SFA) were assessed by Fat Scan software. The predictive factors for surgical complications of LADG were evaluated by univariate and logistic regression analyses.ResultsOf 152 patients, conversion to open surgery due to uncontrollable bleeding was observed in nine male patients, and postoperative complications were detected in seven male and one female patient (four anastomotic leakage, two intraabdominal abscess, one pancreatic fistula, and one lymphorrhea). High body mass index (BMI) and high VFA independently predicted conversion to open surgery and postoperative complications. VFA was significantly higher, operation time was longer, blood loss was greater, and SFA was lower in male than in female patients, whereas no significant difference was observed in BMI between male and female patients.ConclusionsHigh BMI and high VFA can predict technical difficulties during laparoscopic gastric surgery and postoperative complications. Particularly, LADG should be performed cautiously to prevent surgical complications for male patients with high VFA. Predictive impact of VFA should be further determined in a larger set of patients.

Application of the transorally inserted anvil (OrVil) after laparoscopy-assisted total gastrectomy.

BackgroundLaparoscopy-assisted total gastrectomy (LATG) is not a commonly performed procedure due to the surgical difficulty associated with reconstruction. Although various reconstruction methods have been reported, a standard technique has not yet been established. In this study, we compared the short-term outcomes of LATG reconstructed by mini-laparotomy and by the newly developed transorally inserted anvil (OrVil™).MethodsFrom April 2006, a series of 45 patients underwent LATG. Of these, 15 were reconstructed by mini-laparotomy and 30 by OrVil™. Short-term outcomes were compared between the two groups.ResultsOperation time was significantly shortened and intraoperative blood loss significantly reduced by the use of OrVil™. The postoperative course, including morbidity, did not differ between the two groups.ConclusionsLATG using OrVil™ for the treatment of early gastric cancer is a technically feasible surgical procedure with sufficient lymph node dissection, satisfactory early recovery, and acceptable morbidity. It will be necessary to perform this novel technique in a large number of patients to confirm its feasibility.

Risk factors for lymph node metastasis in histologically poorly differentiated type early gastric cancer.

BACKGROUND We retrospectively evaluated the predictive factors for lymph node metastasis in poorly differentiated early gastric cancer (poorly differentiated tubular adenocarcinoma, signet-ring cell carcinoma, mucinous adenocarcinoma) in order to examine the possibility of endoscopic resection for poorly differentiated early gastric cancer. METHODS A total of 573 patients with histologically poorly differentiated type early gastric cancer (269 mucosal and 304 submucosal), who had undergone curative gastrectomy, were enrolled in this study. Risk factors for lymph node metastasis were evaluated by univariate and logistic regression analysis. RESULTS Lymph node metastasis was observed in 74 patients (12.9%) (6 with mucosal cancer and 68 with submucosal cancer). By univariate analysis risk factors for lymph node metastasis were lymphovascular invasion (LVI) (presence), depth of invasion (submucosa), and tumor diameter (> 20 mm), ulcer or ulcer scar (presence), and histological type (mucinous adenocarcinoma). By multivariate analysis, risk factors for lymph node metastasis were LVI, depth of invasion, and tumor diameter. In mucosal cancers, the incidence of lymph node metastasis was 0% irrespective of LVI in tumors smaller than 20 mm, and 1.7% in tumors 20 mm or larger without LVI. In submucosal cancers, the incidence of lymph node metastasis was 2.4% in tumors smaller than 20 mm without LVI. CONCLUSIONS A histologically poorly differentiated type mucosal gastric cancer measuring less than 20 mm and without LVI may be a candidate for endoscopic resection. This result should be confirmed in a larger study with many patients.

Impact of lymphovascular invasion in patients with stage I gastric cancer.

BACKGROUND Patients with stage I gastric cancer often suffer from tumor recurrence despite a generally favorable operative outcome. It is therefore important to determine the prognostic factors in order to improve such outcomes. METHODS Between April 1985 and March 2000, a total of 1,880 patients with histologically proven stage I gastric cancer were included in this study. Operative outcomes (survival time, prognostic factors, pattern of recurrence) were evaluated in these patients. RESULTS Multivariate analysis in patients with all stage I gastric cancer revealed that depth of invasion, lymph node metastasis, and lymphovascular invasion independently influenced prognosis. Moreover, advanced age was selected as an independent prognostic factor in patients with stage IA, and lymphovascular invasion in patients with stage IB gastric cancer by multivariate analyses. The 5-year survival rates in stage T1N1 patients with moderate to severe lymphovascular invasion, T2N0 with moderate to severe lymphovascular invasion, and II were 95.1%, 83.5%, and 76.9%, respectively. There was a significant difference in survival time between stage T1N1 and II (P = .0189) but not between stage T1N1 and T2N0 or stage T2N0 and II. CONCLUSION T2N0 gastric cancer patients with moderate to severe lymphovascular invasion may be suitable candidates for adjuvant chemotherapy.

Impact of splenectomy in patients with gastric adenocarcinoma of the cardia.

