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Novel biomarkers GEP/ABCB5 regulate response to adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 524-530页

作者： charing ching-ning chong Siu Tim Cheung Yue-Sun Cheung Anthony Wing-Hung Chan Stephen Lam Chan Simon Chun-Ho Yu Paul Bo-San Lai Department of Surgery Prince of Wales HospitalThe Chinese University of Hong Kong4/F Clinical Science Building30-32 Ngan Shing StreetShatinHong KongChina Department of Anatomical and Cellular Pathology State Key Laboratory in Oncology in South ChinaPrince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina Department of Clinical Oncology Prince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina Department of Imaging and Interventional Radiology Prince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina

Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor(GEP) and ATP-dependent binding cassette(ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. Methods: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low(GEP-/ABCB5-), intermediate(either GEP +/ABCB5-or GEP-/ABCB5 +) and high(GEP +/ABCB5 +). Early recurrence(recurrence within 2 years after resection) and disease-free survival were analyzed. Results: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone( P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. Conclusions: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group(either GEP +/ABCB5-or GEP-/ABCB5 +). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.

关键词： Adjuvant therapy Hepatocellular carcinoma Drug transporter Transarterial chemoembolisation Granulin-epithelin precursor

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Impact of antiviral therapy on post-hepatectomy outcome for hepatitis B-related hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第20期20卷 6006-6012页

作者： charing ching ning chong Grace Lai Hung Wong Paul Bo San Lai Division of Hepato-biliary and Pancreatic Surgery Department of Surgery Prince of Wales Hospital the Chinese University of Hong Kong Institute of Digestive Disease and Department of Medicine and Therapeutics Prince of Wales Hospital the Chinese University of Hong Kong

The outcome after curative resection for hepatocellular carcinoma(HCC)remains unsatisfactory due to the high recurrence rate after surgery.In patients with hepatitis B virus(HBV)-related HCC,which is the majority of patients with HCC in Asia,a high viral load is a strong risk factor for HCC recurrence.It is logical to believe that antiviral therapy may improve the postoperative outcome by promoting viral clearance and hepatocyte regeneration,as well as improving residual liver volume in HCC patients with hepatitis B.However,the effect of antiviral therapy on clinical outcomes after liver resection in patients with HBV-related HCC remains to be established.There are two main groups of antiviral treatment for HBV-oral nucleos(t)ide analogues and interferon.Interferon treatment reduces the overall incidence of HBV-related HCC in sustained re-sponders.However,side effects may limit its long-term clinical application.Nucleos(t)ide analogues carry fewer side effects and are potent in terms of viral suppression when compared to interferon and are typically implemented for patients with more advanced liver diseases.They may also improve the outcome after curative resection for HBV-related HCC.There are increasing evidence to suggest that antiviral therapy could suppress HBV,decrease the perioperative reactivation of viral replication,reduce liver injury,preserve the liver function before and after operation,and may lower the risk of HCC recurrence.After all,antiviral therapy may improve the survival after liver resection by reducing recurrence and delaying the liver damage by the virus,resulting in a higher chance of receiving aggressive salvage therapy during HCC recurrence.

关键词： Antiviral therapy Hepatitis B infection Hepatocell

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Outcomes of emergency and interval hepatectomy for ruptured resectable hepatocellular carcinoma: a single tertiary referral centre experience

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Hepatoma Research 2017年第9期3卷 196-204页

作者： Andrew Kai Yip Fung charing ching ning chong Kit Fai Lee John Wong Yue Sun Cheung Anthony Kwong Wai Fong Paul Bo San Lai Department of Surgery the Chinese University of Hong KongPrince of Wales HospitalHong Kong 999077Hong KongChina

