High frequency of an otherwise rare phenotype in a small and isolated tiger population.

Most endangered species exist today in small populations, many of which are isolated. Evolution in such populations is largely governed by genetic drift. Empirical evidence for drift affecting striking phenotypes based on substantial genetic data are rare. Approximately 37% of tigers (Panthera tigris) in the Similipal Tiger Reserve (in eastern India) are pseudomelanistic, characterized by wide, merged stripes. Camera trap data across the tiger range revealed the presence of pseudomelanistic tigers only in Similipal. We investigated the genetic basis for pseudomelanism and examined the role of drift in driving this phenotype's frequency. Whole-genome data and pedigree-based association analyses from captive tigers revealed that pseudomelanism cosegregates with a conserved and functionally important coding alteration in Transmembrane Aminopeptidase Q (Taqpep), a gene responsible for similar traits in other felid species. Noninvasive sampling of tigers revealed a high frequency of the Taqpep p.H454Y mutation in Similipal (12 individuals, allele frequency = 0.58) and absence from all other tiger populations (395 individuals). Population genetic analyses confirmed few (minimal number) tigers in Similipal, and its genetic isolation, with poor geneflow. Pairwise FST (0.33) at the mutation site was high but not an outlier. Similipal tigers had low diversity at 81 single nucleotide polymorphisms (mean heterozygosity = 0.28, SD = 0.27). Simulations were consistent with founding events and drift as possible drivers for the observed stark difference of allele frequency. Our results highlight the role of stochastic processes in the evolution of rare phenotypes. We highlight an unusual evolutionary trajectory in a small and isolated population of an endangered species.

To Be or Not to Be - Review of Electrical Bistability Mechanisms in Polymer Memory Devices.

Organic memory devices are a rapidly evolving field with much improvement in device performance, fabrication, and application. But the reports have been disparate in terms of the material behavior and the switching mechanisms in the devices. And, despite the advantages, the lack of agreement in regards to the switching behavior of the memory devices is the biggest challenge that the field must overcome to mature as a commercial competitor. This lack of consensus has been the motivation of this work wherein various works are compiled together to understand influencing factors in the memory devices. Different works are compared together to discover some clues about the nature of the switching occurring in the devices, along with some missing links that would require further investigation. The charge storage mechanism is critically analyzed alongside the various resistive switching mechanisms such as filamentary conduction, redox-based switching, metal oxide switching, and other proposed mechanisms. The factors that affect the switching process are also analyzed including the effect of nanoparticles, the effect of the choice of polymer, or even the effect of electrodes on the switching behavior and the performance parameters of the memory device.

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.

Role of contrast enhanced ultrasound in hepatic imaging.

Grey scale ultrasound (US) is the first line imaging modality used for the evaluation of liver by the radiologists and clinicians worldwide. It is a simple, inexpensive, safe and an easily available technique. US has the ability to delineate the hepatic parenchyma and differentiate the cystic from solid hepatic lesions. However, it has limited accuracy in the detection and characterization of focal liver lesions (FLL). CEUS is a major breakthrough in ultrasound imaging which evolved with the aim of overcoming these limitations of US. With the use of ultrasound contrast agents (UCAs), CEUS has the ability to detect the intranodular hemodynamics and thereby provide information of the enhancement pattern of the lesion resulting in reliable characterization of the FLL. This capability brings it at par with the cross sectional contrast enhanced imaging techniques of computed tomography and magnetic resonance imaging. UCAs are safe, non-nephrotoxic and thus can be used to evaluate patients with renal failure as well. The technique of CEUS is simple, requires few minutes to perform, portable, lacks ionising radiation and above all is a cost-effective modality. These advantages have made CEUS an established modality for hepatic imaging. Besides detection and characterization of FLL, it also plays a vital role in the management and repeated follow up of treated patients of FLL. Newer clinical applications of CEUS with promising results are also being unravelled . This review highlights the multifaceted role of CEUS in hepatic imaging and its upcoming clinical applications.

Portal hypertension: A critical appraisal of shunt procedures with emphasis on distal splenorenal shunt in children.

