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Papers by Prashant Bhangui

Research paper thumbnail of Liver Transplant Outcomes in India

Clinical Liver Disease, 2022

Research paper thumbnail of Evaluation of the Intention-to-Treat Benefit of Living Donation in Patients With Hepatocellular Carcinoma Awaiting a Liver Transplant

JAMA Surgery, 2021

Importance Living-donor liver transplant (LDLT) offers advantages over deceased-donor liver trans... more Importance Living-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC). Objective To investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription. Design, Setting, and Participants This multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020. Main Outcomes and Measures Intention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created. Results A total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated. Conclusions and Relevance This study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.

Research paper thumbnail of Proceedings of the 25th Annual Congress of the International Liver Transplantation Society

Transplantation, 2020

contributed to data collection and critical review of the article. A.C. contributed to critical r... more contributed to data collection and critical review of the article. A.C. contributed to critical review of the article. P.B. contributed to the writing, editing, and critical review of the article.

Research paper thumbnail of Current status of liver transplantation in Asia

International Journal of Surgery, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Living Donor Liver Transplantation after Successful Downstaging Using Targeted Radiotherapy in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombosis

Research paper thumbnail of Novel Prognostic Model Based on Tumor Biology and Morphology to Predict HCC Recurrence after Living Donor Liver Transplantation

Research paper thumbnail of Fast tracking in adult living donor liver transplantation: A case series of 15 patients

Indian journal of anaesthesia, 2018

Fast tracking (FT) for more efficacious use of resources may be difficult after living donor live... more Fast tracking (FT) for more efficacious use of resources may be difficult after living donor liver transplantation (LDLT) due to a partial liver graft, complex vascular anastomoses and longer operating time. Our study was aimed at reporting our experience with FT (on table extubation) in LDLT recipients. A secondary objective of our study was to look at defining a subgroup of patients who could be prospectively planned for FT. We studied the demographics and outcomes of 15 LDLT recipients extubated immediately in the operating suite based on an uneventful intraoperative course, haemodynamic stability after graft reperfusion and improvement of metabolic parameters post-implantation and vascular anastomoses. Twelve recipients were males, and mean age, body mass index (BMI) and Model for End Stage Liver Disease (MELD) score were 43 ± 12 years, 23 ± 3 kg/m and 15.5 ± 6, respectively, most were Child-Turcotte-Pugh Class B. Diabetes and hypothyroidism were present in 1 and 2 patients, res...

Research paper thumbnail of Reply to Letter

Research paper thumbnail of Is Perioperative Chemotherapy Useful for Solitary, Metachronous, Colorectal Liver Metastases?

Annals of Surgery, 2010

Background: Chemotherapy is increasingly used in colorectal liver metastases (CRLMs) even when th... more Background: Chemotherapy is increasingly used in colorectal liver metastases (CRLMs) even when they are initially resectable. The aim of our study was to address the still pending question of whether perioperative chemotherapy is really beneficial in patients developing solitary metastases at a distance from surgery of the primary. Methods: We analyzed a multicentric cohort of 1471 patients resected for solitary, metachronous, primarily resectable CRLMs without extrahepatic disease in the LiverMetSurvey International Registry over a 15-year period. Patients who received at least 3 cycles of oxaliplatin-or irinotecan-based chemotherapy before liver surgery (group CS, n = 169) were compared with those who were resected upfront (group S, n = 1302). Results: Patients of group CS were more frequently females (49% vs 36%, P = 0.001) and had larger metastases (≥5 cm, 33% vs 23%, P = 0.007); no difference was observed with regard to age, site of the primary tumour, time delay to occurrence of metastases, and carcinoembryonic antigen (CEA) levels at the time of diagnosis in the 2 groups. The rate of postoperative complications was significantly higher in group CS (37.2% vs 24% in group S, P = 0.006). At univariate analysis, preoperative chemotherapy did not impact the overall survival (OS) (60% at 5 years in both groups); however, postoperative chemotherapy was associated with better OS (65% vs 55% at 5 years, P < 0.01). At multivariate analysis, age 70 years or older (P = 0.05), lymph node positivity in the primary tumor (P = 0.02), a primary-tometastases time delay of less than 12 months (P = 0.04), raised CEA levels of more than 5 ng/mL at diagnosis (P < 0.01), a tumor diameter of 5 cm or more (P < 0.01), noncurative liver resection (P < 0.01), and the absence of postoperative chemotherapy (P < 0.01) were independent prognostic factors

