Greater Manchester and Cheshire HPB Unit Guidelines for the Assessment & Management of Hepatobiliary and Pancreatic Disease Chapter 5

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1 Greater Manchester and Cheshire HPB Unit Guidelines for the Assessment & Management of Hepatobiliary and Pancreatic Disease Chapter 5

2 Contents 5. Assessment & Management of Liver Metastases Metachronous colorectal liver metastases (CRLM) staging algorithm Metachronous CRLM Treatment Algorithm Treatment order algorithm for synchronous CRLM Timing of treatment of synchronous CRLM Resection of patients with extrahepatic disease Consent Cardiopulmonary Exercise Testing Protocol Radiological Reporting Standards for CRLM Histopathology reporting proforma Colorectal cancer metastasis Follow up after liver resection Treatment of Metastatic Neuroendocrine Tumours Management of GIST Treatment of liver metastases of unknown primary ECOG / WHO Performance Status Differentiation of human epithelial neoplasms based on Immunohistochemistry 63 41

3 5. Assessment & Management of Liver Metastases 42

4 5.1. Metachronous colorectal liver metastases (CRLM) staging algorithm CRLM (Metachronous) MDT staging CT chest/abdomen/pelvis MRI liver PET-CT See radiological protocols & reporting standards Resectable The potential for complete resection with R0 margins. The preservation of 2 segments with viable vascular inflow/outflow and biliary drainage. FLR >25% Potentially Resectable The potential to achieve the definition of Resectable with down sizing chemotherapy Likely Never Resectable Includes unresectable extrahepatic disease. 43

5 5.2. Metachronous CRLM Treatment Algorithm Resectable Potentially Resectable Likely Never Resectable Consider: PVE, 2-stage hepatectomy, resection plus ablation Downsizing / Conversion, chemotherapy Palliative Chemotherapy 2 months Neo-adjuvant/perioperative chemotherapy only in a clinical trial CT/MDT CT (Be aware of unexpected exceptional response) CPET Resectable: Surgical resection should be planned on the basis of the pre-chemotherapy scans Unresectable Fit to proceed Surgery & IOUS See: Liver Perioperative standards & protocols QIP Unfit to proceed Palliative Chemotherapy Also consider: Clinical trials SIRT HAI DEB Ablation smdt Pathology reporting standards: Royal College of Pathologists Consider adjuvant chemotherapy 44

6 5.3. Treatment order algorithm for synchronous CRLM Synchronous CRLM MDT staging (5.1) There is currently no standard of care for treating synchronous CRLM and no consensus reached on treatment order See CRLM treatment order algorithms agreed with the Christie Hospital clinical and medical oncologists 45

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10 5.4. Timing of treatment of synchronous CRLM Normally, colorectal cancer resection and liver resection would not be performed synchronously. However, management of accessible small metastases detected preoperatively should be discussed with the local liver centre for consideration of combined resection (see Table 5.1: Role of combined liver and colorectal surgery for synchrounous CRLM). Lesions discovered at operation should not be biopsied or excised. Patients should be referred for consideration of liver resection after recovery from primary surgery. Patients with potentially resectable liver disease and who have undergone radical resection of the primary tumour should be considered for liver resection before consideration of chemotherapy. Patients with unfavourable primary pathology such as perforated primary tumour or extensive nodal involvement should be considered for adjuvant chemotherapy prior to liver resection and be restaged at three months. Table 5-1: Role of combined liver and colorectal surgery for synchronous CRLM Liver CRC Major (Rectum) Minor (Colon) Major ( 3 segments) No No>Yes Minor ( 2 segments) No>Yes Yes 5.5. Resection of patients with extrahepatic disease Patients with extrahepatic disease that should be considered for liver resection include: (1) resectable/ablatable pulmonary metastases; (2) resectable/ablatable isolated extrahepatic sites for example, spleen, adrenal, or resectable local recurrence; and (3) local direct extension of liver metastases to, for example, diaphragm/adrenal that can be resected. Normal contraindications to liver resection would include uncontrollable extrahepatic disease such as: non-treatable primary tumour; widespread pulmonary disease; locoregional recurrence; peritoneal disease; extensive nodal disease, such as retroperitoneal, mediastinal or portal nodes; and bone or CNS metastases. 49

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12 5.6. Consent A standardised consent form should be signed, either by the consultant or the specialist registrar. The consent form should include the following risks: - General complications of surgery - Chest infection / DVT / PE / Cardiac events - Risk of bleeding (1-2%) - Risk of bile leak from raw surface of liver (up to 5%) - Wound infections, break-down and incisional herniae - Liver failure after major resections <1% - Mortality ~ 2% 5.7. Cardiopulmonary Exercise Testing Protocol CPET testing is now available to all patients over the age of 65 years due to undergo major HPB resection. Patients under the age of 65 years with cardiac, respiratory or other co-morbidity should also be considered for CPET. CPET is requested through the CMFT Clinical Work Station (CWS). 51

