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Much about the etiology, pathophysiology, natural course and optimal treatment of cystic disease of the biliary tree remains under debate. Gastroenterologists, surgeons and radiologists alike still strive to optimize their roles in the management of choledochal cysts. To that end, much has been written about this disease entity, and the purpose of this 3-part review is to organize the available literature and present the various theories currently argued by the experts. In part 3, we discuss the management of choledochal cysts, thus completing our comprehensive review. [ABSTRACT FROM AUTHOR]

Much about the etiology, pathophysiology, natural course and optimal treatment of cystic disease of the biliary tree remains under debate. Gastroenterologists, surgeons and radiologists alike still strive to optimize their roles in the management of choledochal cysts. To that end, much has been written about this disease entity, and the purpose of this 3-part review is to organize the available literature and present the various theories currently argued by the experts. In part 2, we explore the details surrounding diagnosis, describing the presentation and imaging of the disease. [ABSTRACT FROM AUTHOR]

Much about the etiology, pathophysiology, natural course and optimal treatment of cystic disease of the biliary tree remains under debate. Gastroenterologists, surgeons and radiologists alike still strive to optimize their roles in the management of choledochal cysts. To that end, much has been written about this disease entity, and the purpose of this 3-part review is to organize the available literature and present the various theories currently argued by the experts. In part 1, we discuss the background of the disease, describing the etiology, classification, pathogenesis and malignant potential of choledochal cysts. [ABSTRACT FROM AUTHOR]

Over the past decade, advances in immunosuppression, organ preservation, surgical techniques and perioperative management have resulted in improved survival rates for solid organ transplants. Even so, the field of transplantation still presents many challenges. A critical obstacle is the shortage of donor organs. The paucity of cadaveric organs has increased the demand for living donor transplantation. Although this option has expanded the organ pool, concerns over ethical issues and donor safety remain, and there is an ongoing effort to make living donation a safer and less invasive process. An alternative to solid organ transplantation involves the transplantation of cells, such as islet cells for type 1 diabetes mellitus. Whereas transplantation of solid organs has seen steady improvement over the past 2 decades, transplantation of islet cells has not. Recent advances in the field of islet cell transplantation, however, have made this procedure a clinical reality. Stem cell research has provided a glimpse into the possible future of transplantation for organ failure. Another major barrier to transplantation is the lifelong need for immunosuppression. Current immunosuppression protocols place transplant recipients at continuing risk for immunosuppression-associated complications such as infection and malignant disease. New agents continue to reduce the rates of acute graft rejection and to increase long-term survival; however, they have exposed metabolic and cardiovascular complications without affecting the incidence of chronic rejection. The ultimate goal of many investigators in this field is to achieve specific immunologic graft tolerance. In this article we summarize recent technical advances in the field of transplantation that address some of the challenges. [ABSTRACT FROM AUTHOR]

Abstract Background Pancreatic ductal adenocarcinoma is a lethal disease with a 5-year survival rate of 4% and typically presents in an advanced stage. In this setting, prognostic markers identifying the more agrressive tumors could aid in managment decisions. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3, also known as IMP3 or KOC) is an oncofetal RNA-binding protein that regulates targets such as insulin-like growth factor-2 (IGF-2) and ACTB (beta-actin). Methods We evaluated the expression of IGF2BP3 by immunohistochemistry using a tissue microarray of 127 pancreatic ductal adenocarcinomas with tumor grade 1, 2 and 3 according to WHO criteria, and the prognostic value of IGF2BP3 expression. Results IGF2BP3 was found to be selectively overexpressed in pancreatic ductal adenocarcinoma tissues but not in benign pancreatic tissues. Nine (38%) patient samples of tumor grade 1 (n = 24) and 27 (44%) of tumor grade 2 (n = 61) showed expression of IGF2BP3. The highest rate of expression was seen in poorly differentiated specimen (grade 3, n = 42) with 26 (62%) positive samples. Overall survival was found to be significantly shorter in patients with IGF2BP3 expressing tumors (P = 0.024; RR 2.3, 95% CI 1.2-4.8). Conclusions Our data suggest that IGF2BP3 overexpression identifies a subset of pancreatic ductal adenocarcinomas with an extremely poor outcome and supports the rationale for developing therapies to target the IGF pathway in this cancer.

Spontaneous rupture is an uncommon and potentially fatal complication of hepatocellular carcinoma (HCC), occurring in approximately 15% of patients with HCC in Asia and 3% in the United Kingdom.3 The prognosis for hemorrhage of HCC is poor, particularly in those patients with underlying cirrhosis and severe coagulopathy. Computed tomography (CT) rather than angiography is the first-line modality for the detection of rupture. CT can confirm the diagnosis of ruptured HCC and can also help in assessing other organs if the diagnosis is not clear prior to imaging. It allows for an assessment of the entire liver, including the portal vein, which aids in determining the feasibility of embolization and resection. Since the rate of bleeding must normally exceed 1 mL/min before it can be detected on angiography and the extravasation of contrast is present in less than 20% of cases, CT is a more helpful modality. The optimal CT protocol for this condition is triphasic: the precontrast phase allows for assessment of ethiodized oil (lipiodol) uptake, the arterial phase demonstrates enhancement of the mass, and the portal venous phase allows for assessment of the portal veins. Various treatment options have been proposed: transarterial catheter embolization (TACE), emergency liver resection, and delayed resection. Surgical treatment is difficult, if not impossible. In most cases, rupture is a result of diffuse intrahepatic spread of the tumour and underlying liver cirrhosis. Many authors have concluded that a multidisciplinary management that includes TACE as the primary procedure followed by a delayed resection is the preferred treatment. This pictorial essay reviews the radiologic features of spontaneously ruptured HCC on CT imaging and of treatment by angiography. [ABSTRACT FROM AUTHOR]

