Raaj K. Praseedom

Meta-analysis of randomized controlled trials comparing laparoscopic with open mesh repair of recurrent inguinal hernia.

Although there is plentiful evidence regarding the use of laparoscopic surgery for primary inguinal hernia, there is a paucity of literature concerning its role after recurrence. There has been no quantitative review of the evidence, despite suggestions that pooled analysis of existing data is required.

Human primary liver cancer–derived organoid cultures for disease modeling and drug screening

Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease.

The implications of the presence of an aberrant right hepatic artery in patients undergoing a pancreaticoduodenectomy.

PurposeAn aberrant right hepatic artery (ARHA) is a common anomaly and its implications for patients undergoing a pancreaticoduodenectomy (PD) have not yet been previously reported. We compared the outcomes following PD in patients with and without an ARHA. A novel classification of the anatomical course of ARHA, and surgical techniques for its identification and preservation are described herein.MethodsAll patients undergoing PD between June 1, 2002, and May 31, 2007, were divided into two groups, one with ARHA and the other without. These groups were compared to identify differences in the intraoperative variables, the oncological clearance, the postoperative complications, and the survival.ResultsA total of 135 patients underwent PD of which 28 (20.8%) patients were found to have either accessory or replaced right hepatic arteries (ARHA group). There were no significant differences in the intraoperative variables (blood loss and operative time) and the incidence of postoperative complications (pancreatic leak and delayed gastric emptying). Oncological clearance (nodal yield and resection margins) and survival were also similar in the two groups.ConclusionsThe surgical and oncological outcomes of PD remain unaffected by the presence of ARHA provided that the anatomy is recognized and appropriately managed. Aberrant right hepatic artery can be classified into three types according to their anatomical relationship with the head of the pancreas.

Combined transplantation of the heart, lung, and liver.

Combined transplantation of the heart, lung, and liver may be indicated in patients with either end-stage respiratory failure complicated by advanced liver disease or end-stage liver failure complicated by advanced lung disease. A retrospective review of nine patients who underwent combined heart-lung-liver transplantation in Cambridge (1986-99) was carried out. The 1-year and 5-year actuarial survival was 56% and 42%, respectively. Combined heart-lung-liver transplantation is a feasible option for a few patients and has a 5-year survival similar to heart-lung transplantation but with a lower incidence of acute and chronic rejection.

Direct histological processing of EUS biopsies enables rapid molecular biomarker analysis for interventional pancreatic cancer trials

OBJECTIVE Current practice to diagnose pancreatic cancer is accomplished by endoscopic ultrasound guided fine needle aspiration (EUS-FNA) using a cytological approach. This method is time consuming and often fails to provide suitable specimens for modern molecular analyses. Here, we compare the cytological approach with direct formalin fixation of pancreatic EUS-FNA micro-cores and evaluate the potential to perform molecular biomarker analysis on these specimen. METHODS 130 specimens obtained by EUS-FNA with a 22G needle were processed by the standard cytological approach and compared to a separate cohort of 130 specimens that were immediately formalin fixed to preserve micro-cores of tissue prior to routine histological processing. RESULTS We found that direct formalin fixation significantly shortened the time required for diagnosis from 3.6 days to 2.9 days (p<0.05) by reducing the average time (140 vs 33 min/case) and number of slides (9.65 vs 4.67 slides/case) for histopathological processing. Specificity and sensitivity yielded comparable results between the two approaches (82.3% vs 77% and 90.9% vs 100%). Importantly, EUS-FNA histology preserved the tumour tissue architecture with neoplastic glands embedded in stroma in 67.89% of diagnostic cases compared to 27.55% with the standard cytological approach (p < 0.001). Furthermore, micro-core samples were suitable for molecular studies including the immunohistochemical detection of intranuclear Hes1 in malignant cells, and the laser-capture microdissection-mediated measurement of Gli-1 mRNA in tumour stromal myofibroblasts. CONCLUSIONS Direct formalin fixation of pancreatic EUS-FNA micro-cores demonstrates superiority regarding diagnostic delay, costs, and specimen suitability for molecular studies. We advocate this approach for future investigational trials in pancreatic cancer patients.

The quality of information about kidney transplantation on the World Wide Web

Abstract:  Background:  Websites on the Internet are used increasingly by patients and those caring for them as a source of medical information. This study investigated the nature and quality of the kidney transplant‐related information currently available on the World Wide Web (WWW).