Research paper thumbnail of Enhanced recovery for liver transplantation: recommendations from the 2022 International Liver Transplantation Society consensus conference

The Lancet Gastroenterology & Hepatology

Research paper thumbnail of Check point inhibitor-based Immunotherapy in unresectable/non-transplantable hepatocellular carcinoma: Initial experience

Journal of Clinical and Experimental Hepatology

Research paper thumbnail of Tumors located in the central column of the liver are associated with increased surgical difficulty and postoperative complications following open liver resection for colorectal metastases

HPB, 2022

BACKGROUND To assess the impact of difficult location (based on preoperative computed tomography)... more BACKGROUND To assess the impact of difficult location (based on preoperative computed tomography) of liver metastases from colorectal cancer (LMCRC) on surgical difficulty, and occurrence of severe postoperative complications (POCs). METHODS A retrospective single-centre study of 911 consecutive patients with LMCRC who underwent hepatectomy by the open approach between 1998 and 2011, before implementation of laparoscopic surgery to obviate approach selection bias. LMCRC with at least one of the following four features on preoperative imaging: tumor invading the hepatocaval confluence or retro-hepatic inferior vena cava, centrally located (Segments 4,5,8) and >10 cm in diameter, abutting the supra-hilar area, or involving the paracaval portion or caudate process of Segment 1; were considered as topographically difficult (top-diff). Independent predictors of surgical difficulty assessed by number of blood units transfused, duration of ischemia, and number of sessions of pedicle clamping during surgery and of severe POCs were identified by multivariate analysis before, and after propensity score matching. RESULTS Top-diff tumor location independently predicted surgical difficulty. Severe POCs were associated with the tumor location [top-diff vs. topographically non difficult (non top-diff)], preoperative portal vein embolization, and variables related to surgical difficulty. CONCLUSION LMCRC in difficult location independently predicts surgical difficulty and severe POCs.

Research paper thumbnail of Poor Outcomes after Recidivism in Living Donor Liver Transplantation for Alcohol-Related Liver Disease

Journal of Clinical and Experimental Hepatology, 2021

Background Recidivism in patients who underwent liver transplantation for alcohol-related liver d... more Background Recidivism in patients who underwent liver transplantation for alcohol-related liver disease (ALD) is shown to be associated with poor survival in some studies. Methods Living donor liver transplantation (LDLT) recipients for ALD with at least 2 years of follow-up and history of significant alcohol relapse were included. The recipients underwent LDLT from June 2010 to December 2016, and data were analyzed until June 2019. The cohort had a median follow-up of 54 (33-78 IQR) months. Recidivism (significant alcohol intake) was defined as >21 units per week. Results A total of 27 of 463 (5.8%) LDLT recipients (all men), aged 43.5 ± 9.6 years, had significant alcohol intake. A liver biopsy was performed on demand in 14 patients (in the presence of raised levels of liver enzymes or jaundice). The histological diagnoses in these patients were as follows: alcoholic hepatitis in 7 (50%), alcoholic hepatitis and acute cellular rejection or chronic rejection in 4 (28.5%), cirrhosis in 2 (14.2%), and acute cellular rejection and cirrhosis in 1 (7.1%) patient. Four of 5 patients with a biopsy diagnosis of acute or chronic rejection were noncompliant with immunosuppression. Six of these patients died. The mortality after 1 year of transplant was significantly more in patients with recidivism. Conclusion Recidivism was associated with significant morbidity and mortality after liver transplantation.

