Variability of the EG95 antigen-coding gene of Echinococcus granulosus in animal and human origin: implications for vaccine development.

In the present study, the genetic variability of the EG95 protein-coding gene in several animal and human isolates of Echinococcus granulosus was investigated. A total of 24 isolates collected from cattle, buffalo, sheep, goat, dog and man were amplified by Eg95-coding gene-specific primers. From the generated sequence information, a conceptual amino acid sequence was deduced. Phylogenetically, the Eg95 coding gene belongs to the Eg95-1/Eg95-2/Eg95-3/Eg95-4 cluster. Further confirmation on the maximum composite likelihood analysis revealed that the overall transition/transversion bias was 2.913. This finding indicated thatthere is bias towards transitional and transversional substitution. Using artificial neural networks, a B-cell epitope was predicted on primary sequence information. Stretches of amino acid residues varied between animal and human isolates when hydrophobicity was considered. Flexibility also varied between larval and adult stages of the organism. This observation is important to develop vaccines. However, cytotoxic T-lymphocyte epitopes on primary sequence data remained constant in all isolates. In this study, agretope identification started with hydrophobic amino acids. Amino acids with the same physico-chemical properties were present in the middle. The conformational propensity of the Eg95-coding gene of 156 amino acid residues had α-turns and ß-turns, and α-amphipathic regions up to 129, 138-156 and 151-155 residues, respectively. The results indicated potential T-cell antigenic sites. The overall Tajima's D value was negative (-2.404165), indicative of negative selection pressure.

Risk factors for post-discharge venous thromboembolism in patients undergoing colorectal resection: a NSQIP analysis.

BACKGROUND: Extended thromboprophylaxis after abdominal and pelvic cancer surgery to prevent venous thromboembolic events (VTE) is recommended but adherence is sub-optimal. Identifying patients at highest risk for post-discharge events may allow for selective extended thromboprophylaxis. The aim of our study was to identify the different risk factors of venous thromboembolism for in-hospital and post-discharge events. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) 2012-2016 database was queried for all patients having colorectal resection. Primary outcome was postoperative VTE occurrence within 30 days. A multinomial logistic regression was performed to identify in-hospital and post-discharge predictors of VTE, adjusting for potential confounders. RESULTS: Out of 260,258 patients, 5381 (2.1%) developed VTE. A total of 3442 (1.3%) were diagnosed during the initial hospital stay and 1929 (0.8%) post-discharge. Risk factors for in-hospital and post-discharge VTE were different as patients with an in-hospital event were more likely to be older, male, known for preoperative steroid use, have poor functional status, significant weight loss, preoperative sepsis, prolonged operative time, undergoing an emergency operation. In the post-discharge setting, steroid use, poor functional status, preoperative sepsis, and postoperative complications remained significant. Postoperative complications were the strongest predictor of in-hospital and post-discharge VTE. Patients with inflammatory bowel disease had a higher risk of VTE than patients with malignancy for both in-patient and post-discharge events. CONCLUSIONS: Patients at high-risk for post-discharge events have different characteristics than those who develop VTE in-hospital. Identifying this specific subset of patients at highest risk for post-discharge VTE may allow for the selective use of prolonged thromboprophylaxis.

Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma.

BACKGROUND AND AIMS: In this pilot study, we assessed the safety and tolerability of combining sorafenib with 90Y radioembolization for the treatment of unresectable hepatocellular carcinoma (hcc). METHODS: The study, conducted prospectively during 2009-2012, included eligible patients with unresectable hcc and a life expectancy of at least 12 weeks. Each patient received sorafenib (400 mg twice daily) for 6-8 weeks before 90Y treatment. Safety and tolerability were assessed. RESULTS: Of the 40 patients enrolled, 29 completed treatment (combined therapy). In the initial cohort, the most common cause of hcc was hepatitis C (32.5%), and most patients were staged Child A (82.5%). The 29 patients who completed the study had similar baseline characteristics. Grades 1 and 2 toxicities accounted for 77.8% of all adverse events reported. The most common toxicities reported were fatigue (19.0%), alteration in liver function (7.9%), and diarrhea (6.3%). There were 12 grade 3 and 2 grade 4 toxicity events reported. One patient died of liver failure within 30 days after treatment. During the study, the sorafenib dose was reduced in 6 patients (20.7%), and sorafenib had to be interrupted in 4 patients (13.8%) and discontinued in 4 patients (13.8%). The disease control rate was 72.4% per the modified Response Evaluation Criteria in Solid Tumors, and tumour necrosis was observed in 82.8% of patients. Overall survival in patients undergoing combined therapy was 12.4 months. CONCLUSIONS: Preliminary results demonstrate the safety and tolerability of combining 90Y radioembolization and sorafenib for advanced hcc. A larger prospective study is needed to determine the extent of the survival benefit.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.

