Technique of Hepatic Artery Anastomosis in Living Donor Liver Transplantation: Review of Its Results in Over 1200 Adult and Pediatric Transplants.

BACKGROUND: Failure to achieve a good arterial inflow to the graft in living donor liver transplantation (LDLT) has disastrous consequences to the graft and patient survival. Standard microvascular techniques of hepatic artery (HA) anastomosis used in deceased donor liver transplantation are not applicable in LDLT. We present the results of our unique Backwall-first technique of HA anastomosis in both adult and pediatric LDLT. PATIENTS AND METHODS: Retrospective review of all consecutive patients who underwent LDLT from January 2010 to December 2020 was performed from our prospective database. Data with regard to early postoperative (90-day) hepatic arterial complications were analyzed. RESULTS: A total of 1276 LDLTs (876 adults, 400 children) were performed during the study period. In the 90-day postoperative period, HA anastomotic complications [thrombosis in 11 (0.9%); pseudoaneurysm in 3 (0.2%)] were observed in 14 recipients (1.1%) including 8 adults (0.9%) and 6 children (1.5%). Eight of these 14 recipients (0.6%) including 4 adults (0.5%) and 4 children (1%) had standard HA reconstruction. The remaining six (0.5%) including 4 adults and 2 children had complex arterial reconstruction with interposition graft and/or alternative arterial inflow. CONCLUSION: The Backwall-first technique of HA reconstruction described in this study achieved a very low HA complication rate in LDLT.

First report of auxiliary liver transplantation for severe cholangiopathy after SARS-CoV-2 respiratory infection.

Post-coronavirus disease 2019 (COVID-19) cholangiopathy (PCC) is a new entity observed in patients recovering from severe COVID-19 pneumonia. Most patients recover with cholestasis improving over a period of time. In some patients, cholestasis is severe and persists or progresses to liver failure necessitating liver transplant. We present a previously healthy 50-year-old man who developed PCC with peak total bilirubin of 42.4 mg/dl and did not improve with medical management. He underwent living donor auxiliary right lobe liver transplantation. He recovered well after transplant and remains asymptomatic at 6 months follow-up with good graft function and recovering function in native liver remnant.

Liver stiffness-based model predicts hepatic venous pressure gradient in patients with liver disease.

BACKGROUND: The aim was to develop a model to predict clinically significant portal hypertension, hepatic venous pressure gradient (HVPG) ≥10 mmHg using pre-operative noninvasive makers. METHODS: Patients who have been programmed for liver resection/transplantation were enrolled prospectively. Preoperative liver stiffness measurement (LSM), liver function test (LFT), and intraoperative HVPG were assessed. A probability score model to predict HVPG≥10 mmHg called HVPG10 score was developed and validated. RESULTS: A total of 161 patients [66% men, median age of 63 years] were recruited for the study. Median LSM, and HVPG were 9.5 kPa, and 5 mmHg respectively. HVPG10 score was developed using independent predictors of HVPG≥10 mmHg in the training set were LSM, total bilirubin, alkaline phosphatase, and international normalized ratio. Area under receiver operating curve of HVPG10 score in the training and validation sets were 0.91 and 0.93 respectively with a cutoff of 15. In the overall cohort, HVPG10 score≥15 had 83% accuracy, 90% sensitivity, 81% specificity and 96% negative predictive value in predicting HVPG≥10 mmHg. CONCLUSION: HVPG10 score is an easy-to-use noninvasive continuous scale tool to rule out clinically significant portal hypertension in >95% patients with chronic liver disease.

Intention-to-treat analysis of percutaneous endovascular treatment of hepatic artery stenosis after orthotopic liver transplantation.

