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The role of HGF/SF-MET signaling is important in cancer progression, but its relation with Helicobacter pylori-positive gastric cancers remains to be elucidated. In total, 201 patients with primary gastric carcinoma who underwent curative or debulking resection without preoperative chemotherapy were studied. MET4 and anti-HGF/SF mAbs were used for immunohistochemical analysis. Survival of gastric cancer patients was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of MET-staining status with outcome. The effect of live H. pylori bacteria on cell signaling and biological behaviors was evaluated using gastric cancer cell lines. MET4-positive gastric cancers showed poorer prognosis than MET4-negative cases (overall survival, P = 0.02; relapse-free survival, P = 0.06). Positive staining for MET4 was also a statistically significant factor to predict poor prognosis in H. pylori-positive cases (overall survival, P < 0.01; relapse-free survival, P = 0.01) but not in H. pylori-negative cases. Gastric cancers positively stained with both HGF/SF and MET4 showed a tendency of the worst prognosis. Stimulation of MET-positive gastric cancer cells with live H. pylori bacteria directly upregulated MET phosphorylation and activated MET downstream signals such as p44/42MAPK and Akt, conferring cell proliferation and anti-apoptotic activity. In conclusion, positive staining for MET4 was useful for predicting poor prognosis of gastric cancers with H. pylori infection. Helicobacter pylori stimulated MET-positive gastric cancers and activated downstream signaling, thereby promoting cancer proliferation and anti-apoptotic activity. These results support the importance of H. pylori elimination from gastric epithelial surface in clinical therapy., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: In order to improve a patient's quality of life after total gastrectomy, jejunal pouch reconstruction has been employed. However, little information exists regarding the optimal size of the jejunal pouch after total gastrectomy., Methods: The study was designed as a single-center randomized trial in which the results of double-tract reconstruction with pouches of two different sizes were compared, i.e., short and long pouch double tract (SPDT and LPDT, respectively). We conducted a clinical assessment with standard questionnaire after surgery. The amount of residual food in the jejunal pouch was determined by endoscopy., Results: No demographic differences were noted between the two groups. The eating capacity per meal was higher in the SPDT group than in the LPDT group. The postoperative weight loss 24 months after surgery was lower in SPDT group than that in the LPDT group. Although the incidence of early dumping symptoms was higher in the SPDT group, no difference was noted in the other postprandial abdominal symptoms between the two groups., Conclusions: We conclude that the optimal pouch should be relatively short, as a short pouch improves the eating capacity per meal and the weight loss ratio to the preoperative value.

Purpose: This study was designed to apply safely the sentinel node navigation surgery (SNNS) to the malignancies, an accurate and prompt intraoperative diagnosis of SN is essential, and micrometastasis has been frequently missed by conventional frozen sections. Recently, a novel molecular-based rapid diagnosis for the lymph node (LN) metastases has been developed using (OSNA) in breast cancer, which takes approximately 30 min to obtain a final result. We evaluated the efficacy of OSNA in terms of the intraoperative diagnosis of LN metastasis in patients with gastric cancer., Methods: A total of 162 LNs dissected from 32 patients with gastric cancer was included in this study; 45 LNs were pathologically diagnosed as metastatic LNs and 117 LNs were negative. The LNs were bisected; halves were examined with H&E stain, and the opposite halves were subjected to OSNA analyses of CK19 mRNA. The CK19 mRNA expression was examined in the positive or negative metastatic LNs, and the correlation between the tumor volume and CK19 mRNA expression in the metastatic LNs was examined., Results: The CK19 mRNA expressions in the positive metastatic LNs were significantly higher than those of negative LNs. When 250 copies/μl was set as a cutoff value, the concordance rate was 94.4%, the sensitivity was 88.9%, and the specificity was 96.6%. The OSNA expression was significantly correlated with the estimated tumor volumes in the metastatic LNs., Conclusions: The OSNA method is feasible and acceptable for detecting LN metastases in patients with gastric cancer. This should be applied for the intraoperative diagnosis in the SN-navigation surgery in gastric cancer.

The sentinel node (SN) concept has been found to be feasible in gastric cancer. However, the lymphatic network of gastric cancer may be more complex, and it may be difficult to visualize all the SN distributed in unexpected areas by conventional modalities. In this study, we evaluate the feasibility and efficacy of CT lymphography for the detection of SN in gastric cancer. A total 24 patients with early gastric cancer were enrolled in the study. Three modalities (CT lymphography, dye and radioisotope [RI] methods) were used for the detection of SN. The images of CT lymphography were obtained at 10 min after injection of contrast agents. The SN were successfully identified by CT lymphography in 83.3% of patients; detection rates by the dye and RI methods were 95% and 100%, respectively. Most patients, in whom SN were successfully detected by CT lymphography, had positive results at 5 min after injection of the contrast material. The SN stations detected by CT lymphography were consistent with or included those detected by dye and/or RI methods. In conclusion, CT lymphography for the detection of SN in gastric cancer is feasible and has several advantages. However, based on this initial experience, CT lymphography had a relatively low detection rate compared with conventional methods, and further efforts will be necessary to improve the detection rate and widen the clinical application of CT lymphography for the detection of SN in gastric cancer., (© 2010 Japanese Cancer Association.)