Background: The frequency with which patients with high Model for End-Stage Liver Disease (MELD) scores undergo liver transplantation has been increasing. Canadian literature regarding the outcomes of liver transplantation in recipients with high MELD scores is limited. The primary objective of this study was to assess patient and graft survival among recipients with high (> 35) and low (≤ 35) MELD scores. Secondary objectives were to potentially identify independent predictors of graft failure and patient mortality., Methods: We conducted a retrospective chart review of patients undergoing liver transplantation at a single Canadian centre from 2012 to 2017., Results: A total of 332 patients were included in the study: 280 patients had a MELD score of 35 or lower, and 52 had a MELD score above 35. Patients with high MELD scores had higher rates of pretransplant acute kidney injury and dialysis ( p < 0.001), admission to the intensive care unit (ICU) or intubation ( p < 0.001), intraoperative blood product transfusions ( p < 0.001) and post-transplantation acute kidney injury and dialysis ( p < 0.001), as well as longer ICU ( p < 0.001) and hospital stays ( p = 0.002). One- and 3-year patient survival in recipients with MELD scores of 35 or lower was 93.1% and 84.9% versus 85.0% and 80.0% in recipients with MELD scores above 35 ( p = 0.37). One- and 3-year graft survival in recipients with MELD scores of 35 or lower was 91.7% and 90.9% versus 77.2% and 72.8% in recipients with MELD scores above 35 ( p < 0.001). Prior liver transplant was an independent predictor of patient mortality, and no independent predictors of graft failure were identified. When MELD was replaced with D-MELD (donor age × recipient MELD), it predicted graft failure but not patient survival., Conclusion: No difference in patient mortality was found between MELD groups. Graft survival was significantly lower in recipients with MELD scores above 35. D-MELD may potentially be used as an adjunct in determining risk of graft failure in recipients with high MELD scores., Competing Interests: Competing interests: V. Marquez has received personal fees from Abbott Laboratories and Intercept Pharmaceuticals and support for attending meetings and/or travel from Intercept Pharmaceuticals. He has participated on a data safety monitoring board or advisory board for AbbVie, Paladin Labs, Eisai and Lupin Pharma. E. Yoshida has been an investigator for clinical trials sponsored by Gilead Sciences, AbbVie, Merck, Genfit, Pfizer, Intercept Pharmaceuticals, Calgene, Novo Nordisk, Allergan and Madrigal Pharmaceuticals. He has received an unrestricted research grant from Paladin Labs and speaker fees from Gilead Sciences Canada, AbbVie Canada and Merck Canada. S. Chartier-Plante has received consulting fees from Paladin Labs. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Pre-operative biliary bacterial colonisation (bacterobilia) is considered a risk factor for infectious complications after pancreaticoduodenectomy (PD). This study aimed to investigate the role of the PD biliary microbiome grown in the development of post-PD complications., Methods: In a retrospective study of 162 consecutive patients undergoing PD (2008-2018), intra-operative bile cultures were analyzed and sensitivities compared to pre-anesthetic antibiotics and thirty-day post-surgery complications., Results: Bacterobilia was present in 136 patients (84%). Most bile cultures grew bacteria resistant to pre-operative antibiotics (n = 112, 82%). Patients with bacterobilia had significantly higher rates of major complication than patients without (P = 0.017), as well as higher rates of surgical-site infections (SSI) (P = 0.010). Patients with negative bile cultures (n = 26) had significantly lower rates of major complication and SSI than those growing sensitive (n = 24) or non-sensitive (n = 112) bacteria (major complication P = 0.029 and SSI P = 0.011)., Conclusion: Positive bile cultures were associated with a higher incidence of major complications and SSI. Patients with sterile bile cultures had the lowest risk of post-operative complications and efforts to reduce rates of bacterobilia, such as limitation of biliary instrumentation, should be considered. Sensitivity to antibiotics had no effect upon the rate of post-operative complications, but this may reflect low cohort numbers., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Abstract: Liver disease etiology and transplantation outcomes may vary by ethnicity. We aimed to determine if disparities exist in our province.We reviewed the provincial database for liver transplant referrals. We stratified cohorts by ethnicity and analyzed disease etiology and outcomes.Four thousand nine hundred sixteen referrals included 220 South Asians, 413 Asians, 235 First Nations (Indigenous), and 2725 Caucasians. Predominant etiologies by ethnicity included alcohol (27.4%) and primary sclerosing cholangitis (PSC) (8.8%) in South Asians, hepatitis B (45.5%) and malignancy (13.9%) in Asians, primary biliary cholangitis (PBC) (33.2%) and autoimmune hepatitis (AIH) (10.8%) in First Nations, and hepatitis C (35.9%) in Caucasians. First Nations had lowest rate of transplantation (30.6%, P = .01) and highest rate of waitlist death (10.6%, P = .03). Median time from referral to transplantation (268 days) did not differ between ethnicities (P = .47). Likelihood of transplantation increased with lower body mass index (BMI) (hazard ratio [HR] 0.99, P = .03), higher model for end stage liver disease (MELD) (HR 1.02, P < .01), or fulminant liver failure (HR 9.47, P < .01). Median time from referral to ineligibility status was 170 days, and shorter time was associated with increased MELD (HR 1.01, P < .01), increased age (HR 1.01, P < .01), fulminant liver failure (HR 2.56, P < .01) or South Asian ethnicity (HR 2.54, P < .01). Competing risks analysis revealed no differences in time to transplant (P = .66) or time to ineligibility (P = .91) but confirmed increased waitlist death for First Nations (P = .04).We have noted emerging trends such as alcohol related liver disease and PSC in South Asians. First Nations have increased autoimmune liver disease, lower transplantation rates and higher waitlist deaths. These data have significance for designing ethnicity specific interventions., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, particularly for patients with metastatic disease. Treatment for oligometastatic presentation has been reported in recent literature, but the role of intraperitoneal chemotherapy for patients with peritoneal metastases (PM) remains unclear. We performed a systematic literature search of the PubMed, Cochrane and Embase databases in order to identify clinical trials and case-series reporting on the safety and efficacy of intraperitoneal chemotherapy in patients with PDAC-derived PM. Eight publications reporting on 85 patients were identified, using three different therapeutic strategies. First, 37 patients received cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for PDAC with PM. Grade 3 and 4 complications occurred in 37.8% of patients, without perioperative mortality. Median disease-free survival and overall survival (OS) rates varied from 4 to 36 months and 4 to 62 months, respectively. Secondly, 40 patients with resectable PDAC without PM received prophylactic HIPEC following pancreatic resection, with postoperative morbidity and mortality rates of 30% and 5%, and 5-year OS rates of 23-24%. Finally, eight patients with PDAC-derived peritoneal disease were converted to resectable disease after receiving neoadjuvant intraperitoneal chemotherapy and operated on with curative intent, achieving a median OS of 27.8 months. In conclusion, CRS with HIPEC for PDAC-derived PM appears to be safe, conferring the same postoperative morbidity and mortality as reported on non-pancreatic malignancies. In highly selected patients, it could be considered for short-term disease control. However, long-term survival remains poor. The addition of prophylactic HIPEC for resectable PDAC cannot be recommended.