The discard of deceased donor kidneys in the UK

It is essential to minimize the unnecessary discard of procured deceased donor kidneys, but information on discard rates and the extent to which discard can be avoided are limited. Analysis of the UK Transplant Registry revealed that the discard rate of procured deceased donor kidneys has increased from 5% in 2002‐3 to 12% in 2011‐12. A national offering system for hard‐to‐place kidneys was introduced in the UK in 2006 (the Declined Kidney Scheme), but just 13% of kidneys that were subsequently discarded until 2012 were offered through the scheme. In order to examine the appropriateness of discard, 20 consecutive discarded kidneys from 13 deceased donors were assessed to determine if surgeons agreed with the decision that they were not implantable. Donors had a median (range) age of 67 (31–80) yr. Kidneys had been offered to a median of 3 (1–12) centers before discard. Four (20%) of the discarded kidneys were thought to be usable, and nine (45%) were possibly usable. As a result of these findings, major changes to the UK deceased donor kidney offering system have been implemented, including simultaneous offering and broader entry criteria for hard‐to‐place kidneys. Organizational changes are necessary to improve utilization of deceased donor kidneys.

Outcomes and Diagnostic Challenges Posed by Incidental Cholangiocarcinoma After Liver Transplantation

Background. Liver transplantation in the presence of cholangiocarcinoma (CCA) generally carries a poor prognosis. However, the outcome of patients found to have incidental CCA (iCCA) on explanted liver histology is less clear. We have evaluated the outcomes of iCCA in our liver transplant population. Methods. A retrospective search was made of the transplantation and histopathology databases for patients fulfilling our definition for iCCA. All records, including archived histopathologic slides were retrieved and analyzed. Results. Of 1288 patients undergoing liver transplantation over the 20-year period 1988–2008, nine were found to have iCCA (0.70%). Seven of the nine patients underwent liver transplantation for primary sclerosing cholangitis. Three additional patients who were transplanted for presumed hepatocellular carcinoma that subsequently turned out to be CCA were identified, but excluded from survival analysis. The majority of tumors were early stage (T2 or below), but five (55.6%) had positive biliary transection margins. Median follow-up was 51 months. Five patients (55.6%) developed recurrence of CCA after a median interval of 25.8 months, giving a disease-free survival of 100% at 1 year and 66.7% at 3 years. Three patients have died of recurrence, with a median interval from transplantation of 25 months. The overall 3-year survival was 66.7%. Conclusions. Patients found to have iCCA after liver transplantation have a relatively poor prognosis. Prospective liver transplant recipients, especially those with primary sclerosing cholangitis, should be investigated rigorously to exclude CCA.

Extra-hepatic portal vein aneurysm: A case report, overview of the literature and suggested management algorithm

INTRODUCTION Portal venous aneurysms are a rare finding. The reported incidence is on the rise with increasing use of modern imaging techniques in clinical practice. However, there is still much to be elicited regarding their aetiology, natural history, and management. PRESENTATION OF CASE An 80-year-old woman presented with abdominal pain and nausea. Investigations showed a hypoechoic area in the region of the head of pancreas on ultrasound, which was found to be a portal venous aneurysm on CT. In view of her multiple comorbidities, a conservative approach was taken. DISCUSSION Portal venous aneurysms represent approximately 3% of all venous aneurysms with a reported prevalence of 0.43%. They may be congenital, due to failure of complete regression of the right vitelline vein, or acquired secondary to portal hypertension. The primary presentation of portal vein aneurysm is abdominal pain, followed by incidental detection on imaging, with a minority of patients presenting with gastrointestinal bleeding. Complications of PVA include thrombosis, biliary tract obstruction, inferior vena cava obstruction, and duodenal compression. On the whole PVAs are stable and have a low risk of complications with 88% of patients showing no progression of aneurysm size or complications on subsequent follow up scans. CONCLUSION We recommend that portal venous aneurysms be assessed using colour Doppler ultrasonography in the first instance with CT scans reserved for indeterminate cases or symptomatic patients. Due to the slow progression of such aneurysms, surgery is recommended only for symptomatic patients or those with complications secondary to portal venous aneurysms.

Leiomyosarcoma of the Retrohepatic Vena Cava Treated by Excision and Reconstruction With an Aortic Homograft: A Case Report and Review of Literature:

Leiomyosarcoma of the retrohepatic inferior vena cava is a rare entity and presents a number of diagnostic and therapeutic challenges. Here such a case is presented in which the retrohepatic inferior vena cava was excised after full mobilization of the liver under venovenous bypass. The continuity of the vena cava was restored with cryopreserved aortic homograft. The technical details with regard to total vena caval clamping, venovenous bypass, hepatic inflow occlusion, techniques of reconstruction, including the use of cryopreserved aortic homograft, and a brief review of the literature on the surgical management of retrohepatic inferior vena caval tumors are discussed.