High Field Emission Current Density from Patterned Carbon Nanotube Field Emitter Arrays with Random Growth.

High field emission (FE) current density from carbon nanotube (CNT) arrays grown on lithographically patterned silicon substrates is reported. A typical patterned field emitter array consists of bundles of nanotubes separated by a fixed gap and spread over the entire emission area. Emission performance from such an array having randomly oriented nanotube growth within each bundle is reported for different bundle sizes and separations. One typical sample with aligned CNTs within the bundle is also examined for comparison. It is seen that the current density from an array having random nanotube growth within the bundles is appreciably higher as compared to its aligned counterpart. The influence of structure on FE current densities as revealed by Raman spectroscopy is also seen. It is also observed that current density depends on edge length and increases with the same for all samples under study. Highest current density of -100 mA cm(-2) at an applied field of 5 V/µm is achieved from the random growth patterned sample with a bundle size of 2 µm and spacing of 4 µm between the bundles.

Complete Remission of Post-transplantation Recurrence of Focal Segmental Glomerulosclerosis With the Use of Adrenocorticotrophic Hormone Gel: Case Report.

BACKGROUND: Post-transplantation recurrence of primary focal and segmental glomerulosclerosis (FSGS) is estimated to occur in 30%-50% of cases and doubles the risk of allograft failure. Treatment of recurrent FSGS is challenging because specific pathogenic targets are unknown and available therapeutic options have limited efficacy. CASE REPORT: We report a case of recurrent FSGS with nephrotic-range proteinuria (urine protein creatinine ratio [UPCR], >50) and debilitating edema that was resistant to rituximab and plasmapheresis. The patient had a remarkable response to adrenocorticotropic hormone (ACTH) gel and achieved complete remission (UPCR, 0.5; serum albumin, 4.1 g/dL; serum creatinine, 1.0 mg/dL) which was maintained over 10 months on this treatment. CONCLUSIONS: We conclude that ACTH gel is a potential therapeutic option for post-transplantation recurrence of FSGS and warrants further evaluation.

Portal vein embolization and its effect on tumour progression for colorectal cancer liver metastases.

BACKGROUND: The aim of this study was to evaluate the long-term outcomes of patients with colorectal cancer liver metastasis (CRCLM) exhibiting disease progression after portal vein embolization (PVE). METHODS: Patients with CRCLM requiring PVE before hepatectomy between 2003 and 2014 were included. Clinical variables, and liver and tumour volumes determined by three-dimensional CT volumetry were assessed before and after PVE. Overall and disease-free survival data were obtained. Univariable and multivariable logistic regression analyses were performed to identify predictors of tumour progression after PVE. RESULTS: Of 141 patients who underwent PVE, 93 (66.0 per cent) had tumour progression and 17 (12.1 per cent) developed new contralateral lesions. Significantly fewer patients had resectable disease in the group with disease progression than among those with stable disease: 43 (46 per cent) of 93 versus 36 (75 per cent) of 48 respectively (P = 0.001). Median survival was similar in patients with and without tumour growth after PVE: 22.5 versus 26.0 months for patients with unresectable tumours (P = 0.706) and 46.2 versus 52.2 months for those with resectable disease (P = 0.953). However, disease-free survival for patients with tumour progression after PVE was shorter than that for patients with stable disease (6.0 versus 20.2 months; P = 0.045). Response to neoadjuvant chemotherapy was the only significant factor associated with tumour progression in multivariable analysis. CONCLUSION: Tumour progression after PVE did not affect overall survival, but patients with resected tumours who had tumour growth after embolization experienced earlier recurrence. A borderline response to neoadjuvant chemotherapy seemed to be associated with tumour progression after PVE.

Establishing a clinic-based pancreatic cancer and periampullary tumour research registry in Quebec.