Aim: The short and long term outcomes of patients who underwent emergency and interval hepatectomy for ruptured and resectable hepatocellular carcinoma (HCC) were analysed. Methods: The data of patients with ruptured HCC presenting between April 2004 and October 2015 were analysed. Emergency hepatectomy was defined as hepatectomy within 48 h of the clinico-radiological diagnosis of HCC rupture. Results: Thirty patients underwent hepatectomy for ruptured HCC. Nine (30%) patients underwent emergency hepatectomy. The median age was 56 and 54 years (P = 0.13) with a similar gender distribution. The mean HCC size (10.5 vs. 8.3 cm, P = 0.17), total blood loss (3,000 vs. 850 mL, P = 0.002) and total units of red blood cell transfusion (1.9 vs. 0.5 units, P = 0.27) were greater in the emergency hepatectomy group. The complication rate was 44% and 38% (P = 0.53), with median length of hospital stay of 10 and 12 days (P = 0.07) in the emergency and interval hepatectomy groups, respectively, and no 30-day mortality in both groups. The median overall survival was 29 and 15.7 months (P = 0.25), with survival rates of 78%, 45%, 0% and 85%, 43% and 5% at 1, 3 and 5 years in the emergency and interval hepatectomy groups, respectively. Conclusion: Hepatectomy should be considered for ruptured HCC provided the patient could tolerate curative resection.

关键词： Hepatocellular carcinoma rupture hepatectomy

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International consensus statement on robotic pancreatic surgery

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Hepatobiliary Surgery and Nutrition 2019年第4期8卷 345-360页

作者： Rong Liu Go Wakabayashi Chinnusamy Palanivelu Allan Tsung Kehu Yang Brian KPGoh charing ching-ning chong Chang Moo Kang Chenghong Peng Eli Kakiashvili Ho-Seong Han Hong-Jin Kim Jin He Jae Hoon Lee Kyoichi Takaori Marco Vito Marino Shen-Nien Wang Tiankang Guo Thilo Hackert Ting-Shuo Huang Yiengpruksawan Anusak Yuman Fong Yuichi Nagakawa Yi-Ming Shyr Yao-Ming Wu Yupei Zhao Department of Hepatopancreatobiliary Surgical Oncology Chinese People’s Liberation Army(PLA)General HospitalBeijing 100853China Center for Advanced Treatment of Hepatobiliary and Pancreatic Diseases Ageo Central General HospitalAgeoJapan Division of Gastrointestinal Surgery and Minimal Access Surgery GEM Hospital and Research CentreCoimbatoreIndia Division of Surgical Oncology Gastrointestinal Disease Specific Research GroupThe Ohio State University Wexner Medical Center Department of SurgeryColumbusOHUSA Evidence-Based Medicine Center School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China Department of Hepatopancreatobiliary and Transplant Surgery Singapore General HospitalSingapore Department of Surgery Division of Hepatobiliary and Pancreatic SurgeryPrince of Wales Hospitalthe Chinese University of Hong KongHong KongChina Division of HBP Surgery Yonsei University College of MedicinePancreatobiliary Cancer CenterYonsei Cancer CenterSeverance HospitalSeoulKorea Pancreatic Disease Centre Ruijin HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of General Surgery Galilee Medical CenterNahariyaIsrael Department of Surgery Seoul National University College of MedicineSeoul National University Bundang HospitalSeoulKorea Department of Surgery Yeungnam University HospitalDaeguKorea Department of Surgery The Johns Hopkins HospitalBaltimoreMDUSA Division of Hepatobiliary&Pancreas Surgery Department of SurgeryAsan Medical CenterSeoulKorea Department of Surgery Kyoto University HospitalShogoinSakyo-KuKyotoJapan Department of General Surgery Azienda OspedalieraOspedali Riuniti Villa Sofia-CervelloPalermoItaly Division of General and Digestive Surgery Department of SurgeryKaohsiung Medical University HospitalKaohsiung Department of General Surgery Gansu Provincial HospitalLanzhou 730030China Department of General Visceral and Transplantation SurgeryHeidelberg University HospitalHeidelbergGermany Division of General Surge

The robotic surgical system has been applied to various types of pancreatic surgery. However, controversies exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. This study aimed to evaluate the current status of robotic pancreatic surgery and put forth experts' consensus and recommendations to promote its development. Based on the WHO Handbook for Guideline Development, a Consensus Steering Group* and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 19 topics were analyzed. The first 16 recommendations were generated by GRADE using an evidence-based method (EBM) and focused on the safety, feasibility, indication, techniques, certification of the robotic surgeon, and cost-effectiveness of robotic pancreatic surgery. The remaining three recommendations were based on literature review and expert panel opinion due to insufficient EBM results. Since the current amount of;evidence was low/meager as evaluated by the GRADE method, further randomized controlled trials (RCTs) are needed in the future to validate these recommendations.