Background: The aim of this study was to evaluate whether elderly patients undergoing elective hepatectomy experience increased morbidity/mortality and whether these outcomes could be mitigated by minimally invasive hepatectomy (MIH)., Methods: 15,612 patients from 2014 to 2017 were identified in the Hepatectomy Targeted Procedure Participant Use File of the American College of Surgeons National Surgical Quality Improvement Program. Multivariable logistic regression models were constructed to examine the effect of elderly status (age ≥ 75 years, N = 1769) on outcomes with a subgroup analysis of elderly only patients by open (OH) versus MIH (robotic, laparoscopic, and hybrid, N = 4044). Propensity score matching was conducted comparing the effect of MIH to OH in elderly patients to ensure that results are not the artifact of imbalance in baseline characteristics., Results: Overall, elderly patients had increased risk for 30-day mortality, major morbidity, prolonged length of hospital stay, and discharge to destination other than home. In the elderly subgroup, MIH was associated with decreased major morbidity (OR 0.71, P = 0.031), invasive intervention (OR 0.61, P = 0.032), liver failure (OR 0.15, P = 0.011), bleeding (OR 0.46, P < 0.001), and prolonged length of stay (OR 0.46, P < 0.001). Propensity score-matched analyses successfully matched 4021 pairs of patients treated by MIH vs. OH, and logistic regression analyses on this matched sample found that MIH was associated with decreased major complications (OR 0.69, P = 0.023), liver failure (OR 0.14, P = 0.010), bile leak (OR 0.46, P = 0.009), bleeding requiring transfusion (OR 0.46, P < 0.001), prolonged length of stay (OR 0.46, P < 0.001), and discharge to destination other than home (OR 0.691, P = 0.035) compared to OH., Conclusion: MIH is associated with decreased risk of major morbidity, liver failure, bile leak, bleeding, prolonged length of stay, and discharge to destination other than home among elderly patients in this retrospective study. However, MIH in elderly patients does not protect against postoperative mortality.

Background: Timely surgical resection in patients with suspected or diagnosed pancreas adenocarcinoma is an essential part of care. We hypothesized that longer surgical wait time was associated with worse oncologic outcomes., Methods: A retrospective cohort of patients (N = 144) with resectable pancreas adenocarcinoma was divided into four wait time groups (<4, 4-8, 8-12, and >12 weeks), defined from the time of diagnosis on cross-sectional imaging. Overall and recurrence-free survival were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. A higher rate of conversion to palliative bypass in patients waiting over 4 weeks was observed and further analyzed using post-hoc multivariate regression., Results: On multivariable analysis, longer wait time was associated with improved overall (HR 0.49, 95% CI: 0.28-0.85) and recurrence-free survival (HR 0.29, 95% CI: 0.15-0.56) in >12 weeks compared to <4 weeks group. On post-hoc analysis, longer wait time over 8 weeks was positively associated with palliative bypass (OR 5.33, 95% CI: 1.32-27.88)., Conclusion: Wait time over 8 weeks was associated with a higher rate of palliative bypass. There was an improvement in overall and recurrence-free survival in patients who waited over 12 weeks, likely due to selection bias., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Liver transplant programs in Canada require a period of 6 months of abstinence from alcohol before considering a patient with liver disease secondary to alcohol for transplantation. Although some studies have demonstrated good outcomes following a transplant in carefully selected patients before the 6-month abstinence period has been met, there have been arguments against this, including the claim that the public has a general negative perception of those with alcohol dependence. We performed a multicenter cross-sectional survey to determine the perception of people in British Columbia, Canada, toward liver transplantation in patients with liver disease due to alcohol who have not demonstrated the capacity to remain abstinent from alcohol for 6 months. A total of 304 patient questionnaires were completed, and 83.1% agreed with a period of abstinence of 6 months. In those patients who were unlikely to survive 6 months without a transplant, 34.1% of respondents agreed with, 44.1% did not agree with, and 21.4% were neutral about, early transplantation; 42.8% would have less trust in the process of transplantation if a period of abstinence was not maintained, but relaxing the requirement for an abstinence period would not have an impact on the majority's decision to donate organs. Only 30.5% would support abandoning the abstinence criteria. Conclusion: Among patients followed at general gastroenterology, medicine, or transplant clinics, there is a willingness to relax the criteria in selected patients unlikely to survive without a transplant, although a general consensus remains in support of the existing 6-month alcohol abstinence rule. A larger scale survey of all provinces in Canada would be required to assess support for such a change in policy.

Objectives: There is a clear lack of clinical evidence guiding immunosuppressive management in long-term stable liver transplant recipients. As a result, anecdotal experience suggests wide variability across transplant centers. We aimed to identify patterns of immunosuppression practices in liver transplant centers across Canada and the United States., Materials and Methods: From February 9 to May 31, 2015, we invited clinicians from all liver transplant centers in Canada and the United States to answer a 6-question survey generated using SurveyMonkey., Results: Seventeen respondents from 15 liver transplant centers completed the survey. Although immun-suppressive practices are relatively uniform for induction and early maintenance therapy, significant variations exist in the management of long-term immunosuppression in stable transplant recipients with a relative lack of minimization protocols., Conclusions: Our survey confirms a wide variability in immunosuppression practices across Canadian and US liver transplant centers. Research and practice priorities include design of pragmatic randomized controlled trials and development of clinical practice guidelines to standardize immunosuppressive management of long-term stable liver transplant recipients with a focus on immunosuppression minimization.

