Propensity score matched analysis and risk stratification of donors with G6PD deficiency in living donor liver transplantation.

INTRODUCTION: Glucose 6 phosphate dehydrogenase (G6PD) deficiency (G6PDd) can trigger hemolysis following surgical stress. Differentiating G6PDd-related post-operative hemolytic episodes (PHE) and post-hepatectomy liver failure may be challenging especially in living donors where donor safety is paramount. We analysed outcomes of our cohort of G6PDd liver donors. METHODS: G6PDd individuals with no evidence of hemolysis were considered as living donors if there was no alternative family donor. Outcomes of G6PDd donors undergoing left lateral/left lobe donation (Group LL) and right lobe donation (Group RL) were compared with non-G6PDd donors matched in a 1:3 ratio using propensity score matching. RESULTS: 59 G6PDd donors (5.8% of 1011) underwent living donor hepatectomy (LiDH) during the study period. LL-G6PDd donors (22.37%) had higher post-operative peak bilirubin level compared to matched controls, but no difference in morbidity or need for post-operative blood transfusion.RL-G6PDd donors (37.63%) had higher peak bilirubin level, morbidity (16.2% vs. 3.6%, p = 0.017) and more post-operative blood transfusion (21.6% vs. 6.4%, p = 0.023) as compared to matched non-G6PDd cohort. Four RL-G6PDd donors (10.8%) developed PHE. Low G6PD activity (15% vs. 40%, p = 0.034) and lower future liver remnant (FLR) (34.3% vs. 37.8%, p = 0.05) were identified as risk factors for PHE. CONCLUSION: We report the largest to-date series of G6PDd individuals undergoing LiDH and confirm the safety of LL donation in G6PDd. Our analysis identifies specific risk factors for PHE and suggests that right lobe LiDH be avoided in individuals with less than 25% G6PD activity when the FLR is less than 36%.

Review of the validity of DOPS as an assessment tool for the procedural skills of surgical trainees.

INTRODUCTION: Surgical trainees at all stages are mandated to use workplace-based assessments (WBAs) to gain feedback from their trainers. Direct observation of procedural skills (DOPS) is a tool to assess hands-on surgical skills. This review of the literature seeks to ascertain how valid DOPS are as an assessment tool for the procedural skills of surgical trainees according to the American Psychology Association (APA) validity framework. METHODS: Relevant literature was identified through a structured search of Medline, CINAHL and Web of Science databases, with further papers included on citation review. Following this, papers meeting the inclusion and exclusion criteria were included in the final review specifying those investigating WBAs including DOPS, assessments in practice rather than simulation and specifically for postgraduate surgical trainees. FINDINGS: Sixteen papers were included in the final analysis. Extracted data from the returned papers were assessed for evidence of validity in each of the five domains on the APA framework: validity based on consequence, response process, reliability, content and relationship to other variables. There are studies that show good parameters for reliability and validity for specific DOPS used in endoscopy and otolaryngology. However, there is confusion over the purpose of DOPS among trainers and trainees as to whether they should be used formatively or summatively. Recent changes to the surgical curriculum have sought to address this, and further work into the impact of this needs to be done.

Living Donor Liver Transplantation for Budd-Chiari Syndrome: A Propensity Score-Matched Analysis.