Hepatic artery stenosis (HAS) is a rare complication of orthotopic liver transplantation (LT). HAS could evolve into complete thrombosis and lead to graft loss, incurring significant morbidity and mortality. Even though endovascular management by percutaneous transluminal angioplasty ± stenting (PTA) is the primary treatment of HAS, its longterm impact on hepatic artery (HA) patency and graft survival remains unclear. This study aimed to evaluate longterm outcomes of PTA and to define the risk factors of treatment failure. From 2006 to 2012, 30 patients with critical HAS (>50% stenosis of HA) and treated by PTA were identified from 870 adult patients undergoing LT. Seventeen patients were diagnosed by post-LT screening, and 13 patients were symptomatic due to HAS. PTA was completed successfully in 27 (90%) patients with angioplasty plus stenting in 23 and angioplasty alone in 4. The immediate technical success rate was 90%. A major complication that was observed was arterial dissection (1 patient) which eventually necessitated retransplantation. Restenosis was observed in 10 (33%) patients. One-year, 3-year, and 5-year HA patency rates were 68%, 62.8%, and 62.8%, respectively. Overall patient survival was 93.3% at 3 years and 85.3% at 5 years. The 3-year and 5-year liver graft survival rates were 84.7% and 64.5%, respectively. No significant difference was observed in patient and graft survivals between asymptomatic and symptomatic patients after PTA. Similarly, no difference was observed between angioplasty alone and angioplasty plus stenting. In conclusion, endovascular therapy ensures a good 5-year graft survival (64.5%) and patient survival (85.3%) in patients with critical HAS by maintaining HA patency with a low risk of serious morbidity (3.3%). Liver Transplantation 22 923-933 2016 AASLD.

Serial volumetric assessment of large for size liver grafts after whole cadaveric liver transplant in adults: do large liver grafts shrink in size?

BACKGROUND: After whole graft orthotopic liver transplantation (OLT), adaptation of the large grafts' volume to recipient weight is widely accepted despite the paucity of evidence on this subject. METHODS: Thirty nine patients with GRWR > 2.5% were included in this study and subsequently divided into two groups with 3 ≥ GRWR > 3%. Patients had CT scans at three predetermined time points after OLT used for measuring the liver volume. The objective of this study is to evaluate the volumetric changes of whole large liver grafts after adult OLT. RESULTS: At LT, the mean graft recipient body weight ratio (GRWR) was 3.1 ± 0.4%. The mean liver weight was 1881 ± 68 g at LT, 2014 ± 99 ml at one week, 1725 ± 126 ml at 3 months, and 1632 ± 117 (ml) at >6 months. There is an initial increase at 1 week after LT and a subsequent decrease of liver volume on later measurements. None of the late volume measurements were significantly different from the initial graft volume at liver transplant in pair wise comparisons ANOVA repeated measures (p > 0.05). Similarly, the mean GRWR did not change significantly between the initial calculation at transplantation date and the subsequent measurements during the different study time points (F = 0.04, p = 0.96) with a mean of 3.1% (95% CI = 2.2-4.2). AUC ROC discriminated a cutoff of 3% for the initial GRWR above which grafts tend to decrease in size over time (c statistics = 0.74, p = 0.036). In a Clustered ANOVA repeated measures, there was no significant difference in the changes of liver volume between both groups. However, patients with GRWR > 3 showed a trend towards a latent reduction in volume over the tracing period. There was a tendency, but none significant; towards a higher bilirubin, AST, ALT levels over the first postoperative days in recipients with GRWR > 3. CONCLUSION: Large grafts do not significantly decrease in size. Nonetheless, grafts weighing >3% of the GRWR show a different trend towards decrease in size over time.

Small Molecule-Mediated Stage-Specific Reprogramming of MSCs to Hepatocyte-Like Cells and Hepatic Tissue for Liver Injury Treatment.

BACKGROUND: Derivation of hepatocytes from stem cells has been established through various protocols involving growth factor (GF) and small molecule (SM) agents, among others. However, mesenchymal stem cell-based derivation of hepatocytes still remains expensive due to the use of a cocktail of growth factors, and a long duration of differentiation is needed, thus limiting its potential clinical application. METHODS: In this study, we developed a chemically defined differentiation strategy that is exclusively based on SM and takes 14 days, while the GF-based protocol requires 23-28 days. RESULTS: We optimized a stage-specific differentiation protocol for the differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) into functional hepatocyte-like cells (dHeps) that involved four stages, i.e., definitive endoderm (DE), hepatic competence (HC), hepatic specification (HS) and hepatic differentiation and growth. We further generated hepatic tissue using human decellularized liver extracellular matrix and compared it with hepatic tissue derived from the growth factor-based protocol at the transcriptional level. dHep, upon transplantation in a rat model of acute liver injury (ALI), was capable of ameliorating liver injury in rats and improving liver function and tissue damage compared to those in the ALI model. CONCLUSIONS: In summary, this is the first study in which hepatocytes and hepatic tissue were derived from MSCs utilizing a stage-specific strategy by exclusively using SM as a differentiation factor.