Introduction: Damage control laparotomy with vacuum assisted closure (VAC) is used for selective cases in trauma. In liver transplantation, VAC has also been applied for management of intra-operative hemorrhage. The primary objective was to evaluate peri-operative blood loss and blood product utilization in VAC compared to primary abdominal closure (PAC) at the index transplant operation., Methods: Retrospective review of all adults undergoing deceased donor liver transplantation (2007-2011) at a single center tertiary care institution., Results: 201 deceased donor liver transplantations were performed, with 167 PAC and 34 VAC cases. Intra-operative blood loss (4.4L vs 10.7L), cell saver return (1399 ml vs 3998 ml), FFP (7.6U vs 15.9U) and PLT requirements (8.5U vs 18.3U), were all significantly elevated in VAC compared to PAC. VAC patients had significantly increased RBC, FFP, PLT, and total volume requirements during initial ICU admission. 30 PAC cases required on demand laparotomy and most commonly for post-operative bleeding., Conclusion: In liver transplantation, application of VAC secondary to massive intra-operative exsanguination was safely utilized. Further evaluation is required to identify long-term morbidity and mortality., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The goal of treating chronic hepatitis C virus (HCV) infection is sustained virologic response (SVR). There is concern that despite achieving SVR, replication-competent HCV may be sequestered at low levels within the liver and could theoretically reactivate with immunosuppression. We report transplantation of a HCV-seropositive liver donor, who achieved SVR, into a seronegative patient without HCV reactivation despite profound immunosuppression., Method: Retrospective chart review., Results: We present a 21-year-old male who was HCV seronegative and received a liver transplant from a donor who had been treated for HCV and achieved SVR. The liver recipient, despite developing severe acute graft rejection and undergoing intense immunosuppression with T cell-depleting antibodies, did not become HCV RNA-positive with a follow up period of 8 months. The recipient was HCV seronegative before transplant, but became HCV seropositive immediately posttransplant. The antibodies were undetectable after 97 days, in keeping with a passive antibody transmission or B lymphocyte transmission with the graft., Conclusions: To the best of our knowledge, this is the first reported case of an HCV seropositive liver allograft transplanted into an HCV-negative recipient who subsequently received intense immunosuppression. This case, therefore, is an encouraging and novel step in liver transplantation, and demonstrates that SVR may be closer to a true "cure" of HCV in the donor population and that, even in circumstances of very potent immunosuppression in the recipient, this SVR is sustained.

Background: Metronomic chemotherapy has shown promising activity against solid tumors and is believed to act in an antiangiogenic manner. The current study describes and quantifies the therapeutic efficacy, and mode of activity, of metronomic gemcitabine and a dedicated antiangiogenic agent (DC101) in patient-derived xenografts of pancreatic cancer., Methods: Two primary human pancreatic cancer xenograft lines were dosed metronomically with gemcitabine or DC101 weekly. Changes in tumor growth, vascular function, and metabolism over time were measured with magnetic resonance imaging, positron emission tomography, and immunofluorescence microscopy to determine the anti-tumor effects of the respective treatments., Results: Tumors treated with metronomic gemcitabine were 10-fold smaller than those in the control and DC101 groups. Metronomic gemcitabine, but not DC101, reduced the tumors' avidity for glucose, proliferation, and apoptosis. Metronomic gemcitabine-treated tumors had higher perfusion rates and uniformly distributed blood flow within the tumor, whereas perfusion rates in DC101-treated tumors were lower and confined to the periphery. DC101 treatment reduced the tumor's vascular density, but did not change their function. In contrast, metronomic gemcitabine increased vessel density, improved tumor perfusion transiently, and decreased hypoxia., Conclusion: The aggregate data suggest that metronomic gemcitabine treatment affects both tumor vasculature and tumor cells continuously, and the overall effect is to significantly slow tumor growth. The observed increase in tumor perfusion induced by metronomic gemcitabine may be used as a therapeutic window for the administration of a second drug or radiation therapy. Non-invasive imaging could be used to detect early changes in tumor physiology before reductions in tumor volume were evident.

Deficiencies in DNA mismatch repair have been associated with inferior response to 5-FU in colorectal cancer. Pancreatic ductal adenocarcinoma is similarly treated with pyrimidine analogs, yet the predictive value of mismatch repair status for response to these agents has not been examined in this malignancy. A tissue microarray with associated clinical outcome, comprising 254 resected pancreatic ductal adenocarcinoma patients was stained for four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Mismatch repair deficiency and proficiency was determined by the absence or presence of uniform nuclear staining in tumor cells, respectively. Cases identified as mismatch repair deficient on the tissue microarray were confirmed by immunohistochemistry on whole slide sections. Of the 265 cases, 78 (29%) received adjuvant treatment with a pyrimidine analog and 41 (15%) showed a mismatch repair-deficient immunoprofile. Multivariable disease-specific survival in the mismatch repair-proficient cohort demonstrated that adjuvant chemotherapy, regional lymph-node status, gender, and the presence of tumor budding were significant independent prognostic variables (P≤0.04); however, none of the eight clinico-pathologic covariates examined in the mismatch repair-deficient cohort were of independent prognostic significance. Univariable assessment of disease-specific survival revealed an almost identical survival profile for both treated and untreated patients with a mismatch repair-deficient profile, while treatment in the mismatch repair-proficient cohort conferred a greater than 10-month median disease-specific survival advantage over their untreated counterparts (P=0.0018). In this cohort, adjuvant chemotherapy with a pyrimidine analog conferred no survival advantage to mismatch repair-deficient pancreatic ductal adenocarcinoma patients. Mismatch repair immunoprofiling is a feasible predictive marker in pancreatic ductal adenocarcinoma patients, and further prospective evaluation of this finding is warranted.

Tumor budding is a well-established adverse prognostic factor in colorectal cancer. However, the significance and diagnostic reproducibility of budding in pancreatic carcinoma requires further study. We aimed to assess the prognostic significance of tumor budding in pancreatic ductal adenocarcinoma, determine its relationship with other clinicopathologic features, and assess interobserver variability in its diagnosis. Tumor budding was assessed in 192 archival cases of pancreatic ductal adenocarcinoma using hematoxylin and eosin (H&E) sections; tumor buds were defined as single cells or nonglandular clusters composed of <5 cells. The presence of budding was determined through assessment of all tumor-containing slides, and associations with clinicopathologic features and outcomes were analyzed. Six gastrointestinal pathologists participated in an interobserver variability study of 120 images of consecutive tumor slides stained with H&E and cytokeratin. Budding was present in 168 of 192 cases and was associated with decreased overall survival (P=0.001). On multivariable analysis, tumor budding was prognostically significantly independent of stage, grade, tumor size, nodal status, lymphovascular invasion, and perineural invasion. There was substantial agreement among pathologists in assessing the presence of tumor budding using both H&E (K=0.63) and cytokeratin (K=0.63) stains. The presence of tumor budding is an independent adverse prognostic factor in pancreatic ductal carcinoma. The assessment of budding with H&E is reliable and could be used to better risk stratify patients with pancreatic ductal adenocarcinoma.

