Laparoscopic Partial Hepatectomy: Animal Experiments

As a first step in firmly establishing laparoscopic hepatectomy, we introduce a porcine model of laparoscopic partial hepatectomy. This procedure has been successfully performed under the normal-pressure or low-pressure pneumoperitoneum condition supported by the full-thickness abdominal wall lifting technique. An ultrasonic dissector combined with electrocautery, newly developed by Olympus Optical Corporation (Japan) was effectively utilized in facilitating safe and smooth incisions into the liver parenchyma. Although indications for this procedure seem to be limited only to peripheral lesions and not to central lesions, clinical application of this method may be useful for some patients in the near future

Endscopic Submucosal Dissection of a Heterotopic Gastric Mucosa in the Stomach: Report of a Case

A 38-year-old man with a submucosal tumor (SMT) at the anterior wall of the pylorus underwent upper gastrointestinal endoscopy. The tumor was 40 mm in diameter with a long stalk extending into the duodenal bulb. In addition, the long stalk had an ulcer with a blood vessel. Removal of this tumor was initially considered to be possible only by distal gastrectomy. However, endoscopic ultrasound (EUS) was subsequently proven to be a reliable investigative procedure for evaluating the lesion. The tumor was characterized by its origin in the second layer, and endoscopic submucosal dissection (ESD) was performed. En bloc resection of a 32 × 20 × 40 mm area of tissue with tumor-free lateral/vertical margins was accomplished without complication. Histopathological examination confirmed a heterotopic gastric mucosa. By immunostaining, the neoplasm was positive for MUC6 and negative for amylase and trypsin. In this case, EUS was used to investigate a heterotopic gastric mucosa that originated in the second layer, with no infiltration of the fourth layer under the tumor. Therefore, we performed successful ESD at the appropriate layer

Usefulness of Background Coloration in Detection of Esophago-Pharyngeal Lesions Using NBI Magnification

Background and Aim. We evaluated the usefulness of background coloration (BC), a color change in the area between intrapapillary capillary loops (IPCLs) in the early esophago-pharyngeal lesions using NBI with magnificaiton. Methods. Between April 2004 and March 2010, a total of 294 esophago-pharyngeal lesions were examined using NBI with magnification, and the presence of BC and IPCL patterns were assessed. Using BC, discrimination of squamous cell carcinoma (SCC) or high-grade neoplasia (HGN) from low-grade neoplasia (LGN) or nonatypia was conducted. Results. Among 294 lesions, 209 lesions (71.1) were positive for BC, while 85 (28.9) were negative. In the BC-positive group, 187 lesions (89.5) were diagnosed as SCC/HGN. And 68 lesions (80.0) in the BC-negative group were diagnosed as LGN/nonatypia. Overall accuracy of BC to discriminate SCC/HGN from LGN/nonatypia was 87.3. The sensitivity and specificity were 91.9, 76.7. BC could discriminate SCC/HGN from LGN/nonatypia accurately (P 0.0001). Among 68 lesions classified into the IPCL type IV, the BC-positive group (n = 26) included 21 SCC/HGN lesions, while there were 36 LGN/nonatypia lesions in the 42 BC-negative lesions. Conclusions. BC is a useful finding in differentiating SCC/HGN from LGN/nonatypia lesions in the esophagus especially when it is combined with IPCL pattern classification

Complete Response Using Sorafenib Monotherapy for Advanced Hepatocellular Carcinoma with Multiple Lymph Node and Bone Metastases: A Case Report

Hepatocellular carcinoma（HCC）is the sixth most commonly diagnosed cancer worldwide. Sorafenib is an oral multikinase inhibitor used in the palliative treatment of advanced HCC. However, there were no reported cases of complete response（CR）from two previous large phaseⅢ clinical trials. Here, we report a case of CR in a patient with advanced HCC with multiple lymph node and bone metastases, treated with sorafenib monotherapy for 8 months. To our knowledge, this is the first evidence showing CR following sorafenib monotherapy for HCC with bone metastasis

Clinical Efficacy of Endocytoscopy for Gastrointestinal Endoscopy

Endocytoscopy (EC) is a contact-type optical endoscope that allows in vivo cellular observation during gastrointestinal endoscopy and is now commercially available not only in Japan but also in Asian, European Union, and Middle Eastern countries. EC helps conduct a highly accurate pathological prediction without biopsy. Initially, EC was reported to be effective for esophageal diseases. Subsequently, its efficacy for stomach and colorectal diseases has been reported. In this narrative review, we searched for clinical studies that investigated the efficacy of EC. EC seems to accurately diagnose gastrointestinal diseases without biopsy. Most of the studies aimed to clarify the relationship between endocytoscopic findings of gastrointestinal neoplasia and pathological diagnosis. Some studies have investigated non-epithelial lesions or diseases, such as inflammatory bowel disease or infectious diseases. However, there are few high-level pieces of evidence, such as randomized trials; thus, further studies are needed

Cyclic ADP-ribose as an endogenous inhibitor of the mTOR pathway downstream of dopamine receptors in the mouse striatum

The role of cyclic ADP-ribose (cADPR) as a second messenger and modulator of the mTOR pathway downstream of dopamine (DA) receptors and/or CD38 was re-examined in the mouse. ADP-ribosyl activity was low in the membranes of neonates, but DA stimulated it via both D1- and D2-like receptors. ADP-ribosyl cyclase activity increased significantly during development in association with increased expression of CD38. The cADPR binding proteins, FKBP12 and FKBP12.6, were expressed in the adult mouse striatum. The ratio of phosphorylated to non-phosphorylated S6 kinase (S6K) in whole mouse striatum homogenates decreased after incubation of adult mouse striatum with extracellular cADPR for 5 min. This effect of cADPR was much weaker in MPTP-treated Parkinson’s disease model mice. The inhibitory effects of cADPR and rapamycin were identical. These data suggest that cADPR is an endogenous inhibitor of the mTOR signaling pathway downstream of DA receptors in the mouse striatum and that cADPR plays a certain role in the brain in psychiatric and neurodegenerative diseases. © 2016 Springer-Verlag WienEmbargo Period 12 month

