Gourab Sen

Risk factors for recurrent primary sclerosing cholangitis after liver transplantation

BACKGROUND & AIMS The association between primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) is well recognised. However, the relationship between IBD and recurrent PSC (rPSC) is less well understood. We assessed the prevalence of rPSC and analysed the factors associated with rPSC post-liver transplantation and its influence on graft and patient survival. METHODS This is a UK multicentre observational cohort study across six of the seven national liver transplant units. All patients undergoing a first liver transplant for PSC between January 1 1990 and December 31 2010 were included. Prospectively collected liver transplant data was obtained from NHSBT and colitis data was retrospectively collected from individual units. RESULTS There were 679 (8.8%) first transplants for PSC. 347 patients (61.4%) had IBD, of which 306 (88.2%) had ulcerative colitis (UC). 81 (14.3%) patients developed rPSC and 37 (48.7%) of them developed graft failure from rPSC. Presence of UC post-liver transplant (HR=2.40, 95% CI 1.44-4.02) and younger age (HR=0.78, 95% CI 0.66-0.93) were the only factors significantly associated with rPSC. rPSC was associated with over a 4-fold increase in the risk of death (HR=4.71, 95% CI 3.39, 6.56) with 1, 5, and 10-year graft survival rates of 98%, 84%, and 56% respectively compared to 95%, 88%, and 72% in patients who did not develop rPSC. CONCLUSION The presence of UC post-liver transplant is associated with a significantly increased risk of rPSC. Furthermore, the presence of rPSC increases the rate of graft failure and death, with higher re-transplantation rates.

Management strategies in isolated pancreatic trauma

AIM In the absence of damage to other organs, pancreatic injury is rare. We have reviewed our experience with isolated pancreatic injury. METHODS Patients treated for isolated pancreatic trauma at our unit were identified prospectively and then retrospectively entered onto a database. The mode of presentation, mechanism of injury and management strategies were reviewed. RESULTS Seven male and four female patients, median age 30 years (range 13-51 years) were treated. All suffered blunt abdominal trauma with different mechanisms of injury, each being characterised by a direct blow to the central abdomen. In two patients, somatostatin analogue treatment used as primary treatment resulted in early resolution of symptoms and signs. Six patients underwent surgery at various stages post-injury. At a median follow-up of 58 months (range 22-106 months), eight patients are asymptomatic, two patients have chronic pain following distal pancreatectomy and one patient has occasional discomfort. CONCLUSION Confirmation of the mechanism of trauma and suspicion of pancreatic injury are essential for early diagnosis and appropriate management. Early contrast computed tomography examination is vital in the recognition of these injuries. Somatostatin analogue therapy may have an important role in the treatment regimen, especially when patients present early after sustaining a pancreatic injury. Only selected patients require open surgery.

Comparison of multislice computed tomography and endoscopic ultrasonography with operative and histological findings in suspected pancreatic and periampullary malignancy

This study compared multislice computed tomography (MSCT) with endoscopic ultrasonography (EUS) in the diagnosis and staging of pancreatic and periampullary malignancy.

N-acetylcysteine administration does not improve patient outcome after liver resection

BACKGROUND Post-operative hepatic dysfunction is a major cause of concern when undertaking a liver resection. The generation of reactive oxygen species (ROS) as a result of hepatic ischaemia/reperfusion (I/R) injury can result in hepatocellular injury. Experimental evidence suggests that N-acetylcysteine may ameliorate ROS-mediated liver injury. METHODS A cohort of 44 patients who had undergone a liver resection and receiving peri-operative N-acetylcysteine (NAC) were compared with a further cohort of 44 patients who did not. Liver function tests were compared on post-operative days 1, 3 and 5. Peri-operative outcome data were retrieved from a prospectively maintained database within our unit. RESULTS Administration of NAC was associated with a prolonged prothrombin time on the third post-operative day (18.4 versus 16.4 s; P = 0.002). The incidence of grades B and C liver failure was lower in the NAC group although this difference did not reach statistical significance (6.9% versus 14%; P = 0.287). The overall complication rate was similar between groups (32% versus 25%; P = ns). There were two peri-operative deaths in the NAC group and one in the control group (P = NS). CONCLUSION In spite of promising experimental evidence, this study was not able to demonstrate any advantage in the routine administration of peri-operative NAC in patients undergoing a liver resection.

Use of a multilayered stent for the treatment of hepatic artery pseudoaneurysm after liver transplantation.

