Response to endoscopic therapy for biliary anastomotic strictures in deceased versus living donor liver transplantation.

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.

Patient time costs and out-of-pocket costs in hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with substantial costs to patients, their caregivers and society. AIMS: We evaluated time costs (time spent seeking healthcare) and out-of-pocket (OOP) costs for patients with HCV and their caregivers. METHODS: We measured costs for 738 HCV outpatients in a tertiary-care clinic using a patient-completed questionnaire. Time and OOP costs were compared across disease stages and sociodemographic categories. We examined the association between cost and disease stage using linear regression adjusting for age, gender, marital status, education, income and Index of Coexistent Disease (ICED) comorbidity score. Costs were expressed in 2007 Canadian dollars. RESULTS: The mean annual time cost per patient was $2136 (98 h), and ranged from $281 (18 h) in individuals who had cleared the virus to $9416 in transplant recipients (420 h). Caregiver costs were reported in 10% of patients. The mean annual OOP cost per patient was $1326. Patients receiving active treatment and those with late-stage disease spent $2500-2800 per year on HCV-related healthcare, approximately 7% of their annual income. Patients who had cleared the virus had the lowest time and OOP costs. Low income and unemployed patients had higher costs. CONCLUSIONS: In HCV-infected individuals, OOP and time costs represent a significant economic burden and fall disproportionately upon those least able to afford them. The lower cost burden among those who were successfully treated suggests that wider use of antiviral therapy may reduce economic burden in addition to improving health outcomes.

Health utilities and psychometric quality of life in patients with early- and late-stage hepatitis C virus infection.

BACKGROUND AND AIM: Hepatitis C virus (HCV) infection is associated with impairment in health-related quality of life (HRQOL). The purpose of this study was to evaluate HRQOL across the HCV disease spectrum using preference-based (utility) and non-preference-based (psychometric) methods, adjusting for sociodemographic factors and co-morbidity. METHODS: Hepatitis C virus patients (n = 751) were recruited from several tertiary care settings in Vancouver, Canada for this observational, cross-sectional cohort study. Patients completed the Health Utilities Index Mark 2/3, a self-administered time trade-off utility instrument, and the Hepatitis Quality of Life Questionnaire (SF-36 with HCV-specific items). We examined the association between HRQOL and disease stage using linear regression adjusting for age, education, marital status, income, and co-morbidities. RESULTS: Utility scores were low across disease stage and instrument, ranging from 0.51 to 0.80. On the SF-36, the mean Physical Component Summary score ranged from 37.2 to 49.2 across disease stage, and the Mental Component Summary score ranged from 39.7 to 45.7 (United States norms = 50). In general, patients with viral clearance had the highest scores, and those with late-stage disease (cirrhosis, liver cancer) had the lowest. Multivariable linear regression showed that the effect of disease stage was modest overall. Increasing age, lower income, unattached marital status, and high comorbidity were strongly associated with impairment in HRQOL. CONCLUSIONS: The effect of stage of disease on HRQOL is modest, although viral clearance is associated with higher HRQOL. HCV patients' HRQOL is strongly associated with concomitant illness and sociodemographic factors.

Relapse of multiple myeloma presenting with biliary obstruction.

Pancreatic infiltration is a rare feature of multiple myeloma. A case of a 74-year-old man presenting with symptomatic biliary obstruction two years after the original diagnosis of myeloma is described. Confirmation of pancreatic infiltration with myeloma cells was performed by endoscopic ultrasound-guided fine-needle aspiration. Biliary stenting was performed at endoscopic retrograde cholangiopancreatography. Resolution of the pancreatic mass and the associated biliary stricture was observed after radiation and chemotherapy.

The use of endoscopic ultrasonography and other imaging modalities in the preoperative staging of rectal villous tumours: a case of overstaging by magnetic resonance imaging.

