Guideline sources The following summarized guidelines for the evaluation and management of liver metastasis are prepared by our editorial team based on guidelines from the Enhanced Recovery After Surgery Society (ERASS 2023), the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS 2021), the European Federation of Societies for Ultrasound (EFSU 2020), and the European Society of Medical Oncology (ESMO 2016). 1 2 3 4 Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s Guidelines 1. Diagnostic investigations Diagnostic imaging: https://web.pathway.md/diseases/recCoMcAlwCffZtCu 1/6 6/29/23, 6:01 AM Liver metastasis Pathway Diagnostic imaging: As per JSHBPS 2021 guidelines: Obtain preoperative MRI in addition to CT in patients with liver metastases planned to undergo operative resection. B Obtain MRI for the diagnosis of liver metastases disappearing after neoadjuvant therapy. B As per EFSU 2020 guidelines: Consider obtaining contrast-enhanced ultrasound for detection of liver metastasis as part of a multimodality imaging approach. C Obtain contrast-enhanced intraoperative ultrasound for assessment of the region for resection, where previously a pretreatment colorectal liver metastasis was present but has regressed. B Molecular testing: Consider obtaining tissue from either the primary tumor or a liver metastasis for RAS mutation testing in patients with metastatic colorectal cancer. B Consider obtaining tissue from other metastatic sites such as lymph node or lung metastases only if primary tumor or liver metastases samples are not available in patients with metastatic colorectal cancer. C 2. Medical management Adjuvant chemotherapy: Offer systemic adjuvant therapy in patients with liver metastases from colorectal B and gastric cancers. B Offer adjuvant imatinib in patients with liver metastases from gastrointestinal stromal tumors. B 3. Therapeutic procedures Local ablation therapy: As per JSHBPS 2021 guidelines, avoid preferring local ablation therapy over hepatic resection in patients with colorectal liver metastases. D As per ESMO 2016 guidelines: Consider performing local ablation therapy such as thermal ablation or high conformal radiation techniques (e.g. stereotactic ablative body radiotherapy, high-dose rate- brachytherapy) in patients with colorectal cancer with unresectable liver metastases only or oligometastatic disease, decided by a multidisciplinary team based on local experience, tumor characteristics and patient preference. C Consider performing stereotactic ablative body radiotherapy as an alternative in patients with oligometastatic colorectal liver and lung metastases not amenable to surgery or other ablative treatments. C Embolization: consider performing radioembolisation with yttrium-90 microspheres C or chemoembolisation in patients with liver-limited metastatic colorectal cancer failed the available https://web.pathway.md/diseases/recCoMcAlwCffZtCu 2/6 6/29/23, 6:01 AM Liver metastasis Pathway chemotherapeutic options. C 4. Perioperative care Preoperative care (counseling): Provide preoperative information and counseling regarding the upcoming liver surgery. Consider using brochures and multimedia support to improve verbal counseling. B Advise preoperative smoking cessation at least 4 weeks before hepatectomy. Advise alcohol cessation in heavy drinkers (> 24 g/day for females or > 36 g/day for males) 4-8 weeks before surgery. A Preoperative care (nutrition): obtain a nutritional assessment before liver surgery. Administer enteral supplementation at least 7-14 days before surgery to optimize nutritional status in malnourished patients (weight loss > 10% or > 5% over 3 months and reduced BMI or a low fat- free mass index). A Show 2 more Preoperative care (rehabilitation): offer prehabilitation in high-risk patients (elderly, malnourished or overweight patients, smokers, or patients with psychological disorders) before liver surgery. Initiate prehabilitation 4-6 weeks before the operation depending upon the urgency of surgery. Insufficient evidence to recommend the content (physical exercises, dietary interventions, or anxiety reduction exercises) and duration of the prehabilitation program for liver surgery. B Preoperative care (biliary drainage): perform biliary drainage in the cholestatic liver (> 50 mmol/L). Avoid performing surgery until the bilirubin level drops < 50 mmol/L. B Preoperative care (antibiotic prophylaxis): administer antibiotic prophylaxis (such as cefazolin) within 60 minutes before surgical incision with no extension into the postoperative period. Consider administering a targeted antibiotic preemptive regimen based on preoperative bile culture in case of complex liver surgery with biliary reconstruction. B Preoperative care (corticosteroids): administer a preoperative dose of corticosteroids (methylprednisolone 500 mg). Insufficient evidence for its use in diabetic patients undergoing liver surgery. B Preoperative care (preanesthetic medication): avoid administering long-acting anxiolytic drugs, particularly in the elderly. D Show 3 more Intraoperative care (anesthesia and analgesia): Administer multimodal analgesia, including the potential use of intrathecal opioids, both for open A and laparoscopic surgery. B Recognize that