INTRODUCTION: There are unique technical and management challenges associated with living donor liver transplantation (LDLT) for Budd-Chiari Syndrome (BCS). The outcomes of LDLT for BCS in comparison to other indications remain unclear and warrant elucidation. METHODS: Data of 24 BCS patients who underwent LDLT between January 2012 and June 2019 were analyzed. There were 20 adults and 4 children. The early and long-term outcomes of adult LDLT BCS patients were compared to a control group of LDLT patients for other indications and matched using propensity scoring methodology. RESULTS: Primary BCS was observed in 18 (90%) patients. Caval replacement was performed in 7 (35%) patients. Early and late hepatic venous outflow tract (HVOT) complications were seen in 1 (5%) and 3 (15%) patients. Preoperative acute kidney injury was identified as a risk factor for mortality in the BCS cohort (p = 0.013). On comparison, BCS recipients were younger with fewer comorbidities, more large volume ascites and higher rates of PVT. They also had longer cold ischemia time, increased blood loss and transfusion requirements, increased hospital stay, and higher late outflow complications. The 1-year and 3-year survivals were similar to non-BCS cohort (84.2% vs. 94% and 71.3% vs. 91.9%, respectively, log rank test p = 0.09). CONCLUSION: LDLT is a good option for symptomatic BCS who have failed non-transplant interventions. The clinical and risk factor profile of BCS recipients is distinct from non-BCS recipients. By following an algorithmic management protocol, we show on propensity-score matched analysis that outcomes of LDLT for BCS are similar to non-BCS indications.

Ranking list for scientists: From heightening the rat-race to fraying the scientific temper.

Citations and validation of work play a crucial and integral role in a researcher's career. Ranking systems of scientists, on the other hand, potentially scratch and expose the fallible egoistic human face of science, leading to an unhealthy milieu of competition rather than the uplifting one of motivation. We have attempted to highlight and bring to fore these factors in our brief viewpoint. We critically analyze the reasons why ranking systems of scientists, especially in the field of medicine, will shift the focus from advancement of science to advancement of "self."

Optimal diagnostic tool for surveillance of oesophageal varices during COVID-19 pandemic.

AIM: To study the diagnostic accuracy and utility of triphasic abdominal computed tomography (CT) in the diagnosis and grading of oesophageal varices (OVs) as an alternative to endoscopy during the COVID-19 pandemic. MATERIALS AND METHODS: A prospective analysis was undertaken of retrospective data from cirrhotic patients who underwent oesophago-gastro-duodenoscopy (OGD) and a triphasic abdominal CT from January to December 2019. Endoscopists and radiologists provided their respective independent assessment of OV grading after being blinded to the clinical details. Performance of CT grading of OVs was compared with the reference standard endoscopic grading using weighted kappa (k). Non-invasive scores such, as aspartate transaminase (AST)-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4) Index, platelet: spleen (PS) ratio were correlated between the two techniques. RESULTS: OV grading between endoscopists and radiologists showed 81.73% agreement (85 out of 104 patients) in the comparative analysis of 104 cirrhotic patients, of which no varices (57.1%, n=4), small (85.1%, n=23), medium (72.2%%, n=26), and large varices (94.1%, n=32) with a weighted k score of 0.88 (95% confidence interval 0.82-0.94). Overall, the sensitivity of CT in the diagnosis of no, small, medium, and large OVs was 66.6%, 79.3%, 89.6%, and 94.1%, respectively, with an area under the receiver operating curve (AUROC) score of 0.775, 0.887, 0.839, and 0.914. Performance of APRI, FIB-4, and PS ratio correlated well with the severity of OVs with no difference between OGD and CT grading. CONCLUSION: Triphasic abdominal CT can be an invaluable tool in the diagnosis and grading of OVs during the COVID-19 pandemic.

Outcomes for high-risk hepatoblastoma in a resource-challenged setting.

BACKGROUND: Outcomes of high-risk hepatoblastoma have been dismal, especially in resource-challenged countries where access to chemotherapy and paediatric liver transplantation is limited for the underprivileged. This study aimed to assess the results of treatment of high-risk hepatoblastoma in a tertiary centre, including patients who had non-transplant surgical procedures in the form of extended resection. METHODS: A review of patients with high-risk hepatoblastoma treated between January 2012 and May 2018 was carried out. Perioperative data and long-term outcomes were analysed. RESULTS: Of 52 children with hepatoblastoma, 22 were considered to have high-risk hepatoblastoma (8 girls and 14 boys). The mean(s.d.) age at diagnosis was 35(20) months. Of these 22 children, five died without surgery. Of the remaining 17 who underwent surgery, six had a resection (4 right and 2 left trisectionectomies) and 11 underwent living-donor liver transplantation. Median follow-up was 48 (range 12-90) months. Thirteen of the 17 children were alive at last follow-up and four developed disseminated disease (3 had undergone liver transplantation and 1 liver resection). The overall survival rate at 1, 3 and 5 years was 77, 64 and 62 per cent for the whole cohort with high-risk hepatoblastoma. In children who had surgery, 1-, 3- and 5-year survival rates were 91, 82 and 73 per cent for transplantation and 100, 83 and 83 per cent for resection. There was no difference in survival between the two surgical groups. CONCLUSION: Excellent results in the treatment of high-risk hepatoblastoma are possible, even in resource-challenged countries.

