Liver resection and Metastasectomy.pptx

Metastasectomy in liver cancer

1. Liver resection and Metastasectomy Pushpa Lal Bhadel FCPS Resident Department of Surgery Kathmandu Model Hospital Moderator Dr. Bijendra Dhoj Joshi HOD Department of General Surgery

2. History of liver surgery 1888 : Carl Johann August Lagenbuch (German) – first successful hepatic resection 1 1890 : McLane-Tiffany – resected liver tumor at Johns Hopkins 1891 : Lucke – reported first successful removal of malignant tumor 1899 : Keen – performed first anatomical left lateral segmentectomy (sectionectomy) Modern liver surgery began in 1950s 1 Langenbuch C. Ein Fall von Resecktion eines linksseitigen Schnurlappens der Leber. Berl Klin Wochenschr. 1888;25:37.

3. History of liver surgery 1952 : Lorat Jacob (France) – published manuscript on his experiences performing anatomic liver resections 1 1956 : Claude Couinaud : segmental division of liver 2 1958 : Lin – introduced the finger fracture technique 3 Clamp crushing/’ Kellyclasia ’ 1984 : introduction of intraoperative ultrasound: ‘ Hepatectomie à la carte’ 3 Lin TY, Tsu K, Mien C, Chen C. Study on lobectomy of the liver. J Formosa Med Assoc. 1958;57:742–9 2 Couinaud C. Lobes et segments hépatiques. Presse Med. 1954;62:709 1 Lortat -Jacob JL, Robert HG. Well defined technic for right hepatectomy. Presse Med. 1952;60:549–51

4. History of liver surgery Pringle maneuver: to reduce blood loss during liver resection 1950s works by Hjortsjo , Healey and Starzl : modern era of hepatic resection surgery Blumgart , Bismuth, Longmire, Fortner, Schwartz, Starzl , and Ton deserve mention Development of new devices: harmonic scalpel, LigaSure , tissue link, radiofrequency, Habib sealer, CUSA

5. Indications Benign liver tumors Hemangioma Adenoma Cystadenoma Malignant liver tumors HCC Cholangiocarcinoma Metastasis Carcinoma GB Benign conditions Intrahepatic stones Recurrent Pyogenic Cholangitis Caroli’s disease Hydatid cyst Liver cysts Liver trauma Living donor liver transplantation (LDLT )

6. Contraindications Underlying functional liver disease Cirrhosis - FLR: <40%, Non-alcoholic steatohepatitis(NASH) – FLR:<30% Medical comorbidities Location of disease near major vascular or biliary structures IVC invasion: contraindication Hepatic vein: relative contraindication Documented extrahepatic disease

7. IHPBA Brisbane 2000

8. Liver resection steps Pre-op planning Intra-op assessment Inflow control Outflow control Maintenance of low central venous pressure Parenchymal transection

9. Pre-op Planning Computed tomography (CT) 1 Sensitivity: 67.4 - 68% Magnetic resonance Imaging (MRI) 1 Sensitivity: 86.5 – 88.2 % Other modalities: Ultrasound Positron emission tomography (PET) Single photon emission computed tomography (SPECT) 1 Eiber M, Fingerle AA, Brügel M, Gaa J, Rummeny EJ, Holzapfel K. Detection and classification of focal liver lesions in patients with colorectal cancer: retrospective comparison of diffusion-weighted MR imaging and multi-slice CT. Eur J Radiol . 2012;81(4):683-91.

10. Pre-operative preparation Nutrition: high protein diet with increased physical activity (prehabilitation) Medical assessment: CBC, serum chemistries, LFT, Coagulation studies, Tumor markers (CEA, CA 19-9, AFP) Prophylactic antibiotics Thromboprophylaxis Anesthesia and analgesia

11. Liver volume assessment Right liver (segments V to VIII) contributes two thirds of the total liver volume (TLV) The left liver (segments II to IV) represents a third of the TLV Left lateral section ( bisegment II/III) contributes approximately half the volume of the left liver or 16% of the TLV

12. CT volumetry Indications : Extended liver resections Right hepatectomy in cirrhotics LDLT Softwares LiverAnalyzer (Mevis) Osiri X

