R. Ravikumar

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.

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 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.

Impact of portal vein infiltration and type of venous reconstruction in surgery for borderline resectable pancreatic cancer

The International Study Group of Pancreatic Surgery (ISGPS) recommends operative exploration and resection of pancreatic cancers in the presence of reconstructable mesentericoportal axis involvement. However, there is no consensus on the ideal method of vascular reconstruction. The effect of depth of tumour invasion of the vessel wall on outcome is also unknown.

Preoperative Gemcitabine-based Chemoradiation Therapy for Resectable and Borderline Resectable Pancreatic Cancer.

To the Editor: We congratulate the authors not only for their brilliant results but also for highlighting the role of neoadjuvant treatment in the management of patients with pancreatic cancer. The potential benefit of preoperative chemoradiation with or without induction chemotherapy has been long recognized but is commonly avoided in the treatment of resectable lesions because of the potential risk of tumor progression. On the contrary, the borderline resectable group offers a great opportunity to investigate the value of neoadjuvant modalities as the ideal management of these patients is still unknown, differs across the world, and, most importantly, the definition of this condition remains controversial. In this study, the authors applied similar criteria to those suggested by the MD Anderson group in 2006, but the resectability status was defined exclusively by the relationship between the arterial structures and the tumor. In particular, only those patients with limited arterial involvement (no more than 180 degrees of circumferential abutment of the vessel) were considered borderline resectable. Ultimately, 54% of patients in the borderlineresectable group were resected after neoadjuvant chemoradiation and a documented, still not necessarily significant, tumor response. Indeed, pancreatic cancer is associated with intense stromal reaction and fibrosis, which rarely results in sufficient downstaging to restore a normal tissue plane between the artery and the tumor. It is therefore surprising that only 3 patients in this group required reconstruction of the common hepatic artery. As such, it is difficult to reconcile this with an astonishing R0 rate of 98%, even after considering the variation in histopathological reporting across different units, due to the lack of standardization of sampling and processing of periampullary tumors. Second, a 34% 5-year survival in this group is a remarkable achievement in support of neoadjuvant chemoradiation. It further

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.

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

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.