13 5.8. Radiological Reporting Standards for CRLM Staging objectives Number, size, character and location of liver lesions Define relationship with surrounding major vascular structures Identify the primary tumour Identify further sites of metastatic disease and extrahepatic spread of disease Avoid biopsy of potentially resectable lesions to prevent potential tumour seeding Imaging plays three major roles in patient selection: 1. To detect as many liver metastases as possible 2. To accurately characterize benign lesions to avoid unnecessary surgical procedures 3. To detect other sites of metastatic disease, which may themselves be amenable to treatment or render liver resection inappropriate In order to achieve the staging objectives, contrast enhanced magnetic resonance imaging (MRI) of the liver is proven to be more sensitive in detecting liver metastases than CT. MRI has also been shown to be more accurate and sensitive in detecting metastases less than 1cm in diameter when compared to PET CT. PET CT is useful to define extra hepatic disease not identified on CT, thereby reducing the number of nontherapeutic laparatomies. CT Protocol Generally CT will be used for the overall staging of colorectal malignancy. Oral administration of 1l of water or iodinated contrast to delineate the small and large bowel ml iodinated intravenous contrast medium injected at 3-4ml/s MDCT is commenced at 20-25s (chest) and 70-80s (abdomen and pelvis) post injection MRI Liver Protocol Axial T1W In/Out phase Axial and Coronal T2W (eg HASTE, FIESTA) Axial Fat saturated T1W pre contrast (eg VIBE, LAVA) Coronal Fat saturated T1W pre contrast (eg VIBE, LAVA) 52

14 Axial Fat saturated T1W post contrast (eg VIBE, LAVA) immediate, 30secs, 60secs, 5mins and hepatocyte specific phase (20-40mins for Primovist and 60-90mins for MultiHance) Coronal Fat saturated T1W post contrast (eg VIBE, LAVA) 2 mins and 10 mins Diffusion Weighted/ADC sequences The use of hepatocyte specific agents and DWI images in combination has been proven to increase the diagnostic accuracy and sensitivity of liver metastases and should be included. Portal Vein Embolisation If on CT volumetric studies the future liver remnant size is marginal or insufficient after the proposed hepatectomy, then percutaneous portal vein embolisation may be considered as a means to inducing hypertrophy of the unaffected liver and achieving sufficient liver mass of the future liver remnant. Generally, the future liver remnant must be at least 20% of the total estimated liver volume in a liver with normal liver parenchyma, 30-60% in livers injured by chemotherapy, steatosis or hepatitis and 40-70% in the presence of cirrhosis. Surveillance following Liver Resection CEA every 6 months for three years, then every 12 months for up to 5years CT chest/abdomen/pelvis every 6 months for three years, then every 6-12 months up to a total of 5 years Colonoscopy at 1 year if normal then repeat after 5 years (NICE Guidance minimum of two CT thorax/abdomen/pelvis in first 3 years and regular CEA every 6 months in first 3 years; colonoscopy at 1 year). 53

15 5.9. Histopathology reporting proforma Colorectal cancer metastasis Dataset for histopathology reporting of liver resection specimens (including gall bladder) and liver biopsies for primary and metastatic carcinoma (2nd edition) Appendix C5 Reporting proforma for liver resection: colorectal cancer metastasis Surname:... Forenames:... Date of birth:... Sex:... CHI/NHS no:... Hospital:... Hospital no:... Date of receipt:... Date of reporting:... Report no:... Pathologist:... Surgeon:... Gross description Number of liver specimens received. Type of specimen: Segmental resection List segments:... Non-anatomic (wedge) resection Site/segment(s) of origin:... List if several... Specimen weight (all specimens combined). g For segmental resections, specimen dimensions (largest specimen): antero-posterior mm, medio-lateral.mm, supero-inferior mm Number of tumours present Satellite lesions present Yes No List maximum diameters for up to four largest tumours.mm, mm,.mm,.mm Distance from hepatic resection margin of nearest tumour..mm Liver capsule intact and smooth Yes No Invasion of adherent adjacent tissue Yes No Lymph nodes(s) received Yes No Histology Tumour grade/differentiation Well/moderately differentiated Poorly differentiated For tumour closest to margin: tumour cells present at margin Yes No If margin is clear: is clearance >10 mm: Yes No If no: minimum distance to margin mm Microscopic vascular invasion identified: Yes No Neoadjuvant therapy given: Yes No Response to neoadjuvant therapy: Yes No If yes: No residual tumour cells/mucus lak Number of lymph nodes examined:.. Number with metastases:. Background liver Normal Steatosis Chronic liver disease with fibrosis Other Comments/additional information Signature of pathologist... Date././.. SNOMED codes pt.. M... 54

16 5.10. Follow up after liver resection Follow up would normally continue for five years according to local protocol using CT chest, abdomen and pelvis, and CEA. Follow up should be performed by the liver centre or the referring unit following an agreed protocol. Any abnormality should be referred back to the liver centre for consideration of reresection or ablation. In patients who develop recurrence, it is appropriate to consider such lesions in the same way as the initial hepatic metastases and offer re-resection or ablation to patients based on operative risk and likely survival. 55

17 5.11. Treatment of Metastatic Neuroendocrine Tumours 56

18 5.12. Management of GIST 57

19 58

20 5.13. Treatment of liver metastases of unknown primary Definitions Malignancy of undefined primary origin (MUO): Metastatic malignancy identified on the basis of a limited number of tests, without an obvious primary site, before comprehensive investigation. Provisional carcinoma of unknown primary (provisional CUP): Metastatic epithelial or neuroendocrine malignancy identified on the basis of histology/cytology, with no primary site detected despite a selected initial screen of investigations, before specialist review and possible further specialised investigations. Confirmed carcinoma of unknown primary (confirmed CUP): Metastatic epithelial or neuroendocrine malignancy identified on the basis of final histology, with no primary site detected despite a selected initial screen of investigations, specialist review, and further specialised investigations as appropriate. 59

21 Investigation of Patients with MUO 60

22 Patient Pathway 61

23 5.14. ECOG / WHO Performance Status 0 Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction) 1 Symptomatic, but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light housework, office work) 2 Symptomatic, <50% in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours) 3 Symptomatic, >50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours) 4 Bedbound (Completely disabled. Cannot carry out any self-care. Totally confined to bed or chair) 5 Death 62

24 5.15. Differentiation of human epithelial neoplasms based on Immunohistochemistry 63

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