What's Hot and What's not in Hepatobiliary Surgery? Dr. Subash Gupta Gyan Burman Liver Surgery Unit Sir Ganga Ram Hospital New Delhi

Looked at five journals Annals of surgery Journal of American College of Surgeons British journal of surgery HPB surgery World journal of surgery Discuss mainly Annals of Surgery articles in last one year

Papers selected Improved mortality after liver resection Liver Transplantation for HCC Radiofrequency ablation for liver tumours LDLT without blood products Bioartificial liver support Non heart beating liver donation

FDG-PET staging for colorectal liver metastasis 3-D virtual cholangioscopy Delayed cholecystectomy after pancreatitis Extended hepatectomy LDLT for cholangiocarcinoma

Arch Surg. 2003 Nov; 138(11): 1198-206; discussion 1206 Arch Surg. 2003 Nov; 138(11): 1198-206; discussion 1206. One thousand fifty-six hepatectomies without mortality in 8 years. Imamura H, Seyama Y, Kokudo N, Maema A, Sugawara Y, Sano K, Takayama T, Makuuchi M. Division of Hepato-Biliary-Pancreatic Surgery and Artificial Organ and Transplantation, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. CONCLUSIONS: Liver resection can be performed without mortality provided that it is carried out in a high-volume medical center by well-trained hepatobiliary surgeons paying meticulous attention to the balance between the liver functional reserve and the volume of liver to be removed.

Comments High volume hepatobiliary centre 532 hepatocellular cancers 80% are cirrhotic Only a small percentage were colorectal metastasis Liver functional reserve and liver remnant volume

How has this been achieved? Torzilli Arch Surg, 1999, no mortality after 107 consecutive resections, Ascites, serum bilirubin, ICG 15 <14% Precise delineation of vascular relations using CT angiography and volumetry

Assessment of liver reserve Child-Pugh scoring, Class B and above ICG clearance at 15 minutes, retention > 14% bad risk 99m-Tc-galactosyl human serum albumin Functional scintigraphy Needs validation by comparing with outcome So far it has only been compared with CP grade

Low CVP. Vascular inflow occlusion, Ischaemic preconditioning Clavien Ann Surg 2003 CUSA, harmonic scalpel (laparoscopic resection), bipolar drip diathermy, Argon beam coagulator

Annals of Surgery. 240(3):451-461, September 2004 Annals of Surgery. 240(3):451-461, September 2004. Japanese Study Group on Organ Transplantation Living Donor Liver Transplantation for Adult Patients With Hepatocellular Carcinoma: Experience in Japan Results: Currently, 236 (74.7%) of the patients are living. One- and 3-year patient survivals were 78.1% and 69.0%, respectively. Conclusion: LDLTx can achieve acceptable survival in HCC patients, even when liver function is markedly impaired, or HCC is uncontrollable by conventional antitumor treatments.

Comments I Milan criteria, 3 nodules, single nodule < 5 cm in size 316 patients with HCC Milan criteria, disease free survival 79% Beyond Milan, disease free survival 52% LRLT: no issue of better utilization of scarce cadaveric donor livers! Priority for HCC in new MELD scoring

Comments II Fan ST, BJS, leading article Donor safety Right lobe grafts results 64% vs. 74% three year survival May require cadaveric graft for retransplantation Resection and salvage transplantation Rather than primary OLtx

Annals of Surgery. 240(5):900-909, November 2004 Mazzaferro, Milan Group Radiofrequency Ablation of Small Hepatocellular Carcinoma in Cirrhotic Patients Awaiting Liver Transplantation: A Prospective Study Conclusions: RFA is a safe and effective treatment of small HCC in cirrhotics awaiting OLT, although tumor size (>3 cm) and time from treatment (>1 year) predict a high risk of tumor persistence in the targeted nodule. RFA should not be considered an independent therapy for HCC.

