Clinicopathological and prognostic significance of MUC13 and AGR2 expression in intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a primary pancreatic ductal epithelial neoplasm with the potential to develop into an invasive adenocarcinoma. This study aimed to investigate the clinicopathologic and prognostic significance of four potential biomarkers for the preoperative evaluation of patients with IPMN. MATERIALS AND METHODS: Clinicopathologic materials from 104 patients with IPMN who underwent surgical resection at Jichi Medical University Hospital were analyzed. IPMNs (110 lesions in total) were histologically classified into low-grade IPMN (Group 1; n = 68), high-grade IPMN (Group 2; n = 16), or IPMN with an associated invasive carcinoma (Group 3; n = 26). We evaluated the immunohistochemical expression of MUC13, AGR2, FUT8, and FXYD3, which were previously reported to be overexpressed in pancreatic ductal adenocarcinoma. RESULTS: The expression of MUC13 was more common in Group 3 compared with groups 1 and 2 (p < 0.001) and was associated with poor prognosis (p = 0.004). The expression of MUC13 was not associated with age, sex, tumor location, histological subtype, lymphatic or vascular invasion, or neural invasion. In most cases of IPMN, the loss of expression of AGR2 appeared to show an association with tumor recurrence and poorly differentiated histology of invasive carcinoma; however, this association was not statistically significant. The expressions of FUT8 and FXYD3were not associated with the clinicopathological features of IPMNs. CONCLUSIONS: The results suggest that MUC13 overexpression and loss of expression of AGR2 may predict the progression of IPMN and an unfavorable prognosis in patients with IPMN.

Distinct patterns of peritumoral histological findings in subtypes of intraductal papillary mucinous neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are primary pancreatic neoplasms that can act as precursors to invasive adenocarcinoma of the pancreas. The peritumoral stroma has been increasingly recognized to play an important role in many types of tumors. Therefore, to investigate the clinicopathological significance of the peritumoral stroma in IPMNs, we examined the histological features of the peritumoral stroma in each subtype and histological grade of IPMNs. Eighty-two patients with IPMN, who underwent surgical resection, were reviewed clinicopathologically. Intraductal papillary mucinous neoplasms (86 lesions in total) were histologically subclassified into gastric (n = 51), intestinal (n = 22), pancreatobiliary (n = 11), and oncocytic (n = 2) subtypes. Peritumoral histological features between the gastric and intestinal subtypes were evaluated by each histological grade. The results showed that subepithelial edema and inflammatory cell infiltration were more commonly observed in the gastric subtype (74% and 79%, respectively) than in the intestinal subtype (12% and 25%, respectively) of low-grade IPMNs. On the other hand, mucus lakes were more commonly observed in the intestinal subtype (100%) than in the gastric subtype (0%) of high-grade IPMNs. In addition, pancreatobiliary subtype IPMNs tended to exhibit acute inflammation such as neutrophil predominance. This study showed that peritumoral histological features differed among subtypes of IPMNs from low-grade tumors. These differences suggest the possibility that each subtype of IPMNs has a distinct mechanism from an early stage of tumor progression, which is reflected in the properties of the peritumoral stroma.

Direct peroral cholangioscopy using an ultraslim upper endoscope for biliary lesions.

BACKGROUND: The development of direct peroral cholangioscopy (DPOC) using an ultraslim endoscope simplifies biliary cannulation. The conventional techniques are cumbersome to perform and require advanced skills. The recent introduction of the guidewires and balloons has improved the therapeutic outcomes. Here we describe an effective and easier method for performing DPOC using an ultraslim upper endoscope. METHODS: Indications for DPOC were the presence of stones on follow-up of patients who had previously undergone complete sphincteroplasty, including endoscopic sphincterotomy or endoscopic papillary large balloon dilatation. Fifteen patients underwent DPOC. An ultraslim endoscope was inserted perorally and was advanced into the major papilla. The ampulla of Vater was visualized by retroflexing the endoscope in the distal second portion of the duodenum, and then DPOC was performed using a wire-guided cannulation technique with an anchored intraductal balloon catheter. RESULTS: One patient failed in the treatment due to looping of the endoscope in the fornix of the stomach. Fourteen (93.3%) were successfully treated with our modified DPOC technique. Only one patient (6.7%) experienced an adverse event (pancreatitis) who responded well to conservative management. Residual stones of the common bile duct were completely removed in 3 patients. CONCLUSION: The modified method of DPOC is simple, safe and easy to access the bile duct.

Placement of a triple-layered covered versus uncovered metallic stent for palliation of malignant gastric outlet obstruction: a multicenter randomized trial.

