Severe Cholestasis Predicts Recurrent Primary Sclerosing Cholangitis Following Liver Transplantation.

BACKGROUND AIMS: Primary sclerosing cholangitis (PSC) may reoccur following liver transplantation (LT) and the diagnosis established once imaging studies demonstrate the diagnostic cholangiographic appearance. To evaluate whether the development of recurrent PSC (rPSC) is associated with cholestasis soon after LT, we studied whether changes in hepatic biochemistry within the first 12 months were linked with the development of rPSC and graft loss. METHODS: We conducted a retrospective cohort analysis of 158 transplant recipients with PSC in Canada, and 549 PSC transplant recipients from the United Kingdom. We evaluated serum liver tests within 12 months after LT and the subsequent development of a cholangiographic diagnosis of rPSC as a time-dependent covariate using Cox regression. Severe cholestasis was defined as either alkaline phosphatase> 3xupper limit of normal or total bilirubin> 100 µmol/L. RESULTS: Patients who developed rPSC were more likely to have severe cholestasis versus those without at 3 months (20.5% vs 8.2%, p=0.011), at 6 months (17.9% vs. 10.0%, p=0.026) and 12 months (15.4% vs. 7.8%, p=0.051) in the Canadian cohort and at 12 months in the UK cohort (27.9% vs. 12.6%, p<0.0001). By multivariable analysis, development of severe cholestasis in the Canadian cohort at 3 months (HR=2.41, p=0.046) and in the UK cohort at 12 months (HR=3.141, p<0.0001) were both associated with rPSC. Severe cholestasis at 3 months in the Canadian cohort was predictive of graft loss (HR=3.88, p=0.0001). CONCLUSIONS: The development of cholestasis within 3 to 12 months following LT was predictive of rPSC and graft loss.

A randomized trial of normothermic preservation in liver transplantation.

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.

Incidence and outcome of colorectal cancer in liver transplant recipients: A national, multicentre analysis on 8115 patients.

BACKGROUND & AIMS: De novo malignancies after liver transplantation represent one of the leading causes of death in the long-term. It remains unclear whether liver transplant recipients have an increased risk of colorectal cancer and whether this negatively impacts on survival, particularly in those patients affected by primary sclerosing cholangitis and ulcerative colitis. METHODS: In this national multicentre cohort retrospective study, the incidence of colorectal cancer in 8115 evaluable adult patients undergoing a liver transplantation between 1 January 1990 and 31 December 2010 was compared to the incidence in the general population through standardised incidence ratios. RESULTS: Fifty-two (0.6%) cases of colorectal cancer were identified at a median of 5.6 years postliver transplantation, predominantly grade 2 (76.9%) and stage T3 (50%) at diagnosis. The incidence rate of colorectal cancer in the whole liver transplant population was similar to the general UK population (SIR: 0.92), but significantly higher (SIR: 7.0) in the group of patients affected by primary sclerosing cholangitis/ulcerative colitis. One-, five- and ten-year survival rates from colorectal cancer diagnosis were 71%, 48% and 31%, respectively, and the majority of colorectal cancer patients died of cancer-specific causes. CONCLUSIONS: Liver transplantation alone is not associated with an increased risk of colorectal cancer development. The primary sclerosing cholangitis/ulcerative colitis liver transplant population showed a significantly higher risk of colorectal cancer development than the general population, with a high proportion of advanced stage at diagnosis and a reduced patient survival.

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.

Normothermic liver preservation: a new paradigm?

Despite increasing donor numbers, waiting lists and pre-transplant mortality continue to grow in many countries. The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury (IRI). Transplantation of marginal donor organs has led to renewed interest in new techniques which have the potential to improve the quality of preservation, assess the quality of the organ and allow repair of the donor organ prior to transplantation. If successful, such techniques would not only improve the outcome of currently transplanted marginal livers, but also increase the donor pool. Experimental evidence suggests that preservation under near physiological conditions of temperature and oxygenation abrogates IRI. Normothermic perfusion maintains the organ in a physiological state, avoiding the depletion of cellular energy and the accumulation of waste products, which occurs with static cold storage. It enables viability assessment prior to transplantation thereby reducing the risk of transplanting inherently marginal organs. Here we review the use of normothermic machine perfusion as a means of organ preservation.

Role of colectomy in preventing recurrent primary sclerosing cholangitis in liver transplant recipients.