thoracic epidural analgesia can provide excellent analgesia for open liver surgery but has significant disadvantages. Do not use regional anesthesia techniques in laparoscopic surgery as multimodal analgesia combined with judicious IV opioids provide functional analgesia. https://web.pathway.md/diseases/recCoMcAlwCffZtCu 3/6 6/29/23, 6:01 AM Liver metastasis Pathway Perform continuous local anesthetic wound infiltration to provide lower complication rates and overall equivalent analgesia to thoracic epidural analgesia. Perform local anesthetic transversus abdominis plane blockade as a supplement to standard analgesia to improve pain control and reduce opioid usage. A Intraoperative care (temperature management): maintain perioperative normothermia with multimodal temperature management (including circulating water garments or forced warm air) during open and minimally invasive liver surgery. B Intraoperative care (fluid management): Maintain low central venous pressure (< 5 cmH O) with close monitoring during hepatic transection. A Prefer balanced crystalloids over 0.9% saline or colloids for fluid maintenance. Provide goal- directed fluid therapy to optimize cardiac output and end-organ perfusion, recognizing that this may be particularly beneficial after the intraoperative liver resection during a low central venous pressure state to restore tissue perfusion, with patients having comorbidities and reduced cardiac function benefiting the most. A Postoperative care (thromboprophylaxis): administer routine postoperative LMWH or UFH to reduce the risk of thromboembolic events unless exceptional circumstances make this unsafe. Use intermittent pneumatic compression devices to reduce this risk further. B Postoperative care (early mobilization): initiate early mobilization (out of bed) after liver surgery from the operative day until hospital discharge. Insufficient evidence regarding the optimal duration of mobilization. B Postoperative care (nutrition): implement early oral intake with a normal diet after hepatectomy. Assess the individualized needs for artificial nutrition in malnourished patients, patients with complications causing several days of fasting, and patients with liver cirrhosis. Prefer enteral administration for artificial nutrition. A Show 2 more Postoperative care (antiemetics): use a multimodal approach to postoperative nausea and vomiting. Administer postoperative nausea and vomiting prophylaxis with at least 2 antiemetic drugs, such as dexamethasone and ondansetron. A Postoperative care (laxatives): insufficient evidence to support the routine use of postoperative laxatives, gum chewing, herbal medicine, or decoction to stimulate bowel movement after liver surgery. I 5. Surgical interventions Hepatectomy (indications): perform parenchymal-sparing over major hepatectomy in patients with liver metastases from colorectal cancer. B Show 4 more Conversion surgery: perform conversion surgery in patients with liver metastases from colorectal cancer. B https://web.pathway.md/diseases/recCoMcAlwCffZtCu 4/6 6/29/23, 6:01 AM Liver metastasis Pathway Hepatectomy (technical considerations): perform liver resection laparoscopically, in trained teams and when clinically appropriate, to reduce the postoperative length of stay and complication rates. B Show 3 more Clinical findings Symptoms Past medical history Bloating Colorectal cancer Early satiety Abdominal exam Fatigue Fever Ascites Generalized pruritus Hepatomegaly Hematochezia Splenomegaly Loss of appetite RUQ pain Weight loss Vascular exam Peripheral edema Integument exam Caput medusae Jaundice Studies 2023 Lidocaine in Hepatectomy In patients undergoing elective hepatectomy, lidocaine was superior to placebo with respect to a moderate-to-severe movement-evoked pain at 24 hour postoperatively. Yan Xu et al. Br J Anaesth. 2023 May 16. References 1. Ga tan-Romain Joliat, Kosuke Kobayashi, Kiyoshi Hasegawa et al. Guidelines for Perioperative Care for Liver Surgery: Enhanced Recovery After Surgery ERAS Society Recommendations 2022. World J Surg. 2023 Jan;47 1 11 34. Open 2. E Van Cutsem, A Cervantes, R Adam et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27 8 1386 422. Open https://web.pathway.md/diseases/recCoMcAlwCffZtCu 5/6 6/29/23, 6:01 AM Liver metastasis Pathway 3. Masakazu Yamamoto, Masahiro Yoshida, Junji Furuse et al. Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021. J Hepatobiliary Pancreat Sci. 2021 Jan;28 1 1 25. Open 4. Christoph F Dietrich, Christian P llson Nols e, Richard G Barr et al. Guidelines and Good Clinical Practice Recommendations for Contrast-Enhanced Ultrasound CEUS in the Liver-Update 2020 WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS. Ultrasound Med Biol. 2020 Oct;46 10 2579 2604. Open 5. Dervenis C, Xynos E, Sotiropoulos G et al. Clinical practice guidelines for the management of metastatic colorectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists HeSMO . Ann Gastroenterol. 2016 Oct-Dec;29 4 390 416. Open 6. Expert Panel on Gastrointestinal Imaging, Victoria Chernyak, Jeanne M Horowitz et al. ACR Appropriateness Criteria Liver Lesion-Initial Characterization. J Am Coll Radiol. 2020 Nov;17 11S S429 S446. Open https://web.pathway.md/diseases/recCoMcAlwCffZtCu 6/6