Hiroshi Nimura

Infrared ray electronic endoscopy combined with indocyanine green injection for detection of sentinel nodes of patients with gastric cancer.

To avoid unnecessary lymphadenectomy in patients with cancer accurate diagnosis of the sentinel lymph node (SLN) is important.

Validity of modified gastrectomy combined with sentinel node navigation surgery for early gastric cancer

BackgroundThe present study examined the clinical validity of modified gastrectomy for early gastric cancer, in terms of the results of sentinel node navigation surgery (SNNS), using infrared ray electronic endoscopy (IREE) plus indocyanine green (ICG) staining.MethodsOne-hundred and sixty-one patients with fT1N0 gastric cancer were enrolled in the study. ICG (0.5 ml, 5 mg/ml) was injected endoscopically into four quadrants of the submucosa surrounding the cancer. Twenty minutes after the injection, sentinel lymph nodes (SNs) stained with ICG were observed intraperitoneally around the serosa and surrounding fat tissue. IREE was used to illuminate regional lymph nodes from the serosal side.ResultsGroup 2 lymph nodes were judged as SNs in 52 patients (32%). The most common locations of the SNs were stations No. 7 in each of the upper-, middle-, and lower-thirds of the stomach. In two patients, lymph node metastasis was positive. One of these patients, with cancer in the middle one-third of the stomach, had SNs in stations No. 3, 4sb, 4d, 7, and No. 11p, and had metastatic lymph nodes in No. 3 and No. 7 (all SNs). The other patient, with cancer in the lower one-third of the stomach, had SNs in No. 1, 3, 4d, and 6, and had a metastatic lymph node in No. 4d (SN). Skip metastasis was not observed in this study, and metastatic lymph nodes were judged to have been dissected by the D1+a procedure.ConclusionFor T1N0 gastric cancer, modified gastrectomy (D1+a dissection) combined with SNNS is suitable; however, for those whose Group 2 lymph nodes are judged to be SNs, additional dissection of lymphatic basins detected by SNNS should be performed to confirm the absence of lymph node metastasis.

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.

The possibility of performing a limited resection and a lymphadenectomy for proximal gastric carcinoma based on sentinel node navigation

PurposeThis study examined the possibility of performing a limited resection and a lymphadenectomy with sentinel node navigation surgery (SNNS) for the treatment of proximal gastric carcinoma.MethodsThirty patients with cT1N0 (n = 23) and cT2N0 (n = 7) proximal gastric carcinoma that was located primarily in the U area (the upper third of the stomach) were enrolled. indocyanine green (ICG; 0.5 ml) was injected endoscopically into the submucosa of the four quadrants encompassing the cancer. Twenty minutes after injection, infrared ray electronic endoscopy (IREE) was used to identify the lymph nodes that were stained with ICG (sentinel nodes, SNs) around the serosa and surrounding fat tissue.ResultsOne hundred percent of the SNs were identified with our SNNS method. The most common location of SNs was No. 3 (T1: 78%, T2: 100%). The main route of lymphatic drainage was from No. 1 or No. 3 to No. 7 (T1: 95%, T2: 100%). In T1 cancer, Indocyanine green was not distributed to the right gastric area, and no patients had SNs in No. 5 or No. 8a. Four cT2 cancer patients had lymph node metastases, all of which were SNs. There were no cases of postoperative metastasis or recurrence.ConclusionsFor the cT1 proximal gastric carcinoma patients, limited dissection of the ICG tracer-positive lymphatic areas alone by SNNS using IREE may be acceptable. The main lymphatic drainage route of proximal gastric carcinoma is the left gastric artery area (Nos. 1, 3, and No. 7) and dissection of this area is important.

Recurrent gastrointestinal stromal tumor (GIST) of the stomach associated with a novel c-kit mutation after imatinib treatment

A 57-year-old man with gastrointestinal stromal tumor (GIST) of the stomach with peritoneal dissemination underwent gastrectomy. After surgery, he was treated with 400 mg/day of imatinib, without recurrence, for 26 months. At 26 months, the imatinib dose was reduced because of nausea, and 4 months after the dose reduction, recurrence of GIST was detected, for which surgical resection was performed again. The first surgical specimen had a mutation of exon 11 in the c-kit receptor gene. Intriguingly, the second surgical specimen had a novel mutation of exon 17, in addition to the above-mentioned mutation, in the c-kit receptor gene. Based on the result of molecular analysis, the novel mutation of exon 17, induced by longterm chemotherapy, was judged to have been responsible for the recurrence, which perhaps was triggered by the dose reduction of imatinib.

Tailoring treatment for early gastric cancer after endoscopic resection using sentinel node navigation with infrared ray electronic endoscopy combined with indocyanine green injection.

Background: This study evaluated the efficacy of sentinel node navigation surgery using infrared ray electronic endoscopy (IREE) combined with indocyanine green in patients after endoscopic treatments of early gastric cancer. Methods: 14 patients with early gastric cancer after endoscopic treatments were included. Each patient underwent sentinel node navigation surgery using IREE. Sentinel node detection rate, accuracy of sentinel node metastases and clinical efficacy including the presence or absence of recurrence were evaluated. Results: The intraoperative sentinel node detection rate was 100% (14/14), and accuracy for sentinel node metastases was 93% (13/14). Based on the results of sentinel node mapping, 2 patients received standard gastrectomy with D2 lymphadenectomy, and the remaining 12 patients underwent limited surgery with lymphatic basin dissection. After median follow-up of 32 months, no patients had tumor recurrence. Conclusion: The validity of limited surgery based on sentinel node navigation for early gastric cancer remains unclear because the results of a well-designed multicenter clinical trial of sentinel node mapping for gastric cancer have not yet been reported. However, this study suggests that sentinel node navigation surgery using IREE combined with indocyanine green is useful for early gastric cancer after endoscopic resection.

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.

Where Does the First Lateral Pelvic Lymph Node Receive Drainage from

Background: Lateral pelvic lymph node dissection (LPLD) in the treatment of rectal cancer has risks and benefits. Avoidance of unnecessary LPLD is important, however, preoperative and/or intraoperative accurate detection of lateral lymph node metastases have not been established. If the lateral lymph node to which the fluid first spread from the primary lower rectal cancer is detected accurately, it may guide the need for LPLD and may assist in avoiding unnecessary dissection. Methods: A total of 14 patients with T3 lower rectal cancer were evaluated to locate the lymph nodes through which indocyanine green (ICG) reached the lymphatics. After ICG was injected into the lower rectum via an endoscope preoperatively, total mesorectal excision was first performed, and LPLD was performed with infrared ray electronic endoscopy (IREE) to assess the degree of retention of ICG in each regional lymph node. Results: Drainage of ICG to lateral pelvic lymph nodes was observed in 6 of 14 patients (43%). All ICG-containing lymph nodes were detected by IREE. When present, lateral pelvic wall lymph node drainage was limited exclusively to the peri-internal iliac artery nodes. No obturator nodes were involved. Conclusion: The first lateral lymph node that receives lymphatic drainage from lower rectal cancer is located around the internal iliac arteries.