Randomized controlled trial of sustained release tacrolimus vs twice daily tacrolimus in adult living donor liver transplantation.

BACKGROUND: To compare the safety and efficacy of once-daily tacrolimus (ODT) versus twice-daily tacrolimus (BDT) in adult live donor liver transplantation (LDLT). METHODS: In this open-labelled randomized trial, 174 adult patients undergoing LDLT were randomized into ODT or BDT, combined with basiliximab induction and mycophenolate mofetil (steroid-free regimen). Tacrolimus was started at a total dose of 1 mg and the trough level was aimed at 3-7 ng/ml. The primary endpoint was eGFR at 1,3- and 6 months post-transplant, using CKD- EPI equation. Secondary endpoints included biopsy-proven acute rejection (BPAR), metabolic complications, post-operative bilio-vascular complications and patient survival. RESULTS: There was no statistically significant difference in eGFR between the two groups at 6 months (ODT -96 ± 19, BDT -91 ± 21, p value-0.164). BPAR was comparable (18/84 in ODT, 19/88 in BDT, p value-0.981). For a similar dosage of tacrolimus, the median trough tacrolimus levels attained were significantly lower for ODT than BDT during the first-month post-transplant (p value-0.001). Metabolic complications due to immunosuppression, post-operative bilio-vascular complications and patient survival was similar between the two groups at 6 months. CONCLUSION: Once-daily tacrolimus has similar renal safety and efficacy as twice-daily tacrolimus when used in combination with basiliximab induction and mycophenolate in adult LDLT.

Open to robotic right donor hepatectomy: A tectonic shift in surgical technique.

Robotic right live donor hepatectomy (r-LDRH) has been reported with reduced morbidity compared to open donor right hepatectomy (o-LDRH) in few recent series. Nevertheless, its routine use is debated. We present a large series comparing pure r-LDRH with o-LDRH. Consecutive r-LDRH performed from June 2018 to June 2020 (n = 102) were compared with consecutive donors undergoing o-LDRH (n = 152) from February 2016 to February 2018, a period when r-LDRH was not available at this center. Propensity score matched (PSM) analysis of 89 case-control pairs was additionally performed. Primary endpoints were length of high dependency unit (HDU) and hospital stay and Clavien-Dindo graded complications among donors. Although r-LDRH took longer to perform (540 vs. 462 min, P < .001), the postoperative peak transaminases levels (P < .001), the length of HDU (3 vs. 4 days, P < .001), and hospital stay (8 vs. 9 days, P < .001) were lower in in donors undergoing r-LDRH. Clavien-Dindo graded complications were similar (16.67% in r-LDRH and 13.16% in o-LDRH). The rates of early allograft dysfunction (1.6% vs. 3.3%), bile leak (14.7% vs. 10.7%), and 1-year mortality (13.7% vs. 11.8%) were comparable between r-LDRH and o-LDRH recipients. PSM analysis yielded similar results between the groups. These data support the safety and feasibility of r-LDRH in select donors.

Extended criteria donors for robotic right hepatectomy: A propensity score matched analysis.

BACKGROUND: Robotic right donor hepatectomy (RDH) has been reported from experienced centers with reduced morbidity when compared to open RDH. However, outcomes in donors with large grafts/complex biliovascular anatomy are unknown. METHODS: Out of 170 robotic RDH, 100 had one or more of the following: graft weight ≥800 g, type 2/3 portal vein, >1 bile duct or hepatic artery and inferior hepatic veins >5 mm requiring reconstruction (extended criteria donors [ExRDH]), while the remaining 70 had standard anatomy (SRDH). After propensity score matching, 66 ExRDH were compared with 66 SRDH. Additionally, all robotic RDH performed were analyzed in three temporal phases (60, 60, and 50). RESULTS: Peak AST and ALT were higher amongst donors and recipients in the ExRDH arm compared to SRDH. Other intraoperative parameters and postoperative complications were similar between the two groups. During the last phase, donors demonstrated reduction in duration of surgery, postoperative complications, and hospital stay while recipients showed decreased blood loss and hospital stay. CONCLUSION: Robotic right hepatectomy performed in donors with extended criteria have similar perioperative outcomes as standard donors. However, a significant learning curve needs to be traversed. Further studies are required before safely recommending robotic RDH for all donors.

