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.

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) × 10(4)/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.

A selective cyclooxygenase-2 inhibitor (Etodolac) prevents spontaneous biliary tumorigenesis in a hamster bilioenterostomy model.

BACKGROUND: Secondary biliary carcinomas are associated with persistent reflux cholangitis after bilioenterostomy. Cyclooxygenase-2 (COX-2) has been a target for cancer prevention. The aim of this study was to evaluate the chemopreventive efficacy of long-term treatment with a selective COX-2 inhibitor medication during the natural course after bilioenterostomy without chemical induction. METHODS: Syrian golden hamsters which underwent choledochojejunostomy were randomly divided into two groups: the control group (n = 31), which was fed a normal diet, and the etodolac group (n = 33), which was fed 0.01% etodolac (a selective COX-2 inhibitor) mixed in the meal. The hamsters were killed at the postoperative weeks 20-39, 40-59, 60-79, or 80-100. Biliary neoplasms, cholangitis, proliferating cell nuclear antigen labeling index (PCNA-LI) of the biliary epithelium, and prostaglandin E2 (PGE2) production were evaluated. RESULTS: The occurrence rates of biliary neoplasm were 43.8 and 15.2% in the control and etodolac groups, respectively (p < 0.05). The incidence of biliary neoplasm increased as time progressed in the control group, whereas it remained at a low level throughout the experimental period in the etodolac group. PGE2 products tended to be lower in the etodolac group, and PCNA-LI was significantly lower in the etodolac group (p < 0.01). These results suggest that the medication etodolac suppresses cell proliferation of the biliary epithelium, thereby preventing biliary carcinogenesis. CONCLUSIONS: Etodolac is expected to prevent secondary biliary carcinogenesis caused by persistent reflux cholangitis after bilioenterostomy.

Learning Curve for Laparoscopic Pancreaticoduodenectomy: A Single Surgeon's Experience with Consecutive Patients.

BACKGROUND/AIMS: Laparoscopic pancreaticoduodenectomy (LPD) is regarded as one of the most complex surgical procedures. The aim of this study was to examine a single surgeon's learning curve for LPD in consecutive cases. METHODOLOGY: Thirty consecutive patients who underwent an LPD by the same single surgeon were divided into three groups (A, B, and C; 10 cases each). Postoperative complications, operative time, and blood loss for each group were compared. RESULTS: There were no significant differences in the occurrence of postoperative complications among the groups. There were significant differences in both operative time and blood loss between groupA (mean operative time, 796.8 mm; mean blood loss 546.2 mL) and group B (mean operative time, 563.9 mm; mean blood loss 242.0 mL), and between groups A and C (mean operative time, 515.8 mm; mean blood loss 283.0 mL). Regarding operative time and blood loss, the surgeon reached a learning curve plateau after 10 cases/LPD procedures. CONCLUSIONS: LPD is a feasible and safe surgical procedure with a steep learning curve when performed by a surgeon who is experience in open PD, and LPD provides the advantages that would be expected from a minimally invasive surgery.

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's pressure.

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.

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.

Spontaneous pleural aspergillosis in an immunocompetent young adult treated with minimally invasive surgery.

Spontaneous cases of pleural aspergillosis in healthy adults are rare, and the optimal therapeutic approach has not been established. Here we report a rare case of spontaneous pleural aspergillosis in an otherwise healthy young adult. Two-stage surgery with decortication and cavernostomy, followed by systemic antifungal therapy, finally resulted in a successful resolution of his empyema without any serious complications. In young patients with good pulmonary compliance, less invasive procedures, such as thoracoscopic decortication and/or carvernotomy, is a potential treatment option.

Predictors and preventers of postoperative bedridden status in the elderly ages over 75 after emergency general surgery: a retrospective cohort study.

Aim: We investigated the proportion of bedridden patients after emergency surgery among the elderly ages over 75; defined as the latter-stage elderly in Japan, the associated factors, and interventions used to prevent it. Methods: Eighty-two latter-stage elderly patients who underwent emergency surgery for non-traumatic illness between January 2020 and June 2021 in our hospital were included in the study. Backgrounds and various perioperative factors were compared retrospectively between the groups including patients who became bedridden from Performance Status Scale 0 to 3 before admission (Bedridden group) and those who did not (Keep group). Results: Three cases of death and seven patients who were bedridden before admission were excluded. The 72 remaining patients were divided into the Bedridden group (n = 10, 13.9%) and the Keep group (n = 62, 86.1%). There were significant differences in the prevalence of dementia, pre- and postoperative circulatory dynamics, renal dysfunction, coagulation abnormality, length of stay in the high care unit/intensive care unit, and number of hospital days, with a relative risk of 13 (1.74-96.71), a sensitivity of 1.00, and a specificity of 0.67 for a preoperative shock index of 0.7 or higher being associated with the Bedridden group. Among patients with a preoperative shock index of 0.7 or higher, there was a significant difference in SI at 24 h postoperatively between the two groups. Conclusion: Preoperative shock index may be the most sensitive predictor. Early circulatory stabilization seems to be protective against patients becoming bedridden.