BACKGROUND: Extrahepatic portal venous obstruction (EHPVO) is the most common cause of pediatric portal hypertension. We analyzed the investigative protocol and results of portosystemic shunts in this group of patients. MATERIALS AND METHODS: A total of 40 consecutive children aged below 12 years operated with a diagnosis of extra-hepatic portal hypertension formed the study group. Historical data and clinical data were collected. All patients underwent upper gastrointestinal endoscopy, ultrasound Doppler and computed tomographic portogram pre-operatively and post-operatively. Results with respect to shunt patency, hypersplenism and efficacy of different radiological investigations were collected. RESULTS: A total of 40 patients, 28 boys and 12 girls constituted the study group. Lienorenal shunt (LRS) was performed in 14 patients; distal splenorenal shunt in 21 patients and side-to-side lienorenal shunt in 4 patients, inferior mesenteric renal shunt was performed in 1 patient. Follow-up ranged from 36 to 70 months. At a minimum follow-up of 3 years, 32 (80%) patients were found to have patent shunts. Patent shunts could be visualized in 30/32 patients with computer tomographic portogram (CTP) and 28/32 with ultrasound. Varices regressed completely in 26/32 patients and in the rest incomplete regression was seen. Spleen completely regressed in 19/25 patients. Hypersplenism resolved in all patients with patent shunts. CONCLUSIONS: Portosystemic shunting in children with EHPVO is a viable option. While long-term cure rates are comparable with sclerotherapy, repeated hospital visits are reduced with one time surgery. Pre-operative and post-operative assessment can be performed with complimentary use of ultrasound, CTP and endoscopy.

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.

2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

Assessments of TP53 and CTNNB1 gene hotspot mutations in circulating tumour DNA of hepatitis B virus-induced hepatocellular carcinoma.

Background: Hepatitis B virus (HBV) infection is one of the major causes of chronic liver disease, which progresses from chronic hepatitis B (CHB) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Early detection and laboratory-based screening of hepatocellular carcinoma are still major challenges. This study was undertaken to determine whether the cancer hallmark gene signatures that are released into circulation as circulating tumour DNA (ctDNA) can be used as a liquid biopsy marker for screening, early detection, and prognosis of HCC. Methods: A total of 130 subjects, including HBV-HCC (n = 80), HBV-cirrhotic and non-cirrhotic (n = 35), and healthy (n = 15) controls, were evaluated for TP53 and beta-catenin (CTNNB1) gene hotspot mutations in ctDNA by Sanger-based cycle sequencing and droplet digital PCR (ddPCR) assays. Mutation detection frequency, percentage mutant fractions, and their association with tumour stage, mortality, and smoking habits were determined. Results: Sanger-based cycle sequencing was carried out for 32 HCC patients. Predict SNP Tools analysis indicated several pathogenic driver mutations in the ctDNA sequence, which include p.D228N, p.C229R, p.H233R, p.Y234D, p.S240T, p.G245S, and p.R249M for TP53 gene exon 7 and p.S33T for CTNNB1 gene exon 3. The TP53 c.746G>T (p.R249M) mutation was detected predominately (25% cases) by sequencing, but there was no dominant mutation at position c.747G>T (p.R249S) that was reported for HBV-HCC patients. A dual-probe ddPCR assay was developed to determine mutant and wild-type copy numbers of TP53 (p.R249M and p.R249S) and CTNNB1 (p.S45P) and their percentage mutant fraction in all 130 subjects. The TP53 R249M and CTNNB1 S45P mutations were detected in 31.25% and 26.25% of HCC patients, respectively, with a high mutant-to-wild-type fraction percentage (1.81% and 1.73%), which is significant as compared to cirrhotic and non-cirrhotic patients. Poor survival was observed in HCC patients with combined TP53 and CTNNB1 gene driver mutations. The TP53 R249M mutation was also significantly (p < 0.0001) associated with smoking habits (OR, 11.77; 95% CI, 3.219-36.20), but not the same for the TP53 R249S mutation. Conclusion: Screening of ctDNA TP53 and CTNNB1 gene mutations by ddPCR may be helpful for early detection and identifying the risk of HCC progression.

