Clinical Significance of Recurrence Risk Score for Conversion Surgery in Patients With Advanced Gastric Cancer.

BACKGROUND/AIM: To develop a recurrence risk score for determining the clinical indication for adjuvant chemotherapy in patients with initially unresectable advanced gastric cancer who underwent conversion surgery after chemotherapy. PATIENTS AND METHODS: A total of 65 patients with stage IV gastric cancer who underwent conversion surgery after chemotherapy were retrospectively enrolled. We established a risk score based on clinicopathological factors related to recurrence after conversion surgery. RESULTS: Out of 65 patients, 40 (62%) had recurrence after conversion surgery. The 5-year overall survival rates in patients with and without recurrence were 14.4% and 87.1%, respectively (p<0.01). Multivariate logistic regression analysis identified the depth of tumor invasion (pT2-4) and histological tumor response (grade 0-1a) as an independent risk factor for disease recurrence (p=0.033 and p=0.048, respectively). A scoring system determined by these two factors was created; total score ranged from 0 to 2 points, and patients were categorized into three groups (scores of 0 vs. 1 vs. 2 points). This scoring system showed that 12 (18%), 15 (23%), and 38 (58%) patients had recurrence risk scores of 0, 1, and 2 points, respectively. There was a close relationship between a high score and the presence of tumor recurrence (p<0.01). Moreover, our model system had a high sensitivity for the prediction of recurrence, compared with the pathological stage. CONCLUSION: Recurrence risk score is a promising tool for assessing the need for adjuvant chemotherapy in patients with initially unresectable advanced gastric cancer after conversion surgery.

Triple-drug therapy to prevent pancreatic fistula after pancreatectomy in a rat model.

BACKGROUND: Pancreatic fistula (PF) is one of post-operative complications in pancreatic surgery, but there is no consensus about the optimal treatment for PF. Our group has established a rat model of PF, and we conducted the present investigation to determine the efficacy of the triple-drug therapy (somatostatin analogue, gabexate mesilate, and imipenem/cilastatin) against PF using our rat model. METHODS: In the PF rat model, the triple-drug therapy was administered to the treated (T) group (n = 4), and we compared the results with those of a control (C) group (n = 4). The rats were sacrificed on postoperative day 3 (POD 3) and the levels of amylase and lipase in serum and ascites were measured. The intra-abdominal adhesion was scored. Each pancreas was evaluated pathologically, and inflammation was scored. RESULTS: The ascitic amylase levels on POD 3 were 1982 (1738-2249) IU/L in the C group and significantly lower at 136 (101-198) IU/L in the T group (p = 0.02). The ascitic lipase levels on POD 3 were 406 (265-478) U/L in the C group and significantly lower at 13 (7-17) U/L in the T group (p = 0.02). The intra-abdominal adhesion score on POD 3 was 2 (1-2) in the C group and significantly lower at 0 (0-1) in the T group (p = 0.02). The histological evaluation showed that the average of pancreatic inflammatory score was 8.5 (8-9) in the C group and significantly milder at 5 (5-7) in the T group (p = 0.01). CONCLUSION: Our findings suggest that the triple-drug therapy could be useful as a treatment for PF in clinical settings.

Human Fibroblast Sheet Promotes Human Pancreatic Islet Survival and Function In Vitro.

In previous work, we engineered functional cell sheets using bone marrow-derived mesenchymal stem cells (BM-MSCs) to promote islet graft survival. In the present study, we hypothesized that a cell sheet using dermal fibroblasts could be an alternative to MSCs, and then we aimed to evaluate the effects of this cell sheet on the functional viability of human islets. Fibroblast sheets were fabricated using temperature-responsive culture dishes. Human islets were seeded onto fibroblast sheets. The efficacy of the fibroblast sheets was evaluated by dividing islets into three groups: the islets-alone group, the coculture with fibroblasts group, and the islet culture on fibroblast sheet group. The ultrastructure of the islets cultured on each fibroblast sheet was examined by electron microscopy. The fibroblast sheet expression of fibronectin (as a component of the extracellular matrix) was quantified by Western blotting. After 3 days of culture, islet viabilities were 70.2 ± 9.8%, 87.4 ± 5.8%, and 88.6 ± 4.5%, and survival rates were 60.3 ± 6.8%, 65.3 ± 3.0%, and 75.8 ± 5.6%, respectively. Insulin secretions in response to high-glucose stimulation were 5.1 ± 1.6, 9.4 ± 3.8, and 23.5 ± 12.4 µIU/islet, and interleukin-6 (IL-6) secretions were 3.0 ± 0.7, 5.1 ± 1.2, and 7.3 ± 1.0 ng/day, respectively. Islets were found to incorporate into the fibroblast sheets while maintaining a three-dimensional structure and well-preserved extracellular matrix. The fibroblast sheets exhibited a higher expression of fibronectin compared to fibroblasts alone. In conclusion, human dermal fibroblast sheets fabricated by tissue-engineering techniques could provide an optimal substrate for human islets, as a source of cytokines and extracellular matrix.

Sox9 expression in carcinogenesis and its clinical significance in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinomas develop through a multi-step carcinogenesis. Precancerous lesions are defined as biliary intraepithelial neoplasia. Sex determining region Y-box9 (Sox9) is required for the normal differentiation of the biliary tract. AIMS: To evaluate the Sox9 expression in carcinogenesis and its correlation with clinicopathological features in intrahepatic cholangiocarcinoma. METHODS: Sox9 expression in normal epithelium, biliary intraepithelial neoplasia, and intrahepatic cholangiocarcinoma were investigated immunohistochemically using 43 specimens of intrahepatic cholangiocarcinoma. Sox9 expression in intrahepatic cholangiocarcinoma was compared with the clinicopathological features. The molecular effects of Sox9 were investigated by gene transfection to intrahepatic cholangiocarcinoma cell lines. RESULTS: Sox9 expression was decreased from the normal epithelium to the biliary intraepithelial neoplasia in a stepwise fashion. In 51.2% (22/43) of the patients with intrahepatic cholangiocarcinoma, Sox9 expression was positive, and Sox9 expression was significantly associated with the biliary infiltration (P=0.034) and poor overall survival (P=0.039). Upregulation of Sox9 promoted the cell migration and invasion, and decreased the E-cadherin expression and increased the vimentin and α-SMA expression in cell lines. CONCLUSIONS: Decreased Sox9 expression may be related to the early stage of the carcinogenesis of intrahepatic cholangiocarcinoma. Sox9 overexpression in intrahepatic cholangiocarcinoma is related to biliary infiltration and poorer prognosis, and it promotes cell migration and invasion, via the epithelial-to-mesenchymal transition.