Retrospective Analysis of Outcomes Following Percutaneous Cholecystostomy for Acute Cholecystitis.

BACKGROUND: Percutaneous cholecystostomy (PC) is often performed for patients with acute cholecystitis who are too high risk for cholecystectomy. The purpose of this retrospective study was to evaluate the outcomes of this cohort of patients over a 5-year period. METHODS: A retrospective analysis of all patients treated with PC for acute cholecystitis in a tertiary centre teaching hospital was conducted. The study period ranged from January 2010 to December 2015. Clinical data were extracted from the hospitals' electronic database system, as well as reviewing clinical notes and imaging reports. The aims of this study were to detect the reason PC was undertaken as opposed to surgery, the subsequent definitive management of patients initially treated with PC, the incidence of common bile duct stones (CBDS), the complications from PC, and the 30-day mortality. RESULTS: A total of 96 patients were identified. The total number of patients with CBDS was 27 (28.1%). Fourteen (14.6%) patients were shown to have CBDS on initial imaging. CBDS was detected in 12 patients (12.5%) at cholangiogram during their PC procedure. One patient had CBDS detected during a check cholangiogram at 6 weeks, which was not seen on initial imaging. Twenty-eight patients (29.2%) underwent an endoscopic retrograde cholangiopancreatography (ERCP), during their index admission. The main reasons for PC were a high American Society of Anaesthesiologists (ASA) score (49%), sepsis requiring organ support (19.8%), empyema of the gallbladder (29.1%), failed external biliary drainage for biliary obstruction (2.1%), and concomitant palliative malignancy (5.2%). Interval cholecystectomy was performed in 24 patients (25%). The total 30-day in-hospital mortality was 16.7%. CONCLUSION: PC is an effective and safe alternative as salvage therapy in high-risk elderly patients who have multiple comorbidities. It is valuable as a temporising measure before definitive treatment in high-risk patients. A high index of suspicion for CBDS (and further imaging with MRCP or a check cholangiogram) is warranted to detect missed CBDS. This is particularly relevant in this vulnerable group of patients where CBDS may represent a future source of recurrent sepsis.

Improved outcomes of islet autotransplant after total pancreatectomy by combined blockade of IL-1ß and TNFα.

The efficacy of islet transplant is compromised by a significant loss of islet mass posttransplant due to an innate inflammatory reaction. We report the use of a combination of etanercept and anakinra (ANA+ETA) to block inflammatory islet damage in 100 patients undergoing total pancreatectomy with islet autotransplant. The patients were divided into 3 groups: no treatment (control [CTL]), etanercept alone (ETA), or a combination of etanercept and anakinra (ANA+ETA). Peritransplant serum samples were analyzed for protein markers of islet damage and for inflammatory cytokines. Graft function was assessed by fasting blood glucose, basal C-peptide, secretory unit of islet transplant objects (SUITO) index, and hemoglobin A1c . Administration of both antiinflammatory drugs was well tolerated without any major adverse events. Reductions in interleukin-6, interleukin-8, and monocyte chemoattractant protein 1 were observed in patients receiving ANA+ETA compared with the CTL group, while also showing a modest improvement in islet function as assessed by basal C-peptide, glucose, hemoglobin A1c , and SUITO index but without differences in insulin dose. These results suggest that double cytokine blockade (ANA+ETA) reduces peritransplant islet damage due to nonspecific inflammation and may represent a promising strategy to improve islet engraftment, leading to better transplant outcomes.

Treatment Access and Survival Amongst British Asians with Pancreatic Cancer.

