The impact of timing of cholecystectomy following gallstone pancreatitis.

INTRODUCTION: Current guidelines for the management of acute gallstone pancreatitis recommend cholecystectomy as definitive treatment during primary admission or within 2 weeks of discharge, with the aim of preventing recurrent pancreatitis. However, cholecystectomy during the inflammatory phase may increase surgical complication rates. This study aimed to determine whether adherence to the guidelines prevents recurrent pancreatitis while minimising surgical complications. METHODS: Multi-centre review of seven UK hospitals, indentifying patients presenting with their first episode of gallstone pancreatitis between 2006 and 2008. RESULTS: A total of 523 patients with gallstone pancreatitis were identified, of which 363 (69%) underwent cholecystectomy (72 during the primary admission or within 2 weeks of discharge; 291 following this). Overall, 7% of patients had a complication related to cholecystectomy of which a greater proportion occurred when cholecystectomy was performed within guideline parameters (13% vs 6%; p = 0.07). 11% of patients were readmitted with recurrent pancreatitis prior to surgery, with those undergoing cholecystectomy outside guideline parameters being most at risk (p = 0.006). CONCLUSION: This study suggests cholecystectomy within guideline parameters significantly reduces recurrence of pancreatitis but may increase the risk of surgical complications. A prospective randomised study to assess the associated morbidity is required to inform future guidelines.

Endoscopic ultrasound-guided choledoco-duodenostomy as an alternative to percutaneous trans-hepatic cholangiography.

BACKGROUND: Endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (CDS) is an alternative to percutaneous transhepatic cholangiography (PTC) drainage in patients with an obstructed biliary system where conventional endoscopic retrograde biliary drainage (ERBD) has been unsuccessful. METHODS: Five EUS-CDS procedures were reviewed to assess whether successful decompression was achieved and maintained. RESULTS: There was technical success in each instance with no immediate complications. There was a significant fall in the median bilirubin of 164 mmol/l. The median follow-up was 44 days. In one patient the stent migrated with no adverse outcome. CONCLUSION: EUS-CDS is a viable alternative to PTC with fewer complications and comparable success rates. EUS-CDS may offer a future route for novel therapeutic advances.

Postoperative pulmonary complications following major elective abdominal surgery: a cohort study.

BACKGROUND: Postoperative pulmonary complications (PPC) are an under-reported but major cause of perioperative morbidity and mortality. The aim of this prospective, contemporary, multicentre cohort study of unselected patients undergoing major elective abdominal surgery was to determine the incidence and effects of PPC. METHODS: Data on all major elective abdominal operations performed over a 2-week period in December 2014 were collected in six hospitals. The primary outcome measure of PPC at 7 days was used. Univariate and multivariate analyses were performed to investigate how different factors were associated with PPC and the effects of such complications. RESULTS: Two hundred sixty-eight major elective abdominal operations were performed, and the internal validation showed that the data set was 99 % accurate. Thirty-two (11.9 %) PPC were reported at 7 days. PPC was more common in patients with a history of chronic obstructive pulmonary disease compared to those with no history (26.7 vs. 10.2 %, p < 0.001). PPC was not associated with other patient factors (e.g. age, gender, body mass index or other comorbidities), type/method of operation or postoperative analgesia. The risk of PPC appeared to increase with every additional minute of operating time independent of other factors (odds ratio 1.01 (95 % confidence intervals 1.00-1.02), p = 0.007). PPC significantly increase the length of hospital stay (10 vs. 3 days). Attendance to the emergency department within 30 days (27.3 vs. 10.6 %), 30-day readmission (21.7 vs. 9.9 %) and 30-day mortality (12.5 vs. 0.0 %) was higher in those with PPC. CONCLUSIONS: PPC are common and have profound effects on outcomes. Strategies need to be considered to reduce PPC.

Length of Variable Numbers of Tandem Repeats in the Carboxyl Ester Lipase (CEL) Gene May Confer Susceptibility to Alcoholic Liver Cirrhosis but Not Alcoholic Chronic Pancreatitis.