关键词： Robotic surgery consensus statement pancreatectomy pancreaticoduodenectomy pancreatic enucleation

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Current status and future applications of contrast-enhanced endoscopic ultrasonography

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World Journal of Gastrointestinal Endoscopy 2014年第4期6卷 121-127页

作者： Hon Chi Yip Anthony Yuen Bun Teoh charing ching ning chong James Yun Wong Lau Department of Surgery Princeof Wales Hospitalthe Chinese University of Hong Kong Institute of Digestive Disease Chinese University of Hong Kong

Endoscopic ultrasonography(EUS) is currently an in-tegral investigation of many gastrointestinal disorders.It has been shown to have a higher efficacy thanconventional computed tomography in detection andcharacterization of small lesions especially in the pan-creas. Much effort has been put to further improvethe sensitivity, specificity and overall accuracy of EUS.One of the major advances is the utilization of contrastagents for better delineation of the vascularity and tis-sue perfusion of the target lesion. This article describesthe basic principles of ultrasound contrast agents andthe different modalities used in contrast-enhanced EUS(CE-EUS) including contrast-enhanced Doppler EUS(CED-EUS) and contrast-enhanced harmonic EUS(CEH-EUS). In addition, the current applications of contrastenhanced EUS in different gastrointestinal conditionswere discussed. Furthermore, the future developmentof hybrid approaches combining CE-EUS with other im-aging modalities and the potential therapeutic aspectof using it as a vector for drug delivery were also dis-cussed.

关键词： Endoscopic ultrasonography Contrastenhanced endoscopic ultrasonography Advanced endoscopic ultrasonographic imaging

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Feasibility of gallbladder preservation during robotic left hepatectomy:A retrospective comparative study

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Laparoscopic, Endoscopic and Robotic Surgery 2022年第3期5卷 100-105页

作者： Kit-Fai Lee Andrew KY.Fung Hon-Ting Lok Janet WC.Kung Eugene YJ.Lo charing CN.chong John Wong Kelvin KC.Ng Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina

Objective:Traditionally,gallbladder is routinely removed during left hepatectomy even if there is no gallbladder pathology.However,adverse consequence after cholecystectomy,though rare,still occa-sionally occurs.This study aims to evaluate the feasibility of gallbladder preservation during robotic left hepatectomy.Methods:All consecutive robotic left hepatectomy cases between December 2010 and January 2022 in Prince of Wales Hospital,the Chinese University of Hong Kong were retrieved from a prospectively collected database.The gallbladder was preserved by moving the liver transection line just away from the gallbladder fossa.Patients were divided into two groups:gallbladder preservation(GBP)and non-gallbladder preservation(NGBP).Operative results and long-term outcomes were compared between these two groups.Results:There were 11 cases in the GBP group and 25 cases in the NGBP group.The two groups were comparable in terms of the patient demographics and disease characteristics.There was no operative mortality.There was no difference between the two groups in operative time(GBP 270 min vs.NGBP 332 min,p=0.132),blood loss(GBP 50 mL vs.NGBP 150 mL,p=0.115)or complication rate(GBP 27.3%vs.NGBP 24.0%,p>0.999).There was also no difference in 5-year overall survival.In the GBP group,no patient developed specific symptoms or complications related to the preserved gallbladder.Follow-up ultrasound or computed tomography revealed a normal appearance of the preserved gallbladders except in one patient who developed a 3-mm gallbladder polyp.On the other hand,one(4%)patient in the NGBP group developed troublesome diarrhoea after surgery.Conclusion:Gallbladder preservation is safe and feasible during robotic left hepatectomy.The preserved gallbladder does not lead to any symptoms,while postcholecystectomy diarrhoea can be avoided.