Imaging features of breast cancer subtypes on contrast enhanced ultrasound: a feasibility study.

The objective of this research was to study the contrast enhancement patterns of the different molecular subtypes of breast cancer on contrast-enhanced ultrasound (CEUS) using both qualitative and quantitative parameters. This prospective study included females with a single breast mass which was histopathologically proven carcinoma. B mode ultrasound (USG) and CEUS were performed in all patients during baseline assessment. Qualitative CEUS assessment encompassed enhancement pattern, presence of fill-in and washout. Quantitative assessment included measurement of peak enhancement, time to peak; area under the curve and mean transit time. A p-value < 0.05 was considered statistically significant for differentiating the subtypes. The included thirty masses were categorised into two subtypes-triple negative breast cancer (TNBC) (36.7%) and non-TNBC (63.3%) subtypes. With B-mode USG, a statistically significant difference was observed between the two groups with respect to their shape and margins. TNBC lesions showed an oval shape, circumscribed margins and peripheral nodular enhancement on CEUS with the absence of fill-in even in the delayed phase (p-value - 0.04). The two subtypes did not significantly differ in terms of quantitative perfusion parameters. The various subtypes of breast cancer therefore possess distinct contrast enhancement patterns. CEUS potentially allows differentiation amongst these molecular subtypes that may aid in radiology-pathology (rad-path) correlation and follow up of the patients.

Adapting the Utility of Lipiodol CT in Treating Small Hepatocellular Carcinoma.

Introduction: Multiphase MRI liver is the gold-standard imaging modality for staging hepatocellular carcinoma (HCC) in patients with cirrhosis. Often, small HCCs diagnosed on multiphase MRI are occult on B-mode ultrasound and multiphase CT (MPCT) and thus pose a challenge for loco-regional therapy. We adapted the technique of lipiodol CT in treating two such patients of small HCC. Methods: Lipiodol-CT involved an intra-arterial lipiodol injection through the hepatic artery followed by a noncontrast CT liver. CT delineated small, hyperdense, lipiodol-laden hepatic nodules, which served as a target for executing ablation of the nodule and also revealed the true disease stage by depicting the additional number of tumors in the liver. Results: Case one was a 51-year female, known case of chronic hepatitis C who presented with ascites for two months. She was diagnosed with a small HCC (LI-RADS-4) in a cirrhotic liver on multiphase MRI. Percutaneous radiofrequency ablation was planned, but the mass was not located on ultrasound or multiphase CT. Lipiodol-CT was undertaken, which delineated the lipiodol-laden small HCC, which served as a target for executing ablation. Case 2 was a 55-year male, Child-Pugh A cirrhotic, who had undergone right extended hepatectomy for hepatitis B-related HCC. Follow-up MRI revealed a 5 mm segment III nodule, which had increased in size on repeat MRI at 3 months (LI-RADS-4). This nodule, too, was occult on both ultrasound and MPCT. Lipiodol CT revealed additional multiple, variable-sized lipiodol-laden nodules in the liver remnant. Treatment of trans-arterial chemoembolization was performed at one month. Both patients showed complete response to treatment. Conclusion: Lipiodol CT can be safely used in a new role of facilitating treatment of small HCCs diagnosed on MRI but occult on ultrasonography and MPCT.

Evaluation of the cell-free DNA integrity index as a liquid biopsy marker to differentiate hepatocellular carcinoma from chronic liver disease.

