Seigo Kitano

Mammalian target of rapamycin signaling activation patterns in pancreatic neuroendocrine tumors

Phosphatidylinositol 3‐kinase/Akt/mammalian target of rapamycin (mTOR) pathway dysregulation has been implicated in the development of various human cancers. However, expression of mTOR cascade components in pancreatic neuroendocrine tumors (PNETs) has not been fully explored. The aim of this study was to assess the expression of mTOR pathway in PNETs using immunohistochemistry.

Natural orifice transluminal endoscopic surgery (NOTES) for clinical management of intra-abdominal diseases

Clinical research on natural orifice transluminal endoscopic surgery (NOTES) has been increasingly reported over the past 5 years and more than 1200 patients have received various NOTES procedures. The present article reviews the clinical practice of NOTES for the treatment of intra‐abdominal diseases, and was carried out through systematic search with specific keywords in major databases for NOTES‐related clinical literature. The last date of the search was 15 August, 2012. Transvaginal cholecystectomy is the commonest NOTES procedure reported, and its clinical feasibility and safety was established through prospective case series and randomized trials. There is a regional difference in NOTES development with the majority of NOTES fromCaucasian countries being transvaginal cholecystectomy and most reports from Asian countries being NOTES‐related procedures. Safe closure of gastrointestinal access remains challenging, and novel endoscopic instruments are essential to enhance future development of NOTES.

Transrectal peritoneal access with the submucosal tunnel technique in NOTES: a porcine survival study

BackgroundNatural orifice transluminal endoscopic surgery (NOTES) procedures have been performed via transgastric, transvaginal, or transcolonic approaches. However, the transcolonic approach has potential disadvantages including intraperitoneal infection. To avoid such disadvantages, we applied the submucosal tunnel technique to transrectal peritoneal access in this study. Study aims are to clarify the technical feasibility of a submucosal tunnel method for transrectal abdominal access and to assess the healing process of the submucosal tunnel histopathologically.MethodsThe study comprised six female pigs. The following procedures were performed: (1) The mucosa was cut after injection of sodium hyaluronate into the submucosa at the upper rectum. (2) Submucosal tunneling was performed by endoscopic submucosal dissection technique. (3) A small incision was made at the end of the tunnel. (4) After transrectal peritoneoscopy, the mucosal incision site was closed with endoclips.ResultsTransrectal peritoneoscopy was successfully performed in all pigs. Necropsy revealed no findings of peritonitis. Histopathologic examination showed good healing of the submucosal tunnel. The wound healing process of the submucosal tunnel on postoperative day 7 was mainly in the inflammatory phase at the mucosal incision site, the proliferative phase at the submucosal tract, and the proliferative/remodeling phase at the seromuscular incision site.ConclusionsThe submucosal tunnel technique appears to be useful and safe for transrectal peritoneal access because healing at the seromuscular incision site proceeded rapidly.

Effects of sleeve gastrectomy on lipid metabolism in an obese diabetic rat model.

BackgroundLaparoscopic sleeve gastrectomy (SG) is a popular bariatric procedure for treating morbid obesity. This study aimed to investigate the relation between SG and lipid metabolism in an obese diabetic rat model.MethodsForty-five male Zucker diabetic fatty (ZDF) rats were divided into three groups: sham-operated (SO) control, gastric banding (GB), and SG. Six weeks after surgery, metabolic parameters, including plasma adiponectin level, small bowel transit, mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α and PPARγ in the liver, skeletal muscle and white adipose tissue, and that of adiponectin in white adipose tissue, and triglyceride (TG) contents in the liver and skeletal muscle were measured.ResultsMetabolic parameters in the GB and SG groups were significantly improved compared with those in the SO group. However, plasma total cholesterol (TC) and free fatty acid (FFA) concentrations were significantly lower while the plasma adiponectin level was significantly higher in the SG group than in the GB and SO groups. In addition, small bowel transit time was significantly shorter in the SG group than in the other two groups. Furthermore, in the SG group, mRNA expression of PPARα in the liver and skeletal muscle and that of adiponection and PPARγ in white adipose tissue were significantly higher, while TG in the liver and skeletal muscle were significantly lower, compared with those in the other two groups.ConclusionsThese results suggest that SG improves lipid metabolism compared with GB, although there were no significant differences in the effect on weight loss between the two procedures.

