Yo Kurashima

Helicobacter pylori CagA interacts with E-cadherin and deregulates the β -catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells

Infection with Helicobacter pylori cagA-positive strains is associated with gastric adenocarcinoma. Intestinal metaplasia is a precancerous lesion of the stomach characterized by transdifferentiation of the gastric mucosa to an intestinal phenotype. The H. pylori cagA gene product, CagA, is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases. Tyrosine-phosphorylated CagA specifically binds to and activates SHP-2 phosphatase, thereby inducing cell-morphological transformation. We report here that CagA physically interacts with E-cadherin independently of CagA tyrosine phosphorylation. The CagA/E-cadherin interaction impairs the complex formation between E-cadherin and β-catenin, causing cytoplasmic and nuclear accumulation of β-catenin. CagA-deregulated β-catenin then transactivates β-catenin-dependent genes such as cdx1, which encodes intestinal specific CDX1 transcription factor. In addition to β-catenin signal, CagA also transactivates p21WAF1/Cip1, again, in a phosphorylation-independent manner. Consequently, CagA induces aberrant expression of an intestinal-differentiation marker, goblet-cell mucin MUC2, in gastric epithelial cells that have been arrested in G1 by p21WAF1/Cip1. These results indicate that perturbation of the E-cadherin/β-catenin complex by H. pylori CagA plays an important role in the development of intestinal metaplasia, a premalignant transdifferentiation of gastric epithelial cells from which intestinal-type gastric adenocarcinoma arises.

Deregulation of β-catenin signal by Helicobacter pylori CagA requires the CagA-multimerization sequence

Infection with Helicobacter pylori cagA‐positive strains causes gastritis and peptic ulceration and is associated with gastric adenocarcinoma. The cagA gene product CagA is delivered into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases at the C‐terminal EPIYA‐repeat region. Tyrosine‐phosphorylated CagA specifically binds and activates SHP‐2 tyrosine phosphatase, causing cell morphological transformation known as the hummingbird phenotype. CagA also destabilizes the E‐cadherin/β‐catenin complex to elicit aberrant activation of the β‐catenin signal that underlies intestinal metaplasia. Here we show that translocalization of membranous β‐catenin and subsequent activation of the β‐catenin signal by CagA requires the EPIYA‐repeat region, which is characterized by structural variation between CagA of H. pylori isolated in Western countries (Western CagA) and that of East Asian H. pylori isolates (East Asian CagA), but is independent of CagA tyrosine phosphorylation. Detailed analysis using a series of Western and East Asian CagA mutants revealed that deregulation of β‐catenin requires residues 1009–1086 and residues 908–1012 of ABCCC Western CagA and ABD East Asian CagA, respectively, and is mediated by the 16‐amino‐acid CagA multimerization sequence that is conserved between the 2 geographically distinct H. pylori CagA species. Our results indicate that aberrant activation of the β‐catenin signal, which promotes precancerous intestinal metaplasia, is an inherent and fundamental CagA activity that is independent of the structural polymorphism of CagA.

Oncological benefit of preoperative endoscopic biliary drainage in patients with hilar cholangiocarcinoma

Due to advances in endoscopic equipment and techniques, preoperative endoscopic biliary drainage (EBD) has been developed to serve as an alternative to percutaneous transhepatic biliary drainage (PTBD). This study sought to clarify the benefit of EBD in comparison to PTBD in patients who underwent radical resections of hilar cholangiocarcinoma. One hundred and forty‐one patients underwent radical surgery for hilar cholangiocarcinoma between 2000 and 2008 were retrospectively divided into two groups based on the type of preoperative biliary drainage, PTBD (n = 67) or EBD (n = 74). We investigated if the different biliary drainage methods affected postoperative survival and mode of recurrence after median observation period of 82 months. The survival rate for patients who underwent EBD was significantly higher than those who had PTBD (P = 0.004). Multivariate analysis revealed that PTBD was one of the independent factors predictive of poor survival (hazard ratio: 2.075, P = 0.003). Patients with PTBD more frequently developed peritoneal seeding in comparison to those who underwent EBD (P = 0.0003). PTBD was the only independent factor predictive of peritoneal seeding. In conclusion, EBD might confer an improved prognosis over PTBD due to prevention of peritoneal seeding, and is recommended as the initial procedure for preoperative biliary drainage in patients with hilar cholangiocarcinoma.