Research paper thumbnail of Experience With LDLT in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis Postdownstaging

Transplantation, 2020

Background. Median survival in patients with hepatocellular carcinoma (HCC) and portal vein tumor... more Background. Median survival in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) is 2-6 months; conventionally liver transplantation is contraindicated. Methods. We studied outcomes following living donor liver transplantation (LDLT) post-PVTT downstaging (DS) with stereotactic body radiotherapy (SBRT), and tumor ablation (with transarterial chemo-or radio-embolization). Results. Of 2348 consecutive LDLTs, 451 were for HCC, including 25 with PVTT (mainly Vp1-3) after successful DS and 20 with Vp1/2 PVTT without previous treatment. DS was attempted in 43, was successful in 27 (63%), and 25 underwent LDLT. Median alpha fetoprotein (AFP) at diagnosis and pre-LDLT were 78.1 ng/mL (3-58 200) and 55 ng/mL (2-7320), respectively. Mean DS to LDLT time was 10.2 weeks (5-16). Excluding 2 postoperative deaths, 1-and 5-year overall survival (OS) and recurrence-free survival (RFS) were 82%, 57%, and 77%, 51%, respectively, comparable to survival in 382 HCC patients without PVTT undergoing upfront LDLT (5-y OS 65%, P = 0.06; RFS 66%, P = 0.33, respectively). There was a trend toward better OS in DS+LDLT versus non-DS LDLT group (5-y OS/RFS-48%/40%). OS was significantly better than in HCC-PVTT patients receiving no intervention or palliative Sorafenib alone (1-y OS of 0%) or Sorafenib with TARE/SBRT (2-y OS of 17%) at our center during the study period. Initial AFP <400 ng/mL and AFP fall (initial minus pre-LDLT) >2000 ng/mL predicted better RFS; Grade III/IV predicted worse OS in DS patients. Conclusions. HCC patients with PVTT can achieve acceptable survival with LDLT after successful DS. Low initial AFP level, a significant drop in AFP with DS and low tumor grade, favorably influence survival in these patients.

Research paper thumbnail of Liver Transplant Society of India Guidelines for Liver Transplant During COVID-19 times

Journal of Clinical and Experimental Hepatology, 2021

Coronavirus disease-2019 (COVID-19) pandemic has affected liver transplantation in many ways. The... more Coronavirus disease-2019 (COVID-19) pandemic has affected liver transplantation in many ways. There is risk of infection to the transplant recipients; and COVID-19 is associated with significant risk of mortality in patients on wait list. The Liver Transplant Society of India (LTSI) has prepared guidelines regarding selection of adult and pediatric patients for liver transplantation, transplant for acute liver failure, use of deceased donor organs, transplant techniques and minimally invasive donor hepatectomy, pre-and postsurgery testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related coronavirus disease 2019 in donors and recipients, role of COVID-19 antibody testing, shifting of recipients from COVID-19 to non-COVID-19 areas after recovery, isolation policy of team members exposed to COVID-19 patients, drug therapy of proven or suspected COVID-19 infection early posttransplant, care of SARS-CoV-2 positive donors and recipients and a separate COVID-19 consent for surgery. (J CLIN EXP HEPATOL 2022;12:180-185) 1. Liver transplant (LT) indications for adult and pediatric recipients; 2. Transplant in Acute Liver failure (ALF);

Research paper thumbnail of Post liver transplant recurrence in patients with hepatocellular carcinoma: not necessarily the end of the road!

Hepatoma Research, 2020

Aim: We analysed outcomes using multimodality therapy in patients with hepatocellular carcinoma (... more Aim: We analysed outcomes using multimodality therapy in patients with hepatocellular carcinoma (HCC) recurrence post living donor liver transplantation (LDLT). Methods: Of 2363 LDLT's performed between 2005 to mid 2018, 435 (18.4%) were for HCC within our expanded selection criteria (absence of extrahepatic disease and vascular invasion, irrespective of tumor size and number). Survival after recurrence, and prognostic factors for these patients were studied. Results: Of 435 LDLT patients, 51% had HCC beyond Milan and 43% beyond UCSF criteria at the time of LDLT. pre-LT AFP > 100 ng/mL and tumour FDG-18 PET avidity predicted overall survival (OS), whereas pre-LT AFP > 100 ng/mL, UCSF criteria, and FDG-18 PET avidity predicted recurrence-free survival. Hundred patients (23%) developed HCC recurrence at a median time of 16 months (range 2-108 months) post LDLT. Lungs (53%), liver (37%), and bone (21%) were the most common sites of recurrence. Ninety-five patients received tyrosine kinase inhibitors (TKI) after recurrence and 62 received mTOR inhibitors (protocol-based after LDLT, or post recurrence). Surgical resection of metastases was performed in 14 patients, 15 received stereotactic body radiotherapy, and 18 underwent ablation (radiofrequency, microwave ablation, transarterial chemoembolisation, or percutaneous ethanol injection). One-and 3-yr OS after recurrence were 57%, and 24% respectively, with a maximum post recurrence survival of 7.

