Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

BACKGROUND: Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial. AIM: To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future. METHODS: We conducted a survey of major centers in India that performed LT in December 2022. A total of 23 responses were received. The centers were classified as high- and low-volume, and the current trend of care for patients und ergoing LT for HCC was noted. RESULTS: Of the 23 centers, 35% were high volume center (> 500 Liver transplants) while 52% were high-volume centers that performed more than 50 transplants/year. Approximately 39% of centers had performed > 50 LT for HCC while the percent distribution for HCC in LT patients was 5%-15% in approximately 73% of the patients. Barring a few, most centers were divided equally between University of California, San Francisco (UCSF) and center-specific criteria when choosing patients with HCC for LT, and most (65%) did not have separate transplant criteria for deceased donor LT and living donor LT (LDLT). Most centers (56%) preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion. Positron-emission tomography-computed tomography (CT) was the modality of choice for metastatic workup in the majority of centers (74%). Downstaging was the preferred option for over 90% of the centers and included transarterial chemoembolization, transarterial radioembolization, stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications. The alpha-fetoprotein (AFP) cut-off was used by 74% of centers to decide on transplantation as well as to downstage tumors, even if they met the criteria. The criteria for successful downstaging varied, but most centers conformed to the UCSF or their center-specific criteria for LT, along with the AFP cutoff values. The wait time for LT from down staging was at least 4-6 wk in all centers. Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52% of the centers. Approximately 65% of the centers preferred to start everolimus between 1 and 3 months post-LT. CONCLUSION: The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.

Role of non-invasive markers in prediction of esophageal varices and variceal bleeding in patients of alcoholic liver cirrhosis from central India.

BACKGROUND/AIMS: Alcohol is the leading cause of liver cirrhosis, which results in portal hypertension and subsequently, culminates into esophageal varices and esophgeal variceal bleeding. Esophagogastroduodenoscopy is gold standard for diagnosis of varices. Non-invasive markers based on clinical, laboratory - ultrasonographic parameters can be utilised for prediction of risk of esophageal varices - variceal bleed in alcoholic cirrhosis from central India. MATERIALS AND METHODS: This was a cross sectional observational study. Child Turcot Pugh scores, MELD, AST ALT Ratio(AAR), AST Platelet Ratio Index(APRI), FIB-4 index and Platelet count-Spleen diameter(PC/SD) ratio were calculated for all patients and correlated with esophagogastroduodenoscopy findings. Short term follow up was done for variceal bleeding. RESULTS: Total 202 male patients were included with mean age of 43.77±9.95 years. 188(93%) patients had esophageal varices. 61(30.19%) patients had variceal bleeding. On univariate analysis platelet count, APRI, spleen bipolar diameter, and PC/SD ratio were significantly associated with varices. For prediction of esophageal varices, only PC/SD ratio was significant and showed area under the curve of 65.6% at cut-off of <997. CTP score, FIB-4, APRI, and PC/SD ratio were significant for variceal bleeding. At cut-off <985 PC/SD ratio had sensitivity of 82% and specificity of 63% with AUC of 78% for prediction of variceal bleeding. Also, FIB-4 and APRI had diagnostic accuracy of 64% and 61% with AUC of 74% and 72% respectively for bleed. CONCLUSION: FIB-4 and PC/SD may be useful among armamentarium of non-invasive markers for predicting esophageal varices and risk of variceal bleeding in alcoholic liver cirrhosis.

Efficacy of Pancreatic Endotherapy In Pancreatic Ascites And Pleural Effusion.

Pancreatic ascites and effusion is a challenging complication to manage, hence our aim was to evaluate the efficacy of pancreatic endotherapy in pancreatic ascites and pleural effusion. Endotherapy included endoscopic retrograde cholangiopancreatography (ERCP) with a pancreatogram and pancreatic stent placement across the leak in patients with pancreatic ascites/effusion. A total of 53 patients were included after successful cannulation. The male:female ratio was 7.8:1. The pancreatogram revealed a leak from the pancreatic duct in 20/53 (37.73%) patients. The most common leak site was the pancreatic body in 10/53 (18.9%) patients followed by the tail in 6/53 (11.32%) patients and the genu in 4/53 (7.5%) patients. In 29/53 (54.7%) patients, stent was placed beyond the leak site. Sphincterotomy was done in 7/53 (13.2%) patients, and in five patients with an obscure leak site, stent was placed empirically. A total of 39/53 (73.6%) patients benefited in terms of achieving the complete resolution of ascites and pleural effusion. The factors which were significant for the success of pancreatic endotherapy in the multivariate analysis were the site of the pancreatic ductal leak (p value = 0.008) and the ability of the stent to cross the leak site (p value = 0.004). To sum up, bridging the pancreatic ductal leak by stent offers a high rate of success. Pancreatic endotherapy is less invasive and highly effective in managing pancreatic ascites/pleural effusion.

