Tsukasa Tanida

Combined transplantation of pancreatic islets and adipose tissue-derived stem cells enhances the survival and insulin function of islet grafts in diabetic mice.

Background. Overcoming significant loss of transplanted islet mass is important for successful islet transplantation. Adipose tissue-derived stem cells (ADSCs) seem to have angiogenic potential and antiinflammatory properties. We hypothesized that the inclusion of ADSCs with islet transplantation should enhance the survival and insulin function of the islet graft. Methods. Syngeneic ADSCs and allogeneic islets were transplanted simultaneously under the kidney capsules of diabetic C57BL/6J mice. Rejection of the graft was examined by measurement of blood glucose level. Revascularization and inflammatory cell infiltration were examined by immunohistochemistry. Results. Transplantation of 400 islets only achieved normoglycemia with graft survival of 13.6±1.67 days (mean±standard deviation), whereas that of 100 or 200 allogeneic islets never reversed diabetes. Transplantation of 200 islets with 2×105 ADSCs reversed diabetes and significantly prolonged graft survival (13.0±5.48 days). Results of glucose tolerance tests performed on day 7 were significantly better in islets-ADSCs than islets-alone recipients. Immunohistochemical analysis confirmed the presence of insulin-stained islet grafts with well-preserved structure in islets-ADSCs transplant group. Significant revascularization (larger number of von Willebrand factor-positive cells) and marked inhibition of inflammatory cell infiltration, including CD4+ and CD8+ T cells and macrophages, were noted in the islets-ADSCs transplant group than islets-alone transplant group. Conclusions. Our results indicated that cotransplantation of ADSCs with islet graft promoted survival and insulin function of the graft and reduced the islet mass required for reversal of diabetes. This innovative protocol may allow “one donor to one recipient” islet transplantation.

Clinicopathological significance of leucine-rich α2-glycoprotein-1 in sera of patients with pancreatic cancer

Objectives Leucine-rich &agr;2-glycoprotein-1 (LRG-1) is an inflammatory protein. Serum LRG-1 levels can reportedly be used as a cancer biomarker for several types of carcinoma. In the present study, we investigated the clinical usefulness of serum LRG-1 levels as a biomarker of pancreatic cancer. Methods A total of 124 patients with pancreatic cancer, 35 patients with chronic pancreatitis (CP), and 144 healthy volunteers were enrolled in the study. Serum LRG-1 levels were assayed by enzyme-linked immunosorbent assay. Immunohistochemistry was used to examine LRG-1 expression in pancreatic cancer tissues. Results Serum LRG-1 levels were significantly increased in patients with pancreatic cancer compared with CP patients and healthy volunteers. The LRG-1 levels increased with progressive clinical stages of pancreatic cancer. Receiver operator curve analysis showed that a combination of carbohydrate antigen 19-9 and LRG-1 resulted in a higher area under the curve for the diagnosis of pancreatic cancer. Positive staining was observed in all cases of pancreatic cancer, but positive signal was scarcely detected in tissues from CP patients or normal surrounding tissue. Conclusions These results suggest that serum LRG-1 is a promising biomarker for pancreatic cancer.

Outcomes in Colorectal Surgeon-driven Management of Obstructing Colorectal Cancers

BACKGROUND:Emergency surgery for obstructing colorectal cancer is associated with high mortality and morbidity rates. OBJECTIVE:The purpose of this study was to assess outcomes of emergency surgery for obstructing colorectal cancer in a single hospital, where care was primarily provided by colorectal surgeons. DESIGN:This was a retrospective cohort study. SETTINGS:The study was conducted at the Toyonaka Municipal Hospital. PATIENTS:The study included 208 consecutive patients who underwent emergency surgery for obstructing colorectal cancer between 1998 and 2013. MAIN OUTCOME MEASURES:Surgical outcomes, including mortality and morbidity, were evaluated. RESULTS:The obstructing cancers involved the right colon, left colon, and rectum in 78, 97, and 33 of the included patients. Many patients had poor performance indicators, such as age ≥75 years (42%), ASA score of III or more (38%), stage IV colorectal cancer (39%), obstructive colitis (12%), and perforation or penetration (9.6%). Colorectal surgeons performed the operations in all but 5 of the patients. Primary resection and anastomosis were accomplished in 96%, 70%, and 27% of cases involving the right colon, left colon, and rectum. Intraoperative colonic irrigation (n = 32), manual colonic decompression (n = 11), and subtotal or total colorectal resection (n = 34) were performed before left-sided anastomoses. Anastomotic leak was reported in only 2 patients. The in-hospital mortality and morbidity rates were 1.3% and 34.0%. LIMITATIONS:This study was a retrospective analysis of data from a single hospital. CONCLUSIONS:Surgical outcome analysis for obstructing colorectal cancers managed by specialized colorectal surgeons demonstrates low mortality and morbidity rates. Therefore, we concluded that our management of this condition is safe and feasible.

