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Introduction Intraportal islet transplantation is a promising therapeutic approach for patients with type 1 diabetes mellitus (T1DM). However, despite being minimally invasive, the method has some limitations, such as short-term graft loss, portal venous thrombosis, and difficulty in collecting adequate amounts of islets. Subcutaneous islet transplantation on adipose-derived mesenchymal stem cell (ADSC) sheets has been suggested to overcome these limitations, and in this study, we have examined its feasibility in T1DM pigs. Methods Inguinal subcutaneous fat was harvested from young pigs and then isolated and cultured adequate ADSCs to prepare sheets. Islets were isolated from the pancreases of mature pigs and seeded on the ADSC sheets. T1DM pigs were generated by total pancreatectomy, and ADSC sheets with transplanted islets were administered subcutaneously to the waist (n = 2). The effects of the islets on the ADSC sheets and on blood glucose levels were evaluated. Insulin secretion was measured by insulin stimulation index. Results Islet viability was higher on ADSCs compared to islets alone (91.8 ± 4.3 vs. 81.7 ± 4.1%). The insulin stimulation index revealed higher glucose sensitivity of islets on ADSC sheets compared to islets alone (2.8 ± 2.0 vs. 0.8 ± 0.3). After transplantation, the blood glucose levels of two pigs were within the normal range, and sensitive insulin secretion was confirmed by intravenous glucose tolerance tests. After graftectomy, decreased insulin secretion and hyperglycemia were observed. Conclusions Subcutaneous islet transplantation using ADSC sheets can regulate the blood glucose levels of T1DM pigs., Highlights • The adipose-derived mesenchymal stem cell sheet is useful to protect the islets. • Subcutaneous islet transplantation on sheet normalized blood glucose in diabetic pig. • Subcutaneous islet transplantation on sheet can be a useful tool.

BACKGROUND Pancreaticobiliary malignant diseases are primarily treated by surgical resection. However, the surgical indications for elderly patients, especially for pancreaticoduodenectomy (PD), must be carefully considered due to patient compliance. Whether PD can contribute to better prognoses in elderly patients remains unclear. Therefore, we aimed to evaluate the complications, compliance, and survival of elderly and non-elderly patients who underwent PD in our department. METHODS We retrospectively analyzed 282 patients who underwent PD from 2000 to 2017 and divided them into non-elderly (aged ≤ 79 years, n = 238) and elderly (aged ≥ 80 years, n = 44) groups. The estimation of physiologic ability and surgical stress (E-PASS) system was used to evaluate morbidity and mortality using preoperative risk score (PRS), surgical stress score (SSS), and comprehensive risk score (CRS). RESULTS Preoperative risk score was higher in the elderly group than in the non-elderly group, although SSS and CRS were similar. No significant differences were detected in the occurrence of postoperative complications. In the elderly group, CRS was higher in patients with complications than in those without. Long-term outcomes evaluated by overall and disease-specific survival were not significantly different. CONCLUSIONS In the elderly patients, E-PASS especially CRS can predict the occurrence of complications. The safety and prognoses of elderly patients after PD are comparable with those of non-elderly patients.

Background The prognosis of intrahepatic cholangiocarcinoma (ICC) is based on tumor localization; however, the mechanism remains unknown. Therefore, we investigated the biological characteristics of perihilar and peripheral ICC in a mouse model. Methods The model was established by the administration of three oncogenic plasmids harboring myristoylated AKT, mutated human YAP, and pCMV-Sleeping Beauty into the mice. The perihilar and peripheral ICC tumors that developed in the same mouse were assessed for the expression of cell adhesion factors and driver genes with immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Results The perihilar ICC tumors were irregularly shaped, whereas the peripheral tumors were mostly circular, similar to the differences found in patients. Alpha-smooth muscle actin was strongly expressed in the perihilar tumors at 10 weeks, and vimentin expression was significantly up-regulated in the perihilar ICC at 14 weeks. Fgfr2 level significantly increased in peripheral ICC at 10 weeks, whereas Idh2 expression was up-regulated in perihilar ICC. Conclusions Despite diffuse injection of oncogenic plasmid, expression of driver genes and oncogenes in ICC tumor cells differs depending on the tumor localization, resulting in changes in epithelial-mesenchymal transition, which may explain the different outcomes of patients with peripheral and perihilar ICC.