Yield of p53 expression in esophageal squamous cell cancer and its relationship with survival.

BACKGROUND/AIMS: Esophageal squamous cell carcinoma (ESCC) is the most aggressive type of cancer. Mutation of tumor suppressor gene p53 is observed in many gastrointestinal malignancies including ESCC. The immunohistochemical protein expression of mutant p53 has been proposed as a potential tool to evaluate the biological behavior of ESCC. Predictive value of p53 for survival is debatable, hence this study was formulated to know the survival of patients with p53 expression in ESCC. PATIENTS AND METHODS: We prospectively included 91 consecutive patients of ESCC from August 2014 to August 2016. Biopsy specimens were treated immunohistochemically and expression of p53 gene was analyzed by Immunoreactive Score (IRS). These findings were then compared with clinicopathological parameters such as age, gender, histological grades, and TNM stages. All patients received treatment and were kept under regular follow-up. RESULTS: M: F ratio was 2.03:1. p53 expression analyzed by IRS showed low expression (score ≤6) in 35 patients (38.46%) and high expression (>6) in 56 patients (61.54%). Level of p53 expression increased significantly with increasing histological grades of ESCC and TNM stage (P ≤ 0.001). Multivariate analysis shows p53 expression as independent predictor of survival. After 1 year of follow up, survival in the p53 high-expression group was 67.86% [standard error (SE) = 0.0473, confidence interval (CI) = 0.75-0.97) and in low p53 expression group was 91.43% (SE = 0.06, CI = 0.53-0.78) with statistically significant difference P = 0.0001 when analyzed with Kaplan-Meier method. CONCLUSION: Expression of p53 correlates with the survival and is a simple, effective and reproducible modality to determine the prognosis and survival in ESCC.

Handgrip dynamometry: a surrogate marker of malnutrition to predict the prognosis in alcoholic liver disease.

BACKGROUND: The aim of the study was to determine the utility of handgrip dynamometry (HGD) in predicting short term mortality and complications in alcoholic liver disease. METHODS: Patients with alcoholic liver disease were included and nutritional assessment was done using the Subjective Global Assessment (SGA), HGD and other conventional parameters. Mortality rates and complications were compared to nutritional status. RESULTS: 80 patients were included in the study. Mean age of patients was 43.06±10.03 years. 69 patients survived and 11 patients died within the 3 month study duration. Handgrip strength (HGS) was higher in SGA A (28.76±5.48 kg) than SGA B (22.43±4.95 kg) and SGA C (16.78±3.83 kg) (P=<0.001). Number of complications including spontaneous bacterial Peritonitis, gastrointestinal bleeding and encephalopathy in SGA C group were 66.66%, in SGA B 20.75% and SGA A 10%. Mean HGS was significantly higher in the survivors (24.23±5.86) compared to non-survivors (18.04±4.82) (P=0.0011). There was a strong negative correlation between the HGS and Child-Pugh score (P=<0.0012). Multivariate logistic regression analysis to assess the risk factors for death showed handgrip to be in the suggestive significance range (P=0.072). The sensitivity of HGS was 88.41% in predicting short term mortality. CONCLUSIONS: HGS correlates with Child-Pugh score in predicting short term mortality. HGD is a simple, inexpensive and sensitive tool for assessing the nutritional status in alcoholic liver disease and can reliably predict its complications and survival.

Synchronous Dual Primary Malignancies of Liver and Pancreas with Colonic Metastasis: An Unique Presentation.

Synchronous appearance of the primary gastrointestinal malignancies is rare. Coexistence of primary pancreatic and hepatocellular carcinoma as synchronous malignancy is even rarer. We report a case of such combination in a 50 year old female who presented with bleeding per rectum and while evaluating we found simultaneous appearance of primary malignancies of pancreas, liver and solitary colonic metastasis from the pancreas in the background of chronic calcific pancreatitis. To the best of our knowledge this combination of synchronous pancreatic and hepatocellular carcinoma and colonic metastasis from the pancreas is unique.