Andreas Prachalias

Liver transplantation in adults coinfected with HIV

OBJECTIVE To report our experience of prospectively identifying and transplanting livers into HIV-positive patients. DESIGN Liver transplantation in HIV-positive patients remains controversial. The finding of HIV is usually considered a contraindication to any form of transplantation. Previously reported cases are few and refer to patients who tested HIV positive after they had their liver transplantations or who seroconverted in the posttransplantation period. This is, to our knowledge, the only report of patients who were known to be HIV positive at the time of decision for listing for transplantation. METHODS The medical records of five HIV-positive patients who received liver transplants in Kings College Hospital, London, during a 5-year period (January 1995-December 1999) were reviewed. All five were known to be HIV positive at the time of listing for liver replacement. Three of them had end-stage liver disease due to hepatitis C (two of them had underlying Hemophilia A) while the other two had acute liver failure, one due to hepatitis B infection and one due to nonA-nonB-nonC hepatitis. In all but one patient the HIV infection had been asymptomatic. RESULTS All patients survived the immediate posttransplantation period, but the three patients with hepatitis C died of complications of recurrent hepatitis C between 6 and 25 months posttransplantation. The other two patients are currently alive 4 and 34 months posttransplantation with good graft function and without complications from their HIV infection. CONCLUSION The early outcome of liver transplantation in HIV seropositive patients can be good, and patients should not be excluded from transplantation if their liver disease determines their prognosis. More effective antiviral therapy for hepatitis C given posttransplantation, and for hepatitis B reinfection, should improve the longer-term outcome of HIV patients with end-stage liver disease due to hepatitis.

Biliary complications after liver transplantation using grafts from donors after cardiac death: results from a matched control study in a single large volume center.

Objective:To assess the incidence and impact of biliary complications in recipients transplanted from donors after cardiac death (DCD) at one single large institution. Background:Shortage of available cadaveric organs is a significant limiting factor in liver transplantation (LT). The use of DCD offers the potential to increase the organ pool. However, early results with DCD liver grafts were associated with a greater incidence of ischemic cholangiopathy (IC), leading to several programs to abandoning this source of organs. Methods:A retrospective analysis of a prospective database from April 2001 to 2010 focused on 167 consecutive DCD-LT. Each DCD transplant was matched with 2 brain death donors (DBD) grafts (n = 333) according to the period of transplantation. Primary outcome measures were biliary complications including the severity of complications, graft survival and patient survival. Minimum follow-up was 3 months. Results:Anastomotic stricture was the most common biliary complication (DCD = 30, 19% vs. DBD = 41, 13%). Most were treated endocoscopically (grade IIIa = 72%), whereas hepatico-jejunostomy (grade IIIb) was performed in 22%. Primary IC occurred in 4 (2.5%) recipients from the DCD group and was absent in the DBD group (P = 0.005). However, none of these patients required retransplantation. Patient and graft survival at 1, 3, and 5 years were similar between DCD and DBD groups (P = 0.106, P = 0.138, P = 0.113, respectively). Conclusions:The encouraging results with DCD-LT are probably due to the selection of DCD grafts and clear definition of warm ischemia.

Scoring System to Predict Pancreatic Fistula After Pancreaticoduodenectomy: A UK Multicenter Study

OBJECTIVE To validate a preoperative predictive score of postoperative pancreatic fistula (POPF). Other risk factors for POPF were sought in an attempt to improve the score. BACKGROUND POPF is the major contributor to morbidity after pancreaticoduodenectomy (PD). A preoperative score [using body mass index (BMI) and pancreatic duct width] to predict POPF was tested upon a multicenter patient cohort to assess its performance. METHODS Patients undergoing PD at 8 UK centers were identified. The association between the score and other pre-, intra-, and postoperative variables with POPF was assessed. RESULTS A total of 630 patients underwent PD with 141 occurrences of POPF (22.4%). BMI, perirenal fat thickness, pancreatic duct width on computed tomography and at operation, bilirubin, pancreatojejunostomy technique, underlying pathology, T stage, N stage, R status, and gland firmness were all significantly associated with POPF. The score predicted POPF (P < 0.001) with a higher predictive score associated with increasing severity of POPF (P < 0.001). Stepwise multivariate analysis of pre-, intra-, and postoperative variables demonstrated that only the score was consistently associated with POPF. A table correlating the risk score to actual risk of POPF was created. CONCLUSIONS The predictive score performed well and could not be improved. This provides opportunities for individualizing patient consent and selection, and treatment and research applications.

