Norio Mitsumori

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.

Sentinel node mapping with indocyanine green (ICG) and infrared ray detection in early gastric cancer: An accurate method that enables a limited lymphadenectomy

AIM This study compares lymphatic mapping in early gastric cancer with ICG and infrared ray electronic endoscopy (IREE) to ICG alone. It examines the optimal method for intra-operative detection of metastases and shows long term follow up results. METHODS 212 patients underwent the SN procedure with IREE and peritumoural ICG injection. Evaluated parameters were detection of sentinel nodes with IREE versus ICG alone, intra-operative detection rate of lymph node (LN) metastasis with node picking versus lymphatic basin dissection (LBD) and lymphatic drainage patterns. RESULTS 34 patients had LN metastases. The SN identification rate and sensitivity for IREE versus ICG alone were 99.5 versus 85.8% and 97.0 versus 48.4% respectively. Intra-operative accuracy for detecting LN metastasis was 50% with node picking versus 92.3% with LBD. LN metastases were always in the SN basin. Lymphatic invasion and T-stage were risk factors for nodal metastases. Two patients showed recurrent disease. Both had a tumour with signet cell differentiation. One patient had a T3 tumour, the other patient had a tumour with a diameter of 85 mm. CONCLUSION The SN procedure with IREE can detect the SN and is better than ICG alone. LBD of the SN basin is required for accurate intra-operative diagnosis of metastases. LBD dissection based on IREE is a safe method of nodal dissection in patients with T1 or limited T2 tumours.

The advantages and disadvantages of a Roux-en-Y reconstruction after a distal gastrectomy for gastric cancer

In Japan, the Billroth I and Billroth II operations have been used for reconstruction after a distal gastrectomy for gastric cancer. However, a Roux-en-Y reconstruction is increasingly performed to prevent duodenogastric reflux. We herein discuss the indications for Roux-en-Y in gastric surgery and review the literature to determine its advantages and disadvantages. Indications for Roux-en-Y reconstruction after a distal gastrectomy are: (a) When the primary lesion has directly invaded the duodenum or head of the pancreas, the Billroth I operation is likely to result in local recurrence near the anastomosis; (b) in addition, the Billroth I operation is not indicated after a subtotal gastrectomy due to an unacceptable anastomotic tension; reconstruction using a nonphysiological route is therefore preferred. The advantages of Roux-en-Y reconstruction after a distal gastrectomy include a reduction of reflux gastritis and esophagitis, a decreased probability of gastric cancer recurrence, and a reduction in the incidence of surgical complications such as ruptured suture lines. The disadvantages of Roux-en-Y reconstruction include the possible development of stomal ulcer, an increased probability of cholelithiasis, increased difficulty with an endoscopic approach to the ampulla of Vater, and the possibility of Roux stasis syndrome. The principal advantage of a Roux-en-Y reconstruction is that it is less likely than the Billroth I operation to result in duodenogastric reflux. Roux-en-Y reconstruction or Billroth I operation can only be selected after considering their respective advantages and disadvantages.

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.