Expression of alpha smooth muscle actin in living donor liver transplant recipients

Recently, there have been reports from liver biopsies that showed the progression of liver fibrosis in liver transplant patients after the cessation of immunosuppression. Herein, we focused on activated hepatic stellate cells expressing alpha smooth muscle actin (α-SMA) to understand the correlation between immunosuppressant medication and liver fibrosis. The study enrolled two pediatric patients who underwent living donor liver transplantation and ceased immunosuppressant therapy. The number of α-SMA-positive cells in the specimens obtained by liver biopsy from these two patients showed a three-fold increase compared with the number from four transplanted pediatric patients who were continuing immunosuppressant therapy. In addition, the α-SMA-positive area evaluated using the Win- RooF image processing software program continued to increase over time in three adult transplanted patients with liver fibrosis, and the α-SMA-positive area was increasing even during the pre-fibrotic stage in these adult cases, according to a retrospective review. Therefore, α-SMA could be a useful marker for the detection of early stage fibrosis

Decreased Expression of SOX9 in Intraductal Papillary Mucinous Neoplasms of the Bile Duct

Background/Aims: SOX9 is an important transcription factor required for development and has been implicated in several types of malignant tumor. Our recent study showed that SOX9 played an important role in multi-step carcinogenesis in cases of intraductal papillary mucinous tumor of the pancreas (IPMN-P). This study aimed to investigate the expression of SOX9 in cases of intraductal papillary mucinous tumor of the bile duct (IPMN-B). Methodology: SOX9 expression was immunohistochemically evaluated in the tumor and corresponding normal bile-duct epithelium of seven IPMN-B patients. Results: In all cases, SOX9 expression in the IPMN-B was low compared with the normal biliary epithelium. Conclusions: This study demonstrated that SOX9 expression may indicate a link between IPMN-B and IPMN-P. SOX9 may also have potential as a therapeutic target and/or prognostic marker in IPMN-B

Laparoscopic spleen-preserving distal pancreatectomy with and without splenic vessel preservation: The role of the Warshaw procedure

Background/objectives: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) for low-grade malignant pancreas tumors was recently demonstrated. Although the procedure with splenic vessel preservation (SVP) is optimal for LSPDP, SVP is not always possible in patients with a large tumor or a tumor attached to splenic vessels. This study aimed to analyze the safety of two procedures: LSPDP without SVP, known as the Warshaw technique (lap-WT), and LSPDP with SVP (lap-SVP). Methods: Seventeen patients who underwent a lap-WT and seven patients who underwent a lap-SVP were investigated retrospectively. Results: The median follow-up duration was 45 (range 17-105) months. In the lap-WT and lap-SVP patients, the sizes of the tumors were 5 (1.3-12) and 1.5 (1-4) cm; the operative times were 304 (168-512) and 319 (238-387) min; the blood loss was 210 (5-3250) and 60 (9-210) gr; the length of the postoperative hospital stay was 15 (8-29) and 18 (5-24) days; the peak platelet counts were 37.2 (14.6 -65.2) and 26.4 (18.8-41) × 104/μL, and splenomegaly was observed in 10 (59%) and three (43%) patients, respectively. In both procedures, there was no local recurrence. In the lap-WT group, splenic infarctions were seen in four (24%) patients and perigastric varices were seen in two (12%) patients. All of these patients were observed conservatively. Conclusions: Both the lap-WT and lap-SVP were found to be safe and effective, and in cases in which the tumor is relatively large or close to the splenic vessels, lap-WT can be used as the more appropriate procedure

Safety and efficacy of early drain removal and triple-drug therapy to prevent pancreatic fistula after distal pancreatectomy

Objective Prior studies suggested that early drain removal prevented the development of pancreatic fistula (PF) after pancreaticoduodenectomy (PD), but there has been no corresponding prospective trial for distal pancreatectomy (DP). The purpose of this study was to determine the safety and efficacy of early drain removal and triple-drug therapy (TDT) with gabexate mesilate, octreotide and carbapenem antibiotics to prevent PF after DP in patients at high-risk of developing PF. Methods A total 71 patients who underwent a DP were enrolled. We prospectively divided them into two groups: the late-removal group, in which the drain remained in place for at least for 5 days postoperatively (n = 30) and the early-removal group in which the drain was removed on postoperative day 1 (POD1) (n = 41). For the patients with a high drain amylase level (?10,000 IU/L) and patients with symptomatic intraperitoneal fluid collection, our original TDT was introduced. The primary endpoint was the safety and efficacy of this management, and the secondary endpoint was the incidence of PF. Results The incidence of clinical PF was significantly lower in the early-removal group (0% vs. The late removal 16%; p < 0.001). In the early-removal group, TDT was administered to 12 patients (29%) and none of the patients needed additional treatment after TDT. Conclusions Postoperative management after DP with early drain removal and TDT was safe and effective for preventing PF