Analysis of the Vascular Interrelationships Among the First Jejunal Vein, the Superior Mesenteric Artery, and the Middle Colic Artery

BackgroundThe technical difficulty of laparoscopic surgery for transverse colon cancer is partly due to the vascular variability around the middle colic vessels. Although individual variations in the arteries or veins in this area were previously investigated, the vascular interrelationships between these vessels remain unknown. This study was designed to investigate the vascular interrelationships between the arteries and veins around the middle colic vessels and to provide practically useful classifications.MethodsThis study included 105 consecutive patients who underwent colorectal surgery for colorectal tumors in our institution in 2016. Patients with a history of colectomy were excluded. Vascular anatomical classifications were analyzed by evaluating thin-slice images of preoperative contrast-enhanced computed tomography.ResultsVascular anatomical patterns were classified according to whether the first jejunal vein ran behind (type A) or in front (type B) of the superior mesenteric artery. Type B was subclassified into two subtypes, depending on whether the middle colic artery originated cephalad (type B1) or caudad (type B2) to the first jejunal vein. We identified 83 (79.0%) cases of type A, 11 (10.5%) of type B1, and 11 (10.5%) of type B2. In 17 cases, the middle colic vein drained into the inferior mesenteric vein, and all of these were type A (P = 0.0202). Furthermore, in eight cases, the middle colic vein drained into the first jejunal vein, and all of these were type B (P < 0.0001).ConclusionsThis study elucidated the vascular interrelationships around the middle colic vessels. Our findings provided important knowledge for laparoscopic surgery in treating transverse colon cancer.

Pancreatic intraductal tubulopapillary neoplasm with associated invasive cancer successfully treated by total pancreatectomy: A case report

A 74-year-old male was admitted to Departments of Surgery, Toyonaka Municipal Hospital (Osaka, Japan) for treatment of a pancreatic tumor. Contrast enhanced computed tomography (CT) revealed a mass with small cystic lesions in the pancreatic head and body. Fluorodeoxyglucose-positron emission tomography/CT revealed an abnormal uptake of fluorodeoxyglucose, corresponding to the mass lesions. Upper gastrointestinal endoscopy revealed rough mucosa near the opening of the accessory pancreatic duct, and the mucosa biopsy exhibited adenocarcinoma with no mucin observed. The preoperative diagnosis was pancreatic intraductal tubulopapillary neoplasm (ITPN) with cancerous lesions, and a total pancreatectomy with splenectomy was performed. The resected tissue specimen revealed a solid tumor occupying the entire pancreas with intraductal growth into the main pancreatic duct. Histological examination revealed high-grade dysplastic cells in a tubulopapillary growth pattern without overt mucin production beyond the pancreatic duct. Immunohistochemical staining analysis of the tumor was positive for cytokeratin (CK)7, CK19 and mucin (MUC)1, and negative for MUC2, MUC5AC, MUC6 and caudal type homeobox 2. The tumor was finally diagnosed as pancreatic ITPN with associated invasive cancer. The patient remains well without evident recurrence nine months post-surgery. ITPN is a rare type of epithelial neoplasm of the pancreas, and is characterized by intraductal tubulo-papillary growth, ductal differentiation, limited intracellular mucin production, and cellular dysplasia. The present case report may contribute to improved understanding of how to effectively treat patients with ITPN.

Feasibility of laparoscopic cholecystectomy in patients with cerebrospinal fluid shunt

Previous reports of laparoscopic surgery in patients with cerebrospinal fluid (CSF) shunts for intracranial hypertension described shunt‐related complications. Thus, the shunts have been considered a contraindication for laparoscopic procedures. However, with the implementation of recent improvements in surgical techniques, perioperative management, and shunt technology, laparoscopic surgery may now be safe in cases with shunts. The aim of the present study was to examine the safety of such procedures based on our own experiences with laparoscopic surgery in patients with CSF shunts.

Significant improvement in islet yield and survival with modified ET-Kyoto solution: ET-Kyoto/Neutrophil elastase inhibitor.

