Current Surgical treatment of Hepatocellular Carcinoma Edward C.S. Lai 黎卓先 MS(HKU), FRCS(Ed),FRACS,FCSHK, FHKAM, FACS
Hepatocellular Carcinoma : Epidemiology 5th commonest cancer worldwide Annual incidence of 1 million cases > 70 % of cases in Asia In Hong Kong 2nd leading cause of cancer death cancer death 85% HBsAg-positive >95% anti-hbc-positive Parkin et al, Global Cancer Statistics 2002, CA Cancer J Clin 2005
Hepatocellular carcinoma : Presentations Subclinical All HBs Ag & HC patients Every 6 months : AFP assay + Ultrasound Liver (tumor doubling time = 4mth) 20% of small HCC (<5 cm size) normal AFP Small cirrhotic liver +/- Ascites, CT with IV contrast Symptomatic Weight loss; Increasing ascites; Abdominal mass Jaundice; GIB from Peptic ulcer +/- varices Emergency All male > 40 yo with sudden pain/shock from hemoperitoneum Consider Ruptured HCC
Hepatocellular carcinoma: Evaluation of Resectability Computed Tomography + IV contrast Relationship with Major hepatic veins Patency of Main Portal vein Volumetry of residual liver remnant Intra-hepatic metastases Laboratory tests Complete blood picture Hgb; Platelet Liver function test AST/ALT; Bilirubin; Albumin Prothrombin time; AFP; HBV-DNA Indocyanine Green (ICG) retention rate @ 15 minutes Cardio-pulmonary status + General condition Anatomical Functional General
Hepatocellular carcinoma : Evaluation with Computed tomography MHV MHV RHV RHV LHV LHV MHV MHV
Hepatocellular carcinoma : Portal vein thrombectomy for invasion
Hepatocelular carcinoma : CT Volumetry
Liver Resection : Liver volume by CT Volumetry Total liver volume (ml) 1518 + 353 Rt lobe (ml) 997 (66.6) Lt lobe (ml) 493 (33.3) Lt lateral segment (ml) 242 (16) Rt/ TLV (%) 49 ~ 82 Lt/TLV (%) 17 ~ 49 LLS/TLV (%) 5 ~ 27 MDACC; Prospective study x 102 patients Lt lobe < 25%-TLV in > 10% population Lt lateral segment < 20% in > 75% population Abdalla; Surgery, 2004
Hepatocellular Carcinoma : Determinants for Successful Surgical outcome 肝臟功能評估 普通肝功 : 膽紅素 ; 白蛋白特別肝功 ; Indocyanine green retention rate 餘肝體積量度 經電腦掃描體積量度肝實質犧牲體積比例 CT Volumetry Parenchymal resection rate 手術創傷 同温斷流時間失血量 : 肝硬化程度 + 切割面積主刀技術
肝臟切除 : 術前肝功評估 + 風險預測 Prediction score = -84.6 + 0.933 PHRR + 1.11 ICG R15 + 0.999 age Yamanaka ; Ann Surg 1994 ICG R15 > 14%; 3 倍手術風險 Lau; Br J Surg, 1998 Parenchymal hepatic resection rate; PHRR Indocyanine green retention rate at 15 min; ICG R15
Hepatocelular carcinoma : Preoperative Portal vein embolization
Hepatocelular carcinoma : Preoperative Portal vein embolization Triple-lumen balloon catheter 術前 術後
Hepatocelular carcinoma : Preoperative Portal vein embolization 術前 術後
Hepatocellular Carcinoma : Therapeutic options 全身化療 Systemic chemotherapy 經肝動脈血管栓塞化療 Trans-arterial oily chemo-embolization (TOCE) 射頻消融療法 Radio-frequency ablation (RFA) 肝臟切除 Liver resection / Hepatectomy 肝臟移植 Liver transplantation