ANTECEDENTES: Los resultados del hepatoblastoma de alto riesgo (high risk hepatoblastoma, HRH) han sido pésimos, especialmente en países con recursos limitados, donde el acceso a la quimioterapia y al trasplante hepático pediátrico es limitado para los menos privilegiados. Este estudio tuvo como objetivo evaluar los resultados del HRH en un centro de tercer nivel, incluyendo a los pacientes que se sometieron a procedimientos quirúrgicos diferentes del trasplante en forma de resecciones extendidas. MÉTODOS: Se realizó una revisión de los pacientes con HRH tratados entre enero del 2012 y mayo de 2018. Se analizaron los datos perioperatorios y los resultados a largo plazo. RESULTADOS: De 52 niños con hepatoblastomas, 22 fueron considerados HRH (8 pacientes del sexo femenino/14 del sexo masculino). La edad media al diagnóstico fue de 35 ± 20 meses. De estos 22 pacientes, cinco fallecieron sin haber sido intervenidos quirúrgicamente. De los 17 restantes que se sometieron a cirugía, en seis se realizaron resecciones (4 trisectorectomías derechas, 2 trisectorectomías izquierdas) y 11 se sometieron a un trasplante de hígado de donante vivo. La mediana de seguimiento fue de 48 meses (12-90 meses). Trece de 17 niños estaban vivos en el último seguimiento, y cuatro habían desarrollado enfermedad diseminada (3 habían sido sometidos a trasplante hepático y 1 a resección hepática). La supervivencia global a 1, 3 y 5 años fue del 77,3%, 63,6% y 62% para toda la cohorte de HRH. Entre los que se sometieron a cirugía, las supervivencias a 1, 3 y 5 años fueron del 90,9%, 81,8% y 72,7% para el trasplante y del 100%, 83,3% y 83,3% para la resección. No hubo diferencia en la supervivencia entre los dos grupos sometidos a cirugía. CONCLUSIÓN: En países con recursos limitados es posible obtener excelentes resultados en el tratamiento de HRH.

Ischemic Cholangiopathy: Insight From an Explant Liver Allograft Affected by Severe Post-transplant Hypoxemia Due to Hepatopulmonary Syndrome: A Case Report.

Increased biliary complications in hepatopulmonary syndrome (HPS) have been hypothesized due to post-transplant hypoxemia. Supporting this hypothesis, we report histopathological findings from an explant liver allograft where the recipient suffered severe and prolonged post-operative hypoxemia. A 4-year-old child underwent liver transplantation (LT) for decompensated chronic liver disease complicated by severe HPS. The post-operative period was complicated by severe prolonged hypoxemia. HPS resolved completely 6 months after LT only to recur 3 months later due to graft dysfunction. The child underwent retransplantation 8 months after the first LT. The explant liver showed bile duct loss along with ulceration and fibrosis of large hilar bile ducts biliary, suggestive of ischemic cholangiopathy. Based on the histopathology findings, we suggest that severe prolonged hypoxemia during post-transplant period could cause ischemic cholangiopathy, which can lead to biliary complications.

Auxiliary partial orthotopic liver transplantation for acute liver failure.