A tool for training and evaluation of laparoscopic inguinal hernia repair: the Global Operative Assessment of Laparoscopic Skills-Groin Hernia (GOALS-GH)

BACKGROUND the purpose of this study was to develop an assessment tool specific to laparoscopic inguinal hernia repair (LIHR), and to evaluate its reliability and validity in the operating room (OR) and skills laboratory. METHODS the Global Operative Assessment of Laparoscopic Skills-Groin Hernia (GOALS-GH) was developed by surgeon-educators. Participants were assessed in the OR and/or on a physical simulator using GOALS-GH. Interrater reliability, internal consistency, and construct and concurrent validity were evaluated for 23 participants. RESULTS the interrater reliability of GOALS-GH was >.70 for all raters in the OR and during simulated LIHR. The internal consistency of GOALS-GH items was .97. The mean total GOALS-GH score for experts was significantly higher than for novices in both environments. The correlation between GOALS-GH scores in the OR and simulator was .81 (P < .01; n = 12). CONCLUSIONS GOALS-GH is an objective, reliable, and valid measure of the skills required to perform LIHR.

A novel low-cost simulator for laparoscopic inguinal hernia repair.

Despite the advantages of laparoscopic inguinal hernia repair over the open approach in selected situations, laparoscopic inguinal hernia repair (LIHR) remains a challenge to teach and learn. The purpose of this study was to develop and validate a low-cost adaptable simulator for evaluation and training of LIHR. McGill Laparoscopic Inguinal Hernia Simulator (MLIHS) is a physical simulator that accurately represents inguinal anatomy. MLIHS permits to perform both transabdominal pre-peritoneal (TAPP) and totally extraperitoneal (TEP) repairs. Six experienced surgeons performed TAPP repairs using MLIHS. They were surveyed to establish face validity, and were scored using a previously validated global rating scale (maximum score = 25). Experienced surgeons considered MLIHS a useful tool for evaluating and training of LIHR. The mean (SD) global rating scores were 24.0 (± 0.6). The experienced surgeons considered MLIHS very useful for training and assessment. MLIHS is a valuable and affordable tool for training and evaluation of LIHR.

Thoracoscopic enucleation of esophageal submucosal tumor by prone position under artificial pneumothorax by CO2 insufflation.

Recently, the usefulness of the prone position for thoracoscopic esophagectomy has been demonstrated. Thoracoscopic resection of an esophageal submucosal tumor using a prone position also offers advantages over a lateral decubitus position. We describe 2 cases operated on using the prone position for the resection of esophageal submucosal tumor. Case 1 was a 35-year-old man, who was diagnosed with a 50×20 mm leiomyoma in the middle thoracic esophagus, and underwent right thoracoscopic tumor enucleation. Case 2 was a 61-year-old female, who had 45×30 mm esophageal schwannoma in the lower thoracic esophagus with symptoms of dysphagia, and underwent left thoracoscopic tumor enucleation. No complication was observed in both cases. Thoracoscopic esophageal submucosal resection with prone position may add the merits to conventional decubitus position, such as superior visualization, and less bleeding. The side of incision should be determined according to the location of the tumor and anatomic rationality.

Advances in the surgical treatment of hilar cholangiocarcinoma

With the improvement of perioperative management and surgical techniques as well as the accumulation of knowledge on the oncobiological behavior of bile duct carcinoma, the long-term prognosis of hilar cholangiocarcinoma has been improving. In this article, the authors review the recent developments in surgical strategies for hilar cholangiocarcinoma, focusing on diagnosis for characteristic disease extension, perioperative management to reduce postoperative morbidity and mortality, surgical techniques for extended curative resection and postoperative adjuvant therapy.