A case of a 60-year-old man with recurrent rectal villous adenoma is described. Preoperative staging with endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) revealed very discordant results. EUS showed a tumour present in the mucosa with no submucosal invasion, while MRI revealed invasion of the muscularis propria consistent with an invasive stage T2 carcinoma. Based on the MRI findings, the patient underwent a low anterior resection of the tumour. The surgical pathology specimen revealed a villous adenoma with lowgrade dysplasia but no carcinoma and no extension into the muscularis propria. The present case highlights the uncertainty that currently exists as to which imaging modality provides the greatest accuracy in the staging of rectal cancer and in guiding the type of surgical procedure performed. Two recent meta-analyses and a systematic review of the literature point to EUS as the imaging modality of choice for determining muscularis propria and perirectal tissue invasion, as well as nodal involvement.

HCC complicated by PVT: Outcome and the role of anticoagulation therapy.

Background: This retrospective study investigated the clinical impact of PVT on the course of patients with HCC who were and were not treated with anticoagulation (AC). Methods: We retrospectively evaluated a cohort of 60 patients diagnosed with HCC and PVT. Nine patients were excluded for lack of follow-up. HCC, PVT diagnosis, and imaging follow-up were performed using contrast-enhanced computed tomography or MRI. Of the 51 patients evaluated, 12 received AC and 39 did not. Results: Forty-two patients were male; mean age was 60.3 years. Mean survival after HCC diagnosis was 32.9 months; after PVT diagnosis, it was 18.4 months. No symptoms directly related to PVT development were reported. AC therapy was initiated for 12 patients and had to be discontinued for 3 patients because of complications. AC was not associated with a difference in PVT progression (49% in non-AC group vs. 50% in AC group). After adjusting for age, HCC type (single vs. multifocal), and Child-Pugh score, AC was associated with an improved survival after HCC diagnosis (adjusted hazard ratio [HR] = 0.37; 95% confidence interval [CI] 0.14 to 0.99) and after PVT diagnosis (HR = 0.34; 95% CI 0.13 to 0.88). Conclusion: Patients with HCC complicated by PVT in both AC and non-AC groups had a similar rate of progression. Neither group had symptoms attributable to PVT. Possible AC-related complications need to be considered before proceeding with therapy in patients with HCC and PVT. AC may be associated with a survival advantage in patients with HCC and PVT.

Chronic pancreatitis: a sequela of acute fatty liver of pregnancy.

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.

Photodynamic therapy in Barrett's esophagus: results of treatment of 17 patients.

BACKGROUND: Barrett's esophagus (BE) with dysplasia may progress to esophageal adenocarcinoma. Photodynamic therapy is a promising treatment for BE. OBJECTIVE: To determine if photodynamic therapy is an acceptable alternative to esophagectomy in BE patients with high-grade dysplasia or early adenocarcinoma. METHODS: Seventeen patients were treated with photodynamic therapy for BE and high-grade dysplasia or early esophageal adenocarcinoma. Patients with residual Barrett's epithelium were treated with supplemental argon plasma coagulation or potassium titanyl phosphate laser. Patients underwent follow-up endoscopy three, six, nine and 12 months post-treatment, then every six to 12 months. Mean follow-up was 21 months. RESULTS: High-grade dysplasia or early adenocarcinoma was completely eliminated in nine of 15 (60%) patients. High-grade dysplasia was downgraded in one patient, persisted in one patient and progressed in four patients. Two patients with early esophageal adenocarcinoma were nonresponders. Complications included stricture, sunburn, urticaria, small pleural effusions, esophageal spasm and transient atrial fibrillation. CONCLUSIONS: Photodynamic therapy with supplemental ablation is a good, noninvasive therapy for elimination of high-grade dysplasia and early adenocarcinoma in BE. Failure to eliminate dysplastic epithelium occurred in 40% of the patients, thereby necessitating careful follow-up.