INTRODUCTION: Despite increasingly mixed communities in large cities, there remains a paucity of absolute and comparative data concerning the treatment, access and survival of British Asians with pancreatic cancer. METHODS: A prospective database of 1038 patients with a diagnosis of pancreatic cancer from 2003 to 2012 was analysed. Asian/Asian British was defined as patients identifying themselves as originating from India, Bangladesh or Pakistan. RESULTS: No significant difference was observed in gender split for both Asian/Asian British and White British (AAB and WB). The incidence of pancreas cancer was also equivalent between the two groups at 8.1 versus 8.8 per 100,000 of the population. Age at presentation was significantly younger in AABs when compared to WBs (67 vs. 70 years, p = 0.003). Whilst median maximal tumour diameter, node status and the incidence of metastases were not different between AABs and WBs, the AABs had a significantly greater median T-stage (3.0 versus 2.5, p = 0.0024). The percentage of patients referred for chemotherapy was significantly higher in the AAB group (70.5 vs. 47.7 %, p = 0.0015). Overall survival and survival for patients having palliative treatment were significantly greater in AABs (4.6 vs. 6.1 months and 3.7 vs. 5.1 months). CONCLUSION: This study demonstrates that AAB patients are present with pancreatic cancer at a younger age and that when receiving palliative chemotherapy their survival is significantly better. Further studies and larger data sets over a longer period are required. It is important to examine further the complexity of incidence and survival in ethnic minorities and investigate the underlying reasons when differences are demonstrated.

Indeterminate Pulmonary Nodules in Resected Liver Metastases from Colorectal Cancer: A Comparison of Patient Outcomes.

AIMS: Hepatic metastasectomy remains the only potentially curative treatment for colorectal liver metastases (CRLM). Some of these patients develop indeterminate pulmonary nodules (IPNs). This study aimed to compare outcomes of patients with and without IPN undergoing resection of CRLM to ascertain whether their presence is clinically significant. METHODS: Cases and controls were identified from a prospectively maintained database of CRLM resections. Patients with staging radiology demonstrating IPNs were included as cases. Controls were matched to the cases by four primary factors: age, type of resection (primary or redo), clinical risk score (CRS) and chemotherapy. RESULTS: The median disease-free survival (DFS) and overall survival (OS) for the cases were 7.0 months (95% CI 4.8-9.2) and 28.6 months (95% CI 21.2-36.0), respectively, and 12.0 months (95% CI 10.7-13.2) and 30.5 months (95% CI 19.4-41.6) for the controls. The 1-, 3- and 5-year survival rates were 92.7, 39.7 and 0.0% for the IPN group, and 92.4, 32.9 and 21.9% for those without. In total, 60.7% of IPN patients progressed to lung metastases, of which 39.3% underwent pulmonary resections. DFS was significantly shorter in the IPN group (p = 0.022), but OS was not significantly different (p = 0.421). The presence of IPN was independently associated with a shortened DFS (p = 0.027), as was a CRS of 3 or greater (p = 0.007). CONCLUSION: This study suggests that IPN does not significantly affect OS, but may predict earlier disease recurrence. IPN presence alone should not preclude radical resection but could be used to prompt more careful post-operative surveillance to detect lung metastases at a potentially operable stage.

Interaction of partially denatured insulin with a DSPC floating lipid bilayer.

The carefully controlled permeability of cellular membranes to biological molecules is key to life. In degenerative diseases associated with protein misfolding and aggregation, protein molecules or their aggregates are believed to permeate these barriers and threaten membrane integrity. We used neutron reflectivity to study the interaction of insulin, a model amyloidogenic protein, with a DSPC floating lipid bilayer. Structural changes consistent with protein partitioning to the membrane interior and adsorption to a gel phase model lipid bilayer were observed under conditions where the native fold of the protein is significantly destabilised. We propose that the perturbation of the membrane by misfolded proteins involves long term occupation of the membrane by these proteins, rather than transient perforation events.

Clinical utility of panfungal polymerase chain reaction for the diagnosis of invasive fungal disease: a single center experience.

The role of panfungal polymerase chain reaction (PCR) assays for diagnosis of invasive fungal disease (IFD) is inadequately defined. We describe the use of an internal transcribed spacer 1 (ITS-1) region-directed panfungal PCR in this context at a tertiary referral transplant center. A retrospective review of patients at Alfred Health, Melbourne, Australia (2009-2014) who had clinical samples referred for panfungal PCR testing was conducted. Baseline patient characteristics, antifungal drug history, fungal culture/histopathology, and radiology results were recorded. For bronchoalveolar lavage (BAL) fluid samples, identification of a fungus other than a Candida spp. was defined as a potential pathogen.Of 138 panfungal PCR tests (108 patients), 41 (30%) were positive for a fungal product. Ninety-seven percent (134/138) of specimens were from immunocompromised hosts. Thirteen percent (19/138) of panfungal PCR positive results were for potential pathogens and potential pathogens were detected more frequently in tissue as compared with BAL (12/13 vs. 6/26; P = .0001). No positive panfungal PCR results were obtained from CSF specimens. If histopathology examination was negative, panfungal PCR identified a potential pathogen in only 12% (11/94) of specimens. For the 20 culture negative/histopathology positive specimens, diagnosis of IFD to causative species level by panfungal PCR occurred in 35% (6/20).Sterile site specimens, in particular tissue, were more frequently panfungal PCR positive for potential pathogens than BAL. The utility of panfungal PCR appears greatest in tissue specimens, as an adjunct to histopathology to improve diagnostic sensitivity and specificity. Based on the results of this study we are now only testing tissue specimens by panfungal PCR.