Metastatic tumors in the stomach are rare. We report a case of solitary gastric metastasis from renal cell carcinoma (RCC) 19 years after radical excision of the primary tumor. During evaluation for anemia with melena, a small elevated tumor with ulceration was detected in the gastric fundus of this patient. The tumor was diagnosed as RCC based on endoscopic biopsy findings. There was no evidence of any other metastatic lesion, and a wedge resection of the stomach was performed. No additional metastasis or recurrence has been detected in the patient 12 months after discharge. This case confirms the existence of a very slow growing type of RCC with the potential for late solitary metastases and describes the surgical resectability.

Objective: To evaluate the early results of sentinel node (SN)-navigated limited surgery for early gastric cancer., Summary Background Data: False-negative results of SN biopsy cannot be ignored in gastric cancer surgery. Previous studies suggest that dissection of lymph node stations where SNs belong (SN stations) may minimize the possibility of leaving metastasis behind in SN-navigated surgery., Methods: Patients with T1N0M0 gastric cancer <4 cm were informed about the SN-navigated limited surgery from 2003 to 2008. SNs were identified using radioisotope and dye methods. When the SN biopsy by frozen section was negative, limited gastrectomy with dissection of SN stations was performed. Patients with SN stations limited to either the lesser or greater curvature underwent a wedge resection unless it would cause a strong deformity of the stomach. A sleeve gastrectomy was performed in other cases., Results: Six of the 60 enrolled patients chose a standard gastrectomy. Sixteen patients were excluded after laparotomy due to a T2-T3 tumor or tumor location. Three patients with positive SN biopsy underwent D2 gastrectomy, and 35 with negative SN biopsy underwent limited gastrectomy with dissection of SN stations; wedge resection in 8 and sleeve gastrectomy in 27. There were no operative mortalities or morbidities. All patients undergoing the limited surgery had no lymph node metastasis by postoperative pathology, and survived without any recurrence. The average area of the resected stomach for limited surgery was significantly smaller than that for standard procedures (92 +/- 50 vs. 189 +/- 64 cm, P < 0.001)., Conclusions: SN-navigated limited gastrectomy with dissection of SN stations for T1N0M0 gastric cancer was considered safe and acceptable although long-term follow-up is mandatory.

We focused on the impact of postoperative infection on long-term survival after potentially curative resection for gastric cancer. Postoperative surgical and medical complications have been implicated as a negative predictor of long-term outcome in various malignancies. However, there have been no published reports assessing the impact of complications arising from postoperative infection on survival in gastric cancer. We studied a population of 1,332 patients who underwent curative resection for gastric cancer. These patients were divided into two groups based on the occurrence (141 patients, 10.6%) or absence (1,191 patients, 89.4%) of postoperative complications due to infection. We investigated the demographic and clinicopathological features of each patient with and without postoperative complications from infection, and thereby the impact of postoperative infection on long-term survival. Patients with postoperative infection had significantly higher frequency of males, upper side tumor location, and total gastrectomy as a surgical procedure, more advanced stage of gastric cancer, and greater age compared with those without postoperative infection. Patients with complications due to postoperative infection had significantly more unfavorable outcome compared with those patients without postoperative infection. Multivariate analysis demonstrated that age, preoperative comorbidity, blood transfusion, tumor depth, nodal involvement, and postoperative infection correlated with overall survival. We conclude that postoperative complications from infection are a predictor of adverse clinical outcome in patients with gastric cancer. However, further immunological study and prospective trials are necessary to confirm the biological significance of these findings.

Background: In sentinel node (SN) detection for cases of early gastric cancer, the submucosal dye injection method appears to be more reasonable than the subserosal injection. To compare the two injection methods, we have focused on the rate of concordance between hot nodes (HNs) obtained from the radioisotope (RI) method and green nodes (GNs) obtained from the dye-guided method in addition to the number and distribution of GNs detected, and the sensitivity of metastatic detection., Methods: The subjects of this study were 63 consecutive patients with gastric cancer (sT1-T2, sN0, tumor diameter <== 4 cm) in whom we attempted SN detection using a combination of RI and dye methods. 99mTc-tin colloid was injected a day before the surgery, and indocyanine green was injected either submucosally (n = 43) with endoscopes or subserosally (n = 20) by direct vision., Results: An average of hot and green nodes (H&G: 4 +/- 3 vs. 4 +/- 3), hot and non-green nodes (H&NG: 2 +/- 3 vs. 1 +/- 2), cold and green nodes (C&G: 2 +/- 2 vs. 3 +/- 4), and the rate of concordance (H&G/H&G + H&NG + C&G: 45 + 27% vs. 48 +/- 30%) were not significantly different between the submucosal and subserosal injection methods. The spread of GNs to tier 2 stations (24% vs. 30%) and metastatic detection sensitivity (86% vs. 100%) were also not different between the submucosal and subserosal injection methods., Conclusion: The tracer injection sites do not have to be limited to the submucosa.