Background: Hepatocellular carcinoma (HCC) occurs in the majority of patients with underlying chronic liver disease (CLD) of viral and non-viral etiologies, which requires screening for early HCC diagnosis. Liquid biopsy holds great promise now for early detection, prognosis, and assessment of response to cancer therapy. Cell-free DNA (cfDNA) as a liquid biopsy marker can be easily detected by a real-time quantitative PCR (RT-qPCR) assay for a change in its concentration, integrity, and fragmentation in cancer. Methods: Patients with HCC (n = 100), CLD (n = 100), and healthy (n = 30) controls were included in the study. The cfDNA was isolated from serum and real-time quantitative PCR (RT-qPCR) was carried out using primer pairs for large (>205 bp) and small (110 bp) fragments of repetitive elements (ALU and LINE1) and housekeeping genes (ß-Actin and GAPDH). Total cfDNA concentrations and integrity index were determined by the absolute quantitation method (L/S ratio or cfDII-integrity). The cfDII as a measure of fragmentation was determined by comparative Ct (2-ΔΔCt) method of relative quantification (cfDII-fragmentation). Using a receiver operating characteristic (ROC) curve, cfDII-integrity and cfDII-fragmentation were used to differentiate HCC from CLD patients or healthy controls. Results: The total cfDNA concentrations in the sera of HCC (244 ng/ml) patients were significantly higher than those of CLD (33 ng/ml) patients and healthy (16.88 ng/ml) controls. HCC patients have shown poor DNA integrity or excess cfDNA fragmentation than CLD patients and healthy controls. The cfDII-integrity of GAPDH and ALU fragment significantly differentiate HCC from CLD at AUROC 0.72 and 0.67, respectively. The cfDII-fragmentation following normalization with cfDNA of healthy control has shown significant differential capabilities of HCC from CLD at AUROC 0.67 using GAPDH and 0.68 using the ALU element. The ROC curve of LINE1 and ß-actin cfDII was not found significant for any of the above methods. The cfDII-fragmentation trend in HCC patients of different etiologies was similar indicating increased cfDNA fragmentation irrespective of its etiology. Conclusion: The cfDII measuring both DNA integrity (L/S ratio) and fragmentation of the Alu and GAPDH genes can differentiate HCC from CLD patients and healthy individuals.

Role of shear wave elastography as an adjunct to axillary ultrasonography in predicting nodal metastasis in breast cancer patients with suspicious nodes.

OBJECTIVE: To evaluate the role of shear wave elastography (SWE) of suspicious axillary lymph nodes and its combination with B-mode USG in predicting nodal metastasis in breast cancer patients. METHODS: Prospective observational study was performed from June 2018 to August 2020 on breast cancer patients with suspicious axillary nodes on USG. B-mode features (cortical thickness, effacement of fatty hilum, non-hilar blood flow and round shape) and SWE parameters (Emax, Emin, Emean and ESD) of the node with the thickest cortex were evaluated. Diagnostic performances of USG, SWE and their combination were estimated using pathological status of the node on biopsy as the gold standard. RESULTS: Of the 54 patients evaluated, optimal elasticity maps were obtained in 49 nodes of 49 patients (mean age, 46.3 ± 12.1 years; 48/49 (98%) females). On biopsy, 38 nodes (77.6%) had metastasis, while 11 (22.4%) had reactive hyperplasia. Emax, Emin, Emean and ESD of both cortex and hilum were significantly higher in metastatic than reactive nodes. Emax (cortex) ≥14.9 kPa had the best diagnostic performance (sensitivity, 73.7%; specificity, 81.8%). Cortical thickness ≥6.7 mm had the best diagnostic performance among B-mode features (sensitivity, 89.5%; specificity, 72.7%). Combining cortical thickness with effacement of fatty hilum and/or non-hilar blood flow yielded sensitivity of 89.5% and specificity of 90.9%. Addition of Emax (cortex) to cortical thickness and combination of ≥2 B-mode features increased their specificities to 90.9 and 100%, respectively. CONCLUSIONS: Metastatic axillary nodes are stiffer than reactive nodes on SWE in breast cancer patients. Emax (cortex) has the best diagnostic performance in differentiating between reactive hyperplasia and nodal metastasis. Combination of Emax (cortex) and cortical thickness increases the specificity for diagnosing metastasis, especially in nodes showing only cortical thickening. ADVANCES IN KNOWLEDGE: Combination of SWE and B-mode USG is highly specific for differentiating metastasis from reactive hyperplasia in suspicious nodes of breast carcinoma patients, especially in nodes with only cortical thickening.