AIM: To study the published evidence on the impact of colectomy in preventing recurrent primary sclerosing cholangitis (rPSC). METHODS: An unrestricted systematic literature search in PubMed, EMBASE, Medline OvidSP, ISI Web of Science, Lista (EBSCO) and the Cochrane library was performed on clinical studies investigating colectomy in liver transplantation (LT) recipients with and without rPSC in the liver allograft. Study quality was evaluated according to a modification of the methodological index for non-randomized studies (MINORS) criteria. Primary endpoints were the impact of presence, timing and type of colectomy on rPSC. Overall presence of inflammatory bowel disease (IBD), time of IBD diagnosis, posttransplant IBD and immunosuppressive regimen were investigated as secondary outcome. RESULTS: The literature search yielded a total of 180 publications. No randomized controlled trial was identified. Six retrospective studies met the inclusion criteria of which 5 studies were graded as high quality articles. Reporting of IBD was heterogenous but in four publications, either inflammatory bowel disease, ulcerative colitis or in particular active colitis post-LT significantly increased the risk of rPSC. The presence of an intact (i.e., retained) colon at LT was identified as risk factor for rPSC in two of the high quality studies while four studies found no effect. Type of colectomy was not associated with rPSC but this endpoint was underreported (only in 33% of included studies). Neither tacrolimus nor cyclosporine A yielded a significant benefit in disease recurrence of primary sclerosing cholangitis (PSC). CONCLUSION: The data favours a protective role of pre-/peri-LT colectomy in rPSC but the current evidence is not strong enough to recommend routine colectomy for rPSC prevention.

Normothermic Machine Perfusion of Deceased Donor Liver Grafts Is Associated With Improved Postreperfusion Hemodynamics.

BACKGROUND: Graft reperfusion poses a critical challenge during liver transplantation and can be associated with hemodynamic instability/postreperfusion syndrome. This is sequel to ischemia-reperfusion injury and normothermic machine preservation (NMP) may affect hemodynamic changes. Herein, we characterize postreperfusion hemodynamics in liver grafts after NMP and traditional cold preservation. MATERIALS AND METHODS: Intraoperative records of patients receiving grafts after NMP (n = 6; NMP group) and cold storage (CS) (n = 12; CS group) were compared. The mean arterial pressure (MAP) was defined as the average pressure in the radial artery during 1 cardiac cycle by invasive monitoring. Postreperfusion syndrome was defined as MAP drop greater than 30% of baseline, lasting for 1 minute or longer within the first 5 minutes from graft reperfusion. RESULTS: Donor, recipient, demographics, and surgical parameters were evenly matched. Normothermic machine preservation grafts were perfused for 525 minutes (395-605 minutes) after initial cold ischemic time of 91 minutes (73-117 minutes), whereas in CS group cold ischemic time was 456 minutes (347-685 minutes) (P = 0.001). None developed postreperfusion syndrome in the NMP group against n = 2 (16.7%) in CS group (P = 0.529). Normothermic machine preservation group had better intraoperative MAP at 90 minutes postreperfusion (P = 0.029), achieved with a significantly less vasopressor requirement (P = <0.05) and less transfusion of blood products (P = 0.030) compared with CS group. CONCLUSIONS: Normothermic machine perfusion is associated with a stable intraoperative hemodynamic profile postreperfusion, requiring significantly less vasopressor infusions and blood product transfusion after graft reperfusion and may have benefit to alleviate ischemia-reperfusion injury in liver transplantation.

Portal vein resection in borderline resectable pancreatic cancer: a United Kingdom multicenter study.

BACKGROUND: Until recently, in the United Kingdom, borderline resectable pancreatic cancer with invasion into the portomesenteric veins often resulted in surgical bypass because of the presumed high risk for complications and the uncertainty of a survival benefit associated with a vascular resection. Portomesenteric vein resection has therefore remained controversial. We present the second largest published cohort of patients undergoing portal vein resection for borderline resectable (T3) adenocarcinoma of the head of the pancreas. STUDY DESIGN: This is a UK multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection (PDVR), standard pancreaticoduodenectomy (PD), and surgical bypass (SB). Nine high-volume UK centers contributed. All consecutive patients with T3 (stage IIA to III) adenocarcinoma of the head of the pancreas undergoing surgery between December 1998 and June 2011 were included. The primary outcomes measures are overall survival and in-hospital mortality. Secondary outcomes measure is operative morbidity. RESULTS: One thousand five hundred and eighty-eight patients underwent surgery for borderline resectable pancreatic cancer; 840 PD, 230 PDVR, and 518 SB. Of 230 PDVR patients, 129 had primary closure (56%), 65 had end to end anastomosis (28%), and 36 had interposition grafts (16%). Both resection groups had greater complication rates than the bypass group, but with no difference between PD and PDVR. In-hospital mortality was similar across all 3 surgical groups. Median survival was 18 months for PD, 18.2 months for PDVR, and 8 months for SB (p = 0.0001). CONCLUSIONS: This study, the second largest to date on borderline resectable pancreatic cancer, demonstrates no significant difference in perioperative mortality in the 3 groups and a similar overall survival between PD and PDVR; significantly better compared with SB.

