Sunny Y. S. Cheung

Meta‐analysis: the efficacy of anti‐viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B‐related hepatocellular carcinoma

Aliment Pharmacol Ther 2011; 33: 1104–1112

A minimally invasive strategy for Mirizzi syndrome: the combined endoscopic and robotic approach

AbstractBackgroundMirizzi syndrome (MS) is a rare complication of gallstone disease. Despite the fact that successful laparoscopic treatments have been reported, open surgery remains the gold standard approach for this disease due to technical difficulties involved. MethodsA minimally invasive strategy combining endoscopic retrograde cholangiopancreatography (ERCP) and robotic surgery for the management of MS was implemented in early 2012. This consisted of a preoperative ERCP for definitive diagnosis and endoscopic stent insertion. Robotic surgical approach was used during operation to facilitate gall bladder removal and suture of defect over common duct. ERCP was repeated postoperatively for stent removal. Patient demographics and treatment outcomes were collected prospectively. A historical cohort of patients with MS who underwent conventional surgery between 1999 and 2011 was identified for comparison of treatment outcomes.ResultsFive patients with MS were managed with this strategy. Robotic subtotal cholecystectomy was successfully performed in all the patients without conversion or morbidity. When compared with a historical cohort of 17 patients who underwent surgery for MS, this group of patients had significantly less conversion and shorter hospital stay though the operation time was longer. It also showed less blood loss and less postoperative complications but these were not statistically significant.ConclusionMirizzi syndrome can be effectively managed with a minimally invasive approach by adopting a robot-assisted surgery together with a planned pre- and postoperative ERCP.

Robot‐assisted laparoscopic spleen‐preserving distal pancreatectomy

Laparoscopic distal pancreatectomy has been well accepted as a feasible and safe, minimally-invasive procedure in benign and borderline malignant disease of the pancreas. However, due to technical limitation by rigid laparoscopic instruments, splenectomy has to be accomplished in most cases. The advantages of the robotic surgical system make spleen preservation highly possible. In this multi-media article, we describe our technique of robot-assisted laparoscopic spleen-preserving distal pancreatectomy.

Robotic surgery for Mirizzi syndrome

Mirizzi syndrome is a rare complication of gallstone disease. Surgical management usually involves the subtotal removal of the gallbladder, leaving a cuff of tissue to repair the common bile duct. In advanced cases, bile duct resection and hepaticojejunostomy might be required. Open surgery is the current standard for managing patients with Mirizzi syndrome. Although a minimally-invasive approach is desirable, as there is no large specimen to be removed, the common occurrence of dense pericholecystic adhesion and the need for intracorporeal suture is a challenge to the conventional laparoscopic approach. A recent review on the laparoscopic treatment of Mirizzi syndrome showed that the conversion rate was as high as 41 per cent, with 20 per cent morbidity and a 6 per cent reoperation rate. Those authors concluded that the laparoscopic approach could not be recommended for this disease. However, with the use of the robotic approach, such operative difficulties theoretically can be overcome. In the literature, only two cases using the robotic approach for Mirizzi syndrome were reported in one study. This video shows how we used the robotic approach in a patient with Mirizzi syndrome.

Robotic excision of adult choledochal cyst with total intra-corporeal reconstruction

Complete excision with a Roux-en-Y hepaticojejunostomy reconstruction is the standard treatment for type 1 choledochal cysts. With the advancement of laparoscopic and robotic skills, an increasing number of reports on performing this complex operation by minimal access surgery has been noted. However, its development is limited by the technical complexities of the procedures and the rigid nature of the instruments. The robotic surgical system might help to overcome these obstacles, and its use has been reported, but mainly in paediatric patients, where reconstruction is mostly extra-corporeal. Only one adult case had been reported, and reconstruction was performed extra-corporeally. In the present study, we report our experience of robotic excision of a type 1 choledochal cyst with total intra-corporeal reconstruction in a young adult.

