Tatsushi Shingai

Antagonistic and agonistic effects of an extracellular fragment of nectin on formation of E-cadherin-based cell-cell adhesion

Background: Nectin is a Ca2+‐independent immunoglobulin‐like cell‐cell adhesion molecule at the E‐cadherin‐based cell‐cell adherens junctions (AJs), and comprises a family consisting of four members, nectin‐1, ‐2, ‐3, and ‐4. Nectin and E‐cadherin are associated with afadin and α‐catenin, actin filament (F‐actin)‐binding proteins connecting respective adhesion molecules to the actin cytoskeleton, but the role of nectin in the formation of the E‐cadherin‐based cell‐cell AJs has not yet been fully understood. To obtain evidence for this role of nectin, we attempted to develop an antagonist and/or agonist of nectin.

Preoperative chemoradiation reduces the risk of pancreatic fistula after distal pancreatectomy for pancreatic adenocarcinoma

BACKGROUND Pancreatic fistula (PF) is a common complication after pancreatectomy. Previous reports indicate that preoperative irradiation decreases the risk of PF after pancreatoduodenectomy. In this context, the impact of preoperative chemoradiation therapy (CRT) on PF formation after distal pancreatectomy is of interest. METHODS Fifty-eight patients with pancreatic adenocarcinoma who underwent distal pancreatectomy, including 28 patients with preoperative gemcitabine-based CRT and 30 patients without preoperative treatment, were assessed in this study. The incidence and severity of postoperative PF, assessed according to the definition of the International Study Group on Pancreatic Fistula, were compared between the 2 groups. RESULTS In the CRT group, 86% of patients did not develop PF, whereas grades A and B PF were observed in 1 and 3 patients, respectively. In the non-CRT group, 33% of patients did not develop a PF, whereas grades A and B PF were observed in 9 and 11 patients, respectively. The incidence of clinically significant PF, defined as either grade B or grade C PF, was less in the CRT group (P = .031). The amylase activities in the draining fluid on postoperative days 1 and 3 were both less in the CRT group (P = .003 and P = .006, respectively). CONCLUSION Preoperative CRT significantly decreases the incidence of PF after distal pancreatectomy, which potentially provides another benefit to patients in addition to its original advantages (ie, locoregional effect and patient selection effect), allowing more opportunities for the immediate initiation of postoperative adjuvant treatment.

Staging laparoscopy using ALA‐mediated photodynamic diagnosis improves the detection of peritoneal metastases in advanced gastric cancer

This study evaluated the usefulness of photodynamic diagnosis (PDD) using oral 5‐aminolevulinic acid (ALA) for the detection of peritoneal metastases in advanced gastric cancer.

Brain metastasis from colorectal cancer: prognostic factors and survival.

Colorectal cancer (CRC) rarely metastasizes to the brain, and the incidence rate has been reported to be 1–2%. Unfortunately, the median survival for patients with brain metastasis (BM) from CRC is short. In this study, we retrospectively investigated the BM from CRC and examined the prognostic factors.

Outcome of surgical resection for recurrent pulmonary metastasis from colorectal carcinoma.

BACKGROUND The outcomes after repeat pulmonary resection for colorectal cancer (CRC) and the factors associated with the prognosis of these patients remain uncharacterized. METHODS Data on 156 patients who underwent curative resection of pulmonary metastasis from CRC were reviewed. Repeat pulmonary resection was performed in 25 patients; the present study examined the outcomes and factors associated with prognosis after repeat pulmonary resection. RESULTS The 5-year survival rate after the first pulmonary resection was 56.2%. A multivariate analysis identified a histological type other than well-differentiated adenocarcinoma, a high prethoracotomy serum carcinoembryonic antigen (CEA) level, and the presence of hilar or mediastinal lymph node metastasis as poor prognostic factors for the first pulmonary resection. The 5-year survival rate after repeat pulmonary resection was 42.1%. Hilar or mediastinal lymph node metastasis at the time of the repeat resection was significantly associated with poor survival. CONCLUSIONS Repeat pulmonary resection for metastatic CRC provides satisfactory outcomes. Hilar or mediastinal lymph node involvement is consistently associated with a poor prognosis after the first and repeat pulmonary resections.

A novel rabconnectin‐3‐binding protein that directly binds a GDP/GTP exchange protein for Rab3A small G protein implicated in Ca2+‐dependent exocytosis of neurotransmitter

Background: Rab3A, a member of the Rab3 small G protein family, regulates Ca2+‐dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP‐Rab3A is activated to GTP‐Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP) and GTP‐Rab3A is inactivated to GDP‐Rab3A by Rab3 GTPase‐activating protein (Rab3 GAP). We have recently found a novel protein, named rabconnectin‐3, which is co‐immunoprecipitated with Rab3 GEP or GAP from the extract of the crude synaptic vesicle (CSV) fraction of rat brain. Rabconnectin‐3 is abundantly expressed in the brain where it is associated with synaptic vesicles. We have found that two more proteins are co‐immunoprecipitated with Rab3 GEP from the CSV fraction of rat brain. We attempted here to isolate and characterize one of them.