BACKGROUND: Enrolling patients in studies of pancreatic ductal adenocarcinoma (pdac) is challenging because of the high fatality of the disease. We hypothesized that a prospective clinic-based study with rapid ascertainment would result in high participation rates. Using that strategy, we established the Quebec Pancreas Cancer Study (qpcs) to investigate the genetics and causes of pdac and other periampullary tumours (pats) that are also rare and underrepresented in research studies. METHODS: Patients diagnosed with pdac or pat were introduced to the study at their initial clinical encounter, with a strategy to enrol participants within 2 weeks of diagnosis. Patient self-referrals and referrals of unaffected individuals with an increased risk of pdac were also accepted. Family histories, epidemiologic and clinical data, and biospecimens were collected. Additional relatives were enrolled in families at increased genetic risk. RESULTS: The first 346 completed referrals led to 306 probands being enrolled, including 190 probands affected with pdac, who represent the population focus of the qpcs. Participation rates were 88.4% for all referrals and 89.2% for pdac referrals. Family history, epidemiologic and clinical data, and biospecimens were ascertained from 91.9%, 54.6%, and 97.5% respectively of patients with pdac. Although demographics and trends in risk factors in our patients were consistent with published statistics for patients with pdac, the qpcs is enriched for families with French-Canadian ancestry (37.4%), a population with recurrent germ-line mutations in hereditary diseases. CONCLUSIONS: Using rapid ascertainment, a pdac and pat research registry with high participation rates can be established. The qpcs is a valuable research resource and its enrichment with patients of French-Canadian ancestry provides a unique opportunity for studies of heredity in these diseases.

Real-Life Report on Chemoembolization Using DEBIRI for Liver Metastases from Colorectal Cancer.

Background. Transarterial chemoembolization (TACE) has been investigated in patients with liver metastases from colorectal cancer (LMCRC). Limited experience and available data suggest that TACE can achieve disease stabilization or improvement, even in heavily pretreated patients. Methods. Patients with LMCRC, ECOG 0-2, who failed at least 1 line of systemic chemotherapy, received embolizations with 2 mL of microspheres preloaded with 100 mg of irinotecan. Beads were delivered selectively into hepatic arteries. Primary endpoint was overall survival (OS), analyzed using the Kaplan-Meier method. Secondary endpoint was safety, assessed using CTCAE version 4.0. Results. 27 patients were treated using DEBIRI. Patient median age was 57 years (range was 45-82 years). The median number of total embolizations was 1.3 (range 1-3). The median OS was 5.4 months (95% CI; 1.1-22.7 months). The most reported postembolization events were nausea (8/27), vomiting (6/27), right upper quadrant pain (16/27), fatigue (9/27), and the development of ascites (6/27). 5/26 patients required hospitalization after TACE for severe pain. Hospitalization was also required for 1 case of allergic reaction and 1 case of infection. Conclusion. Our data suggest that TACE with DEBIRI could be efficacious in a palliative setting for patients with LMCRC, but they do not necessarily support routine use in clinical practice.

Prospective iterative trial of proteasome inhibitor-based desensitization.

A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLA antibody (Ab) levels was conducted in five phases differing in bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 bortezomib cycles (1.3 mg/m(2) × 6-8 doses), one rituximab dose and plasmapheresis. HLA Abs were measured by solid phase and flow cytometry (FCM) assays. Immunodominant Ab (iAb) was defined as highest HLA Ab level. Forty-four patients received 52 desensitization courses (7 patients enrolled in multiple phases): Phase 1 (n = 20), Phase 2 (n = 12), Phase 3 (n = 10), Phase 4 (n = 5), Phase 5 (n = 5). iAb reductions were observed in 38 of 44 (86%) patients and persisted up to 10 months. In Phase 1, a 51.5% iAb reduction was observed at 28 days with bortezomib alone. iAb reductions increased with higher bortezomib dosing densities and included class I, II, and public antigens (HLA DRß3, HLA DRß4 and HLA DRß5). FCM median channel shifts decreased in 11/11 (100%) patients by a mean of 103 ± 54 mean channel shifts (log scale). Nineteen out of 44 patients (43.2%) were transplanted with low acute rejection rates (18.8%) and de novo DSA formation (12.5%). In conclusion, PI-based desensitization consistently and durably reduces HLA Ab levels providing an alternative to intravenous immune globulin-based desensitization.

(18)F-Fluorodeoxyglucose positron-emission tomography could have a prognostic role in patients with advanced hepatocellular carcinoma.

