Mahmoud Ali

Predictors of long term survival after hepatic resection for hilar cholangiocarcinoma: A retrospective study of 5-year survivors

AIM To determine predictors of long term survival after resection of hilar cholangiocarcinoma (HC) by comparing patients surviving > 5 years with those who survived < 5 years. METHODS This is a retrospective study of patients with pathologically proven HC who underwent surgical resection at the Gastroenterology Surgical Center, Mansoura University, Egypt between January 2002 and April 2013. All data of the patients were collected from the medical records. Patients were divided into two groups according to their survival: Patients surviving less than 5 years and those who survived > 5 years. RESULTS There were 34 (14%) long term survivors (5 year survivors) among the 243 patients. Five-year survivors were younger at diagnosis than those surviving less than 5 years (mean age, 50.47 ± 4.45 vs 54.59 ± 4.98, P = 0.001). Gender, clinical presentation, preoperative drainage, preoperative serum bilirubin, albumin and serum glutamic-pyruvic transaminase were similar between the two groups. The level of CA 19-9 was significantly higher in patients surviving < 5 years (395.71 ± 31.43 vs 254.06 ± 42.19, P = 0.0001). Univariate analysis demonstrated nine variables to be significantly associated with survival > 5 year, including young age (P = 0.001), serum CA19-9 (P = 0.0001), non-cirrhotic liver (P = 0.02), major hepatic resection (P = 0.001), caudate lobe resection (P = 0.006), well differentiated tumour (P = 0.03), lymph node status (0.008), R0 resection margin (P = 0.0001) and early postoperative liver cell failure (P = 0.02). CONCLUSION Liver status, resection of caudate lobe, lymph node status, R0 resection and CA19-9 were demonstrated to be independent risk factors for long term survival.

Hilar cholangiocarcinoma in cirrhotic liver: A case–control study

BACKGROUND Surgical resection is the only hope for patients with cholangiocarcinoma (CC). This study is designed to assess the impact of cirrhosis on the outcome of surgical management for CC. PATIENT AND METHODS We retrospectively studied all patients who underwent surgical resection for hilar CC. Group I (patients with cirrhotic liver) and Group II (patients with non-cirrhotic liver). Preoperative demographic data, intra-operative data, and postoperative details were collected. RESULTS Only 102/243 patients (41.9%) had cirrhotic liver. Caudate lobe resection was more frequently performed in the non-cirrhotic group (P = <0.001). There was no difference between both groups regarding intraoperative blood loss and the need for blood transfusion. The median postoperative stay was higher in the cirrhotic group (P = 0.063). The incidence of early postoperative liver cell failure was significantly higher in the cirrhotic group (P = <0.001). Cirrhosis was associated with significantly lower overall survival (P = <0.001). CONCLUSION Patients with concomitant liver cirrhosis and hilar CC should not be precluded from surgical resection and should be considered for resection at high volume centers with expertise available to manage liver cirrhosis. The incidence of early postoperative liver cell failure was significantly higher in the cirrhotic group.

Cryopreserved arterial grafts as a conduit in outflow reconstruction in living donor liver transplantation.

Few reports have addressed the use of cryopreserved arterial grafts (CAG) for anterior section drainage in right lobe living donor liver transplantation (RL LDLT), and the impact of atherosclerosis on patency rate (PR) is not well studied. Also, those reports have limited case numbers. The aim of the present study is to report the largest experience with CAG in outflow reconstruction in RL LDLT and the impact of atherosclerosis on its patency.

