Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome.

BACKGROUND: There is scant literature on hepatocellular carcinoma (HCC) in patients with Budd-Chiari syndrome (BCS). AIM: To assess the magnitude, clinical characteristics, feasibility, and outcomes of treatment in BCS-HCC. METHODS: A total of 904 BCS patients from New Delhi, India and 1140 from Mumbai, India were included. The prevalence and incidence of HCC were determined, and among patients with BCS-HCC, the viability and outcomes of interventional therapy were evaluated. RESULTS: In the New Delhi cohort of 35 BCS-HCC patients, 18 had HCC at index presentation (prevalence 1.99%), and 17 developed HCC over a follow-up of 4601 person-years, [incidence 0.36 (0.22-0.57) per 100 person-years]. BCS-HCC patients were older when compared to patients with BCS alone (P = 0.001) and had a higher proportion of inferior vena cava block, cirrhosis, and long-segment vascular obstruction. The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up (13029 ng/mL vs 500 ng/mL, P = 0.01). Of the 35 BCS-HCC, 26 (74.3%) underwent radiological interventions for BCS, and 22 (62.8%) patients underwent treatment for HCC [transarterial chemoembolization in 18 (81.8%), oral tyrosine kinase inhibitor in 3 (13.6%), and transarterial radioembolization in 1 (4.5%)]. The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo (P = 0.0001). In contrast to the New Delhi cohort, the Mumbai cohort of BCS-HCC patients were predominantly males, presented with a more advanced HCC [Barcelona Clinic Liver Cancer C and D], and 2 patients underwent liver transplantation. CONCLUSION: HCC is not uncommon in patients with BCS. Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

Prognostic and Therapeutic Potentials of OncomiRs Modulating mTOR Pathways in Virus-Associated Hepatocellular Carcinoma.

BACKGROUND: Dysregulated oncomiRs are attributed to hepatocellular carcinoma (HCC) through targeting mTOR signaling pathway responsible for cell growth and proliferation. The potential of these oncomiRs as biomarker for tumor response or as target for therapy needs to be evaluated. AIM: Tumor response assessment by OncomiR changes following locoregional therapy (LRT) and targeting of these oncomiRs modulating pathway. METHODS: All consecutive viral-HCC patients of BCLC stage-A/B undergoing LRT were included. OncomiRs (miR-21, -221, and -16) change in circulation and AFP-ratio at 1-month post-LRT to baseline was estimated to differentiate various categories of response as per mRECIST criteria. OncomiR modulating mTOR pathway was studied by generating miR-21 and miR-221 overexpressing Huh7 stable cell lines. RESULTS: Post-LRT tumor response was assessed in 90 viral-HCC patients (CR, 40%; PR, 31%, and PD, 29%). Significant increase of miRNA-21 and -221 expression was observed in PD (p = 0.040, 0.047) and PR patients (miR-21, p = 0.045). Fold changes of miR-21 can differentiate response in group (CR from PR+PD) at AUROC 0.718 (95% CI, 0.572-0.799) and CR from PD at AUROC 0.734 (95% CI, 0.595-0.873). Overexpression of miR-21 in hepatoma cell line had shown increased phosphorylation p70S6K, the downstream regulator of cell proliferation in mTOR pathway. Upregulation of AKT, mTOR, and RPS6KB1 genes were found significant (P < 0.005) and anti-miR-21 specifically reduced mTOR gene (P = 0.02) expression. CONCLUSIONS: The miR-21 fold change correlates well with imaging in predicting tumor response. Overexpression of miR-21 has a role in HCC through mTOR pathway activation and can be targeted.

Prognostic role of serial alpha-fetoprotein levels in hepatocellular carcinoma treated with locoregional therapy.