Clinicopathological characteristics and treatment strategies in early gastric cancer: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Both endoscopic and surgical approaches are employed in the treatment of early gastric cancer (EGC). The aim of this study was to establish appropriate treatment strategies for early gastric cancer.</p> <p>Methods</p> <p>We retrospectively examined clinicopathological data of EGC patients who had undergone surgery.</p> <p>Results</p> <p>A total of 327 patients (204 males and 123 females, mean age 63.2 years) were eligible for inclusion in the study. The median follow-up period was 31 months. Of 161 mucosal (pT1a) tumors, 87 were mainly undifferentiated and 110 had an undifferentiated component. Four patients with pT1a tumors had lymph node metastases; all these tumors were signet-ring cell carcinomas and were macroscopic type 0-IIc with ulceration, and only one of them had lymphatic invasion. Among patients with submucosal tumors, four of 43 patients with pT1b1 tumors and 37 of 123 patients with pT1b2 tumors had nodal metastases. Lymph node metastases were significantly higher in mixed undifferentiated type group than differentiated type group for both groups, pT1a-pT1b1 (p = 0.0251) and pT1b2 (p = 0.0430) subgroups. Only four of 45 patients with nodal metastases were diagnosed preoperatively by computed tomography (sensitivity 8.9%, specificity 96.2%). Nine patients with pT1b tumors had recurrence after surgery, and died. The sites of initial recurrence were liver, bone, peritoneum, distant nodes, and the surgical anastomosis.</p> <p>Conclusions</p> <p>The incidence of nodal metastases was approximately 5% in undifferentiated type mucosal (pT1a) tumors, and higher in submucosal (pT1b) tumors. The sensitivity of preoperative diagnosis of nodal metastases in EGC using computed tomography was relatively low in this study. Therefore at present surgery with adequate lymphadenectomy should be performed as curative treatment for undifferentiated type EGC.</p

Improvement of endocytoscopic findings after per oral endoscopic myotomy (POEM) in esophageal achalasia; does POEM reduce the risk of developing esophageal carcinoma? Per oral endoscopic myotomy, endocytoscopy and carcinogenesis

Background: Per oral endoscopic myotomy (POEM) has been reported to be a new therapeutic option for esophageal achalasia. The possibility that POEM could reduce the risk of developing esophageal squamous cell carcinoma was evaluated.Methods: This was a single-centre, retrospective study. Fifteen consecutive patients with esophageal achalasia who underwent POEM in our institution between August 2010 and January 2012 were enrolled. Ultra-high magnification with endocytoscopy was performed, and both histopathological and immunohistochemical evaluations for Ki-67 and p53 were assessed before and 3 months after POEM.Results: POEM was successfully performed and effectively released the dysphagia symptom in all patients without severe complications. Subjective symptoms (mean Ekcardt score, before 7.4 vs. after 0.5, p<0.05) and manometric pressure studies (mean lower esophageal sphincter pressure), before 82.7 vs. after 22.9 mmHg, p<0.05) showed substantial improvement following POEM. The average numbers of esophageal epithelial nuclei before and after POEM on endocytoscopic images were 128.0 and 78.0, respectively (p<0.05). The mean Ki-67-positive ratio was 26.0 (median 25.4, range, 10.3-33.2) before and 20.7 (median 20.0, 13.1-29.9; p=0.07) after POEM, and the mean p53-positive ratio was 2.35 (median 2.61, 0.32-4.23) before and 0.97 (median 1.49, 0.32-1.56; p<0.05) after POEM. A significant positive correlation was seen between the number of nuclei and the Ki-67-positive ratio (p<0.05).Conclusions: POEM appears to be an effective and less invasive treatment of choice against achalasia and may reduce the risk of esophageal carcinogenesis. Endocytoscopy can be useful for the assessment of esophageal cellular proliferation

Background Coloration of Squamous Epithelium in Esophago-Pharyngeal Squamous Cell Carcinoma: What Causes the Color Change?

Objectives: This study aims to clarify the cause of background coloration in the epithelia between each dilated intra papillary capillary loop in esophago-pharyngeal squamous cell carcinoma. Design: This is a single center retrospective study including 124 patients with 160 lesions who underwent esophagogastroduodenoscopy in Nagasaki University Hospital from September 2007 to March 2012; a detailed comparison between endoscopic images and pathology was performed. Immunohistological assessment using anti-human hemoglobin antibody (anti-Hb Ab) was performed to verify the presence of hemoglobin (Hb) component in the cancer cells. Real-time polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) on Hb-β mRNA were performed to assess the production of Hb component within the cancer cells. Results: A strong positivity for anti-Hb Ab was observed in the squamous cell carcinoma area, whereas non-cancerous mucosa showed no immunopositivity for Hb. The concordance rate between anti-Hb Ab immunoreactivity and the presence of BC was as high as 80.9%. The amount of Hb-β mRNA expression was three times higher in cancer tissues compared with the surrounding non-cancerous mucosa. ISH images showed that the expression exclusively occurred in cancer cells, indicating that Hb is probably produced within cancer cells. Conclusions: The background coloration observed is partly due to an extravascular component of Hb. RT-PCR and ISH analyses indicate that Hb is produced within cancer cells