INTRODUCTION: Auxiliary partial orthotopic liver transplantation (APOLT) in acute liver failure acts as a bridge to native liver regeneration with potential for immunosuppression free survival. While technical concerns limit its universal acceptance, the indications in acute liver failure also need to be examined for this procedure to ultimately succeed. CASE HISTORY: We present the case of an eight-month-old girl with cryptogenic acute liver failure who underwent APOLT. She developed postoperative liver dysfunction, most likely owing to the persistence of the diseased native liver, ultimately leading to an orthotopic retransplantation. She remains well on follow-up review. CONCLUSIONS: A tempered approach to selecting patients for APOLT (especially with regard to aetiology of acute liver failure) makes it a safe and effective alternative to orthotopic liver transplantation.

Chemical and structural analysis of gallstones from the Indian subcontinent.

Representative gallstones from north and southern parts of India were analyzed by a combination of physicochemical methods: X-ray diffraction (XRD), infrared spectroscopy (IR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), CHNS analysis, thermal analysis and Nuclear Magnetic Resonance (NMR) spectroscopy (1H and 13C). The stones from north Indian were predominantly consisting of cholesterol monohydrate and anhydrous cholesterol which was confirmed by XRD analysis. FTIR spectroscopy confirmed the presence of cholesterol and calcium bilirubinate in the south Indian gallstones. EDX spectroscopy revealed the presence of carbon, nitrogen, oxygen, calcium, sulfur, sodium and magnesium and chloride in both south Indian and north Indian gallstones. FTIR and NMR spectroscopy confirmed the occurrence of cholesterol in north Indian gallstones. The respective colour of the north Indian and south Indian gallstones was yellowish and black. The morphology of the constituent crystals of the north Indian and south Indian gallstones were platy and globular respectively. The appreciable variation in colour, morphology and composition of south and north Indian gallstones may be due to different food habit and habitat.

Improving the Diagnostic Criteria for Primary Liver Graft Nonfunction in Adults Utilizing Standard and Transportable Laboratory Parameters: An Outcome-Based Analysis.

Current diagnostic criteria for primary nonfunction (PNF) of liver grafts are based on clinical experience rather than statistical methods. A retrospective, single-center study was conducted of all adults (n = 1286) who underwent primary liver transplant (LT) 2000-2008 in our center. Laboratory variables during the first post LT week were analyzed. Forty-two patients (3.7%) had 2-week graft failure. Transplant albumin, day-1 aspartate aminotransferase (AST), day-1 lactate, day-3 bilirubin, day-3 international normalized ratio (INR), and day-7 AST were independently associated with PNF on multivariate logistic regression. PNF score =(0.000280*D1AST)+ (0.361*D1 Lactate)+(0.00884*D3 Bilirubin)+(0.940*D3 INR)+(0.00153*D7 AST)-(0.0972*TxAlbumin)-4.5503. Receiver operating curve analysis showed the model area under receiver operating curve (AUROC) of 0.912 (0.889-0.932) was superior to the current United Kingdom (UK) PNF criteria of 0.669 (0.634-0.704, p < 0.0001). When applied to a validation cohort (n = 386, 34.4% patients), the model had AUROC of 0.831 (0.789-0.867) compared to the UK early graft dysfunction criteria of 0.674 (0.624-0.721). The new model performed well after exclusion of patients with marginal grafts and when modified to include variables from the first three post-LT days only (AUROC of 0.818, 0.776-0.856, p = 0.001). This model is superior to the current UK PNF criteria and is based on statistical methods. The model is also applicable to recipients of all types of grafts (marginal and nonmarginal).

Outcome of partial internal biliary diversion for intractable pruritus in children with cholestatic liver disease.