Aim: The dose-response relationship between doxorubicin and superabsorbent drug-eluting microspheres has not been established. In this study, we investigated the relationships between dose and delivery parameters as they pertain to toxicity and response in surgically resectable hepatocellular carcinoma (HCC)., Patients and Methods: Twenty-five patients with resectable HCC were randomly assigned and divided into four groups, each receiving either bland, 25 mg, 50 mg or 75 mg of doxorubicin loaded Super Absorbent Polymer microspheres, with 24 patients undergoing surgical resection. Response Evaluation and Criteria in Solid Tumors (RECIST) 1.0 and European Association for the Study of the Liver (EASL)-based volumetric response was performed at one month and surgical resection of the reference tumor was performed at two months. Adverse events were collected at regular intervals., Results: Fifty-six percent of patients demonstrated complete response according to EASL criteria as opposed to 0% according to RECIST (v1.0) criteria. Residual tumor was identified in all groups (0 mg: 35%±28.5%; 25 mg: 42%±30.4%; 50 mg: 3.6%±3.3%; and 75 mg: 49.29%±32.6%. A total of 112 adverse events of grades 1-3 occurred (average 5.1 per patient), with no grade 4 or 5. No difference was noted between bland embolic and drug-loaded groups. Subset analysis did demonstrate a significantly increased degree of necrosis in the 50 mg-loaded group (p=0.018). Strong correlation existed between arterial phase Computer Tomography EASL-based response and histopathology (r=0.81; p<0.0001). All groups had residual tumor., Conclusion: Histology correlates strongly with one-month post-procedural imaging and response optimized at 50 mg of loading per vial. Adverse events were a reflection of embolization, with no relationship between loading dose or administered dose of doxorubicin., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The demand for definitive management of end-stage organ disease in HIV-infected Canadians is growing. Until recently, despite international evidence of good clinical outcomes, HIV-infected Canadians with end-stage liver disease were ineligible for transplantation, except in British Columbia (BC), where the liver transplant program of BC Transplant has accepted these patients for referral, assessment, listing and provision of liver allograft. There is a need to evaluate the experience in BC to determine the issues surrounding liver transplantation in HIV-infected patients., Methods: The present study was a chart review of 28 HIV-infected patients who were referred to BC Transplant for liver transplantation between 2004 and 2013. Data regarding HIV and liver disease status, initial transplant assessment and clinical outcomes were collected., Results: Most patients were BC residents and were assessed by the multidisciplinary team at the BC clinic. The majority had undetectable HIV viral loads, were receiving antiretroviral treatments and were infected with hepatitis C virus (n=16). The most common comorbidities were anxiety and mood disorders (n=4), and hemophilia (n=4). Of the patients eligible for transplantation, four were transplanted for autoimmune hepatitis (5.67 years post-transplant), nonalcoholic steatohepatitis (2.33 years), hepatitis C virus (2.25 years) and hepatitis B-delta virus coinfection (recent transplant). One patient died from acute renal failure while waiting for transplantation. Ten patients died during preassessment and 10 were unsuitable transplant candidates. The most common reason for unsuitability was stable disease not requiring transplantation (n=4)., Conclusions: To date, interdisciplinary care and careful selection of patients have resulted in successful outcomes including the longest living HIV-infected post-liver transplant recipient in Canada.

Background: Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT). LDLT is thought to be associated with higher rates of biliary complications, but there are few studies comparing the success of endoscopic management of anastomotic strictures between the two groups. This study aims to compare our experience in the endoscopic management of anastomotic strictures in DDLT versus LDLT., Methods: This is a retrospective database review of all liver transplant patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) after liver transplantation. The frequency of anastomotic stricture and the time to develop and to resolve anastomotic stricture were compared between DDLT and LDLT. The response of anastomotic stricture to endoscopic therapy was also analyzed., Results: A total of 362 patients underwent liver transplantation between 2003 and 2011, with 125 requiring ERCP to manage biliary complications. Thirty-three (9.9%) cases of DDLT and 8 (27.6%) of LDLT (P=0.01) were found to have anastomotic stricture. When comparing DDLT and LDLT, there was no difference in the mean time to the development of anastomotic strictures (98+/-17 vs 172+/-65 days, P=0.11), likelihood of response to ERCP [22 (66.7%) vs 6 (75.0%), P=0.69], mean time to the resolution of anastomotic strictures (268+/-77 vs 125+/-37 days, P=0.34), and the number of ERCPs required to achieve resolution (3.9+/-0.4 vs 4.7+/-0.9, P=0.38)., Conclusions: Endoscopic therapy is effective in the majority of biliary complications relating to liver transplantation. Anastomotic strictures occur more frequently in LDLT compared with DDLT, with equivalent endoscopic treatment response and outcomes for both groups.

Background: The aim of the present study was to determine the utility of computed tomography (CT) and magnetic resonance imaging (MRI) anatomic mapping in the detection of biliary and vascular anomalies prior to a living liver donor (LLD) operation., Methods: A retrospective study of all LLD patient charts, operative and radiology reports from 1 January 2002 to 1 January 2012 was conducted. Primary post-operative outcomes assessed included mortality, re-operation, readmission and need for endoscopic or percutaneous intervention. Sensitivity and specificity of MR and CT pre-operative screening was calculated against the gold standard of intra-operative findings., Results: A total of 34 donors had an average age of 38 years (range: 22-58) with a body mass index (BMI) of 25.6 kg/m(2) (range: 19.8-32.5) and a length of stay (LOS) of 10.1 days (range: 5-41). There were no donor mortalities. Sensitivity and specificity of CT was 70.0% and 91.3%, and of MRI screening 23.1% and 100.0%, respectively. Patients with inaccurate pre-operative CT or MRI did not have an increased risk of complications., Conclusions: Even although it was specific, pre-operative MR screening missed up to 77.0% of biliary anomalies. An impeccable surgical technique remains the key in preventing biliary complications of a living donor hepatectomy where pre-operative MRI screening is false., (© 2013 International Hepato-Pancreato-Biliary Association.)