Primary pancreatic lymphoma: diagnostic and therapeutic dilemma.

Objectives: Non-Hodgkin lymphoma predominantly involving the pancreas is a rare tumor and accounts for less than 0.7% of all pancreatic malignancies and 1% of extranodal lymphomas. Diagnosis of primary pancreatic lymphoma can be difficult because it may mimic carcinoma. The principal aims of this review were to highlight the difficulties encountered in making a diagnosis and to identify the role of surgery. Methods: A PubMed search was conducted using the following terms: primary pancreatic lymphoma and non-Hodgkin lymphoma of the pancreas. Additional references were sourced from key articles. Results: A total of 89 reported cases of pancreatic lymphoma between 1951 and 2005 were reviewed. An accurate preoperative diagnosis of primary pancreatic lymphoma is not always possible. A complete response rate of 100% and a long-term survival rate of 94% have been reported with surgery and adjuvant chemotherapy when compared with a 5-year survival rate of less than 50% and an overall 3-year disease-free survival rate of 44% with current chemotherapy, radiotherapy, or combined methods. Conclusion: Pancreaticoduodenectomy may have a therapeutic role in association with chemotherapy.

Liver transplantation for alpha-1-antitrypsin deficiency in children.

Abstract Alpha‐1‐antitrypsin (a1‐ AT) deficiency is an inborn error of metabolism, which can cause liver disease. The condition is one of the most common genetic disorders in the Caucasian population. Here we review our experience with 21 children suffering from end‐stage liver disease due to a1‐AT deficiency. All children are PIZZ homozygotes. Nineteen of them initially presented with neonatal jaundice and two with hepatosplenomegaly in childhood. Twenty‐five liver transplantions were performed. All children are currently alive at a median follow‐up of 40 months. Liver replacement provides the only definite treatment for children with end‐stage liver disease associated with a1‐AT deficiency. Excellent results can be achieved by reducing waiting time for transplantation and by early referral to a liver transplant centre.

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.

Extracorporeal membrane oxygenation for refractory hypoxemia after liver transplantation in severe hepatopulmonary syndrome: A solution with pitfalls

According to a recent publication by Nayyar et al., severe hypoxemia after liver transplantation (LT) in patients with hepatopulmonary syndrome (HPS) is not uncommon. According to a review of the literature and the authors’ local institutional experience, the prevalence could be as high as 12% with a mortality rate of 45%. Very severe preoperative hypoxemia, defined as a partial pressure of oxygen 50 mm Hg, and the presence of anatomical shunts were identified as predictors of this complication. Among the possible treatment strategies, the authors reported the use of inhaled vasodilator agents and systemic vasoconstrictors such as methylene blue to improve ventilation perfusion matching. The effectiveness of specific rescue ventilation strategies such as high-frequency oscillatory techniques and ventilation in the prone position remains unproven. We would like to propose another potentially beneficial treatment and bridging strategy: venovenous (V-V) extracorporeal membrane oxygenation (ECMO). Long-term ECMO support in this population after transplantation, solely for treating refractory shunt, has thus far not been reported in adults. Cannulation for ECMO after LT can also pose a significant challenge that depends on the configuration used. We have used ECMO in 6 patients (5 adults and 1 child) before and after LT since December 2012. Three patients required extracorporeal cardiac support, whereas the other 3 patients underwent V-V ECMO for hypoxemic respiratory failure. Ethical approval for the reporting of anonymous data was given by the South East London Research Ethics Committee.