Objective This study aims to identify the most effective individual drug in an established triple-drug therapy (TDT) using a postoperative pancreatic fistula (POPF) rat model. Summary of background data POPF is the major complication of pancreatectomy that causes intraperitoneal abscess, sepsis, and pseudoaneurysm rupture, all of which may prolong hospital stays and cause potentially serious events or death. We previously demonstrated that TDT with a somatostatin analog, gabexate mesilate, and imipenem/cilastatin effectively prevents POPF, especially in high-risk patients. Methods POPF-induced rats were killed on postoperative day 3 after control (C), gabexate mesilate (G), imipenem/cilastatin (I), and somatostatin analog (S) treatments. Levels of serum amylase and lipase, or ascitic amylase and lipase were measured. Intraperitoneal adhesion between the abdominal wall and pancreas and pancreatic inflammation were evaluated. Results Serum amylase levels did not significantly differ among the groups. Serum lipase level was significantly higher in group I than in the other groups (P < 0.01). Both ascitic amylase and lipase levels were significantly lower in group S than in the other groups (P < 0.01). Median inflammation scores were significantly lower in groups G, I, and S than in group C (P < 0.01). Moreover, adhesion score was lower in group S than in the other groups (groups C, G, I, and S with scores 3, 2, 3, and 1, respectively, P < 0.01). Conclusion Among the 3 drugs, the somatostatin analog was the most effective against POPF.

Introduction: Cell sheets consisting of adipose-derived stem cells (ADSCs) have been reported to be effective for wound healing. We conducted this study to clarify the efficacy of ADSC sheets in wound healing at the duct-to-duct biliary anastomotic site in pigs. Methods: Eleven female pigs (20?25 kg) were divided into two groups: biliary anastomosis with an ADSC sheet (n = 6) or without an ADSC sheet (n = 5). To follow the transplanted ADSCs, PKH26GL-labeled sheets were used in one of the ADSC pigs. Two weeks prior to laparotomy, ADSCs were isolated from the lower abdominal subcutaneous adipose tissue. After three passages, ADSCs were seeded on temperature-responsive culture dishes and collected as cell sheets. ADSC sheets were gently transplanted on the anastomotic site. We evaluated specimens by PKH26GL labeling, macroscopic changes, infiltration of inflammatory cells, and collagen content. Results: Labeled ADSCs remained around the bile duct wall. In the no-ADSC group, more adhesion developed at the hepatic hilum as observed during relaparotomy. Histopathological examination showed that the diameter and cross-sectional area of the bile duct wall were decreased in the ADSC group. In the no-ADSC group, a large number of inflammatory cells and more collagen fibers were identified in the bile duct wall. Conclusions: The present study demonstrated that autologous ADSC sheet transplantation reduced hypertrophic changes in the bile duct wall at the anastomotic site. A long-term follow-up is required to evaluate the efficacy of this mechanism in prevention of biliary anastomotic strictures., Regenerative Therapy, 14, pp.79-86; 2020

Highlights • In patients with refractory constipation, it is necessary to care in mind that some patients require surgery. • Single incision laparoscopic surgery (SILS) is regarded as the major advance in minimally invasive surgery. • Total colectomy by SILS is very useful for the patients with intestinal neuronal dysplasia-type B., Introduction Intestinal neuronal dysplasia type B (IND-B) is an infrequent disease of the submucosal plexus of intestine manifesting chronic intestinal obstruction or severe chronic constipation. IND is rarely reported in adult patients. Presentation of a case The present study reports on the case of a 36 year-old woman suffering from longstanding chronic constipation and who was diagnosed with severe constipation in more than 20 years. Although she began to take a large amount of stimulant laxatives, such as “senna” and “bisacodyl”, constipation symptoms did not improve, she was admitted to our hospital. It was diagnosed with refractory constipation of the medication treatment-resistance, total colectomy with ileorectal anastomosis by single incision laparoscopic surgery (SILS) was performed. The final pathological diagnosis was IND-B. Discussion Refractory constipation after medical treatment is often seen in young generation. SILS has benefits of better cosmesis, reduced morbidity, reduced postoperative pain, and reduced length of hospital stay. Conclusion For the patients with refractory constipation associated with neuropathy such as IND, total colectomy by SILS was very effective.