A qualitative study of the impact of the UK 'bedroom tax'.

BACKGROUND: The implementation of the 'Removal of the Spare Room Subsidy' in April 2013, commonly known as the 'bedroom tax', affects an estimated 660 000 working age social housing tenants in the UK, reducing weekly incomes by £12-£22. This study aimed to examine the impact of this tax on health and wellbeing in a North East England community in which 68.5% of residents live in social housing. METHODS: Qualitative study using interviews and a focus group with 38 social housing tenants and 12 service providers. RESULTS: Income reduction affected purchasing power for essentials, particularly food and utilities. Participants recounted negative impacts on mental health, family relationships and community networks. The hardship and debt that people experienced adversely affected their social relationships and ability to carry out normal social roles. Residents and service providers highlighted negative impacts on the neighbourhood, as well as added pressure on already strained local services. CONCLUSIONS: The bedroom tax has increased poverty and had broad-ranging adverse effects on health, wellbeing and social relationships within this community. These findings strengthen the arguments for revoking this tax.

Ablation for recurrent hepatocellular carcinoma: a systematic review of clinical efficacy and prognostic factors.

BACKGROUND: Hepatocellular carcinoma (HCC) typically recurs following primary treatment. The primary objective of this systematic review was to evaluate the safety and efficacy of ablative therapies for recurrent HCC. The secondary objective was to identify any factors associated with prognosis following ablation for recurrent disease. METHODS: A systematic search of the literature published between January 2000 and December 2013 was undertaken using the PubMed, Medline and Scopus databases. Reference lists from selected studies were manually searched to ensure complete capture of any relevant data. RESULTS: A total of 19 studies were included in the review. The median age of patients undergoing ablation for recurrent HCC was 58 years (range 52-69 years) and 85 % of patients had cirrhosis (range 56-100 %). HCC recurred as a single nodule in 79 % of those treated with ablation (range 46-100 %). There were few significant complications associated with any form of ablation. Sufficient data were only available to allow analysis of survival outcomes following radiofrequency ablation (RFA). After RFA the median, 1, 3 and 5-year survivals were 84 % (73-99 %), 51 % (42-84 %) and 40 % (28-83 %), respectively. The only factor consistently associated with overall survival following ablation for recurrence was the alpha-fetoprotein (AFP) level. CONCLUSION: Comparable survival figures from previously published systematic reviews suggest that hepatic resection is the most effective treatment for recurrent HCC. However, ablation can be a safe and effective option for the majority of patients with recurrent disease who are unsuitable for surgery. Elevated levels of AFP suggest a poorer prognosis following ablation.

Aspirin may prevent cholangiocarcinoma: a case-control study from the United kingdom.

BACKGROUND: The proliferation of cholangiocarcinoma cells is suppressed in cell culture by nonsteroidal antiinflammatory drugs (NSAIDs) through the inhibition of cyclo-oxygenase-2 enzyme and also by statins which decrease the production of mediators of the cell cycle. AIMS: To investigate whether there is an inverse association between NSAIDs, including aspirin, and the development of cholangiocarcinoma and, for the first time in a Western population, between statin use and the development of cholangiocarcinoma. METHODS: This epidemiological study had a case-control design in which cases of cholangiocarcinoma diagnosed in Norwich between 2004 and 2010 and in Leicester in 2007 were identified from clinical databases. Controls were patients with basal cell carcinomas treated in the respective dermatology departments. The case notes of all subjects were reviewed to confirm diagnoses and obtain information on medication use. The data were analyzed using unconditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI). RESULTS: In total, 81 cases of cholangiocarcinoma and 275 controls were identified. For all cases there was radiological evidence of cancer and 86 % of the cases involved the extrahepatic biliary system. Aspirin use was inversely associated with the development of cholangiocarcinoma (OR 0.45, 95 % CI 0.22-0.92), but there were no significant associations between the development of cholangiocarcinoma and NSAIDs (OR 0.39; 95 % CI 0.11-1.42) or statins (OR 0.58; 95 % CI 0.28-1.19). CONCLUSIONS: The epidemiological data from this study support the biological evidence for aspirin having a protective effect against the development of cholangiocarcinoma. Aspirin use should be measured in future etiological studies and assessed as a chemoprevention agent in those at high risk of developing this type of cancer.