Does Intermittent Pringle Maneuver Increase Postoperative Complications After Hepatectomy for Hepatocellular Carcinoma? A Randomized Controlled Trial

BackgroundIn a previous study, we have shown that intermittent Pringle maneuver (IPM) might increase postoperative complications after hepatectomy for various indications. Complications which thought to be related to IPM were ascites, pleural effusion, wound infection and intra-abdominal collection. The aim of this study was to test the hypothesis that applying IPM during hepatectomy for hepatocellular carcinoma (HCC) could increase postoperative complications.MethodsBetween January 2013 and October 2016, eligible patients who received elective open hepatectomy for HCC were randomized to have IPM or no Pringle maneuver (NPM). Occurrence of various types of postoperative complications was specifically looked for. A routine postoperative day 5 abdominal ultrasound examination and chest X-ray were done to detect and grade any radiological ascites, pleural effusion and intra-abdominal collection.ResultsFifty IPM and 50 NPM patients with histological proven HCC were recruited for final analysis. Demographics and operative parameters were comparable between the two groups. The postoperative complication rates were similar (IPM 36.0 vs. NPM 28.0%, P = 0.391). However, in the IPM group, more patients developed radiological posthepatectomy ascites (42.0 vs. 22.0%, P = 0.032) and pleural effusion (66.0 vs. 38.0%, P = 0.005). In patients with histologically proven cirrhosis, there were 28 IPM and 25 NPM patients. Again, there was no difference in postoperative complication rate but more radiological posthepatectomy ascites and pleural effusion in the IPM group.ConclusionThis trial was not able to detect a difference in postoperative complications whether IPM was applied or not, but use of IPM was associated with more subclinical ascites and pleural effusion. (ClinicalTrials.gov NCT01759901).Trial registration numberClinicalTrials.gov NCT01759901.

Ablative Chemoembolization for Hepatocellular Carcinoma: A Prospective Phase I Case-Control Comparison with Conventional Chemoembolization

Purpose To evaluate the feasibility, safety, and treatment effectiveness of ablative chemoembolization (ACE) in the treatment of hepatocellular carcinoma (HCC) and compare with a similar patient cohort who underwent conventional transarterial chemoembolization (cTACE). Materials and Methods This was a prospective phase I nonrandomized study conducted between March 2013 and October 2016 in accordance to the Declaration of Helsinki and Declaration Good Clinical Practice with written informed consent. There were 36 men and eight women (median age, 64 years [interquartile range, 58-74] and 74.5 years [interquartile range, 70-80], respectively). The primary end points were treatment safety and tumor response. The secondary end points were time to progression, progression-free survival, conversion to partial hepatectomy, and viable HCC within the tumor specimen. The end points of the study group (n = 22) were compared with those of a case-matched control group (n = 22) of patients who underwent conventional cTACE during the same period by using a Pearson χ2 test. Results Treatment with ACE was successfully completed in all patients without adverse effects. The complete response (CR) rates by patient or by tumor were both 100%. The median time to progression and median progression-free survival were significantly longer in the study group than in the control group (both were 28 months vs 10 months, respectively; P < .001). The number of patient conversions to hepatectomy was seven for ACE and three for cTACE. In the tumor specimens, viable tumor was found in two of eight specimens that underwent ACE and three of three that underwent cTACE. Conclusion ACE is a feasible, safe, and well-tolerated treatment for patients with HCC; it is highly effective and may be more effective than cTACE in achieving CR.

Su1031 High Liver Stiffness Measurement by Transient Elastography Predicts High Grade Post-Hepatectomy Liver Failure in Patients With Hepatocellular Carcinoma: A Prospective Cohort Study