13. Functional Liver volume

14. Methods of liver volume augmentation Portal Vein Embolization (PVE) PVE + Trans Arterial Chemo Embolization (TACE ) Staged Hepatic Resection

15. What is PVE? Embolization of PV on the side to be resected Concept – " atrophy hypertrophy complex " Leads to hypertrophy of future liver remnant (FLR) Allows major resection without post op liver failure

16. Contralateral hypertrophy

17. Portal Vein Embolization Indications Normal liver (ICG retention rate at 15 minutes [ICG R15] <10%) if FLRV/TLV is less than 40% Injured liver (10% < ICG R15 < 20%), if FLRV/TLV is less than 50% If ICG R15 exceeds 20%, major hepatectomy is contraindicated even after PVE

18. Results of PVE Leads to an increment of segmental volume in non embolized hemi liver Decrement of segmental volume in embolized hemi liver maintaining a constant TLV In case of right hemi liver PVE, regeneration rate of the Non cirrhotic liver – 12 cm 2 /day at 2 weeks 11 cm 2 /day at 4 weeks 6 cm 2 /day at 32 days In cirrhotic patients regeneration is slower

19. Pre-embolization Post-embolization

20. Complications of PVE

21. TACE Embolization  Ischemia  Necrosis Ischemia  blocks transmembrane pumps  limits chemotherapy from washing out of tumor cells (Ramsey D et al, 2002) Concentration of chemotherapy drug in tumor is 10-100 times greater than given systemically (Konno T et al,1990) Chemotherapy + lipiodol traps chemotherapy & concentrates in HCC (Ramsey D et al, 2002) Because most of the drugs is retained in the liver, systemic toxicity is reduced (Daniels JR, 1988)

22. TACE Exclusion criteria: Hepatic encephalopathy PV thrombosis Serum bilirubin >5mg/dl; serum creatinine >2mg/dl

23. TACE Procedure 7-10ml of chemotherapy solution infused (100mg cisplatin, 50mg doxorubicin & 10mg mitomycin C in a 1:1 or 2:1 volume ratio with ethiodol / lipiodol) Followed by infusion of 1-2ml of gelfoam / PVA particles (300-500 micron) to slow down arterial inflow & prevent washout of chemotherapeutic agents End point - entire amount is delivered & slowed arterial flow as compared to initial flow Forward flow in the HA is to be maintained to preserve patency for re-treatment and minimize theoretical risk of ischemia or infarction

24. TACE Complications : Post-embolization syndrome (fever, pain, vomiting, ALT) – 32-80% Ascites, GI bleed, leucopenia, worsening hepatic function -- <10% Rare – cholecystitis, ischemic hepatitis, abscess, bacteremia, hepatic, renal failure, death

25. Surgery Incision : Bilateral rooftop incision with/without vertical extension J-shaped incision Reverse L-shaped incision with/without left exte nsion Makuuci incision

26. Vascular control Inflow Vascular Occlusion Total Vascular Exclusion

27. INFLOW VASCULAR OCCLUSION Pringle Maneuver Oldest and simplest way Hepatoduodenal ligament encircled with tape Until pulse in hepatic artery disappears Pringle JH et al, ann surg 1909

28. INFLOW VASCULAR OCCLUSION Pringle Maneuver Advantages Little general hemodynamic effect No specific anesthetic management Disadvantages Backflow from hepatic veins Ischaemic-reperfusion injury to the liver parenchyma Splanchnic congestion Kim YI et al, J hepatobiliary pancreat surg 2003

29. I nflow V ascular O cclusion Continuous Pringle Maneuver Up to 60 minutes in normal liver (normothermic conditions) Up to 30 minutes in pathological (fatty or cirrhotic) livers

30. I nflow V ascular O cclusion Intermittent Pringle Maneuver 15-20 minutes clamping, 5 minutes unclamping 5 minutes clamping, 1 minute unclamping Advantages Doubling of ischaemia time Better tolerated by pathological liver Disadvantages Bleeding during unclamping period Increased overall transection time Torzilli G et al, arch surg 1999 Belghiti J et al, ann surg 1999

