A new variant of gallbladder duplication mimicking a choledochal cyst: stepwise management of an unexpected surgical finding.

We present a case of previously unclassified duplicated gallbladder which posed a surgical challenge intraoperatively by mimicking a choledochal cyst. An intraoperative cholangiogram was performed followed by a simple cholecystectomy. No further dissection was performed to avoid bile duct injury and complication from the unconventional anatomy. Postoperative imaging and histology, followed by the second operation confirmed findings consistent with the duplicated gallbladder. Through this case, we have demonstrated the principles of safe cholecystectomy and the importance of a staged approach in an unanticipated encounter of anatomical uncertainty, as well as the description of a new variant of duplicated gallbladder.

Early derangement of INR predicts liver failure after liver resection for hepatocellular carcinoma.

BACKGROUND: Surgical resection, where appropriate, remains one of the best treatment options for hepatocellular carcinoma (HCC), however outcomes can be compromised by the development of liver failure. We reviewed our experience of liver resection for HCC patients to identify factors that may predict the development of post-hepatectomy liver failure (PHLF) and survival. METHODS: A single centre retrospective cohort study. Data was collected between 1999 and 2017 from all patients undergoing HCC resection in a tertiary university hospital from electronic medical records. PHLF was defined as per the International Study Group for Liver Surgery criteria. Variables with p < 0.15 on univariate analysis were included in a multivariate binary logistic regression model. Kaplan-Meier analyses were used to determine correlations with overall survival (OS) and disease-free survival (DFS), and variables with p < 0.15 on univariate analysis selected for a step-down Cox proportional hazard regression model. RESULTS: Overall, 120 patients underwent liver resection within the study period, of which 22 (18%) developed PHLF. Patients with normal INR ≤1.20 at day 2 did not develop PHLF whereas patients with INR >1.60 were at significant risk. Resection of multiple tumours (odds ratio 21.63, p = 0.002) and deranged postoperative day 2 INR>1.6 (odds ratio 21.05, p < 0.0001) were identified as independent prognostic markers of PHLF. CONCLUSION: The use of INR measurement at day 2 predicts PHLF and may enable us to objectively identify and stratify patients who may be eligible for enhanced recovery programs from those who will merit close monitoring in high dependency areas.

Preoperative diagnosis of intraductal papillary neoplasm of the bile duct with endoscopic ultrasound.

Intraductal papillary mucinous neoplasm of the bile duct is a rare tumour only recently classified as a distinct pathological entity. These neoplasms, rarely encountered in clinical practice in the UK, are now considered to be important precursors for the development of cholangiocarcinoma. We present a histologically confirmed case of intraductal papillary neoplasm of the bile duct in a male patient and discuss the main radiographic manifestations of this rare condition across multiple imaging modalities, with an emphasis on the imaging features of endoscopic ultrasonography and its role in establishing the diagnosis.

Biliary cooling during radiofrequency ablation of liver tumours close to central biliary tree: A systematic review and pooled analysis.

INTRODUCTION: Biliary cooling during radiofrequency ablation (RFA) of liver tumour has been proposed as a protective measure for RFA-related biliary complications in cases whereby the RFA site is close to central biliary tree. This systematic review aims to assess the effect of biliary cooling during RFA on: 1) the development of biliary complications and 2) tumour recurrence rates at ablation site. METHODOLOGY: A systematic literature search was performed using the PubMed/EMBASE databases using PRISMA methodology (2000-2019). The initial search yielded 75 reports which were potentially suitable for inclusion. Studies reporting at least one outcome of interest were considered to be suitable for inclusion. Conference abstracts, case reports and animal studies were excluded. Data was retrieved from each study on patient demographics, tumour characteristics, method of cooling, biliary complications, local tumour recurrence and duration of follow-up. RESULTS: The final number of studies which met the inclusion criteria was 7, involving 100 patients. There were no randomized controlled trials identified after the literature search. The mean age of the patients included was 65 years. Biliary cooling was performed with the use of a nasobiliary tube in 4 out of 7 studies, via a choledochal incision in 2 out of 7 studies and through the cystic duct in a single study. The overall biliary stricture rate was 2% and the overall tumour recurrence rate at RFA treated site was 14.5%. CONCLUSION: Biliary complications appear to be low after biliary cooling during RFA close to central biliary tree. More evidence is required to assess the tumour recurrence rates.

A rational approach to postoperative surveillance for resected non-functional pancreatic neuro-endocrine tumours.

BACKGROUND: Non-functional pancreatic neuroendocrine tumours (NF-PNETs) are rare and have highly variable outcomes. Current guidelines recommend surveillance for NF-PNETs <2 cm. Patients who ultimately have surgical resection are at risk of disease recurrence, and data to support postoperative surveillance protocols are lacking. The aims of this study were to i) identify post-operative predictors of recurrence and ii) risk stratify patients at risk of recurrence. METHODS: Consecutive patients who underwent surgery for NF-PNETs between 2002 and 2015 were identified retrospectively. Data were collected on demographics, pre-operative laboratory results and histopathological tumour characteristics. Statistical analyses were based on penalised Cox-regression modelling and a decision-tree model. Comparison of the variables identified was performed using ROC curves to identify the most sensitive and specific variable associated with disease recurrence. RESULTS: We identified 73 patients (38 males) with a median age of 61.5 years (range: 31-79). The median period of follow-up was 49 months (5-131). During follow up, 10 deaths (13.9%) were recorded and disease recurrence occurred in 12 patients (16.4%). The Kaplan-Meier predicted 1-,3- and 5-year recurrence-free survival rates were 98.6% (95% CI = 95.9, 100%), 85.4% (76.9-94.8%) and 72% (58.7-88.2%) respectively. Cox multivariate analysis identified poor tumour differentiation (WHO G3 grade) and lymph node ratio (LNR) as independent predictors for recurrence (p < 0.05). A simple criterion of 'tumour grade G3 or LNR ≥0.1' was found to be sensitive and specific in detecting disease recurrence. CONCLUSION: Our results have identified a simple and sensitive criterion for risk stratifying post-resection surveillance. Prospective validation in larger patient cohort is now warranted.

Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis.

Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC.

High mobility group A: a novel biomarker and therapeutic target in pancreatic adenocarcinoma.

High mobility group A1 (HMGA1) proteins are architectural transcriptional factors that are over-expressed in a wide range of human malignancies. Recently published evidence suggests HMGA1 is a promising candidate biomarker and therapeutic target in pancreatic cancer. This review summarises data implicating HMGA1 as an important mediator of progression in human cancer and in pancreatic cancer.

Overexpression of HMGA1 promotes anoikis resistance and constitutive Akt activation in pancreatic adenocarcinoma cells.

HMGA1 proteins are architectural transcription factors that are overexpressed by pancreatic adenocarcinomas. Roles of HMGA1 in mediating the malignant phenotype of this cancer are poorly understood. We tested the hypothesis that overexpression of HMGA1 promotes resistance to anoikis (apoptosis induced by anchorage deprivation) in pancreatic cancer cells. HMGA1 cDNA was stably transfected into MiaPaCa2 human pancreatic adenocarcinoma cells (which have low baseline expression levels of HMGA1). Cells were grown in suspension on PolyHEMA-coated plates and their susceptibility to anoikis was assayed using flow cytometry. Overexpression of HMGA1 was associated with marked reductions in susceptibility to anoikis in concert with increases in Akt phosphorylation (Ser473) and in Akt kinase activity and with reductions in caspase 3 activation. Inhibition of phosphoinositidyl-3 (PI3-K)/Akt pathway with either the small molecule inhibitor LY294002 or dominant-negative Akt resulted in reversal of anoikis resistance induced by HMGA1 overexpression. Further, RNA interference-mediated HMGA1 silencing in MiaPaCa2 and BxPC3 (a human pancreatic adenocarcinoma cell line with high baseline levels of HMGA1 expression) cells resulted in significant increases in susceptibility to anoikis. Our findings suggest HMGA1 promotes anoikis resistance through a PI3-K/Akt-dependent mechanism. Given the putative associations between anoikis resistance and metastatic potential, HMGA1 represents a potential therapeutic target in pancreatic adenocarcinoma.

Pharmacological modulation of human gastric volumes demonstrated noninvasively using SPECT imaging.

Three-dimensional single-photon emission computed tomography (SPECT) imaging allows noninvasive measurement of human postprandial gastric accommodation. The aim of this study was to determine whether 99mTCO4-SPECT demonstrates effects on pre- and postprandial gastric volumes of intravenous (i.v.) erythromycin lactobionate and sublingual isosorbide dinitrate, as predicted from previous literature. Twenty volunteers received no medication (controls), while 12 were randomized to either i.v. erythromycin 2 mg kg-1 over 20 min, or 10 mg sublingual isosorbide. After a 10-min preprandial SPECT measurement, a standard 300-mL, 300-kcal liquid meal was ingested, followed by a 20-min postprandial measurement. Gastric images were reconstructed from transaxial images and total volume was measured using the Analyseeth software system. Fasting gastric volume was greater with isosorbide [223 +/- 14 (SE) mL vs. 174 +/- 9 mL, control; P < 0.05], and postprandial volume was lower with erythromycin [393 +/- 27 mL vs. 582 +/- 17 mL, control; P < 0.05]. The ratio of postprandial over fasting volume and mean difference between pre- and postprandial volumes were significantly lower in both drug groups compared to controls. We conclude that 99mTCO4-SPECT imaging is able to semiquantitatively demonstrate pharmacological modulation of fasting gastric volume and postprandial accommodation in humans.

Effect of serum in medium on the expression of inducible nitric oxide synthase and superoxide dismutases in cultured C6 glioma cells.

It has been documented that C6 glioma cells can be changed into normal glial cells when they were cultured in serum free medium. In the present study, the expressions of inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD) were investigated. The mRNA level of iNOS was markedly increased by lipopolysaccharide (LPS) in cultured rat brain astrocytes (RBA-1) but not in C6 glioma cells. However, increase of mRNA for iNOS by LPS can be obtained in C6 glioma cells when they were cultured in serum free medium. The mRNA level of magnesium-SOD (Mn-SOD) was increased by LPS in both cells while the expression of constituted SOD (Cu,Zn-SOD) was not stimulated by LPS. Western blotting analysis indicating the amount of protein showed a similar change. After serum deprivation, the protein of iNOS or Mn-SOD was increased by LPS in C6 glioma cells in a way similar as that in RBA-1 cells. These results suggest that serum free conditioned C6 glioma cells were adapted to astroglial cell-like properties which may express more iNOS and Mn-SOD mRNA in the presence of LPS.