Quality Control by Photo Documentation for Evaluation of Laparoscopic and Open Colectomy with D3 Resection for Stage II/III Colorectal Cancer: Japan Clinical Oncology Group Study JCOG 0404

OBJECTIVE The quality of surgery with D3 resection in randomized controlled clinical trial [Japan Clinical Oncology Group study (JCOG0404)] was assessed by evaluation of the photo documentation of both open and laparoscopic surgeries. METHODS A multi-institutional randomized-controlled trial (JCOG0404) was conducted to evaluate open and laparoscopic D3 resection (complete mesocolic excision + ligation and dissection at the root of the main vessels) for Stage II/III colon cancer (UMIN-CTR number C000000105). A total of 1057 (open, 528; laparoscopic, 529) eligible patients were enrolled. For quality control, it was ensured that the surgeries were performed by accredited surgeons, and a central committee reviewed each surgery on the basis of the submitted photographs of the resected field, specimen and skin incision. RESULTS For right-sided tumors, the rate of D3 resection was 98.5% (131/133) in the open arm and 100% (136/136) in the laparoscopic arm, and for left-sided tumors, they were 97.9% (322/329) and 98.2% (320/326), respectively. Sufficient length of the resected longitudinal margin was ensured in all cases. The skin incisions made in all the cases were <8 cm as defined in the protocol in laparoscopic arm. CONCLUSIONS Completion of high quality surgery with D3 resection was confirmed in JCOG0404 by central peer review of photographs of the surgical procedures in addition to operator regulations. This study suggests that the central review of the photo documentation is one of the important tools to assure a quality control of surgical technique in the Phase III randomized-controlled study.

Phototherapy with artificial light suppresses dextran sulfate sodium‐induced colitis in a mouse model

Medical treatment for inflammatory bowel disease (IBD) requires chronic administration and causes side effects. Recently, anti‐inflammatory effects of phototherapy were reported in animal models. The present study evaluated whether phototherapy improves dextran sulfate sodium (DSS)‐induced colitis in a mouse model of IBD.

Evaluation of 0.6% sodium alginate as a submucosal injection material in endoscopic submucosal dissection for early gastric cancer

We have focused on sodium alginate (SA) solution as a potential submucosal injection material for endoscopic submucosal dissection (ESD). A previous SA solution had high viscosity and problems such as difficult handling. After its properties were adjusted, SA solution was examined in vitro and its clinical safety was evaluated.

Biological predictors of survival in stage II colorectal cancer

The routine use of postoperative adjuvant chemotherapy in patients with stage II colorectal cancer is not recommended. However, the incidence of tumor recurrence or distant metastasis in these patients is reported to be 25–35%. The identification of high-risk patients with stage II colorectal cancer remains difficult. Therefore, the aim of this study was to determine the risk factors that may help identify stage II colorectal cancer patients with unfavorable prognosis. Paraffin-embedded tissue samples from 109 patients with stage II colorectal cancer following curative operation were analyzed. Thirteen clinicopathological variables and 5 biological markers were assessed using immunohistochemistry, including p53 (tumor suppressor gene), CD10 (tumor invasion marker), CD34 (angiogenic marker), Ki-67 (cell proliferation index) and CAM 5.2 (marker of lymph node micrometastasis) and investigated for associations with disease-specific survival. Univariate analysis revealed bowel obstruction, lymph node micrometastasis and lymphatic invasion (P<0.01) to be highly significant factors for determining the 5-year disease-specific survival. By contrast, the multivariate analysis revealed lymph node micrometastasis and lymphatic invasion to be independent prognostic factors. Stage II colorectal cancer patients with lymph node micrometastasis and lymphatic invasion may therefore be suitable candidates for adjuvant chemotherapy to improve prognosis.

Risk factors of liver failure after right-sided hepatectomy

BACKGROUND To prevent hepatic failure after major hepatectomy, it is important to assess preoperative factors related to liver failure. METHODS We examined 80 patients who underwent right-sided hepatectomy. Hyperbilirubinemia, uncontrolled ascites, and prolonged postoperative hospital stay were defined as liver failure after hepatectomy, and these 3 factors were evaluated in relation to clinicopathological and surgical factors. RESULTS In the 80 patients, hyperbilirubinemia was observed in 10 (12.7%) patients, uncontrolled ascites in 18 (22.5%) patients, and prolonged hospital stay after surgery in 39 (48.8%) patients. Multivariate analyses identified platelet count as a risk factor of hyperbilirubinemia, uncontrolled ascites, and prolonged postoperative hospital stay, and the ratio of remnant liver volume to body surface area (RLV/BSA ratio) as an additional risk factor of hyperbilirubinemia and prolonged postoperative hospital stay. CONCLUSIONS Platelet count and RLV/BSA ratio are useful risk factors for prediction of liver failure after right-sided hepatectomy.

Assessment of a manipulator device for NOTES with basic surgical skill tests: a bench study.

Advanced complex surgery performed with the natural orifice translumenal endoscopic surgery technique requires use of a multitasking platform. The aim of this study is to evaluate the basic functionality of a prototype multitasking platform “EndoSAMURAI” with the use of a biosimulation model and ex vivo porcine stomach. We compared the performance of basic surgical skill tasks between the EndoSAMURAI and standard laparoscopic instrumentation. Basic surgical tasks include cutting, dissection, and suturing and knot tying. Main outcome measurements were the time to complete each task and leak pressure to evaluate the quality of the suturing and knot tying. Although it took longer to perform all basic surgical tasks with the EndoSAMURAI than with laparoscopic instrumentation, all tasks could be performed precisely and with an accuracy comparable to that of the laparoscopic technique. Leak pressures of the gastric closure site between both techniques were also comparable.