Endoscopic transpapillary pancreatic stenting for internal pancreatic fistula with the disruption of the pancreatic ductal system

Background: Internal pancreatic fistula (IPF) is a well-recognized complication of pancreatic diseases. Although there have been many reports concerning IPF, the therapy for IPF still remains controversial. We herein report our experiences with endoscopic transpapillary pancreatic stent therapy for IPF and evaluate its validity. Method: Six patients with IPF who presented at our department and received endoscopic transpapillary pancreatic stent therapy were investigated, focusing on the clinical and imaging features as well as treatment strategies, the response to therapy and the outcome. Results: All patients were complicated with stenosis or obstruction of the main pancreatic duct, and in these cases the pancreatic ductal disruption developed distal to the areas of pancreatic stricture. The sites of pancreatic ductal disruption were the pancreatic body in five patients and the pancreatic tail in one patient. All patients received endoscopic stent placement over the stenosis site of the pancreatic duct. Three patients improved completely and one patient improved temporarily. Finally, three patients underwent surgical treatment for IPF. All patients have maintained a good course without a recurrence of IPF. Conclusion: Endoscopic transpapillary pancreatic stent therapy may be an appropriate first-line treatment to be considered before surgical treatment. The point of stenting for IPF is to place a stent over the stenosis site of the pancreatic duct to reduce the pancreatic ductal pressure and the pseudocyst\u27s pressure

Increased expression of PHD3 represses the HIF-1 signaling pathway and contributes to poor neovascularization in pancreatic ductal adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is known as one of the most malignant potential diseases with poor neovascularization. By comparing PDAC to hepatocellular carcinoma (HCC), which is well vascularized, we investigated the mechanisms and tumor biological significance of the poor neovascularization in PDAC. Methods: Surgical specimens from primary PDAC and HCC patients were immunohistologically stained to detect the expressions of CD105, CD44, HIF-1α, PHD3, and Siah2. We also used two PDAC and two HCC cell lines to compare the expressions of HIF-1α, PHD3, and CD44, as well as the production of VEGF in hypoxic condition. The role of PHD3 in regulating HIF-1α expression was further confirmed by siRNA knockdown in a PDAC cell line that highly expressed PHD3. Results: There were significantly fewer microvessels but more cancer stem cells in PDAC specimens compared to HCC specimens. The expression of CD105 was reversely related to the expression of CD44 in PDAC and HCC specimens. PDAC specimens also showed higher expressions of PHD3 but lower expressions of HIF-1α. Similarly, the expression of PHD3 was observed clearly in PDAC cell lines, but was almost completely negative in HCC cell lines. Hypoxic stimulation clearly enhanced HIF-1α expression and VEGF secretion in both HCC cell lines, but did not significantly change in PDAC cell lines. The knockdown of PHD3 in PDAC cells restored the hypoxic-induced HIF-1α expression, which accordingly stimulated the cells’ VEGF secretion. Conclusions: The enhanced expression of PHD3 might likely contribute to the poor neovascularization and affect the biological characterization in PDAC cancer cells

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

Combined Resection for Multifocal Lesions of the Pancreas

Background/Aims: Multifocal lesions of the pancreas generally require a total pancreatectomy. However, total pancreatectomy causes severe and permanent pancreatic endocrine and exocrine insufficiency. The aim of this study was to review our experiences of combined resection of the pancreas as an alternative to total pancreatectomy. Methodology: From July 2004 to July 2011, 5 patients were indicated to undergo combined resection for multiple lesions of the pancreas at our institution. Results: The surgical procedures for combined resection of the pancreas in the 5 patients consisted of various limited resections of the pancreas. No patient developed insulin-dependent diabetes mellitus. In addition, no patient developed exocrine insufficiency after pancreatic resection. Conclusions: For multifocal lesions of the pancreas, combined resection of the pancreas should be considered the surgical procedure of choice to reduce the risk of both endocrine and exocrine insufficiency