Research paper thumbnail of Restructuring Living-Donor Liver Transplantation at a High-Volume Center During the COVID-19 Pandemic

Journal of Clinical and Experimental Hepatology, 2020

Background: Coronavirus disease 2019 (COVID-19) pandemic has led to deferral of elective transpla... more Background: Coronavirus disease 2019 (COVID-19) pandemic has led to deferral of elective transplants and proactive pretransplant testing of the donor/recipient. The impact of these on living-donor liver transplantation (LDLT) activity and outcome is not known. We performed LDLT only for sick patients or patients with advanced hepatocellular carcinoma in this period, with special COVID protocols. Methods: Patients undergoing LDLT counseling, evaluation, and transplant in the period March to June 2020 (group A) under COVID-19 restrictions and special protocols were included. LDLT activity and outcomes among these patients were compared with those in the same period in 2019 (group B). Results: In the period March 15-June 10, we performed 39 and 23 (59%) LDLTs in 2019 and 2020, respectively. The adult patients with cirrhosis in group A (n = 20) had a significantly higher MELD score, 19.8 ± 7.0 versus 16.1 ± 5.6 in group B (n = 36), p = 0.034. Early recipient mortality was similar in 2019 (2/39) and 2020 (2/23). One of 23 post-transplant recipients, 3/71 recipients and donors during evaluation, and 8/125 healthcare workers (HCWs) developed COVID-19, all of whom recovered uneventfully. Conclusion: LDLT activity substantially reduced during the COVID era. The incidence and outcome of COVID-19 among the waiting or transplanted patients and HCWs were similar to those of the general population. The outcome after LDLT in the COVID era was similar to that in non-COVID times. These data suggest that LDLT may be extended to more stable patients with strict protocols.

Research paper thumbnail of Current management of portal vein thrombosis in liver transplantation

International Journal of Surgery, 2020

Research paper thumbnail of Biliary reconstruction and complications in living donor liver transplantation

International Journal of Surgery, 2020

For a technically successful liver transplant (LT), secure bile duct anastomosis to prevent bilia... more For a technically successful liver transplant (LT), secure bile duct anastomosis to prevent biliary complications (BC's) like biliary anastomotic stricture (BAS) and bile leak (BL) is mandatory. BC's after living donor liver transplantation (LDLT) are relatively more common compared to deceased donor LT (DDLT), particularly owing to surgical factors (small diameter, and/or multiple bile duct openings on the graft), and non-surgical factors (immunologic reactions). Adequate blood supply to the bile duct both in donor and recipient, meticulous anastomotic technique, mucosal eversion for better approximation thus avoiding lesser fibrosis, proper use of internal or external stent drainage, and tension-free anastomosis, may contribute to the decrease of BC's after LDLT. Further, if BC's are not dealt with in a timely manner, these could progressively lead to severe morbidities and even mortality. While the endoscopic approach is preferred initially to deal with biliary leaks or strictures, the more invasive percutaneous approach may be required in case of endoscopic failure. Dedicated and experienced endoscopists, and interventional radiologists are key members of the multidisciplinary team in a successful LDLT program. In this review, we have tried to summarize current concepts in surgical techniques of biliary reconstruction in LDLT, incidence and risk factors for BC's, and principles followed to try and reduce the incidence of the same.

