Evolution of transplant oncology indications: a single-institution experience over 40 years.

Liver transplantation (LT) for uncommon tumoral indications has changed across the decades, with impaired results reported in the first historical series mainly for non-tumoral-related causes. Recently, renewed interest in liver transplant oncology has been reported. The study aims to analyze a mono-center experience exploring the evolution and the impact on patient survival of LT in uncommon tumoral indications. A retrospective analysis of 851 LT performed during 1982-2023 was investigated. 33/851 (3.9%) uncommon tumoral indications were reported: hepatocellular carcinoma (HCC) on non-cirrhotic liver (n = 14), peri-hilar (phCCA) (n = 8) and intrahepatic cholangiocarcinoma (i-CCA) (n = 3), metastatic disease (n = 4), hepatic hemangioendothelioma (n = 2), and benign tumor (n = 2). Uncommon tumoral indications were mainly transplanted during the period 1982-1989, with a complete disappearance after the year 2000 and a slight rise in the last years. Poor outcomes were reported: 5-year survival rates were 28.6%, 25.0%, 0%, and 0% in the case of HCC on non-cirrhotic liver, phCCA, i-CCA, and metastases, respectively. However, the cause of patient death was often related to non-tumoral conditions. LT for uncommon oncological diseases has increased worldwide in recent decades. Historical series report poor survival outcomes despite more recent data showing promising results. Hence, the decision to transplant these patients should be under the risk and overall benefit of the patient. The results of the ongoing protocol studies are expected to confirm the validity of the unconventional tumor indications.

Outcome of Children Treated for Infantile Hepatic Hemangioendothelioma.

PURPOSE: Infantile hepatic hemangioendothelioma (IHHE) is the most common hepatic vascular tumor in children. We report on the treatment outcome of our large single-center experience of patients with IHHE over a 9-year period. MATERIALS AND METHODS: A retrospective analysis of all IHHE patients treated at the Children Cancer Hospital Egypt from April 2008 through April 2017. RESULTS: In total, 28 patients (18 females, 10 males) were diagnosed with IHHE with a median age at diagnosis of 3 months. The lesions were multifocal (n=12), focal (n=10), and diffuse (n=6). Six (21.4%) patients initially had low T3 and T4. Eleven patients did not receive any treatment, whereas 1 patient underwent resectional surgery. Sixteen patients received drug treatment, 9 of whom responded well to first-line propranolol/prednisolone, whereas 7 patients needed salvage treatment. Twenty-five patients are alive, whereas 3 patients have died. CONCLUSIONS: Overall, patients with IHHE do well, a significant percentage of whom do not require drug therapy, particularly for those with small focal lesions. In patients with multifocal/diffuse disease, there is a high incidence of low T3 and T4 and while some of these patients did well without additional therapy, those with rapidly progressive lesions during treatment may do poorly.

Lymphatic-type "Angiosarcoma" With Prominent Lymphocytic Infiltrate.

We report 21 cases of a distinctive and unique vascular tumor which we propose to be a pure lymphatic-type angiosarcoma characterized by architectural and growth characteristics of angiosarcoma, cytologic, and immunohistochemical features of lymphatic differentiation, a prominent lymphocytic infiltrate, and variable nuclear grade. Patients included 12 males and 9 females with a median age of 65 years (range: 32 to 95 y). Tumors involved the head and neck (n=11), lower extremities (n=5), trunk (n=4), and upper extremity (n=1) and were located superficially in the dermis and/or subcutis. Tumors were designated "low grade" (n=10) when the nuclear grade was low, and vascular channel formation was evident throughout but with multilayering of endothelium within the vessels. Cases were designated "high grade" (n=11) when nuclei appeared higher grade with more rounded contours and prominent nucleoli and when solid areas predominated over vascular channel formation. A striking feature of both groups was the presence of a dense, lymphocytic infiltrate with occasional germinal center formation. All cases strongly and diffusely expressed at least 1 lymphatic marker (21/21) with podoplanin (17/19) and Prox-1 (11/11) more commonly expressed than LYVE-1 (5/10). No consistent molecular alteration was identified. Follow-up on 17 patients (median: 41 mo, mean: 54 mo) showed 10 patients were alive without disease, 5 were alive with disease, 1 died of other cause, and 1 died of disease. Local recurrence developed in 9 cases and metastasis in 2 cases, although neither correlated with grade as defined. On the basis of clinical follow-up to date, the natural history of lymphatic-type angiosarcoma appears to be more favorable than other forms of cutaneous angiosarcoma.

