1. Malignant hepatic lesions Prepared by: Dr. yasser Baashan

2. Anatomy of the liver The liver is divided either into lobes or segments Lobes (Gross anatomy): - A large right lobe and small left lobe utilizing the line of attachment of the falciform ligament - Used customarily by the anatomist Segments (Functional anatomy): - Based on the blood supply and the biliary drainage the liver is divided into 8 segments (I-IIIV) - It is possible to resect a single of several segments without compromising the rest of the liver

3. Liver lobes

4. Liver segments

9. Assessment of liver function “Hepatic functional reserve” -It is essential for the surgeon to estimate the ability of the hepatic remnant to be sufficient after liver resection -A number of scoring systems and functional tests are used: - Child-Pugh Score - MELD Score - CT-Volumetry - Others ( Not often used clinically) - Indocyanine Green Clearance (IGC) - Indocyanine Green Clearance (IGC) - Protrombin activity after administration of vit. K - Dynamic Single Photon Emission Computed Tomography (SPECT) - Aminopyrin breath test

10. Child-Pugh Score 3 Points 2 Points 1 Point Parameter > 3 2-3 < 2 Serum bilirubin (mg/dl) <2.82.8-3.5 > 3.5 Albumin (g/dl) >64-6< Protrombin time ( sec.) ModerateSlightNoneAscitis Grade 3-4 Grade 1-2 NoneEncephalopathy A: 5-6 points B: 7-9, C: 10-15 Currently partial hepatectomy is only offered to patients with Child A and most favorable Child B

11. MELD Score “ Model for End stage Liver Disease ” Score = 0.957 x loge creatinine (mg/dL) + 0.378 x loge bilirubin (mg/dL) + 1.120 loge INR Range: 4-60 Patients receive liver transplantation with MELD > 15

12. CT-Volumetry -Applied in patients planned for extended hepatic resection who have a small future liver remnant -Involves rapid sequence, thin sections helical CT-Scan that directly measures liver volume -The volume of the liver segments remaining after resection is divided by the total estimated liver volume to obtain a percentage of the future liver remnant -This percentage should be: > 20% (in patients with normal liver parenchyma) > 40% (In patients with cirrhosis) -If the future liver remnant is not adequate then portal vein embolisation is considered to induce hypertrophy of the liver remnant

14. Malignant tumors of the liver Primary: 1- HepatoCellular Carcinoma (HCC) 2- Intrahepatic cholangiocarcinoma 3- Others (rare): - Hepatoblastoma - Cystadenocarcinoma - Angiosarcoma - Non-Hodgkins’s lymphoma - Epitheliod haemangioendothelioma Metastatic: 1- Colorectal 2- Neuroendocrine 3- Non-Colorectal, Non-neuroendocrine Breast, lung, melanoma, soft tissue sarcoma, upper GIT tumors, urologic, gynecologic

15. Hepatocellular carcinoma -On of the most common solid cancers -Geographical distribution parallels the incidence of hepatitis B and C (Highest in far east and sub-Saharan Africa) -Majority of cases associated with HBV and HCV -Usually develops in a back ground of cirrhosis but can originate in normal liver - Cirrhotic HCC - Viral cirrhosis: HBV, HCV (Risk of HCC 3-5% per year) - Non-viral cirrhosis: Haemochromatosis (7-9% per year) Alcoholic (1-4 per year) Alcoholic (1-4 per year) Primary biliary cirrhosis Primary biliary cirrhosis Wilson ’ s disease Wilson ’ s disease - Non-cirrhotic HCC Fibrolamellar variant, HBV, HCV (rare)

16. -There are no marked difference between cirrhotic and non- cirrhotic HCC in the symptoms, size of tumor at presentation, serum markers and HBV status -HCC has poor prognosis with fatal outcome (median survival of 4 months in symptomatic patients)

17. Surveillance for HCC -Should be considered for the following high risk groups: - Viral cirrhosis: HBV HCV - Non-viral cirrhosis: Haemochromatosis Alcoholic Primary biliary cirrhosis -Using abdominal US and AFP -The surveillance interval should be 6 months