Research paper thumbnail of Delayed Graft Dysfunction due to Invasive Hepatic Mucormycosis After Living Donor Liver Transplantation

Journal of Clinical and Experimental Hepatology, 2020

Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation (SO... more Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation (SOT), with a

Research paper thumbnail of Liver Transplant Outcomes in India

Clinical Liver Disease, 2022

Research paper thumbnail of Evaluation of the Intention-to-Treat Benefit of Living Donation in Patients With Hepatocellular Carcinoma Awaiting a Liver Transplant

JAMA Surgery, 2021

Importance Living-donor liver transplant (LDLT) offers advantages over deceased-donor liver trans... more Importance Living-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC). Objective To investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription. Design, Setting, and Participants This multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020. Main Outcomes and Measures Intention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created. Results A total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated. Conclusions and Relevance This study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.

Research paper thumbnail of Proceedings of the 25th Annual Congress of the International Liver Transplantation Society

Transplantation, 2020

contributed to data collection and critical review of the article. A.C. contributed to critical r... more contributed to data collection and critical review of the article. A.C. contributed to critical review of the article. P.B. contributed to the writing, editing, and critical review of the article.

Research paper thumbnail of Current status of liver transplantation in Asia

International Journal of Surgery, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Research paper thumbnail of Living Donor Liver Transplantation after Successful Downstaging Using Targeted Radiotherapy in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombosis

Research paper thumbnail of Novel Prognostic Model Based on Tumor Biology and Morphology to Predict HCC Recurrence after Living Donor Liver Transplantation

Research paper thumbnail of Fast tracking in adult living donor liver transplantation: A case series of 15 patients

Indian journal of anaesthesia, 2018

Fast tracking (FT) for more efficacious use of resources may be difficult after living donor live... more Fast tracking (FT) for more efficacious use of resources may be difficult after living donor liver transplantation (LDLT) due to a partial liver graft, complex vascular anastomoses and longer operating time. Our study was aimed at reporting our experience with FT (on table extubation) in LDLT recipients. A secondary objective of our study was to look at defining a subgroup of patients who could be prospectively planned for FT. We studied the demographics and outcomes of 15 LDLT recipients extubated immediately in the operating suite based on an uneventful intraoperative course, haemodynamic stability after graft reperfusion and improvement of metabolic parameters post-implantation and vascular anastomoses. Twelve recipients were males, and mean age, body mass index (BMI) and Model for End Stage Liver Disease (MELD) score were 43 ± 12 years, 23 ± 3 kg/m and 15.5 ± 6, respectively, most were Child-Turcotte-Pugh Class B. Diabetes and hypothyroidism were present in 1 and 2 patients, res...

Research paper thumbnail of Reply to Letter

Research paper thumbnail of Is Perioperative Chemotherapy Useful for Solitary, Metachronous, Colorectal Liver Metastases?

Annals of Surgery, 2010

Background: Chemotherapy is increasingly used in colorectal liver metastases (CRLMs) even when th... more Background: Chemotherapy is increasingly used in colorectal liver metastases (CRLMs) even when they are initially resectable. The aim of our study was to address the still pending question of whether perioperative chemotherapy is really beneficial in patients developing solitary metastases at a distance from surgery of the primary. Methods: We analyzed a multicentric cohort of 1471 patients resected for solitary, metachronous, primarily resectable CRLMs without extrahepatic disease in the LiverMetSurvey International Registry over a 15-year period. Patients who received at least 3 cycles of oxaliplatin-or irinotecan-based chemotherapy before liver surgery (group CS, n = 169) were compared with those who were resected upfront (group S, n = 1302). Results: Patients of group CS were more frequently females (49% vs 36%, P = 0.001) and had larger metastases (≥5 cm, 33% vs 23%, P = 0.007); no difference was observed with regard to age, site of the primary tumour, time delay to occurrence of metastases, and carcinoembryonic antigen (CEA) levels at the time of diagnosis in the 2 groups. The rate of postoperative complications was significantly higher in group CS (37.2% vs 24% in group S, P = 0.006). At univariate analysis, preoperative chemotherapy did not impact the overall survival (OS) (60% at 5 years in both groups); however, postoperative chemotherapy was associated with better OS (65% vs 55% at 5 years, P < 0.01). At multivariate analysis, age 70 years or older (P = 0.05), lymph node positivity in the primary tumor (P = 0.02), a primary-tometastases time delay of less than 12 months (P = 0.04), raised CEA levels of more than 5 ng/mL at diagnosis (P < 0.01), a tumor diameter of 5 cm or more (P < 0.01), noncurative liver resection (P < 0.01), and the absence of postoperative chemotherapy (P < 0.01) were independent prognostic factors