Background and aim: To evaluate early serial AFP changes in responders and non-responders to locoregional therapy and identify differences between significant AFP decliners and non-decliners post-treatment. Methods: Case records of hepatocellular carcinoma (HCC) patients having AFP ≥20 ng/ml and treated with locoregional therapy were examined retrospectively. Patients with complete details were included. Trends of serial AFP change (from baseline to post-treatment one month) in patients showing early tumor response (complete response (CR), partial response (PR), progressive disease (PD)) as assessed on multiphasic MRI/CT liver performed at one month following treatment. Receiver operating curves were drawn to estimate the best AFP reduction cut off for differentiating between responders (CR plus PR) from non-responders (PD). AFP decliners (those with AFP level reduction greater than 20% post-treatment) were identified and comparisons of their clinical parameters, tumor response and survival rate were made with AFP non-decliners. Results: HCC patients (n = 126) had mean age of 52.8 years, male:female ratio (4:1), Child's A 94, BCLC stage A/B/C HCC 49/65/12, respectively. On 4-6 weeks' MRI/CT, 46 patients developed CR, 55 PR and 25 PD. Reduction in median AFP level (83% in CR, 19% in PR) occurred in responders while 16% increase occurred in PD patients (non-responders). A 30% AFP reduction could differentiate responders from non-responders with 70% sensitivity and 68% specificity, AUROC 74% (CI 0.64-0.85). AFP decliners showed better survival and tumor response than non-decliners. Conclusions: Serial AFP change can predict tumor response to locoregional therapy in AFP producing HCC patients. AFP decliners have better survival and tumor response than AFP non-decliners.

Non-alcoholic fatty liver disease associated with hepatocellular carcinoma: An increasing concern.

Hepatocellular carcinoma (HCC) is the sixth most common cancer in world and third largest cause of cancer-related deaths. The last few decades have witnessed the emergence of non-viral causes of HCC, the most important being non-alcoholic fatty liver disease (NAFLD). NAFLD ranges from simple steatosis in the absence of excessive alcohol intake to non-alcoholic steatohepatitis (NASH) with or without cirrhosis. About 3-15 per cent of the obese patients with NASH progress to cirrhosis and about 4-27 per cent of NASH with cirrhosis patients transform to HCC. It is also known that HCC can develop de novo in patients with NASH without the presence of cirrhosis. Yearly cumulative incidence of NASH-related HCC is low (2.6%) compared to four per cent of viral-HCC. NAFLD has been associated with risk factors such as metabolic syndrome, insulin resistance, altered gut flora and persistent inflammation. Due to alarming rise in metabolic diseases, both in the developing as well as the developed world, it is expected that the incidence of NAFLD/NASH-HCC would rise manifold in future. No definite guidelines have been drawn for surveillance and management of NAFLD/NASH-associated HCC. It is thus important to discuss the entity of HCC in NAFLD at length with special focus on its epidemiology, risk factors, pathophysiology, diagnosis, clinical presentation and prevention.

Trans-arterial chemoembolization (TACE) in patients with unresectable Hepatocellular carcinoma: Experience from a tertiary care centre in India.

AIMS: To evaluate the outcome following transarterial chemoembolization (TACE) and to identify the predictors of survival in patients with unresectable hepatocellular carcinoma (HCC). MATERIAL AND METHODS: HCC patients reporting to our hospital (2001-2007) were subjected to clinical, biochemical, and radiological examination. TACE was performed in those who fulfilled the inclusion criteria. Follow-up assessment was done with multiphase CT scan of the liver at 1, 3, and 6 months. Tumor response and survival rate were estimated. Univariate and multivariate analyses were done for determinants of survival. RESULTS: A total of 73 patients (69 males, 4 females; mean age 49±13.4 years) were subjected to 123 sessions of TACE. The Child's classification was: A - 56 patients and B - 17 patients. Barcelona Clinic staging was: A - 20 patients, B - 38 patients, and C - 15 patients. Tumor size was ≤5cm in 28 (38%) patients, >5-10 cm in 28 (38%) patients, and >10 cm in 17 (23%) patients. Median follow-up was for 12 months (range: 1-77 months). No significant postprocedure complications were encountered. Overall survival rate was 66%, 47%, and 36.4% at 1, 2, and 3 years, respectively. Tumor size emerged as an important predictor of survival. CONCLUSION: TACE offers a reasonable palliative therapy for HCC. Initial tumor size is an independent predictor of survival.

Economic evaluation of a surveillance program of hepatocellular carcinoma (HCC) in India.