Clinicopathological features and surgical outcome of patients with fibrolamellar hepatocellular carcinoma (experience with 22 patients over a 15-year period)

AIM To evaluate the clinicopathological features and the surgical outcomes of patients with fibrolamellar hepatocellular carcinoma (FL-HCC) over a 15-year period. METHODS This is a retrospective study including 22 patients with a pathologic diagnosis of FL-HCC who underwent hepatectomy over a 15-year period. Tumor characteristics, survival and recurrence were evaluated. RESULTS There were 11 male and 11 female with a median age of 29 years (range from 21 to 58 years). Two (9%) patients had hepatitis C viral infection and only 2 (9%) patients had alpha-fetoprotein level > 200 ng/mL. The median size of the tumors was 12 cm (range from 5-20 cm). Vascular invasion was detected in 5 (23%) patients. Four (18%) patients had lymph node metastases. The median follow up period was 42 mo and the 5-year survival was 65%. Five (23%) patients had a recurrent disease, 4 of them had a second surgery with 36 mo median time interval. Vascular invasion is the only significant negative prognostic factor CONCLUSION FL-HCC has a favorable prognosis than common HCC and should be suspected in young patients with non cirrhotic liver. Aggressive surgical resection should be done for all patients. Repeated hepatectomy should be considered for these patients as it has a relatively indolent course.

Hepatobiliary rhabdomyosarcoma mimicking choledochal cyst: Lessons learned

INTRODUCTION The differential diagnosis of hepatic cystic lesions is a challenging process especially in case of hepatic rhabdomyosarcoma (HRMS) presenting as hepatic cyst. PRESENTATION OF CASE We introduce our experience with a case of HRMS in a 3-year-old female patient who was misdiagnosed to have type IV-A choledochal cyst and definitive correct diagnosis was reached after the pathological and immunohistochemical examination of the surgically resected lesion. This case presentation is followed by important practical messages to hepatobiliary surgeons regarding HRMS. DISCUSSION HRMS is a rare pediatric tumor. Jaundice is the most common presentation of HRMS followed by abdominal pain and vomiting. Great effort is needed to differentiate the tumor from choledochal cyst and infectious hepatitis. Through evaluation using available imaging studies together with clinical anticipation is mandatory for establishing the correct diagnosis. CONCLUSION Differentiation of HRMs from choledochal cyst mandates through evaluation and clinical anticipation. HRMS should be suspected in any child with obstructive jaundice. Once diagnosis is established, multidisciplinary treatment is the best management strategy and it has proved better surgical outcome and long term survival.

Impact of pathological features of primary hepatocellular carcinoma on the outcomes of intrahepatic recurrence management: single center experience from Southern Taiwan

BACKGROUND Currently, there is no definitive management for hepatocellular carcinoma (HCC) intrahepatic recurrence (IHR) after primary resection (PR). The aim of this study was to analyze the outcomes of three modalities for patients who received curative PR and had IHR within the University of California San Francisco (UCSF) criteria. METHODS Between 2003 and 2010, patients with IHR after PR were treated with salvage liver transplantation (SLT), re-resection (RR) or local ablation (LA). Clinico-pathological features of primary tumor and recurrent HCC were analyzed to determine the risk factors that adversely affected overall survival (OS) and disease free survival (DFS). RESULTS The study included 130 patients with subgroups of SLT (n = 25), RR (n = 31) and LA (n = 74). The 5-year DFS and OS were 75%, 31% and 17% and 80%, 60% and 58% respectively for each subgroup. SLT had a significantly better DFS than other modalities (p < 0.001). There was no difference in OS. In multivariate analysis, two variables adversely affected DFS: microvascular invasion in PR and not treating patients with SLT. CONCLUSIONS SLT provides better DFS for patients with IHR within the UCSF criteria. However, SLT failed to show the same advantage in OS.

Extended central hepatectomy with preservation of segment 6 for patients with centrally located hepatocellular carcinoma.

BACKGROUND In order to preserve functional liver parenchyma, extended central hepatectomy (segments 4, 5, 7 and 8 resection) was proposed for the management of centrally located hepatocellular carcinoma invading the right and middle hepatic veins, reconstructing segment 6 outflow in the absence of the thick inferior right hepatic vein. The present study was to describe our surgical techniques of extended central hepatectomy. METHODS Between 2008 and 2012, 5 patients with centrally located hepatocellular carcinoma invading or in the vicinity of the right and middle hepatic veins underwent extended central hepatectomy. The thick inferior right hepatic vein was preserved during dissection. Gore-Tex graft was used for segment 6 outflow reconstruction in the absence of the thick inferior right hepatic vein. RESULTS The mean future remnant liver volume for segments 2 and 3 was 28% versus 45% on segment 6 preservation. The mean tumor diameter was 7.4 cm. The thick inferior right hepatic vein was found in 1 patient. Outflow reconstruction from segment 6 was performed in 4 patients. Postoperative complications included bile leakage (1 patient), pleural effusion (2) and liver failure (1). The rate of graft patency was 75%. There was no perioperative mortality. CONCLUSION Extended central hepatectomy is a safe alternative for extended hepatic resection in selected patients attempting to preserve the functional liver parenchyma.