Islet transplantation is a feasible treatment option for type 1 diabetes mellitus (T1DM) patients with a poor glycemic control. However, while the outcomes of islet transplantation have recently improved, early graft loss after transplantation remains a problem. Several factors are associated with islet graft loss in intrahepatic islet transplantation, including instant blood-mediated inflammatory reaction, hypoxia and liver immunity, and procedure-related complications, such as portal vein thrombosis and hemorrhaging. To overcome these problems, many researchers have attempted to change the transplantation site from the portal vein to the subcutaneous space using tissue-engineered sheets. However, the subcutaneous space is easy to access, and the procedure itself is minimally invasive, although the efficiency has been lower than that with transplantation via portal vein in previous studies due to the hypoxic environment. Therefore, subcutaneous islet transplantation using tissue engineering has attracted attention in recent years. In this report, we discuss the concept of subcutaneous islet transplantation using tissue engineering.

Retained foreign objects in the abdomen and pelvis are serious clinical problems yet the imaging required can present difficulties. Prolonged retention of lipiodized oil used for hysterosalpingography over years is very rare. However, lipiodized oil had previously been misdiagnosed as residual metallic material. We are reporting a case in which the latest computed tomography (CT) equipment seemed inadequate for obtaining a clear pre-operative diagnosis. Here, we describe the case of a 33-year-old Japanese female whose pelvis had contained retained lipiodized oil that had been suspected as residual metallic material. The preoperative diagnosis was very difficult and included three-dimensional computed tomography (3D-CT) of unclear results despite expectations of resolution. By laparoscopic surgery, we removed a cyst of approximately 2 cm containing a yellowish oily fluid. Postoperatively, we demonstrated that the fluid was lipiodized oil. A postoperative experiment to attempt distinguishing lipiodized oil from metal through gemstone spectral CT imaging did not offer clarity either. Distinguishing between retained lipiodized oil and metallic material in the abdominal cavity may still present unexpected difficulties even with the latest medical equipments.

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.

Background In patients with papillary thyroid carcinoma (PTC), the role of total thyroidectomy (TT) versus that of thyroid lobectomy (TL) has been controversial. Methods This retrospective study was approved by our institutional review board, and the requirement to obtain informed consent was waived. In total, 173 patients with 1- to 5-cm stage cN0 and cM0 PTC tumors treated by curative surgery from 1994 to 2008 were evaluated. Clinicopathologic features and adverse events were compared between patients who underwent TT and those who underwent TL. After adjustment for differences in baseline clinicopathologic factors using propensity score matching, we compared recurrence-free survival (RFS) and OS. Results TL was performed in 120 patients and TT in 53 patients. Patients who underwent TT were older; had larger tumors; more frequently had nodal metastasis, multifocal tumors, and extracapsular invasion; and more frequently underwent radioactive iodine ablation than patients who underwent TL. Hypocalcemia requiring medication and recurrent laryngeal nerve paralysis were more frequent in TT than TL. The 10-year RFS and OS of all patients were 93.3% and 96.7%, respectively. There was no significant difference in RFS (90.6% vs 93.0% in TT and TL groups, respectively) or OS (96.2% vs 96.9% in TT and TL groups, respectively) according to the extent of surgical resection after propensity score matching. Conclusion Equivalent prognoses were observed for patients with 1- to 5-cm stage cN0 and cM0 PTC tumors treated by TL or TT after propensity score matching. Adverse events occurred less frequently in patients who underwent TL than TT.

Background: We previously reported the utility of engineered cell sheets composed of human islets and supporting cells in vitro and in vivo. It is unclear which type of supporting cell is most suitable for constructing cell sheets with human islets. The present study aimed to compare human fibroblasts, bone marrow–derived mesenchymal stem cells (BM–MSCs), and adipose–derived mesenchymal stem cells (ADSCs) as a supporting source for cell sheets. Methods: Engineered cell sheets were fabricated with human islets using human fibroblasts, BM–MSCs, or ADSCs as supporting cells. The islet viability, recovery rate, glucose–stimulated insulin release (determined by the stimulation index), and cytokine secretion (TGF–β1, IL–6, and VEGF) of groups—including an islet–alone group as a control-were compared. Results: All three sheet groups consistently exhibited higher viability, recovery rate, and stimulation index values than the islet-alone group. The ADSC group showed the highest viability and recovery rate among the three sheet groups. There were no discernible differences in the stimulation index values of the groups. The fibroblast group exhibited significantly higher TGF–β1 values in comparison to the other groups. The IL–6 level of the ADSC group was more than five times higher than that of the other groups. The ADSC group showed the VEGF level; however, it did not differ from that of the BM–MSC group to a statistically significant extent. Conclusion: Engineered cell sheets composed of islets and supporting cells had a cytoprotective effect on islets. These results suggest that individual cell types could be a more attractive source for crafting engineered cell sheets in comparison to islets alone.