31. I nflow V ascular O cclusion Ischaemic Preconditioning Endogenous self-protective mechanism Hypothesis: 10 minutes of ischaemia followed by 10 minutes of reperfusion  protection against subsequent transection with complete inflow occlusion Advantage: Lower serum transaminase levels after surgery Longer inflow occlusion in steatotic livers Clavien et al, ann surg 2000

32. Hemi-hepatic clamping (Half-Pringle maneuver) Interrupts arterial and portal inflow selectively one lobe Advantage Avoids ischaemia in the remnant liver Avoids splanchnic congestion Clear demarcation of the resection margin Disadvantage Bleeding from the parenchymal cut surface Horgan PG et al, am J surg 2001

33. Total vascular exclusion Complete mobilization of the liver Encircling of suprahepatic and infrahepatic IVC Pringle maneuver Clamping the infrahepatic IVC & suprahepatic IVC

34. Total vascular exclusion Hemodynamic changes Marked reduction of venous return and cardiac output Trial clamping of two to five minutes Ischemia time 60 minutes in normal liver 30 minutes in diseased liver Extended with hypothermic perfusion of the liver Azoulay D et al, ann surg 2005

35. Total vascular exclusion Disadvantages Hemodynamic intolerance Post-operative abdominal collections/ abscesses and pulmonary complications Venovenous bypass if hemodynamic intolerance Infrahepatic IVC clamp alone with inflow occlusion Reduce back bleeding Abdalla et al, surg clin north am 2004

36. Selective Vascular control Inflow occlusion with extraparenchymal control of hepatic veins Trunks of major hepatic veins can be safely looped in 90% of patients Loops tightened or vessels clamped after inflow occlusion Continuous or intermittent Advantages Liver lobe isolated from systemic circulation Caval flow un-interrupted Elias D wt al, hepatogastroenterology 1998 Smyrniotis VE et al, world J surg 2003

37. Types of liver resection Minor hepatectomy (≤2 segments) Bisegmentectomy Segmentectomy Subsegmentectomy Wedge resection Major hepatectomy (≥3 segments) Left hepatectomy Right hepatectomy Extended left/right

38. P arenchymal T ransection

39. I nstruments C avitron U ltrasonic S urgical A spirator (CUSA) W ater-Jet HABIB P robe H armonic F ocus L igasure V ascular S taplers

40. CUSA Water Jet

41. Harmonic scalpel Bipolar vessel sealing device ( Ligasure )

42. Multiprobe Bipolar Radiofrequency Device (Habib) Vascular stapler

43. Laparoscopy First anatomical laparoscopic liver resection 1996 by Azagra Left lateral sectionectomy for hepatic adenoma Small and localized tumors on anterolateral segments Oncological principal has to be followed Need of intra-operative ultrasound

44. Laparoscopy Laparoscopic assisted hepatectomy (LAH) Total laparoscopic liver resection (TLLR) Tumor size <5cm Wedge resection Left lateral sectionectomy Safe procedure or antero-inferior segment ( Sasaki et al, BJS 2009) Few reports of right hepatectomy ( Ibrahim et al, J am coll surg 2005) Can be performed safely in cirrhotic patient ( Buell et al, J am coll surg 2005)

45. Laparoscopy Advantages: Decreased operative time Lower overall cost (Francesco et al, surg endosc 2008) Less pain, early discharge, faster recovery Less adhesions (Topal et al, surg endosc 2008 Sasaki et al, BJS 2009)

46. Liver resection: Complications Blood loss: 4-12% Bile leakage: 10% Post-operative hepatic failure: 6.3% (Vyas et al., 2014) Pulmonary complications: Pneumonia, pleural effusion Ascites 1-33% Thrombotic complications

47. Associating Liver Partition & Portal Vein Ligation For Staged Hepatectomy (ALPPS) Indications Marginally resectable or primarily non-resectable locally advanced liver tumors of any origin with an insufficient FLR either in volume or quality Need to perform major liver resections combined with synchronous resection of other organs

48. Hepatic metastases Cancerous tumor that has spread to the liver from a cancer that started in another place in the body Also called secondary liver cancer 18-40 times more common than primary liver tumor 1 C/F: localized pain and tenderness due to capsular stretching disordered liver metabolic function ascites low-grade fever 1 Namasivayam S, Martin DR, Saini S. Imaging of liver metastases: MRI. Cancer Imaging. 2007;7:2-9.