Simultaneous laparoscopic hand-assisted hepatectomy and splenectomy for liver cancer with hypersplenism: report of a case.

Hepatocellular carcinoma accompanied by portal hypertension and hypersplenism is difficult to treat medically and surgically due to pancytopenia and the development of collateral circulation. In this study, we were able to safely and simultaneously perform a laparoscopically-assisted splenectomy and partial hepatectomy. The characteristics of this procedure include: (1) the shared use of a medial wound made through laparoscopically-assisted surgery; (2) improved safety for manipulating areas that were difficult to observe with a camera in a case of splenomegaly; (3) a preventive ligation of the splenic artery; (4) improved hemostatic function using LigaSure Impact; and (5) hemorrhage control through manual manipulations and the Pringle maneuver during liver parenchymal transection. The surgery was safely performed using the above points.

The impact of antithrombotic therapy in patients undergoing emergency laparoscopic cholecystectomy for acute cholecystitis - A single center experience.

AIM: The risk of developing hemorrhagic complications during or after surgery in patients receiving antithrombotic therapy remains uncertain. Moreover, the impact of antithrombotic therapy under an acute inflammatory status is unclear. We investigated the impact of antithrombotic therapy in patients undergoing emergency laparoscopic cholecystectomy for acute cholecystitis. METHODS: This record-based retrospective study included patients who underwent emergency laparoscopic cholecystectomy for acute cholecystitis between September 2015 and January 2019. Patients who received elective laparoscopic cholecystectomy, open cholecystectomy, or gallbladder drainage before surgery were excluded. We evaluated the diseases for which antithrombotic therapy was administered, background characteristics, laboratory parameters and perioperative outcomes of patients with acute cholecystitis. The primary outcomes were intraoperative bleeding, blood transfusion requirement, conversion to an open procedure, and postoperative complications, including bleeding. RESULTS: One hundred and twenty-one patients (non-antithrombotic therapy, n = 92; antithrombotic therapy, n = 29) were analyzed. There were differences in age and American Association of Anesthesiologists class (P < .05), but not in the grade of acute cholecystitis (P = .19). There were no differences in the operation time (non-antithrombotic vs antithrombotic therapy: 142 [58-313] vs 146 minutes [65-373], P = .85), bleeding (17.5 mL [1-1400] vs 25 mL [1-1337], P = .58), blood transfusion requirement (n = 3 [3.2%] vs n = 2 [6.9%], P = .59) and the number of cases converted to open surgery (n = 8 [9%] vs n = 2 [7%], P = 1). The rates of postoperative complications, including bleeding, did not differ between the two groups and there was no mortality in either group. CONCLUSION: Emergency laparoscopic cholecystectomy could be planned for patients receiving single antithrombotic therapy, similar to patients who were not receiving antithrombotic therapy.

The Impact of Low Muscle Mass in Patients Undergoing Emergency Surgery for Colonic Perforation - A Single-center Experience.

AIM: The aim was to analyze the correlation between psoas muscle mass and mortality, as well as postoperative complications in patients treated for colonic perforation. PATIENTS AND METHODS: A total of 46 patients met the study criteria. Patients were classified into an elderly (age, ≥75 years, n=24) and a younger group (age, <75 years, n=22). Background factors, postoperative data (including duration of hospital stay and discharge) were collected. The cross-sectional area of the psoas muscle area (PMA) was measured on the same day of operation. RESULTS: The age/length of stay and PMA were significantly correlated in the younger group (p=0.0015, 0.023, respectively). Fifteen and six patients were discharged to return home, and 8 and 16 patients were transferred to another hospital, in the younger and elderly groups, respectively (p=0.02). Discharge was not correlated with the PMA in either group. CONCLUSION: The total psoas muscle mass would be useful as a quick and convenient measure of sarcopenia in younger patients, but not elderly patients.

Acute appendicitis associated with the presence of schistosome eggs in a sailor: a case report.