PURPOSE: Children with cholestatic disorders have undergone liver transplantation for intractable pruritus unresponsive to medical therapy even in the absence of liver failure. Biliary diversion procedures interrupt the entero-hepatic circulation of bile acids allowing them to be excreted in the feces thereby lowering the total bile acid pool. We evaluated the outcome of partial internal biliary diversion (PIBD) in children with intractable pruritus from inherited cholestatic disorders. METHODS: The records of children who underwent PIBD over a 4-year period were reviewed for etiology of liver disease, demographic data, preoperative and postoperative biochemical profile and improvement of pruritus. Standard statistical methods were used for analysis. RESULTS: Of the 12 children, 10 had progressive familial intrahepatic cholestasis (PFIC) and 2 had Alagille syndrome (AS). PIBD was done using an isolated jejunal loop as a conduit from gall bladder to mid ascending colon. Median period of follow up was 30 months. Pruritus resolved in nine children with significant reduction of serum bile acids (P < 0.02). CONCLUSION: To our knowledge, this is the largest reported series of children with PIBD. PIBD is a safe, well-tolerated and effective alternative to liver transplant in children with PFIC and AS who have intractable pruritus in the absence of synthetic liver failure.

Surgical management of hepatic arterioportal fistula in a neonate.

Congenital arterioportal fistulae in the liver are rare malformations which can lead to portal hypertension. We report a hepatic arterioportal fistula in a neonate who presented with intestinal hypoperfusion. Computerised tomography angiography showed a fistulous communication between the left hepatic artery and portal vein with hypoperfusion of small and large bowel. A formal left hepatectomy was done followed by clinical improvement and reduction in portal venous pressures. The case and the literature pertaining to it are discussed.

Prediction models of donor arrest and graft utilization in liver transplantation from maastricht-3 donors after circulatory death.

Shortage of organs for transplantation has led to the renewed interest in donation after circulatory-determination of death (DCDD). We conducted a retrospective analysis (2001-2009) and a subsequent prospective validation (2010) of liver Maastricht-Category-3-DCDD and donation-after-brain-death (DBD) offers to our program. Accepted and declined offers were compared. Accepted DCDD offers were divided into donors who went on to cardiac arrest and those who did not. Donors who arrested were divided into those producing grafts that were transplanted or remained unused. Descriptive comparisons and regression analyses were performed to assess predictor models of donor cardiac arrest and graft utilization. Variables from the multivariate analysis were prospectively validated. Of 1579 DCDD offers, 621 were accepted, and of these, 400 experienced cardiac arrest after withdrawal of support. Of these, 173 livers were transplanted. In the DCDD group, donor age < 40 years, use of inotropes and absence of gag/cough reflexes were predictors of cardiac arrest. Donor age >50 years, BMI >30, warm ischemia time >25 minutes, ITU stay >7 days and ALT ≥ 4× normal rates were risk factors for not using the graft. These variables had excellent sensitivity and specificity for the prediction of cardiac arrest (AUROC = 0.835) and graft use (AUROC = 0.748) in the 2010 prospective validation. These models can feasibly predict cardiac arrest in potential DCDDs and graft usability, helping to avoid unnecessary recoveries and healthcare expenditure.

High model for end-stage liver disease score as a predictor of survival during long-term follow-up after liver transplantation.

BACKGROUND: The allocation of cadaveric livers for transplantation in the United States is now based on the severity of illness as determined by the Model for End-Stage Liver Disease (MELD), which was developed to predict short-term mortality in patients with cirrhosis. However, its impact to predict posttransplantation survival is controversial. The objective of this study was to determine the association of various pretransplantation risk factors, including the MELD score and whether its use to allocate organs is likely to lead to overall poorer outcomes of liver transplantation. METHODS: The 1,032 consecutive adult liver transplantation patients at King's College Hospital between 2 January 1994 and 29 December 2001 were examined for 9 preoperative risk factors, including MELD score, using univariate and multivariate techniques. Based on their pretransplantation MELD scores, we categorized recipients as low (<15) medium (15-25), or high (>25). Kaplan-Meier patient survival analysis was used to identify differences in outcomes. RESULTS: The patients had a mean age of 47.2 years and mean posttransplantation follow-up of 5.3 years. Univariate analysis showed recipient diabetes mellitus, renal dysfunction, and pretransplantation MELD score to be associated with patient survival. Multivariate analysis showed the MELD score to be significantly associated with death during long-term follow-up. CONCLUSIONS: A high pretransplantation MELD score was associated with poor posttransplantation outcomes.