Introduction: Biliary stricture is a common complication following orthoptic Liver transplantation. The reported incidence of biliary stricture is 5-15% following deceased donor liver transplantation (1). There is no published data to suggest renal impairment following OLT either increases or decrease the incidence of strictures. We conducted retrospective review to assess the above. Methods: A retrospective review of all adult patients who had OLT between January 2008 and February 2013 were included. Information was obtained from electronic patient record, radiology, endoscopy and pathology reports. We assessed if renal impairment both during the immediate post operative period and at 3 months and 1 year had any impact on the development of strictures. Statistical analysis was done using PRISM 6. Fisher Exact test and chi-squared test were used as appropriate. Results: 812 patient episodes were reviewed of which 304 patients were repatriated to other centers so, they were excluded.508 patients were included in the analysis. The mean age at which they had OLT was 49.71± 12.56 (Male: female-328: 180). The mean blood loss during surgery was 7.5± 6.5 l. 14.2% (71) had biopsy proven rejection. 39(7.6%) patients developed biliary strictures. The odds ratio for developing BS in DCD is 9.02 (95% CI 4.4-18.4, P <0.0001). Patients who had haemofiltration were at increased risk of developing BS (RR 2.33,95% CI 1.28-4.5). Patients whose glomerular filtration rate (GFR) decreased below 60 in the first 14 days were at increased risk of developing biliary stricture (P=0.01). The above trend was not maintained at 3 months and 1 year. The rest of the comparators are shown in the table. Conclusion: Our study shows that there was a modest but significant increase in risk of developing biliary strictures if they had haemofiltration or if their GFR decreased below 60 in the first 14 days following liver transplant. The risk of developing BS is increased by 9 fold if the graft is DCD.

Abstract 2170: Dissecting the oncogenic function of a novel androgen receptor-dependent direct target, cell cycle-related kinase (CCRK), in hepatocellular carcinoma

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide with a gender prevalence observed in men. Recent genetic studies using knockout mouse models have revealed the causal role of androgen receptor (AR) in hepatocarcinogenesis but the underlying molecular mechanism remains unclear. Here we used genome-wide location and functional analyses to show that cell cycle-related kinase (CCRK) is a direct critical mediator of AR signaling. Chromatin immunoprecipitation microarray identified over 200 high-confidence AR direct target genes in HCC cells of which cell cycle regulators were significantly enriched (n = 21; p < 0.0001). Because CCRK has the highest AR binding affinity amongst the identified cell cycle regulators, its regulation, function and expression in HCC were further investigated. Ligand-activated AR was recruited to the CCRK promoter and increased CCRK expression. AR-induced cell cycle progression was abrogated by siRNA-mediated knockdown of CCRK. On the contrary, over-expression of CCRK rescued the G1 arrest induced by AR knockdown. Ectopic CCRK expression in human immortal liver cells induced anchorage-dependent and -independent growth and tumor formation in immunodeficient mice, whereas CCRK inhibition decreased HCC cell growth in vitro and in vivo; demonstrating the strong oncogenic capacity of CCRK in HCC. Mechanistically, CCRK activated β-catenin/T-cell factor (TCF) signaling through phosphorylation of glycogen synthase kinase-3β to increase the expression of downstream pro-proliferative genes, cyclin D1 and epidermal growth factor receptor. Inhibition of β-catenin/TCF signaling significantly attenuated CCRK-induced cell cycle progression, colony formation and tumorigenicity. Conversely, HCC cell growth inhibition by CCRK knockdown was rescued by constitutively active form of β-catenin or TCF. Importantly, AR, CCRK, and active β-catenin were markedly over-expressed and positively correlated among each other in HCC specimens (p < 0.001). Furthermore, CCRK over-expression was significantly associated with tumor staging and poor disease-free survival of patients (p < 0.05), emphasizing the clinical importance of CCRK in HCC. In conclusion, our findings reveal a novel interplay between AR and β-catenin where activated AR transcriptionally up-regulates CCRK expression, thereby activating β-catenin/TCF signaling to induce aberrant cell proliferation. Dissection of this highly activated AR-CCRK-β-catenin/TCF axis sheds new mechanistic insight into hepatocarcinogenesis and provides novel therapeutic targets for the treatment of this and other male-predominant cancers. Acknowledgements: This study was partially supported by the Research Grant Council General Research Fund (462710) and the Direct Grant from the Chinese University of Hong Kong. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2170. doi:10.1158/1538-7445.AM2011-2170