Graft positioning at liver transplantation in situs inversus

Situs inversus (SI) totalis is a rare congenital anomaly. In the past it was considered an absolute contraindication to liver transplantation (LT) because of associated malformations, and difficulty achieving accurate graft positioning. We describe successful outcome following LT in a 41-year-old with alcoholrelated chronic liver disease and complete SI using a novel technique (Fig. 1). Recipient hepatectomy was uncomplicated. A donor whole liver was implanted using a piggyback technique. Reduced space in the right upper quadrant from the stomach and spleen resulted in 40% clockwise graft rotation. To attenuate this effect, the left diaphragm was plicated and a Sengstaken-Blakemore tube was inserted percutaneously into the left upper quadrant (LUQ). The gastric balloon was inflated with 400 ml of normal saline to support the left lobe (Fig. 2). The donor remnant falciform ligament was fixed to the recipient diaphragmatic surface to effect long-term optimal positioning. Abdominal CT scan on day 7 demonstrated the gastric balloon elevating and supporting the graft (Figure 3). On day 12, 200 ml of normal saline was aspirated with gradual balloon deflation over the next 3 days, and removal of the Sengstaken-Blakemore tube on day 15. Serial Doppler ultrasonography demonstrated normal hepatic venous flow. An abdominal CT scan at 3 months demonstrated no change in graft position (Figure 4A). The hepatic veins, portal vein and hepatic artery appeared patent (Figure 4B). The patient remains well 17 months following LT with normal graft function. Abdominal SI is described in association with the polysplenia syndrome with inferior vena caval absence, preduodenal portal vein, midgut malrotation, aberrant hepatic arterial anatomy, and portal vein hypoplasia. Anatomic anomalies result in a more complex recipient hepatectomy. Consideration has to be given to correct donor graft positioning, and additional vascular reconstruction. However, LT has been performed successfully using modified surgical techniques. Most cases are in the paediatric population in whom graft displacement and hepatic venous pedicle torsion are less due to a smaller abdominal cavity when even split and reduced grafts are typically large-for-size, and greater use of caval replacement techniques. Cadaveric segmental and living related left lateral segment grafts have been successfully placed with suitable orientation for hilar vessel anastomoses. However, in adults following recipient hepatectomy, a large empty space exists in the LUQ predisposing to lateral displacement with supero-lateral graft rotation and torsion of the hepatic venous pedicle particularly with a piggyback technique. Split, reduced, and right lobe living related LT have been performed successfully. Technical modifications with an intact recipient cava include piggyback implantation over the right suprahepatic vein with orthotopic graft position, and graft rotation by 90°. In our patient, only partial volume reduction of the left hepatic fossa was achieved by diaphragmatic plication. Due to its large size, filling the defect with omentum and mobilized hepatic flexure would have been inadequate. The use of a Sengstaken-Blakemore tube represents an innovative and simple technique to provide effective graft support, and reduce the risk of outflow obstruction. Subsequent peri-hepatic adhesion formation and migration of bowel loops into the LUQ would be expected to provide longterm graft fixation.

Developing a donation after cardiac death risk index for adult and pediatric liver transplantation

AIM To identify objective predictive factors for donor after cardiac death (DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index (DCD-RI) to help in prospective decision making on organ use. METHODS The model included objective data from a single institute DCD database (2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated. RESULTS DCD graft survival predictors were primary indication for transplant (P = 0.066), retransplantation (P = 0.176), MELD > 25 (P = 0.05), cold ischemia > 10 h (P = 0.292) and donor hepatectomy time > 60 min (P = 0.028). According to the calculated DCD-RI score three risk classes could be defined of low (DCD-RI < 1), standard (DCD-RI 2-4) and high risk (DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively. CONCLUSION The DCD-RI score independently predicted graft loss (P < 0.001) and the DCD-RI class predicted graft survival (P < 0.001).

Does Donation After Cardiac Death Utilization Adversely Affect Hepatocellular Cancer Survival

Background Hepatocellular cancer (HCC) is an established indication for liver transplantation. This group is often allocated a donor after cardiac death (DCD) liver as a solution for waiting times. There are concerns that this approach may oncologically disadvantage HCC recipients. The aim of this study was to determine whether DCD transplantation was associated with poorer cancer-related survival in HCC. Methods Study population was from a single institute (2001-2014) with an HCC listing diagnosis. Variables related to recipient, tumor, and graft were analyzed to determine association with HCC death. Results There were 347 recipients listed for HCC of which 91 received a DCD. Donor after cardiac death and donor after brain stem death (DBD) had equivalent 1-, 3-, and 5-year overall (P = 0.115) and cancer-specific survival (P = 0.7). On univariate analysis recipient age, sex, model for end stage liver disease, viral etiology had no bearing on the risk of HCC death. Neither did the graft variables of type (DCD vs DBD), donor age, steatosis, cold ischemic time, peak aspartate transaminase, day 5 bilirubin or international normalized ratio after transplant. Only tumor variables of alpha-fetoprotein, number, total diameter, microvascular invasion, and differentiation were predictors of HCC death. On multivariate analysis, predictors of HCC death remained tumor number (P = 0.002), total diameter of tumor(s) (P < 0.001), microvascular invasion (P = 0.025), and poor differentiation (P = 0.021). Conclusions Donor liver quality in terms of graft type (DCD) has no influence on cancer related survival in transplant for HCC (hazards ratio, 1.143; 95% confidence interval, 0.528-2.423; P = 0.752).