Annals of Surgery. 240(1):102-107, July 2004 Annals of Surgery. 240(1):102-107, July 2004., Vivarelli, Marco et al Department of Surgery and Transplantation, University of Bologna and Verona, Verona, Italy. Surgical Resection Versus Percutaneous Radiofrequency Ablation in the Treatment of Hepatocellular Carcinoma on Cirrhotic Liver. One- and 3-year survival were 78 and 33%; 1- and 3-year disease-free survival were 60 and 20%. Overall and disease-free survival were significantly higher in group A (P = 0.002 and 0.001). The advantage of surgery was more evident for Child-Pugh class A patients and for single tumors of more than 3 cm in diameter. Results were similar in 2 groups for Child-Pugh class B patients Conclusions: RFA has still to be confirmed as an alternative to surgery for potentially-resectable HCCs.

Is RFA stand alone treatment for HCC? Complete response rate only 55% (63% for <3 cm) > 3 cm in size and > 1 year wait for OLTx High rate of recurrence in explanted liver Child’s B group, RFA and surgical resection similar survival, therefore they should be transplanted Not an independent therapy for HCC!

Live Donor Liver Transplantation Without Blood Products: Strategies Developed for Jehovah's Witnesses Offer Broad Application Jabbour, Nicolas et al, Departments of Surgery and Medicine, Keck School of Medicine, University of Southern California; and USC University Hospital, Transfusion Free Medicine and Surgery, Los Angeles, CA. All transfusion-free patients underwent preoperative blood augmentation with erythropoietin, intraoperative cell salvage, and acute normovolemic hemodilution. These techniques were used in only 7%, 80%, and 10%, respectively, in transfusion-eligible patients.

Any surgery in Jehovah’s witnessess is fraught with worry 38 patients were operated without blood products Erythropoietin Acute normovolemic haemodilution Meticulous surgical technique Cell saver

Annals of Surgery. 239(5):660-670, May 2004 Annals of Surgery. 239(5):660-670, May 2004. Demetriou, Achilles Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure Results: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL versus 59% for control (n = 147; P = 0.12). When survival was analyzed accounting for confounding factors, in the entire patient population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio = 0.56; P = 0.048).

What's new? Acute liver failure (ALF) is a disease with a high mortality Standard therapy at present is liver transplantation. Liver transplantation is hampered by the increasing shortage of organ donors, BAL therapy is marked as the most promising solution to bridge ALF patients to liver transplantation or to liver regeneration, Bioartificial liver therapy for bridging patients with ALF to liver transplantation or liver regeneration is promising. Its clinical value awaits further improvement of BAL devices, replacement of hepatocytes of animal origin by human hepatocytes, and assessment in controlled clinical trials.

Ann Surg. 2004 Sep;240(3):438-47; Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET). Fernandez FG, Drebin JA, Linehan DC, Dehdashti F, Siegel BA, Strasberg SM. Section of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. RESULTS: One hundred patients (56 men, 44 women) were studied. Metastases were synchronous in 52, single in 63, unilateral in 78, and <5 cm in diameter in 60. Resections were major (>3 segments) in 75 and resection margins were > or = 1 cm in 52. Median follow up was 31 months, with 12 actual greater than 5-year survivors. There was 1 postoperative death. The actuarial 5-year overall survival was 58% (95% confidence interval, 46-72%). Primary tumor grade was the only prognostic variable significantly correlated with overall survival.