INTRODUCTION: We set out to evaluate the prognostic value of (18)F-fluorodeoxyglucose positron-emission tomography (pet) in patients with advanced (non-transplant-eligible) hepatocellular carcinoma (hcc) and to evaluate the correlation between standardized uptake values (suvs) and survival outcomes. METHODS: We identified patients with hcc who, from 2005 to 2013, underwent pet imaging before any treatment. This retrospective study from our hcc database obtained complete follow-up data for the 63 identified patients. RESULTS: Of the 63 patients, 10 underwent surgical resection, and 59 underwent locoregional therapy. In this cohort, 28 patients were pet-positive (defined as any lesion with a suv ≥ 4.0) before any therapy was given, and 35 patients were pet negative (all lesions with a suv < 4.0). On survival analysis, median survival was greater for the pet-negative than for the pet-positive patients: 29 months (range: 16.3-41.1 months) versus 12 months (range: 4.0-22.1 months) respectively, p = 0.0241. The pet-positive patients more often had large tumours (≥5 cm), poor differentiation, and extrahepatic disease, reflecting more aggressive tumours. On multivariate analysis, only pet positivity was associated with poor survival (p = 0.049). CONCLUSIONS: Compared with pet-positive patients, pet-negative patients with hcc experienced longer survival. Imaging by pet can be of value in early prognostication for patients with hcc, especially patients receiving locoregional therapy for whom pathologic tumour differentiation is rarely available. This potential role for pet requires further validation in a prospective study.

Bevacizumab-based therapy for colorectal cancer: experience from a large Canadian cohort at the Jewish General Hospital between 2004 and 2009.

BACKGROUND: Before its regulatory approval in Canada, bevacizumab to treat patients with colorectal cancer (crc) was accessed through the Bevacizumab Expanded Access Trial and a special-access program at the Jewish General Hospital. We retrospectively evaluated patient outcomes in that large cohort. METHODS: All patients (n = 196) had metastatic crc, were bevacizumab-naïve, and received bevacizumab in combination with chemotherapy at the Jewish General Hospital between 2004 and 2009. We collected patient demographics and clinical characteristics; relevant medical history, disease stage and tumour pathology at diagnosis; type, duration, and line of therapy; grades 3 and 4 adverse events (aes), time to disease progression (ttp), and overall survival (os) from diagnosis. RESULTS: Median follow-up was 36.0 months. Median ttp was 8.0 months [95% confidence interval (ci): 7.0 to 9.0 months). Median os was 41.0 months (95% ci: 36.0 to 47.0 months). Of the 40 grades 3 and 4 bevacizumab-related aes experienced by 38 patients (19.4%), the most common were thrombocytopenia (n = 17), deep-vein thrombosis (n = 6), pulmonary embolism (n = 4), and hypertension (n = 3). CONCLUSIONS: In an expanded access setting, our data reflect the efficacy and safety of bevacizumab-based therapy in the controlled post-registration clinical trial setting.

Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma.

BACKGROUND: Downsizing strategies are often attempted for patients with hepatocellular carcinoma (hcc) before liver transplantation (lt). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (tace) before lt for hcc outside the Milan criteria, so as to better select candidates for this strategy. METHODS: In this retrospective study, patients with hcc tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based tace treatments. Exclusion criteria for tace included Child-Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after tace underwent lt. RESULTS: Of 160 hcc patients who received liver grafts between 1997 and 2010, 35 were treated with tace preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8-8.5 cm), which decreased with tace to 5.0 cm (range: 3.3-7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αfp) was a positive predictor (p = 0.0051) and the time from last tace treatment to transplantation was a negative predictor (p < 0.0001) for overall survival. CONCLUSIONS: The percentage drop in αfp and a shorter time from the final tace treatment to transplantation significantly predicted improved overall survival after lt for hcc downsized with tace. As a serum marker, αfp should be followed when tace is used as a strategy to stabilize or downsize hcc lesions before lt.

A real-life experience using panitumumab in chemo-refractory metastatic colorectal cancer patients: a retrospective analysis at the Jewish General Hospital, 2009-2012.