Background/aims: In the treatment of cardiac cancer, the selection of surgical procedures is controversial., Methodology: In this study 297 resectable adenocarcinomas arising around the GE junction, that had their center within 5cm oral and aboral of the anatomical GE junction, were analyzed. They were subdivided into those with the tumor center located more than 1cm above the GE junction (Type 1, N = 7), those with the tumor center located within 1cm oral and 2cm aboral of the GE junction (Type 2) and those with the tumor center 2cm below the junction (Type 3). Type 2 and 3 are subdivided into four groups as Type 2A (N = 47), 2B (N = 18), 3A (N = 37) and 3B (N = 188). Type 2A and 3A have esophageal invasion and Type 2B and 3B have no esophageal invasion. Thoraco-abdominal approach and transhiatal resection were done in 65 and 35 patients. Left and right thoracotomies were performed in 60 and 5 patients, respectively., Results: Esophageal invasion distance of 83 among 84 Type 2A and 3A tumors limited within 5cm from the GE junction. The maximum esophageal length by transhiatal approach was 6cm. Postoperative mortality rates after transhiatal approach and thoracotomy were 0% and 5.8%, respectively. One patient of Type 2A with No110 involvement survived longer than 5 years. No patients with Type 2A and 3A had recurrence in the upper mediastinal nodes after transhiatal approach and left thoracotomy. Mediastinal node involvement was found in 3 of 7 Type 1 tumors. Cox regression analyses revealed that the esophageal invasion distance (< 3cm vs. > 3cm), lymph node status (N0 vs. N2) and extent of lymph node dissection (D1 vs. D2) are the independent prognostic factors., Conclusion: Dissection of the lower thoracic paraesophageal nodes is recommended if the esophageal invasion longer than 1cm. Almost all Type 2A and 3A tumors can be treated by transhiatal approach without positive esophageal margin under a routine use of intraoperative frozen section. Right thoracotomy and the dissection of the upper mediastinal nodes are recommended for Type 1 tumor. Cardiac resection with D2 dissection is indicated for Type 1 and T1 tumors of Type 2. Total gastrectomy +D2 dissection is recommended for T2-3 tumors of Type 2 and T1-4 tumors of Type 3. Treatment should be selected according to the proposed classification.

Background: We have reported that lymphatic mapping using indocyanine green (ICG) solution can be a good tool for identifying sentinel nodes (SNs) in gastric cancer. The purpose of this study was to evaluate individualized operations for gastric cancer guided by SN biopsy and to explore the possibility for more limited operative procedures using SN technology., Methods: SNs were identified by using (99m)Tc-labeled tin colloid and ICG solution in patients with clinically T1N0M0 gastric cancer. When pathologic examination by frozen section revealed metastasis in SNs, we performed a standard D2 gastrectomy. Less extensive lymphadenectomy preserving vagus and pylorus was applied when the SN biopsy was negative. Then, postoperative pathology was analyzed., Results: Among the 80 enrolled patients, 7 patients with apparent node metastasis or T2-3 neoplasms and 10 patients with positive metastasis in SNs underwent D2 gastrectomy. Sixty-one patients with negative metastasis in SNs underwent a less extensive, function-preserving gastrectomy. The false-negative rate in sentinel node biopsy was 23% (3/13) for frozen section and 7% (1/14) for postoperative pathology. In 3 patients with a false-negative result, metastasis was found in lymph nodes located at the station where the tracers were distributed. Of the 7 patients in whom metastasis was detected in 2 or more SNs by frozen section, postoperative pathology revealed that 3 patients (43%) belonged to the N2 category., Conclusions: SN biopsy is a useful tool for individualizing the operative procedure for early gastric cancer. Dissecting the lymph node stations only where the tracers are distributed may be a promising procedure for patients with no metastatic SNs.

Background: The Japanese Gastric Cancer Association's (JGCA's) Gastric cancer treatment guidelines for doctors' reference and the guidelines (GLs) for popular use were both published in 2001. The purpose of this study was to know whether or not it is useful for patients to read the GLs for popular use., Methods: We lent the GLs for popular use to patients with gastric cancer for several days and had them read the GLs before they were informed about their condition and the recommended treatment. Then they received questionnaires concerning the GLs., Results: Most of the patients, even the elderly, had read and understood the GLs. Nearly 70% of the patients answered that it was very useful for them to read the GLs. On the other hand, 34% of the patients suggested negative aspects, such that reading the GLs increased their anxiety about the disease or treatment. Only 9% of the patients expected treatment that followed the GLs, whereas 54% of the patients expected treatment based on the doctor's own experience without adherence to the GLs. If the doctor were to suggest treatment that did not follow the GLs, 87% of the patients answered that they would follow the doctor's suggestion, and it was only 8% who answered that they would seek a second opinion. These results did not differ when patients were requested to fill out questionnaires anonymously., Conclusion: Although the GLs for popular use are useful to provide patients with information concerning the disease and the treatment modalities, they may not have a great impact on patients' decisions about their treatment.