Although islet transplantation can achieve insulin independence in patients with type 1 diabetes, sufficient number of islets derived from two or more donors is usually required to achieve normoglycemia. Activated neutrophils and neutrophil elastase (NE), which is released from these neutrophils, can directly cause injury in islet grafts. We hypothesized that inhibition of NE improves islet isolation and islet allograft survival. We tested our hypothesis by examining the effects of modified ET-Kyoto solution supplemented with sivelestat, a NE inhibitor (S-Kyoto solution), on islet yield and viability in islet isolation and the effect of intraperitoneally injected sivelestat on islet graft survival in a mouse allotransplant model. NE and proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 increased markedly at the end of warm digestion during islet isolation and exhibited direct cytotoxic activity against the islets causing their apoptosis. The use of S-Kyoto solution significantly improved islet yield and viability. Furthermore, treatment with sivelestat resulted in significant prolongation of islet allograft survival in recipient mice. Furthermore, serum levels of IL-6 and TNF-α at 1 and 2 weeks posttransplantation were significantly higher in islet recipients than before transplantation. Our results indicated that NE released from activated neutrophils negatively affects islet survival and that its suppression both in vitro and in vivo improved islet yield and prolonged islet graft survival. The results suggest that inhibition of NE activity could be potentially useful in islet transplantation for patients with type 1 diabetes mellitus.

Indocyanine green fluorescence-guided laparoscopic surgery, with omental appendices as fluorescent markers for colorectal cancer resection: a pilot study

BackgroundCurrently, we lack tools that can reliably guide laparoscopic surgeons to a target anatomical destination for dissection. We aimed to develop and evaluate a fluorescent destination marker (FDM), composed of a resected omental appendix injected with indocyanine green (ICG), for real-time navigation in laparoscopic surgery for colorectal cancer in this pilot study.MethodsThis study included ten patients diagnosed with colorectal cancer. To prepare FDMs, we laparoscopically harvested omental appendices attached to the colon we planned to resect. The harvested appendices were injected with diluted ICG, and a gauze tag was attached. The FDMs were placed at target intra-abdominal sites with a ligation clip.ResultsPatient diagnoses included 1 cecal, 2 ascending colon, 3 transverse colon, 2 sigmoid colon, and 2 rectal cancers. No conversion to open surgery was required and no intraoperative complications occurred. We created 12 sets of FDMs, which were placed at a total of 13 sites in abdominal cavities. FDM fluorescence was successfully detected in all cases. Furthermore, FDMs could be detected earlier than the gauze tags at 12 points, and they were detected at the same time at 1 point.ConclusionsAll FDMs facilitated laparoscopic surgery by allowing the surgeon to find the tissue to be dissected, particularly in procedures that required the dissection of lymph nodes around middle colic vessels and mobilization of the splenic flexure. FDMs showed potential for guiding the laparoscopic surgeon to a target anatomical destination. This marker represents a contribution to the evolution of real-time navigation surgery.

Distinct Clinical Factors in Hospitalized Patients with Diverticular Bleeding and Diverticulitis

Background/Aims: It is unclear why colonic diverticular bleeding and diverticulitis rarely coexist. This study compared the characteristics of these conditions. Methods: This single-center retrospective study examined 310 consecutive patients hospitalized with an episode of diverticular disease (cases) and outpatients without a diverticular episode (controls) from January 2012 to December 2015. We investigated distinct clinical factors in hospitalized patients with diverticular bleeding and diverticulitis. Results: We identified 183 patients with 263 episodes of diverticular bleeding and 127 patients with 135 episodes of diverticulitis during the study period. Patients with diverticular bleeding were significantly older than those with diverticulitis (median age 76 vs. 56 years) and had more cardiovascular disease, hypertension, diabetes, cerebrovascular disease, chronic kidney disease, lipid disorder, or a poorer performance status. Significantly more diverticular bleeding patients were taking antiplatelet drugs, anticoagulant drugs, proton pump inhibitors, or laxative agents. Multivariate analysis revealed that an age > 65 years (OR 5.42), and antiplatelet agent use (OR 7.29) were more significant risk factors for diverticular bleeding than for diverticulitis. Conclusions: Elderly people using antiplatelet drugs may be more susceptible to diverticular bleeding than diverticulitis.

Surgical outcomes of laparoscopic cholecystectomy for acute cholecystitis in elderly patients: Lap cholecystectomy in the elderly

The clinical significance of laparoscopic cholecystectomy (LC) for acute cholecystitis in elderly patients aged 80 years or older has not been determined. This study aimed to investigate surgical outcomes of LC for acute cholecystitis in elderly patients compared to non‐elderly patients.