Competing endogenous RNA network: Potential entrants to gene editing in Hepatocellular Carcinoma

Background Hepatocellular Carcinoma (HCC) is the leading cause of cancer deaths worldwide as well as in Egypt. We aimed to use Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) gene editing technique to induce forced down-regulation of the circRNA which consequently modified miRNA expression in HepG2 cell line to prove the regulatory relationship between the RNA parts of an in silico-detected competing endogenous RNA network in HCC Method We first retrieved hsa_circ_0000064-miR-1285-TRIM2 mRNA from public microarray databases followed by in silico modelling to mimic the regulation kinetics of cirRNA associated ceRNA network. Secondly, we performed polymerase chain reaction (PCR)-based amplification of synthetic fragments, Gibson assembly of both CRISPR and non CRISPR based circuits, E-coli transformation, plasmid purification, HePG2 cell line transfection. Finally Expression levels of the chosen RNAs in hepatocellular carcinoma (HCC) cell line, HepG2, were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the cytotoxic effect was validated by viability assay.TRIM2 protein expression was proved by immunohistochemistry and flowcytometry. Results Induction of hsa_circ_0000064 into HepG2 cell line via CRISPR-and non-CRISPR mediated synthetic circuit resulted in statistically significant decrease in cell number and, then, cellular viability with marked increase in hsa_circ_0000064 and TRIM2 mRNA levels and concomitant decrease in miR-1285 expression in HepG2 cell line compared with control (p<0.0). Moreover exogenous expression of hsa_circ_0000064 in HepG2 cell line showed increased expression of the tumor suppressor protein, TRIM2. Conclusions Our integrative approach, including in silico data analysis and experimental validation proved that CRISPR-mediated synthetic circuit-based overexpression of hsa_circ_0000064 was more efficient than conventional transient transfection, representing a promising therapeutic strategy for HCC. Data Availability Our Data was made available online on the IGEM wiki of team AFCM-EGYPT: http://2017.igem.org/Team:AFCM-Egypt. Synthetic parts have been submitted to IGEM Parts Registry. Financial Disclosure The project was funded by Armed Forces College of Medicine AFCM, Zewail City of Science and Technology, National Research Center NRC, VitaBiotics, PHARCO Pharmaceuticals, Sim Era and DANUB Paintings. IDT provided 20 kb of DNA synthesis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Surgical Strategies for the Management of Perihilar Cholangiocarcinoma

Received: 20.05.2018 Accepted: 24.06.2018 Corresponding author: Mohamed Abdel Wahab, MD Professor of Hepato-biliary Surgery Chair of Liver Transplantation Unit Liver Transplantation Unit Gastrointestinal Surgery Center College of Medicine Mansoura University, Egypt Gastrointestinal Surgery Center Gehan Street, Mansoura, Egypt Postal code: 35516 Mobile: +2 01223134160 E-mail: Wahab_m_eg@yahoo.com ABSTRACT

Serum Levels of Heavy Metals in Cholangiocarcinoma Patients from the Nile Delta Region of Egypt: A Single Centre Study

Gastrointestinal Surgery Center, Department of Surgery, College of Medicine, Mansoura University, Mansoura, Egypt Department of Tropical Medicine, College of Medicine, Mansoura University, Mansoura, Egypt Department of Public Health and Community Medicine,College of Medicine, Mansoura University, Mansoura, Egypt Serum Levels of Heavy Metals in Cholangiocarcinoma Patients from the Nile Delta Region of Egypt: A Single Centre Study