BACKGROUND: Usually, uncovered self-expandable metallic stents (SEMS) are used for palliation of malignant gastric outlet obstruction (GOO). A triple-layered covered SEMS is reported to be efficacious, but its performance has not been compared with uncovered SEMS. The present study is the first to compare the efficacy and safety of a triple-layered covered versus uncovered SEMS. PATIENTS AND METHODS: A multicenter randomized study was conducted in two tertiary referral centers, with 62 eligible patients with symptomatic GOO to receive covered (n = 31) or uncovered SEMS (n = 31). The primary endpoint was SEMS patency, and secondary endpoints were success rate and adverse events after complete follow up. RESULTS: Both groups had a technical success rate of 100% and comparable clinical success rates (P = 0.67). There was nostatistically significant difference in stent patency and adverse events between the two groups (P = 0.52 and P = 0.38, respectively). Although the occurrence rate of persistent obstructive symptoms was comparable (P = 0.42), that of recurrent obstructive symptoms was higher in the uncovered group (29% vs 3.6%, P = 0.0125). Patient survival did not differ between groups (P = 0.34). CONCLUSION: There was no statistically significant difference in stent patency, but use of a triple-layered covered SEMS was associated with less frequent stent dysfunction more than 4 weeks after stenting, despite similar short-term outcomes.

What is the preferred shape for an esophageal stent flange?

AIM: Self-expandable metallic stents (SEMS) for the gastrointestinal tract have different types of flanges at either the oral end or both ends to prevent stent migration. The effect of flange shape on the properties of SEMS, to our knowledge, has not been evaluated. The aim of this study was to measure the strain that a SEMS imposes on the adjacent wall and the anti-migration force (AF) exerted by three stents, each with a different flange shape. METHODS: Stents with one of three different flanges (flared, dumbbell, and barrel) were designed and then their strain and AF values were measured with apparatuses devised in our laboratory. RESULTS: Although the average maximal strain values at the flange were similar (508.4 µm/m, 513.3 µm/m and 486.4 µm/m for flared, dumbbell and barrel, respectively), strain values for each position differed among the three different types of stents. Strain values for the flared shape increased toward the stent end, reaching the maximum value. Maximal strain values for the dumbbell and barrel shapes were observed near the flange's midpoint. Maximal AF values differed significantly according to flange shape. Thus, the median maximal AF values were 1.85 newton, 1.35 newton, and 1.13 newton, for barrel, dumbbell and flared shapes, respectively. CONCLUSIONS: The performance of braided esophageal SEMS with barrel shaped flanges is superior to that of SEMS with dumbbell or flared flanges, based on the strain on the adjacent wall and the prevention of stent migration.

Mechanism underlying H2O2-induced inhibition of acetylcholine-induced contraction in rabbit tracheal smooth muscle.

The mechanism underlying the inhibition by H2O2 of acetylcholine-induced contraction was investigated in epithelium-denuded strips of rabbit trachea. Acetylcholine (10 microM) generated a phasic, followed by a tonic increase in both the intracellular Ca2+ concentration ([Ca2+]i) and force. Although the acetylcholine-induced tonic contraction was around 9 times the high K+ (80 mM)-induced one, the two stimulants induced similar [Ca2+]i increases (around 0.2 microM), indicating that acetylcholine generates tonic contraction via increases in both [Ca2+]i and myofilament Ca2+-sensitivity. H2O2 (30 microM) (a) enhanced the acetylcholine-induced tonic (not phasic) increase in [Ca2+]i but attenuated both phases of the acetylcholine-induced contraction and (b) enhanced the high K+-induced increase in [Ca2+]i but did not modify the high K+-induced contraction. In beta-escin-skinned strips, application of acetylcholine in the presence of GTP enhanced the contraction induced by 0.3 microM Ca2+ so that its amplitude became similar to that induced by 1 microM Ca2+. H2O2 (30 microM) attenuated the contraction induced by 0.3 microM Ca2+ (alone or in the presence of acetylcholine) but not those induced by higher concentrations of Ca2+ alone (0.5 microM and 1 microM). These results indicate that H2O2 acts directly on contractile proteins in rabbit tracheal smooth muscle to inhibit the contraction induced by low concentrations of Ca2+ (<0.5 microM). An action of H2O2 that increases [Ca2+]i (and thereby masks this reactive-oxygen-induced inhibition of myofilament Ca2+-sensitivity) is apparent in the presence of high K+ but not of acetylcholine. Thus, in rabbit tracheal smooth muscle H2O2 downregulates myofilament Ca2+-sensitivity more potently during acetylcholine-induced contraction than during high-K+-induced contraction, leading to an effective inhibition of the former contraction.