Technique of robotic right donor hepatectomy.

BACKGROUND: Although minimally invasive right donor hepatectomy (RDH) has been reported, this innovation is yet to be widely accepted by transplant community. Bleeding during transection, division of right hepatic duct (RHD), suturing of donor duct as well as retrieval with minimal warm ischemia are the primary concerns of most donor surgeons. We describe our simplified technique of robotic RDH evolved over 144 cases. PATIENTS AND METHODS: Right lobe mobilization is performed in a clockwise manner from right triangular ligament over inferior vena cavae up to hepatocaval ligament. Transection is initiated using a combination of bipolar diathermy and monopolar shears controlled by console surgeon working in tandem with lap CUSA operated by assistant surgeon. With the guidance of indocyanine green cholangiography, RHD is divided with robotic endowrist scissors (Potts), and remnant duct is sutured with 6-0 PDS. Final posterior liver transection is completed caudocranial without hanging manoeuvre. Right lobe with intact vascular pedicle is placed in a bag, vascular structures then divided, and retrieved through Pfannenstiel incision. CONCLUSION: Our technique may be easy to adapt with the available robotic instruments. Further innovation of robotic platform with liver friendly devices could make robotic RDH the standard of care in future.

Middle hepatic vein reconstruction in adult living donor liver transplantation: a randomized clinical trial.

BACKGROUND: In adult right lobe living donor liver transplantation (LDLT), venous drainage of the anterior sector is usually reconstructed on the bench to form a neo-middle hepatic vein (MHV). Reconstruction of the MHV for drainage of the anterior sector is crucial for optimal graft function. The conduits used for reconstruction include cryopreserved allografts, synthetic grafts, or the recipient portal vein. However, the ideal choice remains a matter of debate. This study compares the efficacy of the native recipient portal vein (RPV) with PTFE grafts for reconstruction of the neo-MHV. METHODS: Patients in this equivalence-controlled, parallel-group trial were randomized to either RPV (62 patients) or PTFE (60 patients) for use in the reconstruction of the neo-MHV. Primary endpoint was neo-MHV patency at 14 days and 90 days. Secondary outcomes included 90-day mortality and post-transplant parameters as scored by predefined scoring systems. RESULTS: There was no statistically significant difference in the incidence of neo-MHV thrombosis at 14 days (RPV 6.5 per cent versus PTFE 10 per cent; P = 0.701) and 90 days (RPV 14.5 per cent versus PTFE 18.3 per cent; P = 0.745) between the two groups. Irrespective of the type of graft used for reconstruction, 90-day all-cause and sepsis-specific mortality was significantly higher among patients who developed neo-MHV thrombosis. Neo-MHV thrombosis and sepsis were identified as risk factors for mortality on Cox proportional hazards analysis. No harms or unintended side effects were observed in either group. CONCLUSION: In adult LDLT using modified right lobe graft, use of either PTFE or RPV for neo-MHV reconstruction resulted in similar early patency rates. Irrespective of the type of conduit used for reconstruction, neo-MHV thrombosis is a significant risk factor for mortality. REGISTRATION NUMBER: CTRI/2018/11/016315 (www.ctri.nic.in).

Randomized trial of steroid free immunosuppression with basiliximab induction in adult live donor liver transplantation (LDLT).