18. Diagnosis of HCC -A focal lesion in the liver of a patient with cirrhosis is highly likely to be HCC -Hypervascular mass in CT/MR combined with AFP > 400 ng/ml is diagnostic -Initial assessment should be by spiral computed tomography (CT) of the liver (local spread) and thorax (metastases) -Magnetic resonance imaging (MRI) with contrast enhancement may increase the accuracy of detection of other liver lesions -Biopsy is rarely required for diagnosis. Biopsy of potentially operable lesions should be avoided where possible

19. Investigating a mass in cirrhotic liver: Liver mass on ultrasound AFP raised Asses for surgery Diagnostic of HCC AFP normal CT/MR Major diagnostic doubt Biopsy Negative Follow up at 6 months

20. Investigating a mass in non-cirrhotic liver: Liver mass on ultrasound AFP raised Asses for surgery Diagnostic of HCC AFP normal Search for non-liver primary CT/MR Major diagnostic doubt Biopsy Negative Follow up at 6 months Exclude testicular primary

21. α-Fetoprotein: -Normal serum protein synthetize by fetal liver cells and yolk sac -The most useful marker for HCC and teratomas of testis/ovary -Normal range 10-20 ng/ml -A level > 400 ng/ml is diagnostic for HCC -A rising level even if does not reach 400 ng/ml is diagnostic -A level between 20-400 ng/ml my indicate small HCC, regenerative nodules of cirrhosis or teratomas of testis/ovary -Two third of HCC <4 cm have a level < 200 ng/ml -Up to 20% of HCC does not produce AFP even when large

22. CT-Scan: -The smallest detectable lesions size 1cm -As HCC is a hypervascularized lesions they will light up during the arterial phase -Isodense or hypodense during the portal phase -Limited ability to differentiate HCC from macronodular regenerative nodules of cirrhosis

25. Magnetic Resonance Imaging (MRI): More sensitive than helical CT in detecting early HCC and in distinguishing between HCC and macroregenerative nodules

26. Positron Emission Tomography (PET): Less useful because many of these tumors do not have a significantly higher intake of the radioisotope when compared with the surrounding hepatic parenchyma

27. Treatment of HCC Surgical: Resection Orthotopic liver transplantation Ablative: Alcohol injection Thermal ablation (cryotherapy, radiofrequency ablation RFA, microwave) ablation RFA, microwave) Transarterial: Embolization Chemoembolization Systemic: Chemotherapy Hormonal Immunotherapy Immunotherapy External-beam Radiation Therapy

28. Surgical treatment of HCC: Indication: Single small HCC (≤ 5cm) or up to 3 lesions ≤ 3cm (Milan criteria) (Milan criteria)Options: 1. Liver transplantatioin Cirrhotic liver 2. Hepatic resection Non-cirrhotic liver Child A cirrhotic liver not suitable for Tx Child A cirrhotic liver not suitable for Tx

29. -Pre- and postresection chemotherapy is not recommended -In patients with limited residual functional reserve (small liver remnant) resectability my be achieved by: 1. Portal vein embolisation 2. Two-stage hepatectomy 3. Combination of surgery and ablation

30. Nomenclature for Most Common Major Anatomic Hepatic Resections: Segments Type of resection V-VIII Right hepatectomy IV-VIII Extended right hepatectomy II, III Left lobectomy II-IV Left hepatectomy II, III, IV, V, VIII Extended left hepatectomy Other common sublobar resections: Right posterior sectorectomy VI, VII Right anterior sectorectomy V, VIII Single segment or bisegmental resections

31. Right hepatectomy Extended right hepatectomy Left lobectomy Extended left hepatectomy Left hepatectomy

32. Radiofrequency ablation (RFA): -Application of a high-frequency alternating current from the tip of an electrode to the surrounding tissues increase tissue temperature coagulative necrosis -May be applied via a percutaneous, laparoscopic, or open approach -After RF ablation CT scans demonstrate cystic areas ideally larger than the original tumors -Safe and effective for patients who do not meet the criteria for surgery or as a bridge to transplantation

35. Alcohol injection: -The simplest ablative therapy -Absolute alcohol is used to destroy the tumor -Suitable for peripheral lesions < 3cm Transarterial embolisation/chemoembolisation (TACE): -Based on the fact that HCC supply is from the hepatic artery -Induces ischemic necrosis of HCC -Embolisation particles are sponge or oils (lipiodol) that are selectively taken by HCC (with or without chemotherapeutic agents) -Suitable for large/multifocal HCC