关键词： Robotic left hepatectomy Gallbladder preservation Cholecystectomy

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The Hong Kong consensus statements on unresectable hepatocellular carcinoma:narrative review and update for 2021

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 366-385页

作者： Tan-To Cheung Simon Chun-Ho Yu Stephen L.Chan Ronnie T.P.Poon Philip Kwok Ann-Shing Lee Anna Tai Derek Tam Chin-Cheung Cheung Tak-Wing Lai Nam-Hung Chia Ada Law Tracy Shum Yim-Kwan Lam Vince Lau Victor Lee charing chong Chung-Ngai Tang Thomas Yau Department of Surgery Queen Mary HospitalThe University of Hong KongHong KongChina Department of Imaging&Interventional Radiology Prince of Wales HospitalThe Chinese University of Hong KongHong KongChina State Key Laboratory of Translational Oncology and Department of Clinical Oncology Sir YK Pao Centre for CancerPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina Department of Radiology and Imaging Queen Elizabeth HospitalHong KongChina Department of Clinical Oncology Tuen Mun HospitalHong KongChina Department of Clinical Oncology Queen Elizabeth HospitalHong KongChina Department of Surgery United Christian HospitalHong KongChina Department of Surgery Tuen Mun HospitalHong KongChina Department of Surgery Princess Margaret HospitalHong KongChina Department of Surgery Queen Elizabeth HospitalHong KongChina Department of Clinical Oncology Pamela Youde Nethersole Eastern HospitalHong KongChina Department of Clinical Oncology Princess Margaret HospitalHong KongChina Department of Medicine and Geriatrics United Christian HospitalHong KongChina Department of Radiology Queen Mary HospitalHong KongChina Department of Clinical Oncology Queen Mary HospitalThe University of Hong KongHong KongChina Department of Surgery Prince of Wales HospitalThe Chinese University of Hong KongHong KongChina Department of Surgery Pamela Youde Nethersole Eastern HospitalHong KongChina Department of Medicine Queen Mary HospitalThe University of Hong KongHong KongChina

Background and Objective:Hong Kong,like many parts of Asia,faces a high burden of hepatocellular carcinoma(HCC)caused by high endemic rates of hepatitis B virus infection.Hong Kong clinicians have developed a high level of expertise in HCC treatment across surgical,transarterial,ablative,radiotherapeutic and systemic modalities.This publication summarizes the latest evidence-based recommendations on how these modalities should be used.Methods:In two meetings held in 2020,a multidisciplinary panel of surgeons,oncologists and interventional radiologists performed a narrative review of evidence on the management of HCC,with an emphasis on treatment of HCC not amenable to surgical resection.Close attention was paid to new evidence published since the previous version of these statements in 2018.Key Content and Findings:The expert panel has formulated 60 consensus statements to guide the staging and treatment of unresectable HCC.Since the previous version of these statements,considerable additions have been made to the recommendations on use of targeted therapies and immunotherapies because of the large volume of new evidence.Conclusions:Our consensus statements offer guidance on how to select HCC patients for surgical or non-surgical treatment and for choosing among non-surgical modalities for patients who are not candidates for resection.In particular,there is a need for more evidence to aid physicians in the selection of second-line systemic therapies,as currently most data are limited to patients with disease progression on first-line sorafenib.

关键词： Hepatocellular carcinoma(HCC) Hong Kong guidelines consensus

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Robot-assisted minimally invasive procedures for complicated biliary stone disease

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Hepatobiliary Surgery and Nutrition 2018年第3期7卷 185-188页

作者： Kit Fai Lee Andrew K. Y. Fung Hon Ting Lok Anthony K. W. Fong charing C. N. chong Paul B. S. Lai Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina

Introduction A big advancement in endoscopic management for biliary stone diseases was seen in the past three decades. Bile duct stones can be removed after sphincterotomy or balloon sphincteroplasty with stone basket... 详细信息