Hepatocellular carcinoma : Trans-arterial Oily Chemo-embolization (TOCE) Common femoral artery puncture at groin and selective cannulation of tumor-feeding branch of Hepatic artery (Trans-Arterial) Hypervascular lesion with no AV shunting (patent PV) Emulsion of Lipiodol (Oily contrast) -10mL + Cisplatin (Chemotherapeutic agent) By manual mixing between 2 x 20 ml syringes through 3-way Manual injection of emulsion until no further injection possible Embolization with Gelfoam Keep pressure-dressing & limited mobility x 12 hours Conservative treatment for fever, vomiting Long-term gallbladder problem
Hepatocellular carcinoma : TOCE : Indications & Contraindications Indications : Inoperable or Recurrent HCC, especially > 2 foci Temporizing measure before surgery Medical problems Emergency - Ruptured HCC with bleeding Contraindications : Poor liver function Total bilirubin > 50 µmmol/l Gross AV shunting Blocked PV branch NEVER for Operable HCC before surgery
Malignant Liver tumors : Chronological changes in Procedures at 13 Asian centers Year Surgery TACE PEI RFA MW 1998 391(8.0) 3731(76.6) 681(14) 1(0.0) 67(1.4) 1999 465(8.1) 4214(73.8) 457(8.0) 550(9.6) 25(0.4) 2000 484(7.7) 4668(73.9) 224(3.5) 925(14.6) 18(0.3) 2001 703(8.6) 6073(74.7) 140(1.7) 1216(14.9) 3(0.0) 2002 890(9.8) 6757(74.5) 56(0.6) 1364(15.0) 3(0.0) Total 2933(8.6) 25443(74.6) 1558(4.6) 4056(11.9) 116(0.3) Rhim; Int J Hyperthermia, 2004
射頻消融法 : 體外超聲波導引穿刺
射頻消融法 : 經腹腔鏡超聲波導引
射頻消融法 : 經剖腹 + 術中超聲波 7.5 cm
射頻消融法 : 術後電腦掃描變化 術前 術後 1 天 術後 30 天
Radio-frequency ablation for Liver tumors: Summary of Experiences Patient selection : Limited volume for ablation : Tumor < 4cm Previous bilio-enteric anastomosis Peri-operative management : Close cardiac monitoring (arrythmia) Adequate hydration hemoglobinuria (proximity to major blood vessels) Technical details : Position of needle tip Deep margin - 0.5 cm from tip Lateral margin 1.5 cm Duration of ablation 6 8 min (Suggest :12 min ) Prior needle placement for multiple ablation Bile duct cooling Open vs Percutaneous Higher morbidity Better complete ablation
肝癌切除 : 術式命名 右半肝 (S5 ~ 8) 左半肝 (S2 ~ 4) 右後葉 (S6+7) 7 8 4 2 6 5 3 左內葉 (S 4) 左外葉 (S 2+3) 右前葉 (S5+8) 中肝靜脈 鐮狀韌帶 右肝靜脈
Hepatectomy for Hepatocellular carcinoma : 343 patients at Queen Mary Hospital 72 ~ 87 87 ~ 91 92 ~ 94 No. of patients 149 128 66 ~ 91 Resectability (%) 14 20 23 Emergency (n) 14 3 0 Pringle (%) 8.7 96.2 51.6 Subcostal (n) 4 97 62 Blood loss (L) 3.2 2.9 3.3 30-day mortality (%) 14 9.4 4.5 Hospital mortality (%) 21.5 14.8 6 Lai; Ann Surg, 1995
Hepatectomy for Hepatocellular carcinoma : Towards Zero Hospital mortality 92 93 94 95 96 97 No. of patients 30 35 33 39 52 56 Major hepatectomy (%) 67 74 79 64 63 61 Blood loss (L) 3.5 1.6 1.5 1.5 1.7 1 Transfusion (L) 1.8 0.9 0 0 0 0 No transfusion (%) 6 29 58 67 52 77 Complication (%) 40 37 30 36 35 38 Hospital mortality (%) 6 6 3 5 0 0 Fan; Ann Surg, 1999
肝臟切除 : 切口選擇 屋頂式 右腔腹式 - 反 "J" 型
肝臟切除 : 術中超聲波應用 主要血管定位 隱蔽病灶定位 肝段門靜脈注射 / 反注射
Hepatoecellular Hepatoecellular carcinoma carcinoma :: Preservation Preservation of of hepatic hepatic parenchyma parenchyma
Hepatectomy for Hepatocellular carcinoma : Pringle maneuver - RCT Pringle Control No. of patients (n) 50 50 Total blood loss (L) 1.28 1.99 Blood loss/area (ml/cm2) 12 22 Blood transfusion (L) 0 0.6 No transfusion (%) 32 21 Transection time (min) 138 169 Transection time/area (min/cm2) 2 2.8 # # # p > 0.05 Experience of surgeons : <50, >200; Liver status Man; Ann Surg, 1997
