Haemolytic uraemic syndrome managed with subtotal colectomy.

A man in his early 70s was transferred to our hospital due to rapid decline in renal function and inflammation throughout the colon, indicating severe ischaemic enteritis. On the day following the start of intensive care, a stool specimen tested positive for verotoxin, and haemolytic uraemic syndrome (HUS) was diagnosed. On the same day, his vital signs deteriorated suddenly, and emergency surgery was performed due to the possibility of intestinal necrosis and perforation. Severe inflammation extending to the serosal surface of the whole colon was observed, but there was no obvious intestinal necrosis or perforation. Advanced mucosal necrosis of the entire colon suggested sepsis due to bacterial translocation, and subtotal colectomy was performed to remove the infection source. Postoperative management was successful. This case demonstrates the importance of considering HUS in patients with severe renal dysfunction and bloody stools, as well as the significance of colectomy in such patients.

Single-center comparative study of short-term outcomes of transanal and laparoscopic total mesorectal excisions for low and middle rectal cancers.

BACKGROUND: Transanal total mesorectal excision is a promising surgical treatment for rectal cancer. However, evidence regarding the differences in outcomes between the transanal and laparoscopic total mesorectal excisions is scarce. We compared the short-term outcomes of transanal and laparoscopic total mesorectal excisions for low and middle rectal cancers. METHODS: This retrospective study included patients who underwent low anterior or intersphincteric resection for middle (5-10 cm) or low (< 5 cm) rectal cancer at the National Cancer Center Hospital East, Japan, from May 2013 to March 2020. Primary rectal adenocarcinoma was confirmed histologically. Circumferential resection margins (CRMs) of resected specimens were measured; margins ≤ 1 mm were considered positive. The operative time, blood loss, hospitalization length, postoperative readmission rate, and short-term treatment results were compared. RESULTS: Four hundred twenty-nine patients were divided into two mesorectal excision groups: transanal (n = 295) and laparoscopic (n = 134). Operative times were significantly shorter in the transanal group than in the laparoscopic group (p < 0.001). The pathological T stage and N status were not significantly different. The transanal group had significantly lower positive CRM rates (p = 0.04), and significantly lower incidence of the Clavien-Dindo grade III (p = 0.02) and IV (p = 0.03) complications. Both groups had distal margin positivity rates of 0%. CONCLUSIONS: Compared to laparoscopic, transanal total mesorectal excision for low and middle rectal cancers has lower incident postoperative complication and CRM-positivity rates, demonstrating the safety and usefulness of local curability for middle and low rectal cancers.

Therapeutic effect and mechanism of Daikenchuto in a model of methotrexate-induced acute small intestinal mucositis.

BACKGROUND: Daikenchuto (DKT) has positive therapeutic effects on improving various gastrointestinal disorders. The present study investigated whether or not DKT has a potential therapeutic effect on chemotherapy-induced acute small intestinal mucositis (CIM) in a rat model. METHODS: Intraperitoneal injection of 10 mg/kg methotrexate (MTX) every 3 days for a total of 3 doses was used for induction of CIM in a rat model. The MTX and DKT-MTX groups were injected with MTX as above from the first day, and the DKT-MTX and DKT groups were administered 2.7% DKT via the diet at the same time. The rats were euthanized on day 15. RESULTS: The DKT-MTX group showed an improvement in the body weight and conditions of gastrointestinal disorders as well as increased levels of diamine oxidase in plasma and in the small intestinal villi. The pathology results showed that small intestinal mucosal injury in the DKT-MTX group was less severe than that in the MTX group. Immunohistochemistry for myeloperoxidase and malondialdehyde and quantitative real-time polymerase chain reaction (RT-qPCR) for TGF-ß1 and HIF-1α showed that DKT attenuated peroxidative damage. The crypts in the DKT-MTX group contained more Ki-67-positive cells than MTX group. The zonula occluden-1 and claudin-3 results showed that DKT promoted repair of the mucosal barrier. RT-qPCR for the amino acid transporters EAAT3 and BO+AT also confirmed that DKT promoted mucosal repair and thus promoted nutrient absorption. CONCLUSION: DKT protected against MTX-induced CIM in a rat model by reducing inflammation, stimulating cell proliferation, and stabilizing the mucosal barrier.

Subcutaneous transplantation of engineered islet/adipose-derived mesenchymal stem cell sheets in diabetic pigs with total pancreatectomy.

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.

Pancreaticoduodenectomy can be indicated for elderly patients: risk prediction using the estimation of physiologic ability and surgical stress (E-PASS) system.

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.

Difference in driver gene expression patterns between perihilar and peripheral intrahepatic cholangiocarcinoma in an experimental mouse model.

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.

Ameliorated healing of biliary anastomosis by autologous adipose-derived stem cell sheets.

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.

An engineered cell sheet composed of human islets and human fibroblast, bone marrow-derived mesenchymal stem cells, or adipose-derived mesenchymal stem cells: An in vitro comparison study.

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-ß1, 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-ß1 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.

A case of single incision laparoscopic total colectomy for 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.

Total thyroidectomy versus thyroid lobectomy for papillary thyroid cancer: Comparative analysis after propensity score matching: A multicenter study.

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.

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.

Similar metabolic responses to calorie restriction in lean and obese Zucker rats.

Calorie restriction (CR), which is thought to be largely dependent on the neuroendocrine system modulated by insulin/insulin-like growth factor-I (IGF-I) and leptin signaling, decreases morbidity and increases lifespan in many organisms. To elucidate whether insulin and leptin sensitivities are indispensable in the metabolic adaptation to CR, we investigated the effects of CR on obese Zucker (fa/fa) rats and lean control (+/+) rats. CR did not fully improve insulin resistance in (fa/fa) rats. Nonetheless, CR induced neuropeptide Y (NPY) expression in the hypothalamic arcuate nucleus and metabolism related gene expression changes in the liver in (fa/fa) rats and (+/+) rats. Up-regulation of NPY augmented plasma corticosterone levels and suppressed pituitary growth hormone (GH) expression, thereby modulating adipocytokine production to induce tissue-specific insulin sensitivity. Thus, central NPY activation via peripheral signaling might play a crucial role in the effects of CR, even in insulin resistant and leptin receptor deficient conditions.