Comparison Between Radical Esophagectomy and Definitive Chemoradiotherapy in Patients with Clinical T1bN0M0 Esophageal Cancer

BackgroundEsophagectomy remains the mainstay treatment for clinical T1bN0M0 esophageal cancer because pathologic lymph node metastases in these patients are not negligible. Recently, chemoradiotherapy (CRT), which can preserve the esophagus, has been reported to be a promising therapeutic alternative to esophagectomy. However, to our knowledge, no comparative studies of esophagectomy and CRT have been reported in clinical T1bN0M0 esophageal cancer.MethodsA total of 173 patients with clinical T1bN0M0 squamous cell carcinoma of the thoracic esophagus were enrolled in this study, 102 of whom were treated with radical esophagectomy (S group) and 71 with definitive CRT (CRT group). Treatment results of both groups were retrospectively compared.ResultsNo statistically significant difference was found in overall survival, but the S group displayed significantly better progression-free survival than the CRT group. Disease recurrence was observed in 12 S group patients and 20 CRT group patients. The incidence of distant recurrence was similar, while local recurrence and lymph node recurrence were significantly more frequent in the CRT group. In the S group, 20 patients had pathologic lymph node metastasis. The progression-free survival of patients with pathologic lymph node metastasis did not differ from those without nodal metastasis. In the CRT group, local recurrence could be controlled by salvage esophagectomy, but treatment results of lymph node recurrence were poor; only 4 of 12 patients with lymph node recurrences were cured.ConclusionsSelection of patients at high risk of pathologic lymph node metastasis is essential when formulating treatment decisions for clinical T1bN0M0 esophageal cancers.

Impact of metastatic lymph node ratio in node-positive colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant diseases in the world. Presently, the most widely used staging system for CRC is the tumor nodes metastasis classification system, which classifies patients into prognostic groups according to the depth of the primary tumor, presence of regional lymph node (LN) metastases, and evidence of distant metastatic spread. The number of LNs with confirmed metastasis is related to the severity of the disease, but this number depends on the number of LNs retrieved, which varies depending on patient age, tumor grade, surgical extent, and tumor site. Numerous studies and a recent structured review have demonstrated associated improvements in the survival of CRC patients with increasing numbers of LNs retrieved for examination. Hence, the impact of lymph node ratio (LNR), defined as the number of metastatic LNs divided by the number of LNs retrieved, has been investigated in various malignancies, including CRC. In this editorial, we review the literature demonstrating the clinicopathological significance of LNR in CRC patients. Some reports have indicated the advantage of considering the LNR compared to the number of LNs retrieved and/or LN status. When the LNR is taken into consideration for survival analysis, the number of LNs retrieved and/or the LN status is not always found to be a prognostic factor. The cut-off points for LNRs were proposed in numerous studies. However, optimal thresholds for LNRs have not yet received consensus. It is still unclear whether the LNR has more prognostic validity than N stage. For all these reasons, the potential advantages of LNRs in the staging system should be investigated in large prospective data sets.

Significance of the resection of ovarian metastasis from colorectal cancers.

The incidence of ovarian metastases from colorectal cancers (CRCs) has been reported to occur in 3–8% of CRC patients, and the prognosis for patients is very poor. We assessed the clinicopathological characteristics of CRC patients with ovarian metastasis and the significance of the resection of ovarian metastases.

Subtotal gastrectomy for gastric tube cancer after esophagectomy: A safe procedure preserving the proximal part of gastric tube based on intraoperative ICG blood flow evaluation

Recent improvements in the survival of patients after esophagectomy have led to an increase in the occurrence of gastric tube cancer (GTC). Total resection of the gastric tube with lymphadenectomy is a standard and reliable treatment for GTC, but problems may arise during or after surgery, such as laryngeal nerve injury, reduced selection of organs for reconstruction, and impaired swallowing function. We recently performed a less invasive procedure, subtotal gastrectomy with preservation of the upper region of the gastric tube, in two patients. In these patients, blood supply to the gastric tube was evaluated by indocyanine green fluorescence imaging. Blood flow was confirmed as passing from the remnant esophagus to the upper region of the gastric tube through the esophago‐gastric anastomotic site by indocyanine green fluorescence imaging. Therefore, we resected the gastric tube while preserving the upper region of the gastric tube. There was no necrosis of the remnant gastric tube or anastomotic leakage postoperatively, and postoperative swallowing and eating functions were quite good in both patients. In summary, subtotal gastrectomy as a treatment for GTC is potentially safe, curative, and beneficial for the patients quality of life. J. Surg. Oncol. 2012; 106:107–110.