Primary hepatic neuroendocrine tumours are rare tumours effecting relatively young patients. As metastatic neuroendocrine tumours to the liver are much more common, extensive investigations are crucial to exclude a primary tumour elsewhere. We report a case of a 27 year old woman who presented with fatigue, increased abdominal girth and feeling of early satiety and bloating. Extensive work up failed to show tumour at another primary site. Hepatic artery embolization showed no effect, so the patient underwent total hepatectomy and live-donor liver transplant. Grossly the tumour measured 27 cm. Microscopic examination showed bland, monomorphic cells growing in tubuloglandular and trabecular growth patterns. Cells were positive for neuroendocrine (synaptophysin, chromogranin, CD56) and epithelial markers (MOC31, CK7, CK19). Cytoplasmic dense neurosecretory vesicles were seen on ultrastructural examination. Based on the Ki-67 rate, mitotic count, lack of marked nuclear atypia and absence of necrosis, a diagnosis of primary neuroendocrine grade 2 was conferred.

Introduction: Hepatic artery transection presents a technical challenge in vascular reconstruction. Formal arterial repair is indicated in patients with underlying liver disease and those undergoing bile duct reconstructions because of a higher risk of complication following hepatic artery injury. This report highlights a novel approach to hepatic artery transection with splenic artery transposition., Methods: A case of hepatic artery transection repaired with splenic artery transposition is presented with an accompanying literature review., Results: During elective pancreaticoduodenectomy, the common hepatic artery was injured at its origin. The splenic artery was divided and transposed to the hepatic artery, thus restoring arterial flow to the liver and bile duct., Conclusion: Various strategies to manage a hepatic artery injury have been described, ranging from ligation to complex vascular reconstruction. In hemodynamically stable patients, arterial transposition using the splenic artery is a feasible method to ensure adequate arterial supply to the liver and biliary tract.

Introduction: A pancreaticoduodenectomy is the reference treatment for a resectable pancreatic head ductal adenocarcinoma. The probability of 5-year survival in patients undergoing such treatment is 5-25% and is associated with relatively high peri-operative morbidity and mortality. The objective of the present study was to evaluate risk factors predictive of outcome for patients undergoing a pancreaticoduodenectomy for a pancreatic adenocarcinoma., Methods: This retrospective analysis incorporated data from the Vancouver General Hospital and the British Columbia Cancer Agency (BCCA) from 1999-2007., Results: The 5-year survival of 100 patients was 12% with a median survival of 16.5 months. Ninety-day mortality was 7%. Predictors of 90-day mortality included age ≥ 80 years (P < 0.001) and an American Society of Anesthesiologists (ASA) score = 3 (P= 0.012) by univariate analysis and age ≥80 years (P < 0.001) by multivariate analysis. The identifiable predictive factor for poor 5-year survival was an ASA score = 3 (P= 0.043) whereas a Dindo-Clavien surgical complication grade ≥ 3 was associated with a worse outcome (P= 0.013). Referral to the BCCA was associated with a favourable 5-year survival (P= 0.001)., Conclusions:   The present study identifies risk factors for patient selection to enhance survival benefit in this patient population., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background: Simple hepatic cysts are common and infrequently develop into large symptomatic cysts that require surgical therapy. These benign cysts have been shown to be amenable to minimally invasive surgery; however, recurrences of symptoms have been reported. Our experience with over 200 simple hepatic cysts has lead to the development of a novel therapy to resolve symptoms associated with large simple hepatic cysts and reduce the rate of recurrent symptoms., Methods: An observational study demonstrating our experience with a novel minimally invasive technique for the management of symptomatic simple hepatic cyst., Results: A total of 6 cases were identified where laparoscopic mini-fenestration and placement of a falciform pedicle graft was used. There were no operative complications and 4 of 6 patients were discharged home the day of surgery. With mean follow-up of 9.6 months, there has not been any recurrence to date. One patient required an open hepatic resection for the treatment of a cystadenoma., Conclusion: Laparoscopic mini-fenestration and placement of a falciform ligament pedicle graft shows promising early results as a treatment for the simple hepatic cyst. Long term follow-up data is required.

Background: The current standard of care for pancreatic cancer is weekly gemcitabine administered for 3 of 4 weeks with a 1-week break between treatment cycles. Maximum tolerated dose (MTD)-driven regimens as such are often associated with toxicities. Recent studies demonstrated that frequent dosing of chemotherapeutic drugs at relatively lower doses in metronomic regimens also confers anti-tumour activity but with fewer side effects., Methods: Herein, we evaluated the anti-tumour efficacy of metronomic vs MTD gemcitabine, and investigated their effects on the tumour microenvironment in two human pancreatic cancer xenografts established from two different patients., Results: Metronomic and MTD gemcitabine significantly reduced tumour volume in both xenografts. However, K(trans) values were higher in metronomic gemcitabine-treated tumours than in their MTD-treated counterparts, suggesting better tissue perfusion in the former. These data were further supported by tumour-mapping studies showing prominent decreases in hypoxia after metronomic gemcitabine treatment. Metronomic gemcitabine also significantly increased apoptosis in cancer-associated fibroblasts and induced greater reductions in the tumour levels of multiple pro-angiogenic factors, including EGF, IL-1alpha, IL-8, ICAM-1, and VCAM-1., Conclusion: Metronomic dosing of gemcitabine is active in pancreatic cancer and is accompanied by pronounced changes in the tumour microenvironment.

Background: End-stage alcoholic liver disease is common, with many of these patients referred for liver transplantation (LT). Alcohol relapse after LT can have detrimental outcomes such as graft loss and can contribute to a negative public perception of LT., Objective: To identify factors that predict the recurrence of harmful alcohol consumption after LT., Methods: A total of 80 patients who underwent LT for alcoholic cirrhosis or had significant alcohol consumption in association with another primary liver disease, from July 1992 to June 2006 in British Columbia, were retrospectively evaluated by chart review. Several demographic-, psychosocial- and addiction-related variables were studied. Univariate and multivariate logistic regression analyses were used to test possible associations among the variables studied and a return to harmful drinking after LT., Results: The relapse rate of harmful alcohol consumption post-liver transplant was 10%, with two patient deaths occurring directly as a result of alcohol relapse. Univariate analysis revealed relapse was significantly associated with pretransplant abstinence of less than six months (P=0.003), presence of psychiatric comorbidities (P=0.016), female sex (P=0.019) and increased personal stressors (P=0.044), while age at transplant of younger than 50 years approached significance (P=0.054). Multivariate logistic regression analysis revealed the following independent factors for relapse: pretransplant abstinence of less than six months (OR 77.07; standard error 1.743; P=0.013) and female sex (OR 18.80; standard error 1.451; P=0.043)., Conclusion: The findings of the present study strongly support a required minimum of six months of abstinence before LT because duration of abstinence was found to be the strongest predictor of recidivism. Female sex, younger age at transplant and psychiatric comorbidities were also associated with relapse to harmful drinking.