关键词： balloon biliary diseases

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Pattern of disease recurrence and its implications for postoperative surveillance after curative hepatectomy for hepatocellular carcinoma: experience from a single center

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Hepatobiliary Surgery and Nutrition 2018年第5期7卷 320-330页

作者： Kit-Fai Lee charing C. N. chong Anthony K. W. Fong Andrew K. Y. Fung Hon-Ting Lok Yue-Sun Cheung John Wong Paul B. S. Lai Department of Surgery Division of Hepatobiliary and Pancreatic Surgery Prince of Wales Hospital the Chinese University of Hong Kong Hong Kong China

Background: Hepatectomy is a widely accepted curative treatment for hepatocellular carcinoma (HCC). However, the disease frequently recurs after a curative hepatectomy. The objective of this study is to provide a better understanding of the pattern of disease recurrence and the risk factors involved so as to improve the postoperative surveillance. Methods: A retrospective study for all patients receiving hepatectomy for HCC between 2003 and 2014 was performed. Emphasis was made on the timing and pattern of recurrent disease, and type of treatment given. Results: There were 506 patients in the study. Median follow-up was 43.7 months. The 1-, 3-, 5-, 10-year overall and disease free survival were 89.5%, 74.1%, 63.9%, 49.0% and 69.5%, 54.3%, 43.4%, 30.9%respectively. Recurrent disease occurred in 267 patients, 47.2% occurred within 9 months of hepatectomy and 80.1% recurred only in liver. Median survival was shorter for recurrence occurring within 9 months compared with those occurring between 10 months and 2 years postoperatively (36.2 vs. 65.7 months, P3.5 cm and history of rupture were risk factors for recurrence within 9 months. Conclusions: These findings suggest that recurrent diseases are common after curative hepatectomy for HCC and most recurrences occur in the remnant liver. Since almost half of recurrences occurred within first 9 months after hepatectomy, a more stringent postoperative surveillance with target imaging of liver in this period is needed. Early diagnosis of recurrent disease and curative retreatment hopefully can bring about a longer survival.

关键词： Hepatectomy hepatocellular carcinoma (HCC) recurrence

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Management of hepatocellular carcinoma with portal vein tumor thrombosis: Review and update at 2016

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World Journal of Gastroenterology 2016年第32期22卷 7289-7300页

作者： Stephen L Chan charing CN chong Anthony WH Chan Darren MC Poon Kenneth SH Chok State Key Laboratory in Oncology of South China Institute of Digestive Disease The Chinese University of Hong Kong Department of Clinical Oncology Sir YK Pao Center for Cancer Hong Kong Cancer Institute The Chinese University of Hong Kong Prince of Wales Hospital Department of Surgery Prince of Wales Hospital The Chinese University of Hong Kong State Key Laborator in Oncology of South China Department of Anatomical and Cellular Pathology The Chinese University of Hong Kong Department of Surgery Queen Mary Hospital The University of Hong Kong

Portal vein tumor thrombosis(PVTT) is a common phenomenon in hepatocellular carcinoma(HCC). Compared to HCC without PVTT, HCC with PVTT is characterized by an aggressive disease course, worse hepatic function, a higher chance of complications related to portal hypertension and poorer tolerance to treatment. Conventionally, HCC with PVTT is grouped together with metastatic HCC during the planning of its management, and most patients are offered palliative treatment with sorafenib or other systemic agents. As a result, most data on the management of HCC with PVTT comes from subgroup analyses or retrospective series. In the past few years, there have been several updates on management of HCC with PVTT. First, it is evident that HCC with PVTT consists of heterogeneous subgroups with different prognoses. Different classifications have been proposed to stage the degree of portal vein invasion/thrombosis, suggesting that different treatment modalities may be individualized to patients with different risks. Second, more studies indicate that more aggressive treatment, including surgical resection or locoregional treatment, may benefit select HCC patients with PVTT. In this review, we aim to discussthe recent conceptual changes and summarize the data on the management of HCC with PVTT.

关键词： Liver cancer Vascular invasion Targeted agent Surgery Radiotherapy

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