Is endoscopic papillary large balloon dilatation without endoscopic sphincterotomy effective?

AIM: To evaluate the safety and efficacy of endoscopic papillary large balloon dilatation (EPLBD) without endoscopic sphincterotomy in a prospective study. METHODS: From July 2011 to August 2013, we performed EPLBD on 41 patients with naïve papillae prospectively. For sphincteroplasty of EPLBD, endoscopic sphincterotomy (EST) was not performed, and balloon diameter selection was based on the distal common bile duct diameter. The balloon was inflated to the desired pressure. If the balloon waist did not disappear, and the desired pressure was satisfied, we judged the dilatation as complete. We used a retrieval balloon catheter or mechanical lithotripter (ML) to remove stones and assessed the rates of complete stone removal, number of sessions, use of ML and adverse events. Furthermore, we compared the presence or absence of balloon waist disappearance with clinical characteristics and endoscopic outcome. RESULTS: The mean diameters of the distal and maximum common bile duct were 13.5 ± 2.4 mm and 16.4 ± 3.1 mm, respectively. The mean maximum transverse-diameter of the stones was 13.4 ± 3.4 mm, and the mean number of stones was 3.0 ± 2.4. Complete stone removal was achieved in 97.5% (40/41) of cases, and ML was used in 12.2% (5/41) of cases. The mean number of sessions required was 1.2 ± 0.62. Pancreatitis developed in two patients and perforation in one. The rate of balloon waist disappearance was 73.1% (30/41). No significant differences were noted in procedure time, rate of complete stone removal (100% vs 100%), number of sessions (1.1 vs 1.3, P = 0.22), application of ML (13% vs 9%, P = 0.71), or occurrence of pancreatitis (3.3% vs 9.1%, P = 0.45) between cases with and without balloon waist disappearance. CONCLUSION: EST before sphincteroplasty may be unnecessary in EPLBD. Further investigations are needed to verify the relationship between the presence or absence of balloon waist disappearance.

Pseudoaneurysm developed after percutaneous endoscopic gastrostomy: a report of two cases.

Percutaneous endoscopic gastrostomy (PEG) is widely performed. However, despite its widespread use, complications often follow and some of them are life-threatening. We report on two patients who developed pseudoaneurysm after PEG and how the bleeding was stemmed by transcatheter arterial embolization. Case 1 is an 84-year-old man. PEG by the pull method using One Step Button 24 Fr was performed. Blood-laced vomiting, followed by hemorrhagic shock was observed on day 21. Pseudoaneurysm less than 10 mm in diameter was observed in the gastroepiploic artery by urgent percutaneous abdominal angiography. A microcatheter was advanced selectively and the affected area was embolized by metallic coils and n-butyl cyanoacrylate. Case 2 is an 89-year-old man. PEG by the pull method using One Step Button 24 Fr was performed. On day 28, bleeding from the gastrostomy portion occurred and the patient went into shock. On urgent percutaneous abdominal angiography, pseudoaneurysm ∼5 mm in diameter was detected in the left gastric artery. A microcatheter was advanced selectively and the affected area was embolized by metallic coils and n-butyl cyanoacrylate. In the present two cases, gastrostomies were created in the anterior wall of the mid body portion as suitable for PEG position, but the bleedings occurred because of pseudoaneurysm formation accompanied by damage to the gastroepiploic or the left gastric artery. Those who perform PEG on a regular basis should be aware of the possibility of pseudoaneurysm as a serious adverse event.

Newly designed J-shaped tip guidewire: a preliminary feasibility study in wire-guided cannulation.

AIM: To perform wire-guided cannulation using a newly designed J-shaped tip guidewire, and to verify feasibility and safety for use. METHODS: The study was conducted on endoscopic retrograde cholangiopancreatography (ERCP) patients with naïve papilla undergoing diagnosis and treatment of biliary diseases between September 2011 and July 2012. We performed ERCP in a succession of 50 cases with a J-shaped tip guidewire. The first insertion attempt began with a trainee who had 5 min to complete cannulation, followed if necessary by the trainer for another 5 min. We assessed the primary success rate of selective biliary cannulation within 10 min and adverse events such as post-ERCP pancreatitis (PEP), bleeding or perforation. RESULTS: The primary success rate was 90% (45/50) within 10 min, the initial success rate within 5 min by trainee staff was 76% (38/50). The rate of PEP was 6% (3/50), but all 3 cases were mild pancreatitis. All patients were managed successfully with conservative treatment. There was no bleeding or perforation. CONCLUSION: A newly designed J-shaped tip guide-wire has the possibility to facilitate selective biliary cannulation for ERCP and appears to be safe.