Imaging of indeterminate pancreatic cystic lesions: a systematic review.

BACKGROUND: Pancreatic cystic lesions are an increasing problem and investigation of these cysts can be fraught with difficulty. There is currently no gold standard for diagnosis or surveillance. This review was undertaken to determine the present reliability of the characterisation, assessment of malignant potential and diagnosis of pancreatic cystic lesions using available imaging modalities. METHODS: A Medline search using the terms 'pancreatic', 'pancreas', 'cyst', 'cystic', 'lesions', 'imaging', 'PET'. 'CT', 'MRI' and 'EUS' was performed. Publications were screened to include studies examining the performance of CT, MRI, MRCP, EUS and 18-FDG PET in the determination of benign or malignant cysts, cyst morphology and specific diagnoses. RESULTS: Nineteen studies were identified that met the inclusion criteria. 18-FDG PET had a sensitivity and specificity of 57.0-94.0% and 65.0-97.0% and an accuracy of 94% in determining benign versus malignant cysts. CT had a sensitivity and specificity of 36.3-71.4% and 63.9-100% in determining benign disease but had an accuracy of making a specific diagnosis of 39.0-44.7%. MRI had a sensitivity and specificity of 91.4-100.0% and 89.7% in assessing main pancreatic duct communication. CONCLUSION: CT is a good quality initial investigation to be used in conjunction with clinical data. MRCP can add useful information regarding MPD communication but should be used judiciously. PET may have a role in equivocal cases to determine malignancy. Further examination of CT-PET in this patient group is warranted.

The differential effects of statins on the risk of developing pancreatic cancer: a case-control study in two centres in the United Kingdom.

INTRODUCTION: There are plausible biological mechanisms for how statins may prevent pancreatic cancer, although the evidence from epidemiological studies in the general population is conflicting. This study aims to clarify whether statins exert their effects in specific sub-groups, namely, gender, smoking status and diabetes. METHODS: A matched case-control study was conducted in patients diagnosed with pancreatic cancer, and a group of dermatology patients of similar ages and gender, diagnosed with basal cell carcinoma. Participants' medical records were reviewed for information on statin use prior to diagnosis. Odds ratios and 95 % CIs for the development of pancreatic cancer were estimated using conditional logistic regression. Subgroup analysis was performed in men, women, smokers and those with type 2 diabetes. RESULTS: Two hundred fifty-two cases (median age 71 years, range 48-73 years, 51 % women) and 504 controls were identified, of which 23 % of cases were regular statin users versus 21 % of controls. In the general study population there was no association between pancreatic cancer and regular statin use (OR 0.82, 95 % CI 0.53-1.23, p = 0.33). However, in male smokers, regular statin use was associated with significantly reduced odds of pancreatic cancer compared to male smokers not prescribed a statin (OR 0.11, 95 % CI 0.01-0.96, p = 0.05). In patients with type 2 diabetes statins use was not associated with reduced odds (OR 0.92, 95 % CI 0.35-2.45, p = 0.80), with no gender effects. CONCLUSIONS: In male smokers, statins may reduce the odds of pancreatic cancer. Statin use should be measured in aetiological studies of pancreatic cancer but analysed in specific sub-groups. Future work should investigate statins as chemopreventative agents in this high risk sub-group.

Systematic review of total pancreatectomy and islet autotransplantation for chronic pancreatitis.