Axillary ultrasonography combined with pre-operative wire localisation of clipped node in nodal restaging after neoadjuvant chemotherapy in node positive breast cancer patients: a pilot study.

OBJECTIVE: To evaluate the role of axillary ultrasonography (axUS) and ultrasound-guided pre-operative wire localisation of pre-treatment positive clipped node (CN) for prediction of nodal response to neoadjuvant chemotherapy (NACT) in node positive breast carcinoma patients. METHODS AND MATERIALS: A prospective study was conducted between June 2018 and August 2020 after Ethics Committee approval. Breast carcinoma patients (cT1-cT4b) with palpable axillary nodes (cN1-cN3) and suitable for NACT were recruited after written informed consent. Single, most suspicious node was biopsied and clipped. Nodal response to NACT was assessed on axUS. Wire localisation of CN was performed prior to axillary lymph node dissection (ALND). Diagnostic performances of axUS and CN excision were assessed. RESULTS: Of the 69 patients evaluated, 32 patients (mean age, 43.5 ± 11.8 years; females, 31/32 [97%]; pre-menopausal, 18/32 [56.3%]) with metastatic nodes who received NACT were included. Nodal pathological complete response rate was 34.4% (11/32) overall and 70% (7/10) in patients with ≤2 suspicious nodes on pre-NACT axUS. False-negative rates (FNRs) of axUS and CN excision were 4.8% and 28.6% respectively. Combination of post-NACT axUS and CN excision had an FNR of 4.8% overall and 0% in patients with ≤2 suspicious nodes on pre-NACT axUS. CONCLUSION: Combination of AxUS and ultrasound-guided wire localisation of pre-treatment positive CN has high diagnostic accuracy for nodal restaging after NACT in node positive breast cancer patients. ADVANCES IN KNOWLEDGE: Addition of axUS assessment to wire localisation of CN reduces its FNR for detecting residual metastasis after NACT.

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.

2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.

Clinical profile, etiology and therapeutic outcome in 324 hepatocellular carcinoma patients at a tertiary care center in India.

OBJECTIVE: To study the profile and outcome of therapy for hepatocellular carcinoma (HCC) in India. METHODS: Data analysis of HCC patients enrolled in liver clinic between 1990 and 2005. RESULTS: We registered 324 HCC patients [males 284 (88%), mean age 52.4 +/- 13.1 years]. The etiology of HCC was: hepatitis B virus 165 (51%), hepatitis C virus 38 (12%), alcohol 20 (6%), combined 31 (10%) and unknown 70 (21%). Serum alpha-fetoprotein was >400 ng in 36%, portal vein invasion was seen in 40% and distant metastases in 13%. Therapy was offered to 141 (43.5%) patients, but survival data was available in only 130 (93%) of them. Treatment given and median survival time was as follows: surgical resection, 19 months (n = 14); transarterial chemoembolization, 11 months (n = 23); transarterial rhenium therapy, 26 months (n = 7); radiofrequency ablation, 24 months (n = 4); acetic acid ablation, 13 months (n = 17); oral chemotherapy, 26 months (n = 33), and combination therapy, 26 months (n = 32). Vascular invasion, Okuda staging and therapy were independent factors associated with survival. Treated patients had longer median survival compared to untreated ones (16 months vs. 7 months, p < 0.05). CONCLUSIONS: Hepatitis B infection is the predominant cause of HCC in India. Serum alpha-fetoprotein was diagnostic in only one third of our patients. Most patients present late, when curative therapies are not possible. Treated patients had better survival than untreated ones.

Palliative treatment in advanced hepatocellular carcinoma: has it made any difference?