Strategic Approach to the Splenic Artery in Laparoscopic Spleen-preserving Distal Pancreatectomy.

Background: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) is an ideal procedure in selected patients with benign or low-grade malignant tumors in the body/tail of the pancreas. We describe our procedure and experience with splenic vessel-preserving LSPDP (SVP-LSPDP) in a retrospective case series. Methods: Six consecutive patients underwent SVP-LSPDP from January 2011 to September 2013. We evaluated the courses of the splenic artery by preoperative computed tomography and applied an individualized approach (the superior approach or inferior approach) to the splenic artery. Results: All of the operations were successful. The median surgical duration was 249 minutes. The median blood loss was 0 mL. Pathologic examination revealed 4 cases of insulinoma, 1 case of solid pseudopapillary tumor, and 1 case of pancreatic metastasis from renal carcinoma. Conclusions: In performing SVP-LSPDP, it is effective to make a strategic choice between 2 different approaches according to the course of splenic artery.

Description and Preliminary Evaluation of a Low-Cost Simulator for Training and Evaluation of Flexible Endoscopic Skills

Background. The Society of American Gastrointestinal and Endoscopic Surgeons developed the Fundamentals of Endoscopic Surgery (FES) to test the knowledge and skills required to perform flexible endoscopy. The program includes online didactic material to complement the written component, but does not have a practice component for the skills portion. The purpose of this study was to develop and pilot test low-cost models to train for the hands-on component of the FES examination. Methods. Based on the deconstructed skills tested in FES, a low-cost simulator and metrics that model retroflexion, instrumentation and targeting, loop reduction, and mucosal evaluation were developed. The model is reuseable and requires a real endoscope and tower. Validity evidence was obtained by comparing performance between novice endoscopists (NEs) and experienced endoscopists (EEs). Results. Six NEs and 6 EEs participated. In retroflexion, EEs and NEs scored (median [interquartile range]) 72.9 (67.1; 78.6) and 37.9 (25.7; 50.0; P = .004), respectively. In targeting, EEs scored 102.0 (75.0; 110.0) and NEs scored 50.0 (25.0; 50.0; P = .089). In navigation and loop reduction, EEs scored 189.0 (108.0; 267.0) and NEs scored 0.0 (0.0; 0.0; P = .004). In mucosal evaluation, EEs scored 133.3 (103.3; 150.0) and NEs scored 66.7 (50.0; 103.3; P = .015). The median global scores were 116.6 (109.6; 135.8) for EEs and 39.1 (29.1; 40.6; P = .004) for NEs. Conclusion. This pilot study provides preliminary validity evidence to support using these tasks to measure basic flexible endoscopic skills. Subsequent studies will examine the implementation of a proficiency curriculum using this model and its value as a training tool for flexible endoscopy, or to prepare for the FES exam.

Hilar cholangiocarcinoma with intratumoral calcification: A case report

This report describes a rare case of hilar cholangiocarcinoma with intratumoral calcification that mimicked hepatolithiasis. A 73-year-old man presented to a local hospital with a calcified lesion in the hepatic hilum. At first, hepatolithiasis was diagnosed, and he underwent endoscopic stone extraction via the trans-papillary route. This treatment strategy failed due to biliary stricture. He was referred to our hospital, and further examination suggested the existence of cholangiocarcinoma. He underwent left hepatectomy with caudate lobectomy and extrahepatic bile duct resection. Pathological examination revealed hilar cholangiocarcinoma with intratumoral calcification, while no stones were found. To the best of our knowledge, only one case of calcified hilar cholangiocarcinoma has been previously reported in the literature. Here, we report a rare case of calcified hilar cholangiocarcinoma and reveal its clinicopathologic features.