Research paper thumbnail of Enhanced recovery for liver transplantation: recommendations from the 2022 International Liver Transplantation Society consensus conference

The Lancet Gastroenterology & Hepatology

Research paper thumbnail of Check point inhibitor-based Immunotherapy in unresectable/non-transplantable hepatocellular carcinoma: Initial experience

Journal of Clinical and Experimental Hepatology

Research paper thumbnail of Tumors located in the central column of the liver are associated with increased surgical difficulty and postoperative complications following open liver resection for colorectal metastases

HPB, 2022

BACKGROUND To assess the impact of difficult location (based on preoperative computed tomography)... more BACKGROUND To assess the impact of difficult location (based on preoperative computed tomography) of liver metastases from colorectal cancer (LMCRC) on surgical difficulty, and occurrence of severe postoperative complications (POCs). METHODS A retrospective single-centre study of 911 consecutive patients with LMCRC who underwent hepatectomy by the open approach between 1998 and 2011, before implementation of laparoscopic surgery to obviate approach selection bias. LMCRC with at least one of the following four features on preoperative imaging: tumor invading the hepatocaval confluence or retro-hepatic inferior vena cava, centrally located (Segments 4,5,8) and >10 cm in diameter, abutting the supra-hilar area, or involving the paracaval portion or caudate process of Segment 1; were considered as topographically difficult (top-diff). Independent predictors of surgical difficulty assessed by number of blood units transfused, duration of ischemia, and number of sessions of pedicle clamping during surgery and of severe POCs were identified by multivariate analysis before, and after propensity score matching. RESULTS Top-diff tumor location independently predicted surgical difficulty. Severe POCs were associated with the tumor location [top-diff vs. topographically non difficult (non top-diff)], preoperative portal vein embolization, and variables related to surgical difficulty. CONCLUSION LMCRC in difficult location independently predicts surgical difficulty and severe POCs.

Research paper thumbnail of Poor Outcomes after Recidivism in Living Donor Liver Transplantation for Alcohol-Related Liver Disease

Journal of Clinical and Experimental Hepatology, 2021

Background Recidivism in patients who underwent liver transplantation for alcohol-related liver d... more Background Recidivism in patients who underwent liver transplantation for alcohol-related liver disease (ALD) is shown to be associated with poor survival in some studies. Methods Living donor liver transplantation (LDLT) recipients for ALD with at least 2 years of follow-up and history of significant alcohol relapse were included. The recipients underwent LDLT from June 2010 to December 2016, and data were analyzed until June 2019. The cohort had a median follow-up of 54 (33-78 IQR) months. Recidivism (significant alcohol intake) was defined as >21 units per week. Results A total of 27 of 463 (5.8%) LDLT recipients (all men), aged 43.5 ± 9.6 years, had significant alcohol intake. A liver biopsy was performed on demand in 14 patients (in the presence of raised levels of liver enzymes or jaundice). The histological diagnoses in these patients were as follows: alcoholic hepatitis in 7 (50%), alcoholic hepatitis and acute cellular rejection or chronic rejection in 4 (28.5%), cirrhosis in 2 (14.2%), and acute cellular rejection and cirrhosis in 1 (7.1%) patient. Four of 5 patients with a biopsy diagnosis of acute or chronic rejection were noncompliant with immunosuppression. Six of these patients died. The mortality after 1 year of transplant was significantly more in patients with recidivism. Conclusion Recidivism was associated with significant morbidity and mortality after liver transplantation.