BACKGROUND: Panitumumab is a fully human monoclonal antibody, directed against the epidermal growth factor receptor, that was shown to be effective in third-line metastatic colorectal cancer. We performed a retrospective analysis of patients with chemo-refractory non-KRAS-mutated metastatic colorectal cancer, who received panitumumab at the Jewish General Hospital in Montreal, Canada, between 2009 and 2012. METHODS: This chart review included 44 patients (median age: 60 years; performance status: 0-3), of whom 50% had already received three lines of treatment. The primary endpoint was progression-free survival (pfs). Secondary endpoints were overall survival and safety. Tumour progression was determined by radiologic assessments performed once every 3 months per clinical guidelines or by clinical deterioration as determined by the clinician-investigator. RESULTS: In our sample, median pfs was 21.86 ± 5.23 weeks (95% confidence interval: 12.9 to 36.9 weeks) and overall survival was 35.14 ± 7.75 weeks (95% confidence interval: 25.6 to 73.4 weeks) with a median of 5 cycles of panitumumab treatment. The most frequently reported toxicities with panitumumab were skin toxicity (16.2% grade 3) and hypomagnesemia (10.8% grade 3). No infusion reactions were reported. CONCLUSIONS: Despite a small sample size from a single institution, our survival and efficacy data are encouraging and comparable to results obtained from the registration panitumumab trial. Our findings suggest that panitumumab can be effective and tolerable in a real-world setting.

Association of oxidative stress biomarkers and antioxidant enzymatic activity in male infertility of north-East India.

INTRODUCTION: Oxidative stress is a common pathology seen in approximately half of all infertile men. In a normal situation, the seminal plasma contains antioxidant mechanisms which are likely to quench these reactive oxygen species. However, during infertility complications these antioxidant mechanisms may downplay and create a situation which is called oxidative stress. OBJECTIVE: The aim of the present study was to assess the levels of lipid peroxide (LPO), protein peroxide (PPO) and activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX) in blood and semen samples of an infertile male population from North-East India. METHOD: We measured LPO, PPO, SOD and GPX in a total of 50 infertile individuals. For the study 20 fertile donors served as the control group. RESULT: Patients with male factor infertility had significantly higher LPO and PPO levels (60.84 ± 3.55 and 72.84 ± 3.66; P < 0.001) compared with controls (40.20 ± 4.33 and 59.93 ± 5.24) in blood. In semen also, the same trend was found with significantly higher LPO and PPO levels (200.27 ± 6.25 and 149.80 ± 11.47; P < 0.001) compared with controls (116.51 ± 5.49 and 59.10 ± 4.62). The SOD and GPX enzymes in blood (3.40 ± 1.06 and 0.16 ± 0.01; P < 0.001) and in semen (2.42 ± 1.32 and 0.24 ± 0.015; P < 0.001) showed a significantly lower activity when compared with their respective controls (4.85 ± 0.78; 0.36 ± 0.05 and 4.24 ± 0.89; 0.65 ± 0.03). The SOD and GPX activity when compared with the LPO and PPO values, showed a positive correlation. CONCLUSION: We conclude that oxidative stress is associated with male factor infertility. This assessment may help in the treatment of this male infertility by suitable antioxidants.

Prolonged lymphopenia following anti-thymocyte globulin induction is associated with decreased long-term graft survival in liver transplant recipients.

BACKGROUND AND AIM: Induction with anti-thymocyte globulin (ATG) during solid organ transplantation is associated with an improved clinical course and leads to prolonged lymphopenia. This study aims to investigate whether prolonged lymphopenia, caused by ATG induction, has an impact on patient and graft survival following liver and kidney transplantation. PATIENTS AND METHODS: This was a single-center, retrospective study. A total of 292 liver and 417 kidney transplants were performed with ATG induction (6 mg/kgr, divided into four doses), and the transplant recipients were followed for at least three months. The average lymphocyte count for the first 30 days after the operation was calculated, and the cut-off value for defining lymphopenia was arbitrarily set to ≤ 500 cells/mm(3). RESULTS: There were 210 liver transplant recipients (71.9%) who achieved prolonged lymphopenia, whereas the remaining 82 recipients (28.1%) did not. The mean survival time of these patient groups was 10.27 and 12.71 years, respectively (p = 0.1217), and the mean graft survival time was 8.98 and 12.25 years, respectively (p = 0.0147). Of the kidney transplant patients, 330 (79.1%) recipients achieved prolonged lymphopenia, whereas the remaining 87 (20.9%) did not. The mean survival time of these patient groups was 13.94 and 14.59 years, respectively, (p = 0.4490), and the mean graft survival time was 11.84 and 11.54 years, respectively (p = 0.7410). CONCLUSION: The efficacy and safety of ATG induction partially depend on decreased total lymphocyte counts. Following ATG induction in liver transplant recipients, a reasonable average lymphocyte count during the first postoperative month would be above 500 cells/mm(3).

Allocation of renal grafts to older recipients does not result in loss of functioning graft-years.

