Krishna Menon

Impact of margin status on survival following pancreatoduodenectomy for cancer: the Leeds Pathology Protocol (LEEPP)

BACKGROUND In a previous study we reported an 85% R1 rate for pancreatic cancer following the use of the rigorous, fully standardized Leeds Pathology Protocol (LEEPP). As this significantly exceeded R1 rates observed by others, we investigated the reproducibility of margin assessment using the LEEPP in a larger, prospective, observational cohort study and correlated clinicopathological data with survival. METHODS Clinicopathological features, including exact site and multifocality of margin involvement, and survival were collated from a prospective series of 83 pancreatoduodenectomies for pancreatic (n = 27), ampullary (n = 24) and bile duct cancer (n = 32). Data were compared with those of the previous study in which the same pathology protocol, based on axial slicing and extensive tissue sampling from the circumferential margin, had been used. RESULTS The R1 rate was high in pancreatic (82%) and bile duct (72%) cancer and significantly lower in ampullary cancer (25%). Margin positivity was often multifocal, the posterior margin being most frequently involved. Margin status correlated with survival in the entire cohort (P = 0.006) and the pancreatic subgroup (P = 0.046). These findings were consistent with observations in our previous study. CONCLUSIONS Margin involvement in pancreatic cancer is a frequent and prognostically significant finding when specimens are assessed using the LEEPP.

Meta‐analysis: recurrence and survival following the use of sirolimus in liver transplantation for hepatocellular carcinoma

The use of sirolimus (SRL)‐based immunosuppression protocols have been reported to reduce recurrence rates following liver transplantation (LT) for hepatocellular carcinoma (HCC), although this is still a matter for debate.

Results of pancreatic surgery in the elderly: is age a barrier?

BACKGROUND By 2033, the number of people aged 85 years and over in the UK is projected to double, accounting for 5% of the total population. It is important to understand the surgical outcome after a pancreatic resection in the elderly to assist decision making. METHODS Over a 9-year period (from January 2000 to August 2009), 428 consecutive patients who underwent a pancreatic resection were reviewed. Data were collected on mortality, complications, length of stay and survival. Patients were divided into two groups (younger than 70 and older than 70 years old) and outcomes were analysed. RESULTS In all, 119 (27.8%) patients were ≥ 70 years and 309 (72.2%) patients were < 70 years. The median length of stay for the older and younger group was 15 days (range 3-91) and 14 days (range 3-144), respectively. The overall mortality was 3.4% in the older group and 2.6% in the younger group (P = 0.75). The older cohort had a cumulative median survival of 57.3 months (range 0-119), compared with 78.7 months (range 0-126) in the younger cohort (P < 0.0001). In patients undergoing a pancreatic resection for ductal adenocarcinoma and cholangiocarcinoma there was a significant difference in survival with P-values of 0.043 and 0.003, respectively. For ampullary adenocarcinoma, the older group had a median survival of 47.1 months compared with 68.3 months (P = 0.194). CONCLUSION Results from this study suggest that while elderly patients can safely undergo a pancreatic resection and that age alone should not preclude a pancreatic resection, there is still significant morbidity and mortality in the octogenarian subgroup with poor long-term survival with the need for quality-of-life assessment.

Images of the Month: MDMA-Induced Acute Liver Failure and Transient Abdominal Pneumatosis.

An 84-year-old woman with a history of diabetes and hypertension presented with complaints of abdominal pain. Upper endoscopy revealed congestive and erythematous gastric mucosa with elevated whitish plaques scattered through the gastric antrum. Histology demonstrated chronic gastritis lesions with focal activity and extensive intestinal metaplasia without dysplasia or malignancy. Helicobacter pylori was not detected by a modified Giemsa method. Upper endoscopy repeated two months later showed persistence of the previous findings.

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).

An in silico argument for mitochondrial microRNA as a determinant of primary non function in liver transplantation

Mitochondria have their own genomic, transcriptomic and proteomic machinery but are unable to be autonomous, needing both nuclear and mitochondrial genomes. The aim of this work was to use computational biology to explore the involvement of Mitochondrial microRNAs (MitomiRs) and their interactions with the mitochondrial proteome in a clinical model of primary non function (PNF) of the donor after cardiac death (DCD) liver. Archival array data on the differential expression of miRNA in DCD PNF was re-analyzed using a number of publically available computational algorithms. 10 MitomiRs were identified of importance in DCD PNF, 7 with predicted interaction of their seed sequence with the mitochondrial transcriptome that included both coding, and non coding areas of the hypervariability region 1 (HVR1) and control region. Considering miRNA regulation of the nuclear encoded mitochondrial proteome, 7 hypothetical small proteins were identified with homolog function that ranged from co-factor for formation of ATP Synthase, REDOX balance and an importin/exportin protein. In silico, unconventional seed interactions, both non canonical and alternative seed sites, appear to be of greater importance in MitomiR regulation of the mitochondrial genome. Additionally, a number of novel small proteins of relevance in transplantation have been identified which need further characterization.