Reasons 19 studies (6070 patients) 30% median 5-year survival Results not improved in recent studies Operative mortality <2% FDG-PET scan detects 25% extrahepatic disease Primary tumor grade was the only prognostic variable significantly correlated with overall survival A resection margin which was often less than 1cm but microscopically negative Poor for HCC and false negative for patients on chemotherapy

Annals of Surgery. 240(6):1002-1012, December 2004. One Hundred Thirty-Two Consecutive Pediatric Liver Transplants Without Hospital Mortality: Lessons Learned and Outlook for the Future Departments of Surgery, Pediatrics, Radiology, and Anesthesiology, University Hospital Eppendorf, University of Hamburg, Hamburg, Germany. Conclusions: Progress during the past 15 years has enabled us to perform pediatric liver transplantation with near perfect patient survival. Advances in post transplant care of the recipients, technical refinements, standardization of surgery and monitoring, and adequate choice of the donor organ and transplantation technique enable these results, which mark a turning point at which immediate survival after transplantation will be considered the norm. The long-term treatment of the transplanted patient, with the aim of avoiding late graft loss and achieving optimal quality of life, will become the center of debate.

Highlights Most important prognostic factor Multivariate analysis the year of transplantation Only 3 recipients (2%) died during further follow-up Sixteen children (12%) had to undergo retransplantation This paper marks a turning point at which immediate survival after transplantation will be considered the norm!

Annals of Surgery. 239(1):87-92, January 2004 Annals of Surgery. 239(1):87-92, January 2004. Abt, Peter L et al Department of Surgery, University of Pennsylvania, Philadelphia, PA; and University of Colorado Health Sciences Center, Division of Gastroenterology-Hepatology, Denver, CO. Survival Following Liver Transplantation From Non-Heart-Beating Donors Conclusions: Graft and patient survival is inferior among recipients of NHBD livers. NHBD donors remain an important source of hepatic grafts; however, judicious use is warranted, including minimization of cold ischaemia and use in stable recipients.

Important paper NHBD HBD n 144 26,856 One year survival 70.2% 80% 63% 72% Primary non function 11.8% 6.4%

Prolonged cold ischaemia Recipient on life support Scarce resource Prolonged cold ischaemia Recipient on life support Importance can not be ignored in India Where very few brain dead donors

Detailed preoperative reconstruction of biliary anatomy and Annals of Surgery. 240(1):82-88, July 2004. Three-Dimensional Virtual Cholangioscopy: A Reliable Tool for the Diagnosis of Common Bile Duct Stones. Simone, Michele Strasbourg, France Detailed preoperative reconstruction of biliary anatomy and Reliable identification of choledocholithiasis Acceptable sensitivity and specificity in a clinical setting. Newer software developments may further enhance its accuracy Replace more invasive diagnostic measures in the near future.

Annals of Surgery. 240(1):95-101, July 2004 Annals of Surgery. 240(1):95-101, July 2004. Kondo, Satoshi et al Department of Surgical Oncology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan. Forty Consecutive Resections of Hilar Cholangiocarcinoma With No Postoperative Mortality and No Positive Ductal Margins: Results of a Prospective Study Results: Hospital or 30-day mortality and morbidity rates were 0% and 48%, respectively. Hepatic failure was not encountered. Histopathologic examination revealed no positive ductal margins in all 40 patients, but 2 showed positive separation margins from the right hepatic artery. The overall 3-year survival rate and median survival time were 40% and 27 months. Survival of patients with Bismuth type III or IV tumors or of patients who underwent right hepatectomy was significantly better. Survival of patients who underwent concomitant vascular resection was similar to survival of those who did not. Univariate analysis indicated the type of hepatectomy, histopathologic grade, Bismuth classification, concomitant hepatic artery resection, and International Union Against Cancer stage as significant prognostic factors.

Preoperative biliary decompression Portal vein embolization No positive ductal margins

Annals of Surgery. 239(6):741-751, June 2004 Annals of Surgery. 239(6):741-751, June 2004. Nealon, William Departments of Surgery and Radiology, University of Texas Medical Branch, Galveston, TX. Appropriate Timing of Cholecystectomy in Patients Who Present With Moderate to Severe Gallstone-Associated Acute Pancreatitis With Peripancreatic Fluid Collections Conclusion: Cholecystectomy should be delayed in patients who survive an episode of moderate to severe acute biliary pancreatitis and demonstrate peripancreatic fluid collections or pseudocysts until the pseudocysts either resolve or persist beyond 6 weeks, at which time pseudocyst drainage can safely be combined with cholecystectomy.

