Atsuo Shida

Expression of vascular endothelial growth factor (VEGF)-C and -D in gastric carcinoma.

BackgroundBoth vascular endothelial growth factor (VEGF)-C and (VEGF)-D are ligands of VEGF receptor (VEGFR)-3 (Flt-4) and VEGFR-2 (KDR/FLK-1) and are supposed to participate in lymphangiogenesis. The purpose of this study was to clarify the clinical significance of the expression of these factors and to evaluate their relationship with prognosis in patients with gastric carcinoma.MethodsFifty pairs of normal mucosa and cancer specimens were obtained from patients who had undergone gastrectomy for primary gastric carcinoma and subjected to reverse transcriptase-polymerase chain reaction for VEGF-C, VEGF-D, and VEGFR-3.ResultsBoth VEGF-C and VEGF-D mRNA expression significantly correlated with lymphatic invasion (P < 0.05). Although VEGF-C and -D were concomitantly expressed in most cases, only VEGF-C expression was related to lymph node metastasis. VEGFR-3 expression was associated both with VEGF-C and VEGF-D expression, but not with lymph node metastasis. Tumors expressing these mRNAs tended to correlate with poorer prognosis, but the relationships were not statistically significant.ConclusionOur study suggests that both VEGF-C and VEGF-D are involved in lymphatic spreading of gastric cancer cells, which is clinically useful for the evaluation of lymphatic invasion in patients with gastric carcinoma.

Prognostic significance of vascular endothelial growth factor D in gastric carcinoma.

The angiogenic factor called vascular endothelial growth factor (VEGF)-D is a ligand for VEGF receptor-2 (VEGFR-2/KDR) and receptor-3 (VEGFR-3/Flt-4). It is implicated in the development of lymphatic vessels and promotion of lymphatic metastasis. The purpose of this study was to investigate the prognostic significance of VEGF-D expression in patients with gastric carcinoma. We assessed the expression of VEGF-D in gastric carcinoma by immunohistochemistry on 143 consecutive patients’ stored sections and evaluated the lymphatic vessel count (LVC) in tumors using the novel selective lymphatic endothelium marker D2-40. VEGF-D expression was observed in 55 (39%) tumor sections. The expression of VEGF-D correlated significantly with tumor size, T of the TNM classification, lymphatic and venous system invasion, LVC, lymph node metastasis, M of TNM, and pTNM stage. Multivariate analysis indicated that VEGF-D expression was an independent prognostic factor for both relapse-free survival (RFS) and overall survival (OS). Our data indicate the involvement of VEGF-D in tumor progression via lymphoangiogenic pathways. Practically, VEGF-D expression can be useful for predicting RFS and OS in patients with gastric carcinoma.

Sentinel lymph node navigation surgery for early stage gastric cancer

We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patients quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation.

Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer

Accurate prediction of lymph node (LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer (EGC). However, consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search, we identified several independent variables associated with LN metastasis in EGC, which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand, even if we use these promising parameters, we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN (SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review, we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition, we evaluated the history of sentinel node navigation surgery and the usefulness for EGC.

Modified Billroth-I reconstruction after distal gastrectomy

To the Editor: Although Billroth I (B-I) or Billroth II (B-II) has traditionally been the method for reconstruction after distal gastrectomy, Roux-en-Y (R-Y) is now being increasingly employed at many institutions, mainly to prevent duodenogastric refl ux and to ensure safe anastomosis. We do perform R-Y in our department, but only in limited cases in patients with special conditions, i.e., locally invasive tumors in the pylorus or the antrum in which the tumor may recur locally, or in patients having a subtotal distal gastrectomy for which a gastroduodenal anastomosis would result in excessive tension. The advantages of R-Y after distal gastrectomy include the absence of or a low incidence of refl ux gastritis and esophagitis [1] and a possible reduction in the future development of stump carcinoma [2]. On the other hand, with R-Y, stomal ulcer may develop [3, 4] and the incidence of cholelithiasis, for which endoscopic sphincterotomy is almost impossible, may increase [5, 6]. The notorious Roux stasis syndrome [7] may also develop in some cases. The advantages of B-I over R-Y include food passage through the physiological route, single anastomosis, low risk of stomal ulcer or cholelithiasis, and easy access to the duodenal papilla in case there is cholelithiasis or pancreatic disease. Thus, we select B-I reconstruction whenever possible. Because the main problem with B-I is duodenogastric refl ux, we recently developed a modifi ed B-I technique, in which the gastric mucosa is inverted like a checkvalve in the duodenum to prevent refl ux (Fig. 1). Since we fi rst reported the technique in 2007 [8], ten such patients have been followed up for a mean of 17.7 Fig. 1. Schematic view of the newly developed modifi ed Billroth I technique. With permission from the publishers of Surgery [8]