The use of TachoSil in children undergoing liver resection with or without segmental liver transplantation.

INTRODUCTION: Local haemostatic agents are used for the control of surgical haemorrhage when standard techniques are inadequate, but there are few studies of these products in children. PATIENTS AND METHODS: This was a prospective, open-label study in which children (aged 4 weeks to 6 years) undergoing liver resection with or without segmental liver transplantation were treated with TachoSil, a collagen patch coated with a dry layer of human fibrinogen and human thrombin, if minor (i. e., oozing) or moderate bleeding was present after primary haemostatic treatment. Time to haemostasis after TachoSil application was the primary endpoint. Safety was assessed by adverse events (AEs), including post-operative infections, symptoms of graft rejection and re-operations. RESULTS: Enrolment was stopped early after 16 children had entered the study. 13 children underwent whole liver resection and transplantation and 3 patients underwent segmental resection. Satisfactory haemostasis was achieved in 13 children (81.3%; 95% CI: 61.8-100%) at 3 min and in 1 child at 8 min. Occurrence of AEs was as expected, with most being known complications of the underlying disease, surgical procedure, or use of immunosuppressive medication. No AEs were considered to be related to the use of TachoSil. CONCLUSIONS: The use of TachoSil for haemostasis after primary haemostatic treatment appears to be safe and effective in children undergoing liver resection.

Manganese-enhanced MRI predicts the histological grade of hepatocellular carcinoma in potential surgical candidates.

AIM: To evaluate the role of manganese-enhanced magnetic resonance (Mn-MRI) in predicting tumour differentiation prior to liver transplant or resection for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The inclusion criteria were patients with HCC who underwent Mn-MRI prior to transplantation or resection from 2001-2008. T1-weighted MRI images were acquired at 0 and 24h after manganese dipyridoxal diphosphate (MnDPDP) intravenous contrast medium and reviewed prospectively. Manganese retention at 24h was correlated with tumour differentiation and disease-free survival. RESULTS: Eighty-six patients underwent Mn-MRI (transplantation 60, resection 26); 114/125 lesions (91%) that were arterialised as evidenced at computed tomography (CT) and had manganese uptake on MRI were HCC. There were 11 false positives (9%) that were regenerative nodules. Ten of fourteen non-manganese-retaining HCC (71%) were poorly differentiated, compared with only 13/114 manganese-retaining HCC (11%) (p<0.0001). Sensitivity, specificity, positive and negative predictive values of non-retention of MnDPDP in predicting poorly differentiated tumours were 0.43, 0.96, 0.71 and 0.88. Median disease-free survival of patients with non-manganese-retaining HCC was less than for patients with manganese-retaining HCC (14±5 months versus 39±3 months, log rank p=0.025). CONCLUSION: Non-manganese-retaining HCCs are likely to be poorly differentiated and have a poor prognosis. Manganese-enhanced MRI appears to have a role in preoperative assessment of HCC and warrants further evaluation.

Living related liver transplantation in children.

BACKGROUND: Living related liver transplantation (LRLT) has become established for treating children with end-stage liver disease. The aim of this study was to review a single-centre experience of left lateral segment liver transplants from living donors in children. METHODS: Fifty left lateral segment LRLT procedures have been performed since 1993. There were 17 girls and 33 boys, of median age 1.5 years (range 0.5 to 13 years), with a median weight of 10 (range 0.7-44) kg. Donors included 23 mothers, 26 fathers and one uncle, with a median age of 33 (range 19-46) years. RESULTS: At a median follow-up of 86 months, there was no donor mortality and low morbidity. Patient and graft survival rates were 98, 96 and 96 per cent, and 98, 96 and 93 per cent at 1, 3 and 5 years respectively. Three children had a second transplant at a median of 9 years after the first. The incidence of hepatic artery thrombosis, portal vein thrombosis and biliary complications was 6, 4 and 14 per cent respectively. CONCLUSION: Living related liver transplantation has good long-term results in children.