Hephaestin (Hp) is a membrane protein with ferroxidase activity that converts Fe(II) to Fe(III) during the absorption of nutritional iron in the gut. Using anti-peptide antibodies to predicted immunogenic regions of rodent Hp, previous immunocytochemical studies in rat, mouse, and human gut tissues localized Hp to the basolateral membranes of the duodenal enterocytes where the Hp was predicted to aid in the transfer of Fe(III) to transferrin in the blood. We used a recombinant soluble form of human Hp to obtain a high-titer polyclonal antibody to Hp. This antibody was used to identify the intracellular location of Hp in human gut tissue. Our immunocytochemical studies confirmed the previous localization of Hp in human enterocytes. However, we also localized Hp to the entire length of the gastrointestinal tract, the antral portion of the stomach, and to the enteric nervous system (both the myenteric and submucous plexi). Hp was also localized to human pancreatic beta-cells. In addition to its expression in the same cells as Hp, ferroportin was also localized to the ductal cells of the exocrine pancreas. The localization of the ferroxidase Hp to the neuronal plexi and the pancreatic beta cells suggests a role for the enzymatic function of Hp in the protection of these specialized cell types from oxidative damage.

Integrin-linked kinase (ILK) is a key molecule involved in mediating several biological functions including cell-matrix interactions, angiogenesis, and invasion, as well as playing a role in epithelial to mesenchymal transition (EMT) in cancer cells. In ductal pancreatic adenocarcinoma, increased expression of ILK has been linked to tumor prognosis and correlated with increased chemoresistance to drugs, such as gemcitabine. However, the precise relationship between ILK, Snail, E-cadherin, and N-cadherin expression on the stepwise development of pancreatic cancer is unknown. Hence, the purpose of this work was to investigate levels of expression of ILK, Snail, and the cadherins in pancreatic intraepithelial neoplasia (PanIN), and cancer. Resection specimens of 25 randomly selected patients, who underwent a pyloric preserving pancreatoduodenectomy for ductal pancreatic adenocarcinoma, were utilized for this study. Formalin-fixed paraffin embedded pancreatic tissue was immunostained for ILK, E-cadherin, N-cadherin, and Snail by standard techniques. The extent of staining positivity was scored and the results correlated with clinicopathological parameters. In 23 of 25 cases, ILK expression showed extensive positivity (>50%), while two cases did not demonstrate any ILK staining. PanIN grades 1 (n = 16), 2 (n = 11), and 3 (n = 19) lesions demonstrated only focal positivity (<10%) for ILK. E-cadherin showed a reciprocal staining pattern to ILK in 21 of 25 cases, with only focal expression of the marker in pancreatic adenocarcinoma. Interestingly, 15 of 19 PanIN-3 lesions expressed extensive E-cadherin staining. N-cadherin, however, was moderately expressed in the majority of cases (n = 18). Snail expression (n = 22) correlated with ILK expression in ductal pancreatic adenocarcinoma (rho = 0.8168, p = 0.02), but only minimal Snail staining activity was detected in PanIN lesions. The increase in expression of the E-cadherin repressor Snail, as well as the related increase in the ILK expression, may point towards an ILK-mediated induction, opening possible avenues for targeted drug therapy.

Objective: To evaluate the survival benefit of multimodal therapy for the treatment of HCC., Background: Orthotopic liver transplantation (OLT) is considered the treatment of choice for selected patients with hepatocellular carcinoma (HCC). However, donor organ shortages and patients whose HCCs exceed OLT criteria require consideration of alternate therapeutic options such as hepatic resection, radiofrequency ablation (RFA), ethanol injection (EI), transarterial chemoembolization (TACE), and chemotherapy (CTX). This study was performed to evaluate the survival benefit of multimodal therapy for treatment of HCC as complementary therapy to OLT., Methods: A retrospective review was conducted of HCC patients undergoing therapy following multidisciplinary review at our institution from 1996 . 2006 with a minimum of a 2 year patient follow-up. Data were available on 247/252 patients evaluated. Relevant factors at time of diagnosis included symptoms, hepatitis B (HBV) and C (HCV) status, antiviral therapy, Child-Pugh classification, portal vein patency, and TNM staging. Patients underwent primary treatment by hepatic resection, RFA, EI, TACE, CTX, or were observed (best medical management). Patients with persistent or recurrent disease following initial therapy were assessed for salvage therapy. Survival curves and pairwise multiple comparisons were calculated using standard statistical methods., Results: Mean overall survival was 76.8 months. Pairwise comparisons revealed significant mean survival benefits with hepatic resection (93.2 months), RFA (66.2 months), and EI (81.1 months), compared with TACE (47.4 months), CTX (24.9 months), or observation (31.4 months). Shorter survival was associated with symptoms, portal vein thrombus, or Child-Pugh class B or C. HCV infection was associated with significantly shorter survival compared with HBV infection. Antiviral therapy was associated with significantly improved survival in chronic HBV and HCV patients only with earlier stage disease., Conclusion: Multimodal therapy is effective therapy for HCC and may be used as complementary treatment to OLT.

Hepatic artery thrombosis (HAT) is relatively infrequent, but possibly a devastating complication of orthotopic liver transplantation (OLT). It often requires urgent retransplantation. Two main forms of HAT are recognized as early and late HAT (diagnosis within or after 30 days following LT). Early HAT typically results in graft failure. Late HAT features biliary obstruction, cholangitis, and hepatic abscess formation. We report here the case of a patient of Wilson's disease who presented twelve years post-liver transplant symptoms typical of acute HAT and hepatic infarction. On diagnostic imaging, celiac axis and hepatic artery were thrombosed, resulting in ischemic necrosis of the left hepatic lobe. The resulting sepsis and transient hepatic insufficiency were managed conservatively, and repeat OLT was avoided. The patient remains stable more than one year later. To the best of our knowledge this case report is unique in the literature for the unusually long interval between OLT and late acute HAT, as well as celiac and portal vein occlusion. The acute presentation of sub massive hepatic necrosis is also uncharacteristic of late HAT and more typical of acute HAT. This report describes our experience in managing this and a literature review of the topic.

