Biliary Stenosis and Gastric Outlet Obstruction: Late Complications After Acute Pancreatitis With Pancreatic Duct Disruption.

OBJECTIVES: Pancreatic duct disruption (PDD) after acute pancreatitis can cause pancreatic collections in the early phase and biliary stenosis (BS) or gastric outlet obstruction (GOO) in the late phase. We aimed to document those late complications after moderate or severe acute pancreatitis. METHODS: Between September 2010 and August 2014, 141 patients showed pancreatic collections on computed tomography. Percutaneous drainage was primarily performed for patients with signs or symptoms of uncontrolled pancreatic juice leakage. Pancreatic duct disruption was defined as persistent amylase-rich drain fluid or a pancreatic duct cut-off on imaging. Clinical course of the patients who developed BS or GOO was investigated. RESULTS: Among the 141 patients with collections, 33 patients showed PDD in the pancreatic head/neck area. Among them, 9 patients (27%) developed BS 65 days after onset and required stenting for 150 days, and 5 patients (15%) developed GOO 92 days after onset and required gastric decompression and jejunal tube feeding for 147 days (days shown in median). All 33 patients recovered successfully without requiring surgical intervention. CONCLUSIONS: Anatomic proximity of the bile duct or duodenum to the site of PDD and severe inflammation seemed to contribute to the late onset of BS or GOO. Conservative management successfully reversed these complications.

Better Outcomes if Percutaneous Drainage Is Used Early and Proactively in the Course of Necrotizing Pancreatitis.

PURPOSE: To compare outcomes after percutaneous catheter drainage (PCD) for acute necrotizing pancreatitis versus those in a randomized controlled trial as a reference standard. MATERIALS AND METHODS: Between September 2010 and August 2014, CT-guided PCD was the primary treatment for 39 consecutive patients with pancreatic necrosis. The indication for PCD was the clinical finding of uncontrolled pancreatic juice leakage rather than infected necrosis. Subsequent to PCD, the drains were proactively studied with fluoroscopic contrast medium every 3 days to ensure patency and position. Drains were ultimately maneuvered to the site of leakage. These 39 patients were compared with 43 patients from the Pancreatitis, Necrosectomy versus Step-up Approach (PANTER) trial. RESULTS: The CT severity index was similar between studies (median of 8 in each). Time from onset of acute pancreatitis to PCD was shorter in the present series (median, 23 d vs 30 d). The total number of procedures (PCD and subsequent fluoroscopic drain studies) per patient was greater in the present series (mean, 14 vs 2). More patients in the PANTER trial had organ failure (62% vs 84%), required open or endoscopic necrosectomy (0% vs 60%), and experienced in-hospital mortality (0% vs 19%; P < .05 for all). CONCLUSIONS: Even though patients in the present series had a similar CT severity index as those in the PANTER trial, the former group showed lower incidences of organ failure, need for necrosectomy, and in-hospital mortality. The use of a proactive PCD protocol early, before the development of severe sepsis, appeared to be effective.

A percutaneous drainage protocol for severe and moderately severe acute pancreatitis.

BACKGROUND: According to the revised Atlanta classification, severe and moderately severe acute pancreatitis (AP) includes patients with pancreatic and peripancreatic collections with or without organ failure. These collections suggest the presence of pancreatic juice leakage. The aim of this study was to evaluate the efficacy of a percutaneous catheter drainage (PCD) protocol designed to control leakage and decrease disease severity. METHODS: Among 663 patients with clinical AP, 122 were classified as moderately severe or severe AP (all had collections). The computed tomography severity index (CTSI) score was calculated. The indication for PCD was based on progressive clinical signs and symptoms. Drain patency, position, and need for additional drainage sites were assessed using CT scans and drain studies initially every 3 days using a proactive protocol. Drain fluid was examined for amylase concentration and microbiological culture. Clinicopathological variables for patients with and without PCD were compared. Since there was no mortality, we used prolonged drainage time to measure the success of PCD. Within the group treated with PCD, variables that resulted in prolonged drainage time were analyzed. RESULTS: PCD was used in 47/122 (39 %) patients of which 33/47 (70 %) had necrosis. PCD cases had a median CTSI of 8 and were classified as moderately severe AP (57 %) and severe AP (43 %). Inhospital mortality was zero. Surgical necrosectomy was not required for patients with necrosis. Independent risk factors for prolonged drainage time were persistent organ failure >48 h (P = 0.001), CTSI 8-10 (P = 0.038), prolonged duration of amylase-rich fluid in drains (P < 0.001), and polymicrobial culture fluid in drains (P = 0.015). CONCLUSIONS: A proactive PCD protocol persistently maintaining drain patency advanced to the site of leak controlled the prolonged amylase in drainage fluid resulting in a mortality rate of zero.

A highly conserved alanine in the S6 domain of the hERG1 K+ channel is required for normal gating.

The central cavity of K(+)-selective ion channels is lined by four S6 transmembrane alpha-helices. An Ala residue is located near the midpoint of each S6 and marks the narrowest point of the central cavity. In hERG1 channels, we determined the functional consequences of substituting this conserved Ala (Ala653) with other hydrophobic or charged amino acids. Mutant channels were expressed in Xenopus oocytes and ionic currents measured by using the two-microelectrode voltage clamp technique. Substitution of Ala653 with bulkier hydrophobic residues (Val, Leu, Ile, Met, Phe, Trp) did not prevent ion conduction, but the mutant channels activated at more negative potentials compared to wild-type channels. The half-point for voltage dependent activation was shifted by -54 mV for the most conservative hydrophobic mutation, A653V. Oxidation of A653C hERG1 channels induced a maintained current at negative membrane potentials. This effect was not reversible with dithiothreitol, indicating that the sulfhydryl side-chains of Cys653 were oxidized to a negatively charged sulfinic or sulfonic acid. Substitution of Ala653 with acidic (Asp, Glu) or basic (Arg, Lys) residues prevented channel deactivation. Thus, an Ala at position 653 in hERG1 is required for normal voltage dependence of channel gating and a charged residue in this position prevents channel closure.