Reduced expression of Rho GDP dissociation inhibitor 2 mRNA is associated with lymph node metastasis in gastric carcinoma

Small GTPase proteins, including RhoA, RhoB, RhoC, Rac1 and cdc42, are molecules that have significant roles in linking cell shape and cell cycle progression in cytoskeletal arrangements and mitogenic signaling. Rho GDP dissociation inhibitor 2 (RhoGDI2) has recently been identified as a metastasis suppressor gene in models of bladder cancer. RhoGDI2 has also been identified as a potential regulator of tumorigenesis and cancer progression. The present study aimed to clarify the significance of RhoGDI2 gene expression in gastric carcinoma and to evaluate the outcome of affected patients. A total of 46 pairs of normal mucosa and cancer specimens were obtained from patients who had undergone a gastrectomy for primary gastric carcinoma and were subjected to semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) for RhoGDI2. The expression of RhoGDI2 mRNA was significantly higher in early-stage gastric cancer specimens compared with the normal gastric epithelium samples. By contrast, the depth of the tumor was negatively correlated with RhoGDI2 mRNA expression. In addition, a reduced expression of RhoGDI2 mRNA was associated with venous system invasion and lymph node metastasis. RhoGDI2 mRNA was more frequently expressed in differentiated adenocarcinoma compared with poorly-differentiated adenocarcinoma. Although the statistical significance was not established, RhoGDI2-positive patients tended to have a superior oncological outcome compared with RhoGDI2-negative patients. The reduced expression of RhoGDI2 mRNA in gastric carcinoma is associated with venous system invasion and lymph node metastasis.

Comparison of Short-term and Long-term Clinical Outcomes Between Laparoscopic and Open Total Gastrectomy for Patients With Gastric Cancer.

Background and Purpose: Validation of laparoscopic total gastrectomy (LTG) for patients with gastric cancer has not been fully investigated. In particular, the technique for esophagojejunostomy remains controversial. We performed 103 cases of LTG for patients with gastric cancer between 2007 and 2013, in which all esophagojejunostomy reconstruction was performed with intracorporeal circular stapling esophagojejunostomy using the OrVil system except for the first 3 cases. The purpose of this study is to retrospectively analyze the clinical usefulness of LTG with intracorporeal circular stapling esophagojejunostomy using the OrVil system and oncological feasibility of LTG as compared with open total gastrectomy (OTG). Patients and Method: We retrospectively analyzed clinical course of consecutive 100 operations with LTG in comparison with consecutive 53 operations with OTG for patients with gastric cancer. As an estimation of short-term outcome, operative time, blood loss, postoperative hospital days and postoperative data of blood and drain examination were included. Moreover, relapse-free survival time and overall survival time stratified by each stage were calculated by log-rank test as an estimation of prognostic relevance. Results: Blood loss and postoperative hospital stay of LTG were significantly less than that of OTG. Postoperative complications were equivalent between the 2 groups and no patient died within 1 month post-LTG. Only 1 patient had recurrence and died for carcinomatosa peritonitis 50 months after LTG (median follow-up period: 44 mo). Conclusions: Our experience revealed that LTG with intracorporeal circular stapling esophagojejunostomy using the OrVil system could be performed safely and with acceptable oncological outcome for patients with gastric cancer.

Pre-pyloric site gastric cancer after pylorus- preserving gastrectomy (PPG): A case report

Pylorus-preserving gastrectomy (PPG) is a function-preserving surgical procedure which is now applied to treat early gastric cancer in the mid-portion of the stomach. We report a patient who developed a pre-pyloric site gastric cancer after PPG. To our knowledge, this is the first report on the development of pre-pyloric site gastric cancer after PPG in the English literature using PubMed.