Delaying cholecystectomy may aggravate another episode of pancreatitis If pseudocyst does not resolve, may need surgery Early ERCP in biliary pancreatitis may improve outcome No data was available to guide timing of cholecystectomy Complication rates were higher in the early group(5.5% versus 44%)

Annals of Surgery. 239(2):265-271, February 2004 Annals of Surgery. 239(2):265-271, February 2004. Spanish Experience in Liver Transplantation for Hilar and Peripheral Cholangiocarcinoma Results: The actuarial survival rate for hilar cholangiocarcinoma at 1, 3, and 5 years was 82%, 53%, and 30%, and for peripheral cholangiocarcinoma 77%, 65%, and 42%. The main cause of death, with both types of cholangiocarcinoma, was tumor recurrence (present in 53% and 35% of patients, respectively). Poor prognosis factors were vascular invasion (P < 0.01) and IUAC classification stages III-IVA (P < 0.01) for hilar cholangiocarcinoma and perineural invasion (P < 0.05) and stages III-IVA (P < 0.05) for peripheral cholangiocarcinoma.

Comments Requires correct staging, no lymph nodes, essentially those with vascular invasion, or poor liver function Unresectable cholangiocarcinoma no 5 year survival 30% five year survival and 42% for peripheral cholangiocarcinoma Good results by oncology standards but not for liver transplant operation Is it right to subject a healthy donor to risks?

Annals of Surgery. 239(5):722-732, May 2004 Annals of Surgery. 239(5):722-732, May 2004. Vauthey, Jean-Nicolas Departments of Surgical Oncology and Anesthesiology, the University of Texas M.D. Anderson Cancer Center, Houston, TX. Is Extended Hepatectomy for Hepatobiliary Malignancy Justified? Results: The patients underwent extended hepatectomy for colorectal metastases (n = 86; 67.7%), hepatocellular carcinoma (n =12; 9.4%), cholangiocarcinoma (n =14; 11.0%), and other malignant diseases (n =15; 11.5%). Thirty-two left and ninety-five right extended hepatectomies were performed. Eight patients also underwent caudate lobe resection, and 40 patients underwent a synchronous intraabdominal procedure. Twenty patients underwent radiofrequency ablation, and 31 underwent preoperative portal vein embolization. The median blood loss was 300 mL for right hepatectomy and 600 mL for left hepatectomy (P = 0.02). Thirty-six patients (28.3%) received a blood transfusion. The overall complication rate was 30.7% (n = 39), and the operative mortality rate was 0.8% (n = 1). Significant liver insufficiency (total bilirubin level > 10 mg/dL or international normalized ratio > 2) occurred in 6 patients (4.7%). Multivariate analysis showed that a synchronous intraabdominal procedure was the only factor associated with an increased risk of morbidity (hazard ratio [HR], 4.9; P = 0.02). The median survival was 41.9 months. The overall 5-year survival rate was 25.5%. Conclusions: Extended hepatectomy can be performed with a near-zero operative mortality rate and is associated with long-term survival in a subset of patients with malignant hepatobiliary disease. Combining extended hepatectomy with another intraabdominal procedure increases the risk of postoperative morbidity.

127 patients with more than 5 segment resection Median survival 42 months 5 year survival 26% Operative mortality 0.8% Adverse outcome if combined with any other intraabdominal procedure Behari A, (SGPGI) extended resection for CaGb also showed good long term results (BJS)

What's not ? Preoperative biliary decompression Intraarterial chemotherapy for colorectal mets PVE alone without TACE in HCC Wait, wait, wait for biliary fistula

What’s hot? LRLT for HCC NHBD of liver Staging with FDG-PET for colorectal mets Near zero mortality for liver resection