PURPOSE: Surveillance of patients of cirrhosis of liver is practiced for early detection of HCC. No data from any developing country on cost-effectiveness of such a program are available. METHODS: Economic evaluation of HCC surveillance was embedded in a prospective study undertaken to estimate the incidence of HCC in 194 cirrhotics. The protocol consisted of 6 monthly abdominal ultrasound (US) and serum alphafetoprotein (AFP) estimation, and yearly triple phase CT. Cost was estimated from the hospital and patient perspectives. Cost-effectiveness ratios for detecting a case of HCC were estimated. Modeling was done to estimate cost effectiveness with different combinations of diagnostic tests. RESULTS: Cost-effectiveness ratios of HCC surveillance program per HCC case detected were estimated as US$ 280 from the hospital perspective. From patient perspective, these were US$ 9,965 for outstation and US$ 2,808 for local patients. Cost-effectiveness ratio for direct medical cost per case of HCC detected by 6 monthly US and AFP, the EASL protocol, was estimated to be US$ 1,510 in the private sector. CONCLUSION: The cost of HCC surveillance program is exorbitant for India (gross national income per capita US$ 620) and possibly other low/middle income countries.

Evaluating patients with cirrhosis for hepatocellular carcinoma: value of clinical symptomatology, imaging and alpha-fetoprotein.

OBJECTIVE: This study was undertaken to assess the value of clinical symptomatology, abdominal ultrasound (US), triple-phase CT (TPCT) and serum alpha-fetoprotein (AFP) estimation in predicting presence of hepatocellular carcinoma (HCC) among patients with cirrhosis. MATERIALS AND METHODS: In this cross-sectional study, Child's A/B cirrhosis patients were subjected to clinical evaluation, US, TPCT and serum AFP estimation. Sensitivity and specificity of clinical symptoms and of AFP at different cut-off levels were determined. Detection rate of HCC and agreement between US and TPCT was estimated. RESULTS: A high proportion of enrolled subjects had HCC at first presentation (40.7%). Significantly higher prevalence of abdominal pain, weight loss, and anorexia was seen in patients with cirrhosis with HCC compared to those without HCC. Sensitivity and specificity of any of these symptoms was 73 and 79%, respectively (positive and negative predictive values of 65 and 85%, respectively). A 100% agreement between TPCT and US was observed for diagnosing HCC cases. However, TPCT detected a greater number of smaller HCCs. Sensitivity of AFP at 400 ng/ml cut-off was only 25.7%, too low to be useful. Best mix of sensitivity (77.2%) and specificity (78.1%) of AFP was found to be at 10.7 ng/ml cut-off which falls within the conventional limits of normalcy. CONCLUSION: The study highlights the importance of symptomatology of weight loss, abdominal pain or anorexia as markers for HCC in patients with cirrhosis. AFP was not found to be a useful screening test. TPCT should be undertaken in all cirrhotics presenting to the hospital for the first time.

Acral and palmo-plantar hyperpigmentation in a patient with disseminated hepatocellular carcinoma.

Capecitabine (5-fluorouracil prodrug) is being evaluated for the management of hepatocellular carcinoma, and is associated with a peculiar skin reaction called hand and foot syndrome (HFS). We describe one patient with HCC and drug-induced HFS.

Incidence of hepatocellular carcinoma among Indian patients with cirrhosis of liver: an experience from a tertiary care center in northern India.

BACKGROUND/AIM: Despite bearing the main burden of HCC, prospective studies from developing countries are lacking. This prospective observational study was designed to estimate the incidence of HCC among Indian patients with hepatic cirrhosis. METHODS: Between April 2001 and November 2004, we enrolled 301 patients with liver cirrhosis. Patients found to be free of HCC using baseline abdominal ultrasound, triple-phase computed tomography (TPCT) and serum alpha-fetoprotein (AFP) levels were followed up prospectively for detection of HCC using ultrasound and AFP every 6 months, and TPCT annually. RESULTS: Among the 194 patients (mean age [SD] 45.1 [+/-13.1] years; male:female 6.1:1.0) followed up, 154 had Child's A and 40 had Child's B disease. The causes of cirrhosis were: hepatitis B-71 (36.6%), hepatitis C-54 (27.8%), dual infection with hepatitis B and C-12 (6.2%) and others including autoimmune, alcoholic and cryptogenic cirrhosis 57 (29.4%). During a cumulative follow up period of 563.4 person-years, 9 cases of HCC were detected, with an incidence rate of 1.60 per 100 person-years. CONCLUSION: In our study, the incidence of HCC among patients with liver cirrhosis was intermediate, being lower than that in Japan but higher than that reported from Europe.