Deceased Donor Liver Transplantation in India: First Report of 5-y Outcomes.

BACKGROUND: Paucity of deceased donor livers has resulted in a 10-fold rise in living donor liver transplantations (LDLTs) performed in India over the past decade. Nonetheless, number of deceased donor liver transplantation (DDLT) performed has improved with the establishment of simplified legal framework for certification of brain death and organ donation. In this study, we present our outcomes of DDLT performed at various centers, comparing their outcomes and provide a snapshot of the increasing number of DDLT across the state over the years. METHODS: All consecutive patients who underwent liver transplants from January 2010 till December 2019 by our transplant team in the state of Tamil Nadu, India, were included in the study. The program was established initially at the primary hospital in the year 2010 and with the evolution of the initial experience, transplant programs were expanded to the others hospital from the year 2015. Preoperative clinical data, intraoperative characteristics, and posttransplant outcomes of DDLT were analyzed from our prospective database. RESULTS: A total of 362 DDLTs (331 adults, 31 children) were performed at 11 centers. Median (range) model for end-stage liver disease score was 16 (6-39). Forty-eight split, 11 combined liver kidney, and 4 auxiliary DDLTs were performed. One-, 3-, and 5-y survival was 87.2%, 80.4%, and 76.6% in adults and 80.6%, 80.6%, and 80.6% in children, respectively. CONCLUSIONS: In a country where over 80% of the LTs are performed as LDLT, we provide the first report of a heartening trend of increasing number of DDLT programs being established with excellent 5-y outcomes.

Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.

Aggressive Variant of Hepatic Epstein-Barr Virus-Associated Inflammatory Pseudotumor-like Follicular Dendritic Cell Sarcoma with PD-L1 and SSTR2a Expression.

An aggressive Epstein-Barr virus (EBV)-associated inflammatory pseudotumor-like follicular dendritic cell (IPT-like FDC) sarcoma is reported in an adult female. The patient developed multifocal recurrence and passed away 13 months after the initial surgical resection. A bright field microscopic examination of the tumor demonstrated a classical growth pattern and the diffuse expression of Programmed death ligand 1 (PD-L1) and somatostatin receptor 2a (SSTR2a).

Predictive nomograms for postoperative 90-day morbidity and mortality in patients undergoing liver resection for various hepatobiliary diseases.

BACKGROUND: Postoperative complications affect the long-term survival and quality of life in patients undergoing liver resection. No model has yet been validated to predict 90-day severe morbidity and mortality. METHODS: The prospective recruitment of patients undergoing liver resection for various indications was performed. Preoperative clinical and laboratory data, including liver stiffness, indocyanine green retention, and intraoperative parameters, were analyzed to develop predictive nomograms for postoperative severe morbidity and mortality. Calibration plots were used to perform external validation. RESULTS: The most common indications in 418 liver resections performed were colorectal metastases (N = 149 [35.6%]), hepatocellular carcinoma (N = 106 [25.4%]), and benign liver tumors (N = 60 [14.3%]). Major liver resections were performed in 164 (39.2%) patients. Severe morbidity and mortality were observed in 87 (20.8%) and 9 (2.2%) of patients, respectively, during the 90-day postoperative period. Post-hepatectomy liver failure was observed in 19 (4.5%) patients, resulting in the death of 4. The independent predictors of 90-day severe morbidity were age (odds ratio:1.02, P = .06), liver stiffness (odds ratio: 1.23, P = .04], number of resected segments (odds ratio: 1.28, P = .004), and operative time (odds ratio: 1.01, P = .01). Independent predictors of 90-day mortality were diabetes mellitus (odds ratio: 6.6, P = .04), tumor size >50 mm (odds ratio:4.8, P = .08), liver stiffness ≥22 kPa (odds ratio:7.0, P = .04), and operative time ≥6 hours (odds ratio: 6.1, P = .05). Nomograms were developed using these independent predictors and validated by testing the Goodness of fit in calibration plots (P = .64 for severe morbidity; P = .8 for mortality). CONCLUSION: Proposed nomograms would enable a personalized approach to identifying patients at risk of complications and adapting surgical treatment according to their clinical profile and the center's expertise.

Prognostic impact of incidentally detected hepatocellular carcinoma in explanted livers after living donor liver transplantation.