Research paper thumbnail of Experience With LDLT in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis Postdownstaging

Transplantation, 2020

Background. Median survival in patients with hepatocellular carcinoma (HCC) and portal vein tumor... more Background. Median survival in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) is 2-6 months; conventionally liver transplantation is contraindicated. Methods. We studied outcomes following living donor liver transplantation (LDLT) post-PVTT downstaging (DS) with stereotactic body radiotherapy (SBRT), and tumor ablation (with transarterial chemo-or radio-embolization). Results. Of 2348 consecutive LDLTs, 451 were for HCC, including 25 with PVTT (mainly Vp1-3) after successful DS and 20 with Vp1/2 PVTT without previous treatment. DS was attempted in 43, was successful in 27 (63%), and 25 underwent LDLT. Median alpha fetoprotein (AFP) at diagnosis and pre-LDLT were 78.1 ng/mL (3-58 200) and 55 ng/mL (2-7320), respectively. Mean DS to LDLT time was 10.2 weeks (5-16). Excluding 2 postoperative deaths, 1-and 5-year overall survival (OS) and recurrence-free survival (RFS) were 82%, 57%, and 77%, 51%, respectively, comparable to survival in 382 HCC patients without PVTT undergoing upfront LDLT (5-y OS 65%, P = 0.06; RFS 66%, P = 0.33, respectively). There was a trend toward better OS in DS+LDLT versus non-DS LDLT group (5-y OS/RFS-48%/40%). OS was significantly better than in HCC-PVTT patients receiving no intervention or palliative Sorafenib alone (1-y OS of 0%) or Sorafenib with TARE/SBRT (2-y OS of 17%) at our center during the study period. Initial AFP <400 ng/mL and AFP fall (initial minus pre-LDLT) >2000 ng/mL predicted better RFS; Grade III/IV predicted worse OS in DS patients. Conclusions. HCC patients with PVTT can achieve acceptable survival with LDLT after successful DS. Low initial AFP level, a significant drop in AFP with DS and low tumor grade, favorably influence survival in these patients.

Research paper thumbnail of Liver Transplant Society of India Guidelines for Liver Transplant During COVID-19 times

Journal of Clinical and Experimental Hepatology, 2021

Coronavirus disease-2019 (COVID-19) pandemic has affected liver transplantation in many ways. The... more Coronavirus disease-2019 (COVID-19) pandemic has affected liver transplantation in many ways. There is risk of infection to the transplant recipients; and COVID-19 is associated with significant risk of mortality in patients on wait list. The Liver Transplant Society of India (LTSI) has prepared guidelines regarding selection of adult and pediatric patients for liver transplantation, transplant for acute liver failure, use of deceased donor organs, transplant techniques and minimally invasive donor hepatectomy, pre-and postsurgery testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related coronavirus disease 2019 in donors and recipients, role of COVID-19 antibody testing, shifting of recipients from COVID-19 to non-COVID-19 areas after recovery, isolation policy of team members exposed to COVID-19 patients, drug therapy of proven or suspected COVID-19 infection early posttransplant, care of SARS-CoV-2 positive donors and recipients and a separate COVID-19 consent for surgery. (J CLIN EXP HEPATOL 2022;12:180-185) 1. Liver transplant (LT) indications for adult and pediatric recipients; 2. Transplant in Acute Liver failure (ALF);

Research paper thumbnail of Post liver transplant recurrence in patients with hepatocellular carcinoma: not necessarily the end of the road!

Hepatoma Research, 2020

Aim: We analysed outcomes using multimodality therapy in patients with hepatocellular carcinoma (... more Aim: We analysed outcomes using multimodality therapy in patients with hepatocellular carcinoma (HCC) recurrence post living donor liver transplantation (LDLT). Methods: Of 2363 LDLT's performed between 2005 to mid 2018, 435 (18.4%) were for HCC within our expanded selection criteria (absence of extrahepatic disease and vascular invasion, irrespective of tumor size and number). Survival after recurrence, and prognostic factors for these patients were studied. Results: Of 435 LDLT patients, 51% had HCC beyond Milan and 43% beyond UCSF criteria at the time of LDLT. pre-LT AFP > 100 ng/mL and tumour FDG-18 PET avidity predicted overall survival (OS), whereas pre-LT AFP > 100 ng/mL, UCSF criteria, and FDG-18 PET avidity predicted recurrence-free survival. Hundred patients (23%) developed HCC recurrence at a median time of 16 months (range 2-108 months) post LDLT. Lungs (53%), liver (37%), and bone (21%) were the most common sites of recurrence. Ninety-five patients received tyrosine kinase inhibitors (TKI) after recurrence and 62 received mTOR inhibitors (protocol-based after LDLT, or post recurrence). Surgical resection of metastases was performed in 14 patients, 15 received stereotactic body radiotherapy, and 18 underwent ablation (radiofrequency, microwave ablation, transarterial chemoembolisation, or percutaneous ethanol injection). One-and 3-yr OS after recurrence were 57%, and 24% respectively, with a maximum post recurrence survival of 7.