To the Editor: We would like to use this opportunity to share with the wider clinical community our experience in managing a hepatic artery pseudoaneurysm (HAP) of a 59-year-old man after liver transplant using a multilayered stent. HAP is a rare but well-recognised complication occurring after orthotopic liver transplantation (OLT). The reported incidence is 0.3% to 2.6% [1, 2]. The majority of cases of HAP occurring after OLT arise in the context of endovascular intervention or secondary to diathermy injury to the artery during surgery [3]. They have also been reported to complicate other hepato-pancreatico-biliary surgical procedures [4]. With time, the natural history of HAP is of enlargement and an associated risk of rupture, which can be fatal [5]. Patients most commonly present with intraperitoneal bleeding or gastrointestinal haemorrhage secondary to haemobilia; however, incidental and asymptomatic HAP may be recognised [6]. Established management options include surgical ligation and endovascular coil embolisation; however, both of these methods are associated with a significant risk of hepatic ischaemia, which often requires retransplantation [5]. Coronary artery stent-grafts have also been used to treat HAP, often after failure of coil embolisation [7]. The introduction of the Multilayer Aneurysm Repair System (MARS) stent (Cardiatis SA, Belgium) is a recent development in endovascular aneurysm repair. This is an uncovered stent comprised of three-dimensional braided tubing that decreases blood flow velocity in the aneurysmal sac whilst improving laminar blood flow in the main artery and surrounding arterial tributaries [8]. Its use for the treatment of HAP occurring after OLT has not previously been reported. Our case involves a 59 year-old man who underwent OLT for alcoholic cirrhosis in January 2011. The patient’s main indication for OLT was recurrent ascites. A transjugular intrahepatic portosystemic shunt was inserted in November 2010 before emergency surgical repair of a ruptured umbilical hernia. He was transplanted in early January 2011. He received a whole liver from a 74-year-old brainstem-dead donor who was involved in a road-traffic accident. His hepatectomy was performed whilst he was on veno-venous bypass and was uncomplicated. The implantation included a cavocavostomy, end-to-end pulmonary vein anastomosis using 5.0 Prolene (Ethicon, UK) suture material, end-to-end arterial anastomosis to the common hepatic artery using 6.0 Prolene (Ethicon, UK) suture material, and duct-to-duct biliary anastomosis using 5.0 polydioxanone (Ethicon, UK) suture material. The cold ischaemic time was 12 h and 40 min. During surgery, he received 4 U of blood, 1 pool of platelets, and 6 U of fresh frozen plasma. His postoperative recovery was complicated by mild acute cellular rejection on day 10, which required augmentation with intravenous methylprednisolone. He was discharged home on day 16. His immunosuppression medication included tacrolimus, azathioprine, and prednisolone. Because he was a cytomegalovirus mismatch, vanganciclovir was given for 100 days. At 3 months after OLT, the patient was admitted to our hospital for investigation of graft dysfunction. Liver histology showed evidence of perivenular haemorrhage and A. M. Elsharkawy (&) G. Sen M. Hudson S. Masson D. M. Manas Liver Unit, Freeman Hospital, Freeman Road, Newcastle Upon Tyne NE7 7DN, UK e-mail: ahmede@doctors.org.uk

Increase in serum bilirubin levels in obstructive jaundice secondary to pancreatic and periampullary malignancy--implications for timing of resectional surgery and use of biliary drainage.

BACKGROUND Routine preoperative biliary drainage in cases of jaundice secondary to pancreatobiliary malignancy is associated with a significant risk of complications, failure and stent occlusion. It may be possible to avoid biliary drainage in those patients who are not deeply jaundiced. AIMS To measure presenting serum bilirubin and its rate of increase in patients with malignant obstructive jaundice. To predict the urgency with which surgery should be performed to avoid preoperative biliary drainage. PATIENTS AND METHODS Prospective data collection for all pancreatic and periampullary malignancies over a period of 18 months was carried out. Serum bilirubin levels before successful drainage were recorded. Rates of increase in bilirubin and the number of days for bilirubin to reach different thresholds were calculated. RESULTS Of 111 patients, 66 (59%) had resectable disease on imaging investigations. Median serum bilirubin on presentation was 160 micromol/l. Median increase was 13.1 micromol/l/day or approximately 100 micromol/l/week. The predicted number of days for bilirubin levels to reach a variety of thresholds varied significantly. For a patient presenting with a serum bilirubin of 160 micromol/l, the mean number of days for it to rise to 200 micromol/l, 300 micromol/l, 400 micromol/l and 500 micromol/l was 3, 13, 22 and 31 days, respectively. CONCLUSIONS There is a variable window of opportunity in jaundiced patients with pancreatic and periampullary malignancy during which surgery may be performed to avoid biliary drainage procedures, depending on the threshold for operating on the jaundiced patient.