Previous reports have suggested that splenectomy treatment of gastric carcinoma of the cardia results in poor patient outcome, but the reason for this is unclear. This study aimed to clarify the impact of splenectomy for gastric carcinoma patients. A total of 118 patients with gastric carcinoma of the cardia were enrolled in this study. The characteristics of patients with lymph node metastasis at the splenic hilum were determined, and the effects of lymph node dissection or splenectomy on postoperative morbidity, mortality, and pattern of recurrence were evaluated. Advanced tumors were common in patients with lymph node metastasis at the splenic hilum, Siewert type III, greater curvature sites, larger and deeper tumors, multiple metastatic lymph nodes, and high incidences of para-aortic lymph node metastasis frequently observed. The effectiveness of lymph node dissection of the splenic hilum was low and equal to that of dissection of the para-aortic lymph nodes. Postoperative morbidity, as represented by pancreatic fistula, was high following splenectomy or pancreaticosplenectomy, but patient mortality did not occur. Hematogenous metastasis was common, as well as peritoneal metastasis after curative gastrectomy. Splenectomy should be limited in those patients with gastric cardia tumors invading the spleen or with metastatic bulky lymph nodes extending to the spleen.

Clinical Significance of the Metastatic Lymph-Node Ratio in Early Gastric Cancer

The metastatic lymph-node ratio has important prognostic value in gastric cancer; this study focused on its significance in early gastric cancer. In total, 1,472 patients with early gastric cancer underwent curative gastrectomy between 1992 and 2001. Of these, 166 (11.3%) had histologically proven lymph-node metastasis. Prognostic factors were identified by univariate and multivariate analyses. Metastasis was evaluated using the Japanese Classification of Gastric Carcinoma (JGC) and the Union Internationale Contre le Cancer/Tumor, Node, Metastasis (UICC/TNM) Classification. The metastatic lymph-node ratio was calculated using the hazard ratio. The cut-off values for the metastatic lymph-node ratio were set at 0, <0.15, ≥0.15 to <0.30, and ≥0.30. The numbers of dissected and metastatic lymph nodes were correlated, but the number of dissected lymph nodes and the metastatic lymph-node ratio was not related. The JGC and UICC/TNM classification demonstrated stage migration and heterogeneous stratification for disease-specific survival. The metastatic lymph-node ratio showed less stage migration and homogenous stratification. The metastatic lymph-node ratio may be a superior method of classification, which provides also accurate prognostic stratification for early gastric cancer patients.

Clinicopathological Features of Gastric Carcinoma in Younger and Middle-Aged Patients: A Comparative Study

Gastric carcinoma is relatively rare in patients under the age of 40. This study was undertaken to clarify the clinicopathological characteristics and surgical outcomes of gastric carcinoma in younger patients compared with those of middle-aged patients. The surgical results from 131 younger patients (aged ⩽40 years) and 918 middle-aged patients (aged 55–65 years) were compared retrospectively. Female gender, undifferentiated tumor type and lymphatic invasion were significantly more common in the younger patients. Survival time did not differ between the two groups. The depth of tumor invasion was the only prognostic factor in younger patients, whereas macroscopic appearance, tumor diameter, depth of invasion, lymph node metastasis, and venous invasion were all significant prognostic factors in middle-aged patients. Peritoneal recurrence was significantly more common in younger patients. A family history of gastric adenocarcinoma was observed in 25.9% of younger patients, but this did not affect survival outcomes. As depth of invasion affects prognosis independently, and peritoneal metastasis is the predominant pattern of recurrence, it is essential to establish an optimal prophylactic treatment for peritoneal metastasis to improve surgical outcomes in younger patients with advanced gastric cancer.

Effect of obesity on laparoscopy-assisted distal gastrectomy compared with open distal gastrectomy for gastric cancer

This study compared surgical outcomes between patients undergoing laparoscopy‐assisted distal gastrectomy (LADG) and those undergoing open distal gastrectomy (ODG) from the viewpoint of obesity.

High expression of KIBRA in low atypical protein kinase C-expressing gastric cancer correlates with lymphatic invasion and poor prognosis

Overexpression of atypical protein kinase Cλ/ι (aPKCλ/ι), a regulator of cell polarity, is frequently associated with the poor prognoses of several cancers, including gastric cancer. Recent studies revealed a molecular link between aPKC and KIBRA, an upstream regulator of tumor suppressor Hippo pathway that regulates cell proliferation and apoptosis. Further, KIBRA directly inhibits the kinase activity of aPKC to regulate epithelial cell polarity. These observations suggest that the KIBRA‐aPKC connection plays a role in cancer progression; however, clinical significance of the correlation between these factors remains unclear. Here we examined the correlation between KIBRA/aPKCλ/ι expression, as detected by immunohistochemistry, and clinicopathological outcomes in 164 gastric cancer patients using Fishers exact test and Kaplan–Meier log‐rank test. We found an intimate correlation between the expression level of KIBRA and aPKCλ/ι (P = 0.012). Furthermore, high expression of KIBRA is correlated with lymphatic (P = 0.046) and venous invasion (P = 0.039). The expression level of KIBRA by itself did not correlate with the prognosis; however, high expression of KIBRA in low aPKCλ/ι‐expressing gastric cancer correlated with disease‐specific (P = 0.037) and relapse‐free survival (P = 0.041) by Kaplan–Meier with log‐rank test and higher lymphatic invasion cases by Fishers exact test (P = 0.042). Furthermore, overexpression of the aPKC‐binding region of KIBRA disrupted tight junctions in epithelial cells. These results suggest that high expression of KIBRA in low aPKC‐expressing cells causes massive loss of aPKC activity, leading to loss of polarity and invasiveness of gastric cancer cells.