Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma.

Background/aims: The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and methods: Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function. Results: Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively (P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (P = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively (P-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (P-0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively (P-<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis. Conclusion: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Multi-center prospective survey of hepatocellular carcinoma in Kerala: More than 1,200 cases.

BACKGROUND: Hepatocellular carcinoma (HCC) is considered uncommon in India. The aim of this study was to document the demographic characteristics and clinical aspects of HCC in Kerala, India. METHODS: A survey of HCC in Kerala was performed. All gastroenterologists in the region were invited. From May 2018 to April 2020, data was collected in a standardized questionnaire. RESULTS: Forty-three doctors from 15 centers contributed the data. Total 1217 patients were analyzed. This is the largest state-wide survey of HCC in India. HCC was more common in men (90%) than in women (p < 0.01). The etiology of liver disease was hepatitis B virus (7%), hepatitis C virus (4%) and alcohol (40%). Diabetes mellitus was present in 64%, hypercholesterolemia in 17% and hypertension in 38%. Obesity was present in 33% and 15% were overweight. Non-alcoholic fatty liver disease (NAFLD) with or without metabolic syndrome was present in 44%. Serum alpha-fetoprotein was > 400 ng/mL in 24%, total tumor diameter was > 5 cm in 59%, portal vein invasion was seen in 35% and distant metastasis was seen in 15%. Specific therapy was given to 52%. Treatments given included liver transplantation (n = 24), liver resection (n = 39) and transarterial chemoembolization (TACE, n = 184). Although the study was not designed to compare survival, patients who had liver transplantation had longer survival (median 69 months) compared to matched patients given only TACE (median 18 months) (p = 0.03). CONCLUSION: HCC is common in Kerala, India. NAFLD has a predominant association with HCC in Kerala. Most of the patients report late when curative treatment is not possible.

Correlation between insulin resistance and liver histology in patients with nonalcoholic steatohepatitis with and without obesity.

INTRODUCTION: Insulin resistance (IR) plays a central role in pathogenesis of nonalcoholic steatohepatitis (NASH). The aim of this study was to correlate histopathological grading and IR in overweight/obese patients with NASH as compared with lean NASH. METHODS: Patients with NASH who underwent liver biopsy between January 2012 and December 2012 were included. Anthropometric, clinical, and biochemical features, necro-inflammatory grades, and fibrosis stage on liver biopsies were scored according to Brunt and non-alcoholic fatty liver disease (NAFLD) activity score (NAS). RESULTS: Of 42 patients, 33 (78.6%) had body mass index (BMI) ≥ 23 kg/m2 (overweight/obese) while 9 had BMI < 23 kg/m2 (lean). Mean fasting blood sugar (FBS) and HbA1c levels in overweight/obese patients with NASH were higher than in lean NASH (p < 0.05). The median homeostatic model assessment-estimated insulin resistance (HOMA-IR) among NASH patients with BMI ≥ 23 kg/m2 was higher than among those with BMI < 23 kg/m2 (3.02 [0.34-17.22] vs. 2 [0.52-5.26]; p = 0.045). However, fasting insulin levels were comparable among lean and overweight/obese patients with NASH. Metabolic syndrome could be predicted with 75% sensitivity and 85.3% specificity at a HOMA-IR cutoff value of 3.9. No significant difference was observed with regard to HOMA-IR levels with Brunt grades, Brunt staging, Brunt grades 1 and 2, Brunt scores < 2 and > 2, and NAS scores, and NAS scores < 4 and > 4. CONCLUSIONS: Although IR was significantly higher in overweight/obese patients with NASH as compared with that in lean patients with NASH, there was no difference in the correlation of HOMA-IR with histology between these groups.

Adrenal insufficiency in decompensated cirrhotic patients without infection: prevalence, predictors and impact on mortality.