肝臟切除 : 超聲刀的應用
肝癌切除 : 遠期成績 - 1989 ~ 2002 100 Cumulative Survival (%) 80 60 40 20 N = 694 Median survival = 47 months Median DF survival = 16 months Overall survival Disease free survival 0 0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 Survival time (months) Queen Mary Hospital
肝癌治療方案選擇 嚴格甄選程序 手術切除為首選治療方法 術前 TAE/ TOCE + 全身化療 不能改善病者術後遠景對手術造成負面影響 肝臟移植 手術切除機會排除挑選條件 : 肝瘤大小及數目, 肝內血管侵反 術後加強性治療 選擇性
Hepatocellular carcinoma: Expectations for Hepatectomy in 2013 Overall risk :3-5% Intraoeprative blood loss:1000ml under Normal hemoglobin : No peri-operative transfusion (90%) Normal cardio-pulmonary status,no ICU Resumption of oral feeding at 24 hr after surgery Discharge at Day 5 depending on cirrhosis Laparoscopic hepatectomy for selected site & size
Laparoscopic Hepatectomy : Current Status Small lesions at different Laparoscopic segments with acceptable degree of cirrhosis - candidates Standard techniques in Open surgery should be used for laparoscopic liver resection Variations such as gasless surgery; Hand-assisted devices are useful depending on individual center Superior peri-operative and comparable long-term outcomes with Open surgery were observed with malignant tumors Right hepatectomy remains a technical challenge
經腹腔鏡肝臟切除 : 合適位置 II V IVb III VI Mouiel; JHBPS, 2000
Hepatocellular carcinoma: Liver Transplantation 肝移植 Pros 優點 : Extends limit of resection 適用範圍超過肝切除術 Removes multicentric tumor/intrahepatic metastasis 去除多中心腫瘤及肝内轉移 Prevents metachronous disease 預防多中心肝癌 Prevents liver failure 預防肝功能衰竭 Cons 缺點 : Higher operative risk 手術風險高 Expensive 費用昂貴 Need for immunosuppression 需要免疫抑制劑 Limited organ supply 供體有限
Hepatocellular carcinoma: Patient Survival 病人存活率 Limited graft supply Equitable allocation 有限的供體公平的分配 NOT selecting the best treatment for the patient BUT selecting the best patient for the treatment 不是為病人選擇最好的治療方法而是選擇最適宜的病人 Patient survival (%) 100 90 80 70 60 50 40 30 20 10 0 cirrhosis HCC 0 12 24 36 48 60 Months
Hepatocellular carcinoma: Transplantation -Selection Criteria Tumor number/size based on pre-transplant imaging 腫瘤數量及大小取决於移植前影像 Criteria n long-term survival Milan solitary 5 cm 48 75% (NEJM 1996) 1-3 lesions, 3 cm USCF solitary 6.5 cm 70 72.4% (Hepatology 2001) 1-3 lesions, 4.5 cm total diameter 8 cm Expected 5-year survival >70% Recurrence <10%
Hepatocellular carcinoma: Liver Transplantation: Cadaver Graft Limited availability 供應有限 restricted candidacy 有限的供體 Prolonged waiting time 延長等待時間 tumor progression and dissemination 腫瘤進展和播散 Unpredictable timing 時間不確定 impossible to plan neoadjuvant treatment 不可能安排新輔助治療 need repeated staging of tumor 需要重複腫瘤分期
Hepatocellular carcinoma: Liver Transplantation: Cadaver vs Living Donor Cadaver donor Living donor 屍肝 活體肝 Availability Source 來源 Limited 有限 Unlimited 無限 Candidacy 受體 Maximal benefit Risk/benefit analysis 最大受益 風險 / 受益分析 Allocation 分配 Objective criteria Dedicated gift 客觀標準 指定禮物 Waiting time Long Short 等候時間 長 短 Timing Unpredictable Planned 手術時間 不可預知 擇期手術