49. Common sites of primary malignancy that metastasize to the liver are: Gastrointestinal tract (via portal circulation) Colorectal ca Pancreatic ductal adenocarcinoma Esophageal ca Gastric ca GIST NET Breast ca Lung ca Genitourinary system Ovarian ca Endometrial ca RCC Ureteral and bladder ca Melanoma Uveal melanoma Sarcomas A drenocortical carcinomas Essentially all metastatic solid malignancies Testicular ca

50. Hepatic metastases Synchronous liver metastases : Liver metastases presenting at the same time with the primary or shortly thereafter Generally occurring within 3,6 or 12 months of primary disease Metachronous liver metastases : Delayed presentation, often after the primary has been treated

51. Metastasectomy American Hepato-Pancreato-Biliary Association, the Society for Surgery of the Alimentary Tract, and the Society of Surgical Oncology in 2006 Positive surgical margin is associated with a higher local recurrence and worse OS and should be avoided whenever possible. While a wide (>1 cm) resection margin should remain the goal when performing a liver resection, an anticipated margin of <1 cm should not be used as an exclusion criterion for resection Assessment of resectability of hepatic colorectal metastases should focus on the ability to obtain a complete resection (negative margins). The presence of extrahepatic disease should no longer be considered an absolute contraindication

52. Metastasectomy The feasibility of hepatic resection should also be based on three criteria related to the remaining liver following resection: T he ability to preserve two contiguous hepatic segments Preservation of adequate vascular inflow and outflow as well as biliary drainage, and The ability to preserve adequate future liver remnant (>20 percent in a healthy liver; >30 percent after chemotherapy).

53. Conventional indications Modern aggressive approach <4 metastases, unilobar disease No limits. Multiple/bilobar metastases acceptable, using neoadjuvant chemotherapy, staged resection, and resection/local ablative therapy. Size <5 cm No limits No extrahepatic disease Pulmonary metastases can be resected Resection margin >1 cm Resection margin <1 cm managed with ablative treatment of narrow margin (cryosurgery or radiofrequency ablation) Adequate remnant liver parenchyma Preoperative portal vein embolization to increase liver remnant volume Resection of all macroscopic disease NED can be achieved with combination of resection and local ablative therapy No metachronous liver metastases Synchronous and metachronous metastases acceptable Absence of vena cava and hepatic vein confluence invasion No limits. Caval /hepatic vein resection with reconstruction can be performed Absence of hepatic pedicle lymph node metastases In absence of celiac axis metastases, hepatic pedicle lymph node metastases may be resected for improved 3-year survival

54. Metastasectomy Simultaneous resection  — Liver resection is performed first Asymptomatic from primary disease Disease in favorable location (right colon) Limited liver Mets Staged resection  —  Treated with initial resection of the colorectal primary followed by administration of systemic chemotherapy and CRLM resection 2-3 months later

55. Metastasectomy Staged resection: Classic (colorectal-first) approach Extensive bilobar disease Reverse (liver-first) approach Delaying primary allow hepatic Metastasectomy with/without systemic chemotherapy

56. Surveillance after Metastasectomy Guidelines from the National Comprehensive Cancer Network (NCCN) CEA testing every 3-6 mths for two years, then every 6 mths for three years. CT of the chest/abdomen and pelvis every 3-6 mths for two years, then every 6 to 12 mths up to a total of five years. Colonoscopy in one year; if no advanced adenoma, repeat in three years, then every five years; if advanced adenoma is found, repeat in one year.

57. References Sabiston Textbook of Surgery, 20 th edition Schwartz’s Principles of Surgery. 10 th edition Bailey & Love’s short practice of Surgery, 27 th edition Blumgart’s Surgery of Liver, Biliary tract and Pancreas, 6 th edition https://www.uptodate.com