Research paper thumbnail of Restructuring Living-Donor Liver Transplantation at a High-Volume Center During the COVID-19 Pandemic

Journal of Clinical and Experimental Hepatology, 2020

Background: Coronavirus disease 2019 (COVID-19) pandemic has led to deferral of elective transpla... more Background: Coronavirus disease 2019 (COVID-19) pandemic has led to deferral of elective transplants and proactive pretransplant testing of the donor/recipient. The impact of these on living-donor liver transplantation (LDLT) activity and outcome is not known. We performed LDLT only for sick patients or patients with advanced hepatocellular carcinoma in this period, with special COVID protocols. Methods: Patients undergoing LDLT counseling, evaluation, and transplant in the period March to June 2020 (group A) under COVID-19 restrictions and special protocols were included. LDLT activity and outcomes among these patients were compared with those in the same period in 2019 (group B). Results: In the period March 15-June 10, we performed 39 and 23 (59%) LDLTs in 2019 and 2020, respectively. The adult patients with cirrhosis in group A (n = 20) had a significantly higher MELD score, 19.8 ± 7.0 versus 16.1 ± 5.6 in group B (n = 36), p = 0.034. Early recipient mortality was similar in 2019 (2/39) and 2020 (2/23). One of 23 post-transplant recipients, 3/71 recipients and donors during evaluation, and 8/125 healthcare workers (HCWs) developed COVID-19, all of whom recovered uneventfully. Conclusion: LDLT activity substantially reduced during the COVID era. The incidence and outcome of COVID-19 among the waiting or transplanted patients and HCWs were similar to those of the general population. The outcome after LDLT in the COVID era was similar to that in non-COVID times. These data suggest that LDLT may be extended to more stable patients with strict protocols.

Research paper thumbnail of Current management of portal vein thrombosis in liver transplantation

International Journal of Surgery, 2020

Research paper thumbnail of Biliary reconstruction and complications in living donor liver transplantation

International Journal of Surgery, 2020

For a technically successful liver transplant (LT), secure bile duct anastomosis to prevent bilia... more For a technically successful liver transplant (LT), secure bile duct anastomosis to prevent biliary complications (BC's) like biliary anastomotic stricture (BAS) and bile leak (BL) is mandatory. BC's after living donor liver transplantation (LDLT) are relatively more common compared to deceased donor LT (DDLT), particularly owing to surgical factors (small diameter, and/or multiple bile duct openings on the graft), and non-surgical factors (immunologic reactions). Adequate blood supply to the bile duct both in donor and recipient, meticulous anastomotic technique, mucosal eversion for better approximation thus avoiding lesser fibrosis, proper use of internal or external stent drainage, and tension-free anastomosis, may contribute to the decrease of BC's after LDLT. Further, if BC's are not dealt with in a timely manner, these could progressively lead to severe morbidities and even mortality. While the endoscopic approach is preferred initially to deal with biliary leaks or strictures, the more invasive percutaneous approach may be required in case of endoscopic failure. Dedicated and experienced endoscopists, and interventional radiologists are key members of the multidisciplinary team in a successful LDLT program. In this review, we have tried to summarize current concepts in surgical techniques of biliary reconstruction in LDLT, incidence and risk factors for BC's, and principles followed to try and reduce the incidence of the same.

Research paper thumbnail of Delayed Graft Dysfunction due to Invasive Hepatic Mucormycosis After Living Donor Liver Transplantation

Journal of Clinical and Experimental Hepatology, 2020

Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation (SO... more Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation (SOT), with a