BACKGROUND: The impact of incidentally detected hepatocellular carcinoma (iHCC) in explanted liver on the prognosis of the patients undergoing orthotopic liver transplantation remains controversial with several studies reporting survival worse than true non-hepatocellular carcinoma (non-HCC) recipients. Patients undergoing living donor liver transplantation (LDLT) have the benefit of a shorter waiting time to transplant which in principle should reduce the frequency of new tumors developing while waiting for transplant. We aimed to evaluate the incidence, histopathological features, and impact of iHCC on short- and long-term outcomes in adult LDLT recipients. METHODS: The present study retrospectively analyzed the patients' demographics, tumor characteristics, and outcomes of iHCC in adult patients undergoing LDLT for non-HCC indications at our center between August 2009 and March 2018. RESULTS: Five hundred and forty-five adults underwent LDLT in our center during the study period. iHCC was detected in the explanted livers in 28 patients (5.1%) out of 545 LDLTs. Only one patient had iHCC beyond Milan criteria. No tumor recurrence was observed in the iHCC cohort after a median follow-up of 28 months. Five-year overall and recurrence-free survival was 96.4%. CONCLUSIONS: Incidence of iHCC in explanted livers after LDLT is low and most patients have very early-stage tumors with excellent recurrence-free survival. Hence, no specific post-transplant surveillance or treatment is necessary.

Revisiting the Surgical Management of Giant Hepatic Hemangiomas: Enucleation Versus Anatomical Resection?

BACKGROUND: Resection is rarely indicated in giant hepatic hemangiomas (HHs) that are symptomatic. Enucleation (EN), compared with anatomical resection (AR), is considered the better technique to resect them as EN has been reported to have lower morbidity while conserving the normal liver tissue. But no study has yet clearly established the superiority of EN over AR. In addition, the independent predictors of postoperative morbidity have not been established. METHODS: All consecutive patients operated for HH at two specialized hepatobiliary centers were reviewed. Patient demographics, operative variables, and postoperative outcomes were analyzed and compared between two techniques. Postoperative complications were graded as per Clavien-Dindo classification of surgical complications. The aims of this study were to compare two techniques of HH resection with respect to postoperative outcomes and to identify the risk factors for 90-day major postoperative morbidity and mortality. RESULTS: A total of 64 patients, including 41 who underwent AR, 22 who underwent EN, and 1 who underwent liver transplantation, were operated for hemangiomas during the study period. Ten patients (9 who were operated for hemangiomas of size ≤4 cm and 1 who underwent transplantation) were excluded. Fifty-four patients, the majority being women (85%), with a median age of 48 years, were operated for giant HH. These patients were classified into two groups based on the technique of resection, namely, EN (22 patients) and AR (32 patients). Both groups were comparable in all aspects except that the number of liver segments resected was significantly more with AR. Postoperative outcomes were similar in both groups. Independent predictors of 90-day major complications including mortality were the use of total vascular exclusion (relative risk [RR]: 2.3, p = 0.028) and duration of surgery >4.5 h (RR: 2.3, p = 0.025). CONCLUSION: Both techniques yield similar results with respect to 90-day postoperative morbidity and mortality. The choice of technique should be based on the location of tumor and simplicity of liver resection.

Isolated mesenteric fibromatosis.

Fibromatosis is a rare, locally aggressive but non-metastasising fibrous mass often associated with familial adenomatous polyposis in Gardner's Syndrome (GS). Although sporadic cases occur, unlike in GS, they are predominantly extra-abdominal. We report the case of a 40-year-old lady who underwent laparotomy for a large isolated abdominal mass three years after a Whipple's procedure for adenocarcinoma of the distal common bile duct. A spherical, football sized tumour was found in the jejunal mesentery. Resection of the tumour with jejunum was carried out. No metastasis was detected. This case is peculiar in that mesenteric fibromatosis occurred in a patient with prior history of periampullary carcinoma and without history of familial adenomatous polyposis.

Is Cure Possible After Sequential Resection of Hepatic and Pulmonary Metastases From Colorectal Cancer?