Hepatocellular carcinoma (HCC) is a global health problem, the fifth most common cancer in the world. HCC occurs in a histologically abnormal liver due to underlying chronic liver disease resulting as a sequele of the chronic viral infections, hepatitis B and C. Since these two viral infections are endemic in Asia and Africa, more than 80% of cases are encountered in these regions. In India, a large proportion of the population is "at risk" for developing chronic liver disease and, therefore, HCC. Due to the lack of screening programmes in the country, the majority of HCC patients are diagnosed at an advanced stage of the disease, thus treatment remains a challenge. Palliative therapy forms the mainstay of treatment for this group of patients. The current era provides a plethora of options for the palliative management of HCC. This review concisely summarises the historical perspective and the current status of palliative treatment in advanced HCC.

Inkjet Printing of Functional Electronic Memory Cells: A Step Forward to Green Electronics.

Nowadays, the environmental issues surrounding the production of electronics, from the perspectives of both the materials used and the manufacturing process, are of major concern. The usage, storage, disposal protocol and volume of waste material continue to increase the environmental footprint of our increasingly "throw away society". Almost ironically, society is increasingly involved in pollution prevention, resource consumption issues and post-consumer waste management. Clearly, a dichotomy between environmentally aware usage and consumerism exists. The current technology used to manufacture functional materials and electronic devices requires high temperatures for material deposition processes, which results in the generation of harmful chemicals and radiation. With such issues in mind, it is imperative to explore new electronic functional materials and new manufacturing pathways. Here, we explore the potential of additive layer manufacturing, inkjet printing technology which provides an innovative manufacturing pathway for functional materials (metal nanoparticles and polymers), and explore a fully printed two terminal electronic memory cell. In this work, inkjetable materials (silver (Ag) and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS)) were first printed by a piezoelectric Epson Stylus P50 inkjet printer as stand-alone layers, and secondly as part of a metal (Ag)/active layer (PEDOT:PSS)/metal (Ag) crossbar architecture. The quality of the individual multi-layers of the printed Ag and PEDOT:PSS was first evaluated via optical microscopy and scanning electron microscopy (SEM). Furthermore, an electrical characterisation of the printed memory elements was performed using an HP4140B picoammeter.

Role of Indocyanine Green in Predicting Post-Transarterial Chemoembolization Liver Failure in Hepatocellular Carcinoma.

BACKGROUND/AIM: Post-Transarterial Chemoembolization (TACE) Liver Failure (LF) is common in patients with Hepatocellular Carcinoma (HCC). No definitive objective parameters predict its occurrence. We assessed the role of Indocyanine Green (ICG) in prediction of post-TACE LF. METHODS: Consecutive HCC patients with Child A/B class, categorized as Barcelona Clinic Liver Cancer (BCLC) staging A/B, were included between August 2012 and July 2014. All underwent ICG dynamics: Plasma Disappearance Rate (PDR) was recorded on the day of TACE. Area Under Receiver Operator Characteristic Curve (AUROC) of ICG-PDR was compared with existing prognostic scores: Model for End Stage Liver Disease (MELD), MELD-Na and Child-Turcotte-Pugh (CTP) using Hanley and McNeil method. RESULTS: A total of 43 patients, mean age (±sd) 55.1 ± 12.8 years were included; 35 (81.4%) patients were males. Post-TACE LF developed after 17 (28.8%) of 59 procedures. Patients with post-TACE LF had significantly elevated baseline bilirubin (P = 0.006), alkaline phosphatase (P = 0.040) and prolonged international normalized ratio (P = 0.004). The median prognostic scores were higher in patients with post-TACE LF (CTP 7 vs 6; P < 0.001 and MELD 10.5 vs 6.3; P = 0.005). There was no difference in the MELD-Na score. ICG-PDR values were lower in those patients who developed post-TACE LF (7.4%/min vs 10.6%/min; P = 0.008). AUROC for ICG-PDR was 0.72 and a cut-off value <9.25%/min predicted the development of post-TACE LF with a sensitivity, specificity, positive predictive value and negative predictive value of 64.7%, 61.9%, 40.7% and 81.2%, respectively. There were no differences in the AUROC between ICG-PDR and other prognostic markers (Hanley and McNeil, P: 0.244-0.900). CONCLUSION: ICG-PDR performs similar to MELD, MELD-Na and CTP score for predicting development of post-TACE LF.