BACKGROUND: Carboxyl-ester lipase (CEL) contributes to fatty acid ethyl ester metabolism, which is implicated in alcoholic pancreatitis. The CEL gene harbours a variable number of tandem repeats (VNTR) region in exon 11. Variation in this VNTR has been linked to monogenic pancreatic disease, while conflicting results were reported for chronic pancreatitis (CP). Here, we aimed to investigate a potential association of CEL VNTR lengths with alcoholic CP. METHODS: Overall, 395 alcoholic CP patients, 218 patients with alcoholic liver cirrhosis (ALC) serving as controls with a comparable amount of alcohol consumed, and 327 healthy controls from Germany and the United Kingdom (UK) were analysed by determination of fragment lengths by capillary electrophoresis. Allele frequencies and genotypes of different VNTR categories were compared between the groups. RESULTS: Twelve repeats were overrepresented in UK ACP patients (P = 0.04) compared to controls, whereas twelve repeats were enriched in German ALC compared to alcoholic CP patients (P = 0.03). Frequencies of CEL VNTR lengths of 14 and 15 repeats differed between German ALC patients and healthy controls (P = 0.03 and 0.008, respectively). However, in the genotype and pooled analysis of VNTR lengths no statistical significant association was depicted. Additionally, the 16-16 genotype as well as 16 repeats were more frequent in UK ALC than in alcoholic CP patients (P = 0.034 and 0.02, respectively). In all other calculations, including pooled German and UK data, allele frequencies and genotype distributions did not differ significantly between patients and controls or between alcoholic CP and ALC. CONCLUSIONS: We did not obtain evidence that CEL VNTR lengths are associated with alcoholic CP. However, our results suggest that CEL VNTR lengths might associate with ALC, a finding that needs to be clarified in larger cohorts.

Carcinoma showing thymus-like elements of the thyroid gland: report of three cases including one case with breast cancer history.

Carcinoma showing thymus-like elements (CASTLE) is a rare malignant tumor of the thyroid or adjacent neck soft tissues, whose histogenesis is still debated. It may resemble other primary or metastatic poorly differentiated tumors histologically and the differential diagnosis is crucial for CASTLE has a better prognosis. However, CASTLE as a second primary tumor has not been reported in the literature. We report three cases of thyroid CASTLE, including a unique tumor following breast-conserving surgery for early-stage breast invasive carcinoma. There were two female and one male. All three tumors were located in the right lobe of the thyroid, and one tumor showed extension into the surrounding soft tissue. Histologically, all tumors showed expansive growth and consisted of cords, nests or sheets of epithelial cells divided into irregularly shaped lobules by fibrous connective tissue with lymphoplasmacytic infiltration. Focal squamous differentiation resembling Hassall's corpuscles were observed. All cases stained positively for CD5, CD117, high molecular weight cytokeratin, cytokeratin, P63, carcinoembryonic antigen and epithelial membrane antigen. Positive staining for Bcl-2 in two cases and chromogranin A in one case was noted. Ki-67 expression ranged from 15 to 25%. Thyroid transcription factor and CD3 were negative. There was no evidence of recurrent or metastatic disease at following surgery. These features demonstrated CASTLE may arise from branchial pouch remnants, the thyroid solid cell nests. CASTLE is a rare entity, awareness of its occurrence as a second primary tumor is important to avoid overtreatment because it is associated with a favorable prognosis.

Protocol for a multicentre, prospective, population-based cohort study of variation in practice of cholecystectomy and surgical outcomes (The CholeS study).

INTRODUCTION: Cholecystectomy is one of the most common general surgical operations performed. Despite level one evidence supporting the role of cholecystectomy in the management of specific gallbladder diseases, practice varies between surgeons and hospitals. It is unknown whether these variations account for the differences in surgical outcomes seen in population-level retrospective data sets. This study aims to investigate surgical outcomes following acute, elective and delayed cholecystectomies in a multicentre, contemporary, prospective, population-based cohort. METHODS AND ANALYSIS: UK and Irish hospitals performing cholecystectomies will be recruited utilising trainee-led research collaboratives. Two months of consecutive, adult patient data will be included. The primary outcome measure of all-cause 30-day readmission rate will be used in this study. Thirty-day complication rates, bile leak rate, common bile duct injury, conversion to open surgery, duration of surgery and length of stay will be measured as secondary outcomes. Prospective data on over 8000 procedures is anticipated. Individual hospitals will be surveyed to determine local policies and service provision. Variations in outcomes will be investigated using regression modelling to adjust for confounders. ETHICS AND DISSEMINATION: Research ethics approval is not required for this study and has been confirmed by the online National Research Ethics Service (NRES) decision tool. This novel study will investigate how hospital-level surgical provision can affect patient outcomes, using a cross-sectional methodology. The results are essential to inform commissioning groups and implement changes within the National Health Service (NHS). Dissemination of the study protocol is primarily through the trainee-led research collaboratives and the Association of Upper Gastrointestinal Surgeons (AUGIS). Individual centres will have access to their own results and the collective results of the study will be published in peer-reviewed journals and presented at relevant surgical conferences.

Incidence of post-ERCP pancreatitis from direct pancreatic juice collection in hereditary pancreatitis and familial pancreatic cancer before and after the introduction of prophylactic pancreatic stents and rectal diclofenac.