Is there a role for arterial reconstruction in surgery for pancreatic cancer?

Surgery remains the only potentially curative treatment for patients with pancreatic cancer. Locally advanced pancreatic cancer with vascular involvement remains a surgical challenge because high perioperative risk and the uncertainty of a survival benefit. Whilst portal vein resection has started to gather momentum because the perioperative morbidity and long term survival is comparable to standard pancreatectomy, there isn't yet a consensus on arterial resections. There have been various reports and case series of arterial resections in pancreatic cancer, with mixed survival results. Mollberg et al have appraised the heterogeneous published literature available on arterial resection in pancreatic cancer in an attempt to compare this to standard pancreatectomy. In this article, we discuss the results of this systematic review and meta-analysis, and the limitations associated with analysing results from heterogenous data. We have outlined the important features in surgery for pancreatic cancer and specifically to arterial resections, and compared arterial resections to the published literature on venous resections.

Dexamethasone reduces emesis after major gastrointestinal surgery (DREAMS).

BACKGROUND: Postoperative nausea and vomiting is one of the most common complications affecting patients after surgery and causes significant morbidity and increased length of hospital stay. It is accepted that patients undergoing surgery on the bowel are at a higher risk. In the current era of minimally invasive colorectal surgery combined with enhanced recovery, reducing the incidence and severity of postoperative nausea and vomiting is particularly important. Dexamethasone is widely, but not universally used. It is known to improve appetite and gastric emptying, thus reduce vomiting. However, this benefit is not established in patients undergoing bowel surgery, and dexamethasone has possible side effects such as increased risk of wound infection and anastomotic leak that could adversely affect recovery. DESIGN: DREAMS is a phase III, double-blind, multicenter, randomized controlled trial with the primary objective of determining if preoperative dexamethasone reduces postoperative nausea and vomiting in patients undergoing elective gastrointestinal resections. DREAMS aims to randomize 1,350 patients over 2.5 years.Patients undergoing laparoscopic or open colorectal resections for malignant or benign pathology are randomized between 8 mg intravenous dexamethasone and control (no dexamethasone). All patients are given one additional antiemetic at the time of induction, prior to randomization. Both the patient and their surgeon are blinded as to the treatment arm.Secondary objectives of the DREAMS trial are to determine whether there are other measurable benefits during recovery from surgery with the use of dexamethasone, including quicker return to oral diet and reduced length of stay. Health-related quality of life, fatigue and risks of infections will be investigated. TRIAL REGISTRATION: ISRCTN21973627.

The operative management of gallstone ileus.

INTRODUCTION: Gallstone ileus is an uncommon entity, which accounts for 1-4% of all presentations to hospital with small bowel obstruction and for up to 25% of all cases in patients over 65 years of age. Despite medical advances over the last 350 years, gallstone ileus is still associated with high rates of morbidity and mortality. The management of gallstone ileus remains controversial. Whilst open surgery has been the mainstay of treatment, more recently other approaches have been employed, including laparoscopic surgery and lithotripsy. However, controversy persists primarily in relation to the extent of surgery performed. MATERIALS AND METHODS: A literature review was performed in an attempt to discover the optimal surgical treatment of gallstone ileus, particularly the timing of biliary surgery. Published articles were identified from the medical literature by electronic searches of Pubmed and Ovid Medline databases, using the search terms 'gallstone ileus', 'gallstone/intestinal obstruction' and 'gallstone/bowel obstruction'. The related articles function of the search engines was also used to maximise the number of articles identified. Relevant articles were retrieved and additional articles were identified from the references cited in these articles. RESULTS AND CONCLUSIONS: The literature on gallstone ileus is composed entirely of retrospective analysis of small numbers of patients accumulated over many years. The question as to whether one stage or interval biliary surgery should be performed remains unanswered and it is unlikely that further case series will help decision making in the management of gallstone ileus. Whilst many authors conclude that enterolithotomy alone is the best option in most patients, a one-stage procedure should be considered for low-risk patients.

Small bowel evisceration through the rectum in childhood.

Small bowel evisceration through the rectum is extremely rare in childhood and has previously been reported in association with swimming pool suction injuries. We report a case of ileal evisceration resulting from a self-inflicted injury in a teenaged boy. Such a mechanism of injury leading to evisceration of the small bowel is previously unreported in children or adults.