BACKGROUND: Corticosteroids are an integral part of immunosuppression following solid organ transplantation, despite their metabolic complications. We conducted a randomized trial to evaluate the efficacy of steroid-free immunosuppression following live donor liver transplantation (LDLT). METHODS: We randomized 104 patients stratified based on pre-transplant diabetic status to either a steroid-free arm (SF-arm) (Basiliximab + Tacrolimus and Azathioprine,n = 52) or Steroid arm (S-Arm) (Steroid + Tacrolimus + Azathioprine,n = 52). The primary endpoint was the occurrence of metabolic complications (new-onset diabetes after transplant (NODAT), new-onset systemic hypertension after transplant (NOSHT), post-transplant dyslipidemia) within 6 months after transplant. Secondary endpoints included biopsy-proven acute rejection (BPAR) within six months, patient and graft survival at 6 months. RESULTS: The incidence NODAT was significantly higher in S-arm at 3 months (64.5%vs. 28.1%,p-0.004) and 6 months (51.6% vs. 15.6%,p-0.006). Likewise, the incidence of NOSHT (27.8% vs. 4.8%,p-0.01) and hypertriglyceridemia (26.7% vs. 8%,p-0.03) at six months was significantly higher in S-arm. However, there were no differences in BPAR (19.2% vs. 21.2%, p-0.81), time to first rejection (58 vs. 53 days, p-0.78), patient and graft survival (610 vs. 554 days,p- 0.22). CONCLUSION: Following LDLT, basiliximab induction with tacrolimus and azathioprine maintenance resulted in significantly lower metabolic complications compared to the triple-drug regimen of steroid, tacrolimus, and azathioprine.

Double-blind placebo-controlled randomized trial of N-acetylcysteine infusion following live donor liver transplantation.

BACKGROUND: The role of N-acetylcysteine (NAC) in improving outcomes following live donor liver transplantation (LDLT) is not well established. We designed a randomized double-blind placebo-controlled trial to study the role of NAC infusion in recipients undergoing LDLT. METHODS: We assigned 150 patients who underwent LDLT by computer-generated random sequence on 1:1 ratio to either NAC group or placebo group. Patients in the NAC group received NAC infusion which was started at beginning of graft implantation at an initial loading dose of 150 mg/kg/h over 1 h, followed by 12.5 mg/kg/h for 4 h and then at 6.25 mg/kg/h continued for 91 h. Placebo group received normal saline. The primary endpoint was composite occurrence of acute kidney injury (AKI) and early allograft dysfunction (EAD) in the recipient. Secondary endpoints included levels of bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, INR, primary graft non-function, intraoperative bleeding, post-transplant hospital stay and in-hospital mortality. RESULTS: The composite endpoint did not show any significant difference between the NAC and placebo group (21.3% vs 29.3%, p = 0.35). Peak AST (425.65 IU/L vs 702.24 IU/L, p = 0.02) and peak ALT (406.65 IU/L vs 677.99 IU/L, p = 0.01) levels were significantly lower in the study group. Time to normalization of transaminases was also significantly low in the study group. CONCLUSIONS: Perioperative NAC infusion following LDLT resulted in significantly lower postoperative AST and ALT levels. Rapid normalization of transaminases was also observed. This, however, did not translate to improvement in AKI or EAD.

Lack of Association of B-type Raf Kinase V600E Mutation with High-risk Tumor Features and Adverse Outcome in Conventional and Follicular Variants of Papillary Thyroid Carcinoma.

INTRODUCTION: Somatic B-type Raf kinase (BRAF) V600E mutation in exon 15 was frequently found in high frequencies associated with papillary thyroid cancer (PTC). The phenotype of these cancers expressed aggressive clinical and pathological features. The present study aimed to assess the prevalence of BRAF V600E mutation among conventional and follicular variants of PTC and its association with aggressive tumor factors and outcome. STUDY DESIGN: Patients who were operated and received further treatment for PTC during 2012 were included in the study. BRAF V600E mutation analysis was done by extracting genomic DNA from tumor tissue. RESULTS: Of the 59 patients included in the study, 51% harbored BRAF V600E mutation, but the mutation status was not associated with aggressive tumor factors and adverse outcome. CONCLUSION: BRAF V600E mutation was not significant predictor of aggressive tumor behavior in conventional and follicular variants of PTC.