BACKGROUND: Surgical resection is an established therapeutic strategy for colorectal cancer (CRC) metastasis. However, controversies exist when CRC liver and lung metastases (CLLMs) are found concomitantly or when recurrence develops after either liver or lung resection. No predictive score model is available to risk stratify these patients in preparation for surgery, and cure has not yet been reported. PATIENTS AND METHODS: All consecutive patients who had undergone surgery for CLLMs at our institution during a 20-year period were reviewed. Our policy was to propose sequential surgery of both sites with perioperative chemotherapy, if the strategy was potentially curative. Overall survival, disease-free survival, and cure were evaluated. RESULTS: Sequential resection was performed in 150 patients with CLLMs. The median number of liver and lung metastases resected was 3 and 1, respectively. The median follow-up period was 59 months (range, 7-274 months). The median, 5-year, and 10-year overall survival was 76 months, 60%, and 35% respectively. CRC that was metastatic at the initial diagnosis (P = .012), a prelung resection carcinoembryonic antigen level > 100 ng/mL (P = .014), a prelung resection cancer antigen 19-9 level > 37 U/mL (P = .034), and an interval between liver and lung resection of < 24 months (P = .024) were independent poor prognostic factors for survival. The 5-year survival was significantly different for patients with ≤ 2 and ≥ 3 risk factors (77.3% vs. 26.5%). Of 75 patients with ≥ 5 years of follow-up data available from the first metastasis resection, 15 (20%) with disease-free survival ≥ 5 years were considered cured. The use of targeted therapy was the only independent predictor of cure. CONCLUSION: Curative-intent surgery provides good long-term survival and offers a chance of cure in select patients. Patients with ≤ 2 risk factors are good candidates for sequential resection.

Liver stiffness measurement by transient elastography predicts late posthepatectomy outcomes in patients undergoing resection for hepatocellular carcinoma.

BACKGROUND: Postoperative hepatic decompensation is a serious complication of liver resection in patients undergoing hepatectomy for hepatocellular carcinoma. Liver fibrosis and clinical significant portal hypertension are well-known risk factors for hepatic decompensation. Liver stiffness measurement is a noninvasive method of evaluating hepatic venous pressure gradient and functional hepatic reserve by estimating hepatic fibrosis. Effectiveness of liver stiffness measurement in predicting persistent postoperative hepatic decompensation has not been investigated. METHODS: Consecutive patients with resectable hepatocellular carcinoma were recruited prospectively and liver stiffness measurement of nontumoral liver was measured using FibroScan. Hepatic venous pressure gradient was measured intraoperatively by direct puncture of portal vein and inferior vena cava. Hepatic venous pressure gradient ≥10 mm Hg was defined as clinically significant portal hypertension. Primary outcome was persistent hepatic decompensation defined as the presence of at least one of the following: unresolved ascites, jaundice, and/or encephalopathy >3 months after hepatectomy. RESULTS: One hundred and six hepatectomies, including 22 right hepatectomy (20.8%), 3 central hepatectomy (2.8%), 12 left hepatectomy (11.3%), 11 bisegmentectomy (10.4%), 30 unisegmentectomy (28.3%), and 28 partial hepatectomy (26.4%) were performed in patients for hepatocellular carcinoma (84 men and 22 women with median age of 67.5 years; median model for end-stage liver disease score of 8). Ninety-day mortality was 4.7%. Nine patients (8.5%) developed postoperative hepatic decompensation. Multivariate logistic regression bootstrapped at 1,000 identified liver stiffness measurement (P = .001) as the only preoperative predictor of postoperative hepatic decompensation. Area under receiver operating characteristic curve for liver stiffness measurement and hepatic venous pressure gradient was 0.81 (95% confidence interval, 0.506-0.907) and 0.71 (95% confidence interval, 0.646-0.917), respectively. Liver stiffness measurement ≥22 kPa had 42.9% sensitivity and 92.6% specificity and hepatic venous pressure gradient ≥10 mm Hg had 28.6% sensitivity and 96.3% specificity. CONCLUSION: In selected patients undergoing liver resection for hepatocellular carcinoma, transient elastography is an easy and effective test to predict persistent hepatic decompensation preoperatively.

Disseminated rhinosporidiosis - an unusual presentation with pulmonary involvement.

BACKGROUND AND AIM: Rhinosporidiosis is a chronic granulomatous disease that commonly affects the nasal and nasopharyngeal mucosa. It rarely presents as disseminated disease. CASE REPORT: We describe a rare case of a patient who had undergone treatment for recurrent nasal rhinosporidiosis and who presented with multiple subcutaneous swellings and pulmonary lesions.