Gastrointestinal Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsy Specimens: Adequate Diagnostic Yield and Accuracy Can Be Achieved without On-Site Evaluation.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is the preferred method for biopsying the gastrointestinal tract, and rapid on-site cytological evaluation is considered standard practice. Our institution does not perform on-site evaluation; this study analyzes our overall diagnostic yield, accuracy, and incidence of nondiagnostic cases to determine the validity of this strategy. DESIGN: Data encompassing clinical information, procedural records, and cytological assessment were analyzed for gastrointestinal EUS-FNA procedures (n = 85) performed at Vancouver General Hospital from January 2012 to January 2013. We compared our results with those of studies that had on-site evaluation and studies that did not have on-site evaluation. RESULTS: Eighty-five biopsies were performed in 78 patients, from sites that included the pancreas, the stomach, the duodenum, lymph nodes, and retroperitoneal masses. Malignancies were diagnosed in 45 (53%) biopsies, while 24 (29%) encompassed benign entities. Suspicious and atypical results were recorded in 8 (9%) and 6 (7%) cases, respectively. Only 2 (2%) cases received a cytological diagnosis of 'nondiagnostic'. Our overall accuracy was 72%, our diagnostic yield was 98%, and our nondiagnostic rate was 2%. Our results did not significantly differ from those of studies that did have on-site evaluation. CONCLUSION: Our study highlights that adequate diagnostic accuracy can be achieved without on-site evaluation.

The effect of doxorubicin loading on response and toxicity with drug-eluting embolization in resectable hepatoma: a dose escalation study.

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.

In a 'real-world', clinic-based community setting, sorafenib dose of 400 mg/day is as effective as standard dose of 800 mg/day in patients with advanced hepatocellular carcimona, with better tolerance and similar survival.

BACKGROUND: Sorafenib, an oral multityrosine kinase inhibitor, has been approved for treatment of unresectable hepatocellular carcinoma (HCC). British Columbia (BC) was the first province in Canada to provide drug coverage for sorafenib. OBJECTIVE: To review the BC experience with sorafenib to assess its effectiveness and tolerance in a 'real-world' clinical setting. METHODS: A retrospective clinic chart review identified 99 patients referred to the BC Cancer Agency from 2008 to 2010 with a diagnosis of HCC who qualified for treatment with sorafenib. RESULTS: Therapy with sorafenib was initiated and continued at a reduced dosage of 400 mg/day in 66 of 99 patients, with 22 patients requiring further dose reduction. Full- and reduced-dose group patients had similar baseline characteristics, except for a higher proportion of female patients (P=0.02) and individuals with alcoholic liver disease (P=0.04) in the full-dose group. The incidence of any grade of adverse effects was higher in the full-dose group (94% versus 77% in the reduced-dose group; P=0.04). Dose reduction rates were significantly higher in the full-dose group, occurring in 66% versus 24% of reduced-dose group patients (P=0.001). The overall survival rates were similar between the two groups: 7.8 months versus 7.1 months in full- versus reduced-dose groups (P=0.14), as were radiological progression rates and alpha-fetoprotein levels. CONCLUSIONS: In a review of 99 patients in a 'real-world' community setting, a sorafenib dose of 400 mg/day was better tolerated and had similar efficacy compared with a sorafenib dose of 800 mg/day with respect to survival and outcomes.

A rare case of isolated duodenal metastases from hepatocellular carcinoma associated with p53 and ki-67 expression: a case report.

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver worldwide. The incidence of HCC is increasing in North America secondary to rises in chronic liver disease from alcohol abuse and viral hepatitis. HCC most commonly metastasizes hematogenously or through lymphatics to the lungs and regional lymph nodes. Involvement of small bowel is rare and typically results from direct invasion and extension. We examined the molecular features related to this extremely rare case of isolated duodenal metastasis of HCC and noted p53 and Ki-67 positive staining. Here, we review the possible molecular and immunohistochemical studies that may aid definitive diagnosis and the evidence for the management of metastatic hepatocellular carcinoma.