BACKGROUND: Most deceased donor kidney allocation protocols are based on waiting time and do not take into account either recipient's life expectancy. This study investigates whether graft survival is affected by patient life expectancy. METHODS: A total of 640 adult kidney transplants were performed. Recipients were divided in group A (patients ≤ 50 years) and group B (patients > 50 years). The status of graft+recipient combination was characterized as: a) deceased recipient with functional graft, b) alive recipient with functional graft and c) deceased or alive recipient with nonfunctional graft. RESULTS: Mean kidney recipient survival was 15.15 (95% CI: 14.54, 15.77) and 12.40 (95% CI: 11.47, 13.33) years for groups A and B respectively (p < 0.0001). Mean graft survival was 13.62 (95% CI: 12.81, 14.43) and 12.42 (95% CI: 11.59, 13.25) years for groups A and B respectively (p=0.6516). Non-functional grafts were identified in 18.4% (n=57) and 16.4% (n=54) of group A and B respectively. CONCLUSIONS: Allocation of renal grafts to older patients does not result in significant loss of graft-years. Recipients' life expectancy has a small impact on graft survival. We should not deviate from the basic principles of equality, when kidney allocation systems are designed.

Multidisciplinary Canadian consensus recommendations for the management and treatment of hepatocellular carcinoma.

Globally, hepatocellular carcinoma (hcc) is the third most common cause of death from cancer, after lung and stomach cancer. The incidence of hcc in Canada is increasing and is expected to continue to increase over the next decade. Given the high mortality rate associated with hcc, steps are required to mitigate the impact of the disease. To address this challenging situation, a panel of 17 hcc experts, representing gastroenterologists, hepatologists, hepatobiliary surgeons, medical oncologists, pathologists, and radiologists from across Canada, convened to provide a framework that, using an evidence-based approach, will assist clinicians in optimizing the management and treatment of hcc. The recommendations, summarized here, were developed based on a rigorous methodology in a pre-specified process that was overseen by the steering committee. Specific topics were identified by the steering committee and delegated to a group of content experts within the expert panel, who then systematically reviewed the literature on that topic and drafted the related content and recommendations. The set of recommendations for each topic were reviewed and assigned a level of evidence and grade according to the levels of evidence set out by the Centre for Evidence-based Medicine, Oxford, United Kingdom. Agreement on the level of evidence for each recommendation was achieved by consensus. Consensus was defined as agreement by a two-thirds majority of the 17 members of the expert panel. Recommendations were subject to iterative review and modification by the expert panel until consensus could be achieved.

Complete response of hepatocellular carcinoma with sorafenib and Y radioembolization.

Advanced hepatocellular carcinoma has a dismal prognosis, with a median overall survival of 7.9 months if untreated and of 10.7 months if treated with sorafenib. We present a case of advanced previously unresectable hepatocellular carcinoma in a 49-year-old man that achieved a pathologic complete response and was made amenable to surgery with sorafenib in combination with (90)Y radioembolization. The patient's survival was more than double the median for patients treated with sorafenib alone.

Re-vascularization may not increase graft survival after hepatic artery thrombosis in liver transplant recipients.

BACKGROUND AND AIM: Hepatic artery thrombosis (HAT) occurs in 3% to 11% of all liver transplantations. Some authors have reported good outcomes with early thrombectomy. To investgate the impact of re-vascularization on graft survival. METHODS: A total of 566 primary, cadaveric, single organ, adult liver transplants were performed. Hepatic arterial Doppler was performed routinely and patients with abnormal findings during the first two post-operative weeks were reexplored. Abnormal findings after this time-point were verified by non-invasive angiogram. The 47 patients that were diagnosed with arterial thrombosis, either intra-operatively or by angiogram, were divided into three groups. No further action was taken for group A, thrombectomy alone was performed for group B1, thrombectomy and anastomotic revision was employed for group B2. RESULTS: Arterial thrombosis was diagnosed in 47 (8.3%) patients. Mean patient survival was 42, 62 and 98 months for groups A, B1 and B2 respectively (p: 0.0629). Mean graft survival was 24, 29 and 60 months for groups A, B1 and B2 respectively (p: 0.3386). Re-transplant incidence was 8.7%, 40% and 28.6% for groups A, B1, and B2 respectively (p: 0.035). CONCLUSIONS: Early diagnosis of HAT by surveillance Doppler may lead to improved recipient survival secondary to earlier re-transplantation and not because of successful graft re-vascularization.