BACKGROUND: Total pancreatectomy and islet autotransplantation (TP/IAT) is a treatment option in a subset of patients with chronic pancreatitis. A systematic review of the literature was performed to evaluate the outcome of this procedure, with an attempt to ascertain when it is indicated. METHODS: MEDLINE (1950 to present), Embase (1980 to present) and the Cochrane Library were searched to identify studies of outcomes in patients undergoing TP/IAT. Cohort studies that reported the outcomes following the procedure were included. The MOOSE guidelines were used as a basis for this review. RESULTS: Five studies met the inclusion criteria. The techniques reported for pancreatectomy and islet cell isolation varied between studies. TP/IAT was successful in reducing pain in patients with chronic pancreatitis. Comparing morphine requirements before and after the procedure, two studies recorded significant reductions. Concurrent IAT reduced the insulin requirement after TP; the rate of insulin independence ranged from 46 per cent of patients at 5 years' mean follow-up to 10 per cent at 8 years. The impact on quality of life was poorly reported. The studies reviewed did not provide evidence for optimal timing of TP/IAT in relation to the evolution of chronic pancreatitis. CONCLUSION: This systematic review showed that TP/IAT had favourable outcomes with regard to pain reduction. Concurrent IAT enabled a significant proportion of patients to remain independent of insulin supplementation.

Surgical therapy in chronic pancreatitis.

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas which causes chronic pain, as well as exocrine and endocrine failure in the majority of patients, together producing social and domestic upheaval and a very poor quality of life. At least half of patients will require surgical intervention at some stage in their disease, primarily for the treatment of persistent pain. Available data have now confirmed that surgical intervention may produce superior results to conservative and endoscopic treatment. Comprehensive individual patient assessment is crucial to optimal surgical management, however, in order to determine which morphological disease variant (large duct disease, distal stricture with focal disease, expanded head or small duct/minimal change disease) is present in the individual patient, as a wide and differing range of surgical approaches are possible depending upon the specific abnormality within the gland. This review comprehensively assesses the evidence for these differing approaches to surgical intervention in chronic pancreatitis. Surgical drainage procedures should be limited to a small number of patients with a dilated duct and no pancreatic head mass. Similarly, a small population presenting with a focal stricture and tail only disease may be successfully treated by distal pancreatectomy. Long-term results of both of these procedure types are poor, however. More impressive results have been yielded for the surgical treatment of the expanded head, for which a range of surgical options now exist. Evidence from level I studies and a recent meta-analysis suggests that duodenum-preserving resections offer benefits compared to pancreaticoduodenectomy, though the results of the ongoing, multicentre ChroPac trial are awaited to confirm this. Further data are also needed to determine which of the duodenum-preserving procedures provides optimal results. In relation to small duct/minimal change disease total pancreatectomy represents the only valid surgical option for the treatment of pain. Though previously dismissed as a valid treatment due to the resultant brittle diabetes, the advent of islet cell autotransplantation has enabled this procedure to produce excellent long-term results in relation to pain, endocrine status and quality of life. Given these excellent short- and long-term results of surgical therapy for chronic pancreatitis, and the poor symptom control provided by conservative and endoscopic treatment (coupled to near inevitable progression to exocrine and endocrine failure), it is likely that future years will see a further shift towards the earlier and more frequent surgical treatment of chronic pancreatitis. Furthermore, the expansion of islet cell autotransplantation to a wider range of pancreatic resections has the potential to even further improve the outcomes of surgical treatment for this problematic yet increasingly common disease.

Branch-type intraductal papillary mucinous neoplasms: an update.

BACKGROUND/AIMS: Branch-type intraductal papillary mucinous neoplasms (BT-IPMNs) are a subset of non-inflammatory mucinous lesions of the pancreas. Selected BT-IPMNs can be managed conservatively by surveillance because of their lower malignant potential. This review aims to update the reader on advances in our knowledge of BT-IPMNs since the consensus guidelines published in 2006. METHODS: A Pubmed search for BT-IPMNs was undertaken and relevant papers were reviewed. RESULTS: Due to the relative scarcity of this condition, still little is known about the natural history, the best method of surveillance or the surgical and non-surgical options. CONCLUSION: A national database of BT-IPMNs would enable a large enough cohort of patients to be followed up and valid conclusions drawn regarding the best method of treatment or surveillance. and IAP.