Parvovirus B19 induced acute hepatitis and hepatic failure have been previously reported, mainly in children. Very few cases of parvovirus induced hepatic failure have been reported in adults and fewer still have required liver transplantation. We report the case of a 55-year-old immunocompetent woman who developed fulminant hepatic failure after acute infection with Parvovirus B19 who subsequently underwent orthotopic liver transplantation. This is believed to be the first reported case in the literature in which an adult patient with fulminant hepatic failure associated with acute parvovirus B19 infection and without hematologic abnormalities has been identified prior to undergoing liver transplantation. This case suggests that Parvovirus B19 induced liver disease can affect adults, can occur in the absence of hematologic abnormalities and can be severe enough to require liver transplantation.

Background: Over the past decade there has been an increasing trend toward minimally invasive liver surgery. Initially limited by technical challenges, advances in laparoscopic techniques have rendered this approach safe and feasible. However, as health care costs approach 50% of some provincial budgets, surgical innovation must be justifiable in costs and patient outcomes. With introduction of standardized postoperative liver resection guidelines to optimize patient hospital length of stay, the advantages of laparoscopic liver resection (LLR) compared with open liver resection (OLR) measured by perioperative outcomes and resource utilization are not well defined. It remains to be established whether LLR is superior to OLR by these measurements., Methods: Eighteen LLRs performed at the Vancouver General Hospital from 2005 to 2007 were prospectively analyzed. These data were compared with an equivalent group of 12 consecutive OLRs undertaken immediately prior to the introduction of LLR. Outcomes were evaluated for differences in perioperative morbidity, hospital length of stay, and operative costs., Results: There were no differences between LLRs and OLRs in demographics, pathology, cirrhosis, tumour location or extent of resection. There were no deaths. LLRs had significantly decreased intraoperative blood loss (287 ml versus 473 ml, p = 0.03), postoperative complications (6% versus 42%, p = 0.03), and length of stay (4.3 versus 5.8 days, p = 0.01) compared with OLRs. There were no differences in operating time for LLRs compared to OLRs (135 min versus 138 min, respectively), total time in the operating theatre (214 min versus 224 min), or costs related to stapler/trocar devices (CA $1267 versus CA $1007)., Conclusions: LLR is associated with decreased morbidity and decreased resource utilization compared with OLR. Perioperative patient outcomes and cost-effectiveness justify LLR despite introduction of standardized postoperative liver resection guidelines and decreased length of stay for OLR.

Portopulmonary hypertension (PPH) is an infrequent, but well-recognized complication of liver cirrhosis. PPH in those with end-stage liver disease has a significant impact on per-operative and intra-operative mortality, with liver transplantation being contraindicated in those individuals with mean pulmonary artery pressure exceeding 50 mmHg. Vasodilatory therapy is the mainstay of pharmacotherapy for PPH, although the evidence of benefit is largely extrapolated from the pulmonary hypertension literature. We report the use of the phosphodiesterase inhibitor, sildenafil, in a patient with end stage liver disease and PPH, with a pulmonary artery pressure before transplantation of 75 mmHg, to reduce pulmonary artery pressure prior to a successful liver transplant.

The prevalence of obesity is increasing globally, with nearly half of a billion of the world's population now considered to be overweight or obese. Obesity and overweight patients are one of the major health issues in Canada, resulting in approximately 57,000 deaths related to obesity over the last 15 years. The effect of obesity on outcomes following liver transplantation remains largely unclear. To determine the effect of obesity on outcome we reviewed 167 liver transplants, performed at the Vancouver General Hospital, between February 1999 and October 2003. Severe obesity was defined as body mass index (BMI) > 35 kg/m2 and moderate obesity as BMI of 30 - 34 kg/m2. One hundred forty three transplants were performed in patients with a body mass index (BMI) < 30 kg/m2, 14 in patients with a BMI of 30 - 34 kg/m2, and 10 in patients with a BMI > 35 kg/m2. Non-weight related patient demographics were similar between the groups. A very high proportion of Hepatitic C patients (7/10) were observed in the severely obese group. In the early postoperative course severely obese patients had a higher rate of wound infection (20% vs. 4%, p = 0.0001) and wound dehiscence (40% vs. 1.2%, p = 0.0001). Within the first twelve postoperative months severely obese liver transplant recipients had a higher rate of ventral wound herniation (30% vs. 2.8%, p = 0.0001) when compared to obese or non-obese recipients. The one-year graft and patient survival were similar to non-obese patients. An increased BMI in liver transplant recipients in our centre did not increase the risk of early postoperative mortality, but did increase surgical complications, such as wound infection and wound dehiscence. The 1-year patient and graft survival however was indistinguishable from those of non-obese patients.

Background: Chronic pancreatitis following acute fatty liver of pregnancy is rarely reported., Methods: We treated a 34-year-old woman who developed acute fatty liver of pregnancy (AFLP) after delivery by caesarean section at 32 weeks of gestation. AFLP was complicated by acute pancreatitis and multiple organ failure. The management of the disease was primarily supportive. She recovered from acute fulminant liver failure and multi-organ failure, apart from the development of symptomatic chronic pancreatitis thereafter., Results: Investigations failed to identify any other causes of chronic pancreatitis. The patient responded very well to pancreatic enzyme supplement for the treatment of steatorrhoea., Conclusion: To our knowledge, this is the first report of chronic pancreatitis as a consequence of multi-organ dysfunction caused by AFLP.

Background: Hepatocellular cancer (HCC) is one of the most common malignancies worldwide, and is known to be associated with a poor prognosis. Unfortunately there are no available reliable markers of prognosis. The aim of this study was to determine whether integrin-linked kinase (ILK) expression correlates with post-resection survival from HCC., Patients and Methods: A tissue microarray was constructed using HCC samples, and immunohistochemical analysis for ILK was then carried out and scored by three independent observers. Clinical chart review was performed to determine survival parameters., Results: Of the 52 cases of HCC, 22 cases were associated with hepatitis B (HBV), 18 with hepatitis C (HCV), 2 with HBV and HCV co-infection; 81% of all patients were male and 19% female. Western immunoblotting showed a highly significant correlation between levels of expression of ILK and ser473-PKBphosphorylation, both in control and tumor sections (Spearman rank correlation, r=0.8155, p=0.0004), however, there was no direct correlation between the levels of expression of ILK with patient survival (log-rank test, p= 0.864)., Conclusion: ILK expression does not appear to have a role in predicting outcome in patients with resected HCC.