Surgical resection is to be considered when no extrahepatic disease is present. Hemihepatectomy or segmental resection is feasible when metastases are solitary and resection can be radical with enough functional liver tissue remaining. Symptomatic response rates have been reported to be 90% for a mean duration of 19.3 months after surgical resection 26. Unfortunately, neuroendocrine metastases are usually multiple and diffuse and therefore resection is often impossible. Furthermore, in most patients treated by surgical resection with curative intent, additional metastases develop that presumably were occult at the time of surgery 26. Therefore even in resectable cases, liver tissue sparing therapies should be considered, allowing future repeated treatment.

Local therapy using radiofrequency ablation (RFA) or laser induced thermotherapy (LITT) is a well-established treatment for unresectable hepatocellular carcinomas and liver metastases from colorectal carcinomas 2728. A few small series and case reports have also shown good response in neuroendocrine hepatic metastases 2930313233. Up until now, a disadvantage of these therapies has been the relatively small volume of tissue that can be coagulated. Clinical trials with RFA have shown that complete tumour eradication is more likely to occur with small tumours, i.e. diameter ≤ 4 cm, than with large tumours 34. With the use of simultaneous multiple fiber LITT or next generation bipolar RFA, we have been able to ablate tumours as large as 7 cm in diameter 35 (Figure 1). Furthermore, up to 7 lesions at one time may be ablated using specialized techniques to increase lesion size 36. It has been reported that cytoreduction of ≥ 90% is adequate for durable symptomatic relief 9. In our most recent strategy, we aim at complete destruction of the intrahepatic tumour to prevent the occurrence of surgically untreatable disease. The largest reported study of 34 patients with neuroendocrine hepatic metastases treated with RFA showed symptom relief in 95% of these patients with significant or complete symptom control in 80%, for a mean of 10 months 29. Even in patients with extrahepatic disease and liver metastases ablation may also provide symptom relief 29. The complication rate is 5–10% and the mortality rate is about 0.5% 373839. Therefore these techniques are especially suitable for repeated treatment in patients in which local recurrence or new metastases developing during follow up.

All invasive procedures during surgery such as liver resection and ablation and even anaesthesia can induce hormone release and even provoke a life-threatening carcinoid crisis 40. In the severe crisis of carcinoid syndrome the flush is usually accompanied by hypotension and occasionally shock. Injection of octreotide, the long-acting analog of somatostatin, usually prevents or aborts this vasomotor reaction 41. Studies have shown that the use of octreotide intraoperatively for patients with metastatic carcinoid tumours undergoing surgery with manipulation of tumour is associated with a decreased frequency of intraoperative complications 4243.

Hepatic arterial embolisation with or without chemotherapy is a palliative option for those unresectable lesions in which the predominant mass of tumour is localised in one of the liver lobes. In the past, more radical blunt techniques to occlude the main hepatic artery were used. However, recently, superselective techniques have become available with the advantage of leaving the main segmental arteries open. Contraindications of hepatic arterial embolisation include complete portal vein occlusion, hepatic failure and previous biliary anastomoses 44. Symptomatic improvement after hepatic arterial embolisation is reported to occur in 64–90% 4546. Reports on chemoembolisation show a slight better biochemical response and tumour response than hepatic artery embolisation 47. Embolisation techniques are associated with mortality rates of about 5% and almost all patients develop the 'postembolic syndrome' (elevated liver function tests and fever) although mostly transient and in different grades of severity 484950. In addition, serious complications have occurred in about 10% of patients treated with hepatic embolisation for neuroendocrine tumours 51. Complications can be reduced by prophylactic octreotide infusion during the procedure and the use of forced diuresis during and after the embolisation. In case of partial or no response, supplementary embolisation or additional RFA or LITT could be an option. In selected cases with good response to embolisation a partial hepatic resection may be considered.

Pharmacological therapy consists of long-lasting octreotide injections, Iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG), interferon-α (IFN-α) or targeted chemo- and radiotherapy. Octreotide is a somatostatin analogue and appears to be an efficacious treatment for carcinoid syndrome, reducing symptoms in more than 70% of patients 5253. Some patients with partial response after local ablation have relief of symptoms by additional treatment with octreotide 37. Prolonged symptomatic relief can be provided by ¹³¹I-MIBG therapy. In individual cases, improved quality of life may be obtained 54. Even improved survival was seen by symptomatic response to ¹³¹I-MIBG treatment 55. The clinical benefit of IFN-α treatment has been limited by their modest anti-tumour effect as well as serious side-effects 5657. In addition, combination treatment with octreotide and IFN-α showed little advantage. Biochemical responses were observed in 72–77%, however no objective tumour regression was observed 5758. A promising approach is the concept of somatostatin receptor (SSTR)-mediated chemo-or radiotherapy of SSTR-expressing metastatic carcinoid. Currently, clinical trials with cytotoxic compounds, such as methotrexate and doxorubicin, linked to an analog of somotostatin are under way 5960. Also promising is targeted SSRT-mediated radiotherapy using radionuclides such as ⁹⁰Y and ¹⁷⁷Lu. Experimental studies in patients who have somatostatin-positive tumours show complete remission by the use of tetra-azacyclododecane tetra-acetic acid Tyr³-octreotide 61. After surgical reduction of tumour load, repeated intermediate-dosage ⁹⁰Y, Tyr-octreotide, ¹⁷⁷Lu or ¹³¹I-MIBG treatment appears to be a reliable and well-tolerated radionuclide therapy and might be a useful adjunct in patients with malignant neuroendocrine carcinoma, providing long-lasting palliation and prolonged survival 62.

Young patients with surgically unresectable tumours, hepatomegaly and uncontrollable symptoms, in whom all other therapies have been unsuccessful, may benefit from liver transplantation 63. However, liver transplantation for metastatic disease is controversial and in most cases even contraindicated, as the results have been poor due to complex operative procedures 646566. Well differentiated tumours and a low proliferation rate (Ki67<10%) are important selection criteria 67. Overall, post-operative mortality of 19% is reported in a group of 31 patients undergoing orthotopic liver transplantation for metastatic neuroendocrine tumours 65. In the same study, 50% of the carcinoid patients suffered from one or more major complications i.e. peritoneal bleeding, acute/chronic rejection and acute pancreatitis 65.