OBJECTIVES: Individuals from hereditary pancreatitis (HP) and familial pancreatic cancer (FPC) kindreds are at increased risk of developing pancreatic cancer. Premalignant molecular changes may be detected in pancreatic juice collected by endoscopic retrograde cholangiopancreatography (ERCP). The objective was to determine the risk of post-ERCP pancreatitis (PEP). METHODS: A prospective study (1999-2013) was undertaken of 80 ERCPs (24 in HP and 56 in FPC) from 60 individuals and the impact of PEP prophylaxis using a self-expelling pancreatic stent and 50 mg diclofenac per rectum from 2008. RESULTS: There was no PEP in the HP cohort and 13 (23.2%) PEP from 56 procedures in the FPC cohort (P = 0.0077). Up to 2008 PEP had occurred in 7 (43.8%) of 16 procedures in FPC individuals versus none of 18 procedures in HP individuals (P = 0.0021). After the introduction of prophylaxis, the incidence of PEP fell to 6 (15.0%) of 40 procedures in FPC individuals (P = 0.0347).The odds ratio (95% confidence interval) was 0.23 (0.06-0.84) in favor of prophylaxis (0.035). CONCLUSIONS: Individuals with HP are at minimal risk for PEP. Although the risk of PEP in individuals with FPC can be reduced by using prophylactic self-expelling stents and diclofenac, it remains too high for routine screening.

Short-term continuous high-volume hemofiltration on clinical outcomes of severe acute pancreatitis.

OBJECTIVES: This study aimed to conduct a single-center prospective trial of short-term continuous high-volume hemofiltration (HVHF) in patients with predicted severe acute pancreatitis (SAP). METHODS: Patients with acute pancreatitis with Acute Physiology and Chronic Health Evaluation II scores of greater than 15 on admission between January 2008 and December 2010 were allocated to receive either optimal standard therapy or 72 hours of continuous HVHF on an alternate basis, beginning as soon as possible after admission. Biomarkers and clinical outcomes were compared between the 2 groups. RESULTS: A total of 61 patients received either conventional therapy (n = 29) or HVHF (n = 32). High-volume hemofiltration treatment was associated with a significant reduction in the incidence of renal failure (P = 0.013), infected pancreatic necrosis (P = 0.048), length of hospitalization (P = 0.005), mortality (P = 0.033), as well as duration of renal (P < 0.001), respiratory (P = 0.002), and hepatic failure (P = 0.001). Acute Physiology and Chronic Health Evaluation II score and C-reactive protein and interleukin 6 levels were significantly reduced after the start of HVHF on days 1, 3, and 7 (all, P < 0.05). CONCLUSIONS: This study suggests that short-term HVHF may reduce local and systemic complications and mortality in patients with SAP with Acute Physiology and Chronic Health Evaluation score of greater than 15.

Prediction of the severity of acute pancreatitis on admission by urinary trypsinogen activation peptide: a meta-analysis.

AIM: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission. METHODS: Major databases including Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched to identify all relevant studies from January 1990 to January 2013. Pooled sensitivity, specificity and the diagnostic odds ratios (DORs) with 95%CI were calculated for each study and were compared to other systems/biomarkers if mentioned within the same study. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated. RESULTS: In total, six studies of uTAP with a cut-off value of 35 nmol/L were included in this meta-analysis. Overall, the pooled sensitivity and specificity of uTAP for predicting severity of acute pancreatitis, at time of admission, was 71% and 75%, respectively (AUC = 0.83, DOR = 8.67, 95%CI: 3.70-20.33). When uTAP was compared with plasma C-reactive protein, the pooled sensitivity, specificity, AUC and DOR were 0.64 vs 0.67, 0.77 vs 0.75, 0.82 vs 0.79 and 6.27 vs 6.32, respectively. Similarly, the pooled sensitivity, specificity, AUC and DOR of uTAP vs Acute Physiology and Chronic Health Evaluation II within the first 48 h of admission were found to be 0.64 vs 0.69, 0.77 vs 0.61, 0.82 vs 0.73 and 6.27 vs 4.61, respectively. CONCLUSION: uTAP has the potential to act as a stratification marker on admission for differentiating disease severity of acute pancreatitis.

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis.

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 (P < 1 × 10(-12)) and X-linked CLDN2 (P < 1 × 10(-21)) through a two-stage genome-wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 cases and 4,170 controls). The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous in males) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07).

Mirtazapine: a solution for postoperative gastroparesis?

This report describes the case of a 52-year-old man with an obstructed para-oesophageal hiatus hernia who required a gastropexy, who postoperatively developed gastroparesis which inadequately responded to conventional prokinetics including erythromycin, metoclopramide, ondansetron, and domperidone. The patient's symptoms were relieved rapidly with a trial of mirtazapine. A review of related literature is presented.