Three-dimensional helical computed tomography cholangiography with minimum intensity projection in gallbladder carcinoma patients with obstructive jaundice: comparison with magnetic resonance cholangiography and percutaneous transhepatic cholangiography.

OBJECTIVE: Computed tomography (CT) is traditionally used for evaluation and staging of gallbladder carcinoma (GC). However, in the subgroup of patients with obstructive jaundice, magnetic resonance cholangiography (MRC) is generally required to assess the level of biliary obstruction. The present study was undertaken to evaluate the diagnostic potential of three-dimensional helical CT cholangiography (3-D CTC) with minimum intensity projection (minIP), to determine the presence and level of biliary obstruction. MATERIALS AND METHODS: Twenty-five consecutive patients with proven GC, presenting with clinical and biochemical features of obstructive jaundice, over a 1-year period were included in the study. Dual phase helical CT data was obtained in the arterial and venous phases, respectively, after intravenous contrast injection using a pressure injector. Axial CT data (both arterial and venous phase) was studied for staging and resectability of tumor. Three-dimensional helical CT cholangiography using minIP obtained from the venous phase data set, was used to assess the level of biliary obstruction and isolation of hepatic segmental ducts. Three-dimensional helical CT cholangiography findings were compared with MRC and percutaneous transhepatic cholangiography (PTC) (gold standard). None of the patients were operated on as they were all considered inoperable on axial CT images due to extensive local disease or distant metastasis. RESULTS: In all patients, 3-D CTC demonstrated dilated intrahepatic ducts up to tertiary branch level. The 3-D CTC correctly diagnosed the level of biliary obstruction and demonstrated isolated segmental ducts in all patients and correlated well in all cases with MRC and PTC findings in this regard. However, the 3-D CTC did not add any additional information over the axial source images. CONCLUSION: Three-dimensional helical CT cholangiography with minIP can correctly determine the level of biliary obstruction in patients with GC and may be a strong competitor with MRC, because it gives equivalent information with regard to the level of ductal obstruction even while being a part of an overall comprehensive CT staging study. Even though 3-D CTC did not provide additional information on top of the source images, the referring physicians found them very useful for conceptualization of the 3-D biliary anatomy.

Tuberculous pseudoaneurysm of gastroduodenal artery.

We report a patient with Gastroduodenal artery (GDA) pseudoaneurysm of tuberculous aetiology, who presented with massive hematemesis and who was successfully managed with transarterial steel coil embolization. Pseudoaneurysms are a rare but potentially fatal complication of tuberculosis and hence early recognition and management of this complication is important. To the best of our knowledge this is the first report of a GDA pseudoaneurysm resulting from tuberculosis.

Helical CT evaluation of aortic aneurysms and dissection: a pictorial essay.

The relative noninvasive nature, easy accessibility, convenience and accuracy of helical CT in the rapid evaluation of not only the aorta and its branches, but the entire thorax/abdomen, makes it the best suited imaging modality for use in evaluation of aortic aneurysms and dissection. Excellent vascular opacification, the advantage of reconstructing overlapping scans without respiratory misregistration, multiplanar reconstruction and 3D rendering of the vessels highlight the benefits of helical CT. Helical CT evaluation combines the advantages of conventional CT, giving true information about the exact transverse and longitudinal extent of the aneurysm, the vessel wall, luminal thrombus and structures around the aorta, and those of aortography in the form 3D volumetric information display. The purpose of this essay is to present a spectrum of aortic aneurysms and dissection to highlight the role of helical CT in their evaluation.

Spectrum of hepatocellular carcinoma on triple phase helical CT: a pictorial essay.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. With the availability of a variety of treatment options for HCC, it is essential to detect, localize and stage HCC comprehensively. Recent application of helical computed tomography (CT) using the triple phase technique, along with optimized rapid delivery of contrast material has significantly improved the diagnostic confidence of the radiologist in not only detection and characterization of HCC, but also in defining the extent of the tumor. In this pictorial essay, we present a spectrum of findings in HCC as evaluated by triple phase helical CT. A variety of imaging features are described, and the utility of the technique in localization and characterization of HCC is emphasized.