Endoscopic ultrasound in patients with normal liver blood tests and unexplained dilatation of common bile duct and or pancreatic duct

Abstract Objective. To determine the yield of endoscopic ultrasound (EUS) in the investigation of patients with normal liver function tests (LFTs) and unexplained dilatation of common bile duct (CBD) and/or pancreatic duct (PD), following CT and/or magnetic resonance cholangiopancreatography. Materials and methods. Consecutive patients undergoing linear EUS between January 2007 and August 2011 for the indication of dilated CBD and/or PD, normal LFT, and nondiagnostic cross-sectional imaging formed the study group. The study was performed as a retrospective analysis of prospectively collected data. Results. During the study period, 83 patients (CBD and PD dilatation n = 38, PD dilatation n = 5, CBD dilatation n = 40) met the inclusion criteria and underwent EUS. Five (13.1%) of the CBD and PD groups had a new finding, which in one (2.6%) case was causal. In this group, men were significantly more likely to have a new finding (p = 0.012). Eight (20%) of the CBD group had a new finding, which in seven (17.5%) cases was causal. In the CBD group, cholecystectomy was significantly (p = 0.005) more common in those without a finding. Three (60%) of the PD group had a finding on EUS, all of which were causal, including a case of pancreatic malignancy. Conclusion. There is a significant yield from EUS in individuals with isolated PD dilatation and isolated CBD dilatation. Previous cholecystectomy is significantly associated with a negative EUS in the group with isolated CBD dilatation. The yield in those with CBD and PD dilatation was low and a finding was more likely in males.

Laparoscopic Pringle's manoeuvre for liver resection – how I do it

Abstract Although experience with the laparoscopic approach for liver resection has increased in recent years, it still remains a challenging procedure. One of the manoeuvres to reduce catastrophic haemorrhage is occlusion of hepatic inflow by compression of the hepato-duodenal ligament, the so-called Pringles manoeuvre. One of the limitations of laparoscopic liver resection is the safe placement of a tape around the hepato-duodenal ligament to facilitate intermittent clamping of the porta-hepatis (Pringles manoeuvre) prior to hepatic transection. We present a novel, safe and efficient technique that has evolved during this series of laparoscopic liver resections.

Laparoscopic repair of a rare case of falciform ligament herniation.

Epigastric herniation occurs through a weakness in the linea alba from the xiphisternum to the umbilicus. Frequently, the sac is empty or contains a small portion of greater omentum. We report the first case of falciform ligament herniation through an epigsatric hernial defect repaired laparoscopically.

Incidence of De-Novo Donor Specific Anti-Human Leucocyte Antigen (HLA) Antibodies (DSA) in Simultaneous Pancreas Kidney (SPK) Transplant Patients: A comparison between alemtuzumab and basiliximab based immunosuppression regimes

Introduction De-novo Donor Specific Human Leucocyte Antigen (HLA) Antibodies (DSA) are detrimental to organ transplants. Few studies have explored the incidence of DSA’s and subsequent outcomes after SPK transplant, and none have compared different immunosuppression regimes. The aim of this study was to compare two different immunosuppression regimes (Alemtuzumab versus Basiliximab) with regard to the development of DSA and their long-term outcomes. Materials and Methods We introduced Alemtuzumab for all our SPK recipients from March 2008 onwards along with a Tacrolimus and MMF (from day 7) for maintenance. Prior to this, we used Basiliximab along with our standard immunosuppression regime of a CNI, MMF and steroids. We performed a retrospective analysis of all our SPK transplant patients between 2003 – June 2016. DSA were measured as early (within 2 years) and late (>2 years post-transplantation). HLA antibody testing was performed as per clinical need using a Luminex 200 flow cytometer (Luminex, Inc., Austin, TX). Samples were initially screened for the presence or absence of HLA antibodies using Labscreen mixed HLA antibody screening kits (One Lambda Inc., Canoga Park, CA, USA). For all positive and reactive results, HLA antibody specificities were determined using a combination of Lifecodes ID (Immucor USA) and Labscreen single antigen kits (One Lambda Inc.). Data was analysed using Microsoft Excel 2011 and SPSS 23. Chi-square test was used to compare the groups. Results and Discussion A total of 83 SPK transplants were performed Alemtuzumab (n=53) and Basiliximab (n=30). For early DSA, 20 patients were tested in the Basiliximab group; none developed DSA. In contrast, 34% patients (14 out of 41 tested) in the Alemtuzumab group developed early DSA (p=0.009). Of those 14 patients, 3 (21%) lost their kidney grafts, 6 (43%) lost their pancreas and 3 (21%) eventually died. For late DSA, 18 patients were tested in the Basiliximab group and 3 (17%) were found to be positive. 2/3 patients suffered pancreas graft loss, 1 lost the kidney graft and 1 died as a complication of post-transplant lymphoproliferative disorder. In the Alemtuzumab group, 12 (41%) out of 29 tested developed DSA (p=0.077). Out of those 12 patients, 4 (33%) kidneys and 5 (42%) pancreas were lost and 3 (25%) deaths were recorded. 11 patients (92%) out of the 12 who were positive for late DSA, had early DSA as well. Conclusion Patients on an Alemtuzumab based regime had a significantly higher incidence of early DSA in comparison to a Basiliximab based regime in those patients that were tested. A higher proportion continued to develop late DSA in the Alemtuzumab group. The presence of DSA was associated with very high rates of both pancreas and kidney graft loss.