Irreversible electroporation in borderline resectable pancreatic adenocarcinoma for margin accentuation

Abstract Achieving clear microscopic resection margins following pancreaticoduodenectomy (PD) is challenging particularly in borderline resectable pancreatic carcinoma (BRPC). Positive resection margins has been identified as a major independent prognostic factor. Irreversible electroporation (IRE) has emerged as a promising non-thermal ablative method that could be used in the treatment of pancreatic cancer as an adjunct to chemotherapy and surgery. This case report describes the successful simultaneous intraoperative IRE and PD in a patient with BRPC, achieving clear microscopic resection margins. Technical aspects and histology showing the effect of IRE are presented. The role of IRE in the treatment of pancreatic adenocarcinoma should be further evaluated in prospective studies.

The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced gallbladder cancer – A systematic review

BACKGROUND Neoadjuvant chemotherapy for advanced gallbladder cancer (GBC) has recently been proposed as an alternative to adjuvant chemotherapy, with potential increase in resectability rate and overall survival. AIM To undertake a systematic review and critical appraisal of available literature on the use of neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) in the treatment of advanced GBC. METHODS Systematic review carried out in line with the Meta-analysis Of Observational Studies in Epidemiology guidelines. Primary outcomes were clinical benefit rate (CBR) of neoadjuvant therapy, defined as percentage of complete response, partial response and stable disease, resectability rate and R0 resection. Secondary outcomes were overall and disease-free survival. RESULTS 8 studies met the inclusion criteria (n = 474), of which 398 (84.0%) received NACT and 76 (16.0%) received NACRT. 133 of 434 patients (30.6%) had progressive disease despite NACT or NACRT. The CBR was 66.6%. 17% of the patients who responded to chemotherapy did not proceed to surgery. 50.4% of the patients were considered suitable for surgical resection, of which 191 (40.3%) underwent curative resection. The R0 rate for the whole cohort was 35.4%. Overall survival ranged from 18.5 to 50.1 months for those who underwent curative resection versus 5.0-10.8 months for non-resected group. CONCLUSIONS There is insufficient data to support the routine use of NACT or NACRT in advanced GBC, as this has only benefited a third of whole cohort, who eventually achieved a R0 resection. Future studies should be in the form of randomized controlled trials to investigate the role of neoadjuvant therapy in advanced GBC.

Successful endoscopic management of a persistent bronchobiliary fistula with Histoacryl®/Lipiodol® mixture

INTRODUCTION A bronchobiliary fistula (BBF) following liver directed therapy (resection/ablation) is a rare complication in which an abnormal communication between the biliary tract and bronchial tree is formed. This case report describes the successful management of a persistent BBF following multiple liver wedge resections and microwave ablation in a patient with a metastatic neuroendocrine tumour of the terminal ileum. CASE HISTORY A 69‐year‐old man presented with unexplained weight loss and was subsequently diagnosed with a neuroendocrine tumour of the terminal ileum and liver metastasis. Following elective right hemicolectomy and multiple bilobar liver wedge resections combined with liver microwave ablation, he developed an early bile leak. A month later, a right subphrenic collection was identified and four months following surgery, biloptysis was noted. Numerous attempts with endoscopic retrograde biliary drainage (ERBD) failed to achieve sufficient drainage. The patient was treated successfully with endoscopic injection of a mixture of Histoacryl® glue (B Braun, Sheffield, UK) and Lipiodol® (Guerbet, Solihull, UK). There was no evidence of the BBF one year following intervention. CONCLUSIONS This novel approach for persistent BBF management using endoscopic Histoacryl® glue embolisation of the fistula tract should be considered either as an adjunct to ERBD or when biliary tract decompression by drainage and/or sphincterotomy fails, prior to proceeding with surgical interventions.

The Effect of Recipient Body Mass Index and Its Extremes on Survival and Graft Vascular and Biliary Complications After Liver Transplantation: A Single Center Retrospective Study

BACKGROUND This is the largest UK-based study on the effect of recipient body mass index (BMI) and its extremes (BMI <18.5 and BMI ≥35 kg/m²) on liver transplant (LT) outcomes. Its purpose was to analyze the BMI effect on post-LT mortality, graft loss, primary non-function (PNF), and graft vascular and biliary complications. MATERIAL AND METHODS Data were retrieved from a single-center LT database of 2,115 consecutive patients receiving first LT during period February 2004 to September 2015. Survivals were compared across the BMI groups; the effects of recipient BMI on survival, PNF, and graft vascular and biliary complications were analyzed via regression. RESULTS Autoimmune disease and nonalcoholic steatohepatitis were prevalent among underweight and morbidly obese adults, respectively. Graft survival was similar across BMI classes at 30 days and in 1, 2, 5, and 10 years (p=0.75) and on obese versus non-obese (p=0.33). BMI <35 kg/m² versus BMI ≥35 kg/m² mean graft survival was similar (p=0.84). BMI <18.5 kg/m² recipients tended to have inferior mean graft and patient survivals; however, the difference was non-significant (p=0.09 and p=0.1 respectively). BMI <18.5 kg/m² recipients were at higher risk of hepatic artery thrombosis (HR, 1.73, 95% CI 1.73-3, p<0.05). Adult underweight status was an independent HAT risk factor (HR 3, 95% CI 1-8.6, p=0.046). BMI class did not affect ischemic cholangiopathy risk (p=0.84). However, the overall biliary complication risk increased by 3% for every 1 kg/m² BMI rise. CONCLUSIONS Post-LT survival is independent of recipient BMI. Underweight status is linked to higher HAT risk. Biliary complication risk increases with rising recipient BMI. After appropriate recipient selection, recipient BMI extremes are not a contraindication for LT.