36. Pre TACE AngiographyPost TACE Angiography Post TACE CT-ScanPre TACE CT-Scan

38. Colorectal cancer liver metastases - The liver is often the first site of metastases -The only site of spread in 30-40% -20-35% of patients have clinically detectable liver met. at initial presentation -40-50% eventually develop liver met. after resection of primary usually within the first 3 years -20-30% of liver met. are potentially resectable -Survival: Without treatment median < 8 months, 5-years exceptional After resection 5-years survival 25-44%

39. Investigations for detection of hepatic and other metastases Investigations in patients with primary colorectal cancer: 1. CT-Scan Abdomen and pelvis 2. Chest CT (chest x-ray is considered satisfactory) 3. Colonoscopy or Barium enema 4. Baseline measurements of CEA Investigations for follow-up after curative resection of primary: 1. CT-Scan Abdomen and pelvis (as a minimum in the two years following resection) 2. Colonoscopy repeated after 5 years 3. Serial CEA measurements

40. Investigations to detect extrahepatic met. in patients with liver met. 1. CT-Scan chest, abdomen, pelvis 2. Biopsy of hepatic lesions ? 3. PET 4. Laparoscopy Patients with high risk primary disease (T4, perforation)

42. Treatment of colorectal metastases - Liver resection -Ablative therapy -Chemotherapy and neoadjuvant chemotherapy

43. Liver resection: Patients without extrahepatic disease: Indication: When it is possible to remove all macroscopic disease with clear (negative) margin and leave sufficiet functioning liver - Acceptable residual functioning volume is 1/3 of liver volume or a minimum of two segments - In patients with small residual functioning volume resectability may be achieved by: 1. Portal vein embolisation 2. Two-stage hepatectomy 3. Combination of surgery and ablation

44. Liver resection in patients with extrahepatic disease: Indications: - Resectable/ablatable pulmonary metastases - Resectable/ablatable isolated extrahepatic sites (spleen, adrenal, or respectable local recurrence) - Local direct extension of liver metastases (to diaphragm/adrenal) Contraindications: - Non-treatable primary tumor - Widespread pulmonary disease - Locoregional recurrence - Peritoneal disease - Extensive nodal disease, such as retroperitoneal, mediastinal or portal nodes - Bone or CNS metastases

45. Ablative therapy: Indications: - Patients who are not candidate for resection - Associated comorbidity that preclude resection - Patients who refuse surgery - Tumor downsized by chemotherapy but are not resectable

46. Chemotheray and neoadjuvant chemotherapy: Indications: - Advanced disease unsuitable for resection or ablation - Downsizing of tumor if they are unable to be resected initially due to location or inadequate hepatic functional reserve Regimens: Firstline: Oxaliplatin, 5-fluorouracil, folinic acid (Folfox) Secondline: Irinotecan, 5-fluorouracil, folinic acid (Folfiri)

47. Increase resectability with chemotherapy

48. Synchronous metastases -Normally colorectal cancer and liver resection would not be performed synchronously. Liver resection should be performed after recovery from primary surgery If radical resection of primary Liver resection before chemo. Unfavorable primary (perforation, extensive nodes) Adjuv. chemo before liver resection -New strategy (Liver first strategy) Chemo Liver Chemo CRC - To downstage the metastases in 80% - To select responders, avoiding unnecessary surgery in non-responders - To deliver preoperative rectal radiotherapy without the fear that liver metastases would meanwhile progress beyond the possibility of cure

49. - Accessible small met. detected preop. may be considered for combined resection -Lesions discovered at operations should not be biopsed (significant risk of local dissemination)

50. Follow-up after liver resection -Continue for 5 years -Using CT-Scan chest and abdomen -Recurrent lesions are treated in the same way as the initial hepatic metastases

51. Non-resectable metastases -Resectability is becoming a new end-point in strategies involving chemotherapy in non-resectable patients -15-30% of patients could be switched to resectability -Benefit in survival: 35% at 5 years

52. Thank You!