BACKGROUND: Relative adrenal insufficiency (RAI) is common in compensated and decompensated chronic liver disease in the presence of sepsis. This study was performed to find out the prevalence of RAI in decompensated cirrhotic patients presenting with hepatic encephalopathy and variceal bleeding without any evidence of infection. METHODS: The study prospectively included 75 cirrhotic patients with signs of decompensation. The short Synacthen test (SST) was performed on all patients after ruling out infection. Patients with positive blood, urine, sputum, ascitic and pleural fluid cultures or evidence of infection on chest X-ray and those with elevated procalcitonin levels (>0.05 ng/ml) were excluded. RAI in critical illness was defined by a delta cortisol level (difference between basal and post-stimulation cortisol) of ≤9 µg/dl after SST. RESULTS: The mean age of the study population was 54 ± 11 years. Upper gastrointestinal bleed and hepatic encephalopathy were seen in 56.6% and 41.5%, respectively, and both were seen in 1.9%. Of the 75 patients, 55 (73%) were in Child-Turcotte-Pugh (CTP) class C and the mean model for end-stage liver disease (MELD) score was 21 ± 7. Forty-five patients (60%) met our criteria for RAI. Those with RAI had lower serum albumin (2.4 ± 0.5 g/dl vs 2.7 ± 0.5 g/dl, p = 0.03) and higher MELD scores (22 ± 7 vs 19 ± 6, p = 0.03). Prevalence of RAI in CTP class C was 65% (36 out of 55 patients) compared to 45% (9 out of 20 patients) in Child-Pugh stage A and B. Similarly, 82% (23 out of 28 patients) with MELD scores >25 had RAI compared to 54% with MELD scores <20. None of biochemical parameters were predictive of RAI on logistic regression analysis. Three-month mortality rate was not significantly different in patients with or without adrenal insufficiency (44% vs 28%, p = 0.11). CONCLUSION: The present study showed RAI to be common in noninfected decompensated cirrhotic patients, but did not predict 3-month mortality. There were no other predictive factors in those with RAI. Hence, in patients with cirrhosis without infection, the clinical utility of routine adrenal function testing needs further elucidation.

Embolization of portosystemic shunt for treatment of recurrent hepatic encephalopathy.

Hepatic encephalopathy in the setting of advanced chronic liver disease, occurs following a precipitating factor and generally responds to correction of the precipitating factor and anticoma measures. We report the case of a lady with Child A cirrhosis who presented with frequent episodes of hepatic encephalopathy without any precipitating factors. She was found to be having a large portosystemic shunt. The shunt was obliterated by coil embolotherapy following which there was no further episodes of encephalopathy.

Strategy to differentiate autoimmune pancreatitis from pancreas cancer.

Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organs of AIP patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease". Clinically, AIP patients and patients with pancreatic cancer share many features, such as preponderance of elderly males, frequent initial symptom of painless jaundice, development of new-onset diabetes mellitus, and elevated levels of serum tumor markers. It is of uppermost importance not to misdiagnose AIP as pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, and approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological, and histopathological features. Findings suggesting AIP rather than pancreatic cancer include: fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed enhancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography, presence of other organ involvement such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis; negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.

Management strategies for autoimmune pancreatitis.

INTRODUCTION: Autoimmune pancreatitis (AIP) is a newly developed concept for a peculiar type of pancreatitis, and at present is recognized as a pancreatic lesion reflecting IgG4-related systemic disease. It is of utmost importance to differentiate AIP from pancreatic cancer to avoid unnecessary surgery. AREAS COVERED: The current management strategies for AIP, including its clinical features, diagnostic criteria, clinical subtypes, steroid therapy and prognosis are discussed, based on our 66 AIP cases and papers searched in PubMed from 1992 to March 2011, using the term 'autoimmune pancreatitis'. A new clinicopathological entity, an 'IgG4-related sclerosing disease' is also mentioned. EXPERT OPINION: AIP should be considered in the differential diagnosis in elderly male patients presented with obstructive jaundice and pancreatic mass. Steroids are a standard therapy for AIP, but their regimen including maintenance therapy should be evaluated in prospective trials.