BACKGROUND: Schistosomiasis is prevalent in tropical and subtropical areas and rarely reported in developed countries. Schistosomiasis often occurs as a chronic illness, which can cause liver and intestinal damage. Appendicitis is an unusual complication of schistosomiasis. We herein present a case of acute appendicitis associated with the presence of schistosome eggs in a sailor from the Philippines. CASE PRESENTATION: A 34-year-old Filipino man who worked as a sailor presented to our hospital with a 2-day history of acute right lower quadrant abdominal pain and fever. A physical examination revealed right lower quadrant abdominal pain with signs of peritoneal irritation, including rebound tenderness. Computed tomography revealed thickening of the appendix associated with mural calcification and fluid collection around the cecum. Based on these findings, the preoperative diagnosis was acute appendicitis. Laparoscopic appendectomy was performed. Swelling of the appendix and contaminated ascites were observed intraoperatively, but there was no evidence of appendiceal perforation. A histopathological examination showed inflammation of the appendix wall and numerous ovoid bodies present within the submucosa, many of which were calcified. Severe infiltration of lymphocytes and fibrosis were recognized around the oval bodies. The numerous oval bodies were morphologically consistent with schistosomiasis. The final diagnosis was acute phlegmonous appendicitis associated with the presence of schistosome eggs. We examined the patient for signs of adult worm activity, but the results of stool ova and parasite examinations performed twice were negative. He was discharged and returned to his country on postoperative day 9. CONCLUSIONS: The incidence of schistosomal appendicitis, which is seldom reported in developed countries, is expected to increase in Japan in the near future. Clinicians should suspect schistosome eggs as a cause of acute appendicitis in patients who have emigrated from or are traveling from endemic areas, and when mural calcification of the appendix is observed on imaging.

Gallbladder small cell carcinoma: a case report and literature review.

Gallbladder small cell carcinoma (SCC) comprises only 0.5 % of all gallbladder cancer and consists of aggressive tumors with poor survival outcomes against current treatments. These tumors are most common in elderly females, particularly those with cholecystolithiasis. We report the case of a 79-year-old woman with gallbladder small cell carcinoma. The patient had intermittent right upper quadrant abdominal pain and was admitted to our hospital due to suspected acute cholecystitis. She regularly received medical treatment for diabetes, hypertension, and dyslipidemia. On initial laboratory evaluation, the levels of aspartate aminotransferase (AST), total bilirubin, and C-reactive protein (CRP) were markedly elevated. She underwent computed tomography (CT) for screening. CT images showed a thick-walled gallbladder containing multiple stones and multiple 3-cm-sized round nodular lesions, which were suggestive of metastatic lymph nodes. After percutaneous transhepatic gallbladder drainage was performed, endoscopic ultrasound-guided fine needle aspiration of enlarged lymph nodes resulted in a diagnosis of small cell carcinoma or adenocarcinoma. However, we could not identify the primary lesion before the surgery because of no decisive factors. We performed cholecystectomy because there was a possibility of cholecystitis recurrence risk and also partial liver resection because we suspected tumor invasion. The final pathological diagnosis was neuroendocrine carcinoma of the gallbladder, small cell type. The tumor stage was IVb, T3aN1M1. The patient died 13 weeks after the surgery. In the present paper, we review the current available English-language literature of gallbladder SCC.

Metastasis of colon cancer to the thyroid and cervical lymph nodes: a case report.

The incidence of thyroid metastasis among colorectal cancer patients is extremely rare. We report a case of colonic adenocarcinoma metastasis to the thyroid gland with treatment of lung and liver metastases, in a 61-year-old woman with a history of colon cancer. She showed a thyroid mass related to a 3-month history of hoarseness. Physical and imaging examinations disclosed a diffuse large thyroid mass with swollen cervical lymph nodes. Fine-needle aspiration cytology of the thyroid mass suggested malignancy. The patient underwent total thyroidectomy. Histopathological examination and immunohistochemical staining revealed adenocarcinoma, which was consistent with a diagnosis of metastases from primary colon cancer to the thyroid and cervical lymph nodes. At 2 years after thyroid surgery, the patient has been continuing outpatient chemotherapy for the lung and liver metastases. Thyroidectomy appeared to both relieve the patient and prevent local symptoms.

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.

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.

A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are known to have a protective effect on islet cells. Cell sheets developed using tissue engineering help maintain the function of the cells themselves. This study describes a tissue engineering approach using islets with MSC sheets to improve the therapeutic effect of islet transplantation. MSCs were obtained from Fischer 344 rats and engineered into cell sheets using temperature-responsive culture dishes. The islets obtained from Fischer 344 rats were seeded onto MSC sheets, and the islets with MSC sheets were harvested by low-temperature treatment after coculture. The functional activity of the islets with MSC sheets was confirmed by a histological examination, insulin secretion assay, and quantification of the levels of cytokines. The therapeutic effects of the islets with MSC sheets were investigated by transplanting the sheets at subcutaneous sites in severe combined immunodeficiency (SCID) mice with streptozotocin-induced diabetes. Improvement of islet function and viability was shown in situ on the MSC sheet, and the histological examination showed that the MSC sheet maintained adhesion factor on the surface. In the recipient mice, normoglycemia was maintained for at least 84 days after transplantation, and neovascularization was observed. These results demonstrated that islet transplantation in a subcutaneous site would be possible by using the MSC sheet as a scaffold for islets.