Kaposiform hemangioendothelioma without cutaneous involvement.

PURPOSE: We sought to characterize the clinical features and management of patients diagnosed as Kaposiform hemangioendothelioma (KHE) without cutaneous involvement. METHODS: The electronic patient chats at six Triple A hospitals in China were searched to find all patient diagnoses with KHE without cutaneous involvement. RESULTS: Of 30 patients (mean age at diagnosis, 55.6 months), 17 (56.7%) were male. Fourteen (46.7%) patients were associated with Kasabach-Merritt phenomenon (KMP). Patients with KMP were significantly more likely to have lesions involving truck compared to patients without KMP (odds ratio 10.000; 95% confidence interval 1.641-60.921; P = 0.011). Other common complication included severe anemia and decreased range of motion. In the majority of cases (93.3%), the lesions were highly infiltrative and locally invasive with ill-defined margins. Histological examination was required in all patients without KMP for precise diagnosis. In all, 16 (53.3%) patients received corticosteroid treatment, 19 (63.3%) received oral sirolimus treatment, 7 (23.3%) received intravenous vincristine, and 5 (16.7%) patients used propranolol. Patients had varied responses to conventional drugs, whereas all patients receiving sirolimus treatment had better response. In all, three patients (10%) died of disease, all presented with KMP. Feature of these recalcitrant cases (death) included young age, visceral location, extensive involvement, and lack of improvement with high-dose corticosteroids. CONCLUSIONS: Our study clearly demonstrated that KHE without cutaneous involvement could be associated with important complication, which might result in death or severe morbidity. Increased awareness of KHE without cutaneous involvement is required for early diagnosis and aggressive therapy in an attempt to prevent complication.

Long-term outcome for kaposiform hemangioendothelioma: A report of two cases.

Kaposiform hemangioendothelioma (KHE) is a rare aggressive vascular tumor of skin and deep soft tissues that typically presents in infancy and may be associated with a potentially life-threatening coagulopathy known as Kasabach-Merrit phenomenon (KMP). Recent advances in medical therapy have successfully treated many patients. However, our knowledge regarding the natural history of these lesions and optimum surveillance strategies remains rudimentary. We report two young women who had KHE with KMP treated in infancy and presented in adolescence with comorbidities related to their KHE tumor. This presentation supports the need for long-term surveillance in these patients.

Interferon-alpha therapy for refractory kaposiform hemangioendothelioma: a single-center experience.

Kaposiform hemangioendothelioma (KHE) is a relatively rare vascular tumor with an aggressive and infiltrating nature. Previous studies have revealed an exclusive relationship between KHE and Kasabach-Merritt Phenomenon (KMP), which is associated with high morbidity and mortality. No universally accepted treatment modality exists for refractory KHE with or without KMP. The aim of this study was to evaluate the safety and efficacy of interferon-alpha (IFN-α) therapy for treatment of refractory KHE. Twelve consecutive patients with KHE were treated with subcutaneous injections of IFN-α after other treatments had failed. Eleven patients exhibited a reduction in tumor size of more than 50%, and the platelet count for all five patients with KMP returned to normal level after IFN-α therapy. The duration of IFN-α treatment ranged from 3 months to 9 months (mean: 6.3 months). The response time for IFN-α treatment ranged from 10 days to 5 weeks (mean: 3.6 weeks). Additionally, no severe complications, such as neurological damage or spastic diplegia, were observed in these patients. In conclusion, our study suggested that IFN-α therapy is effective and safe for refractory KHE, and IFN-α may be used as an alternative after other treatments have failed.

Thalassemia major between liver and heart: Where we are now.

The aim of the study was to assess the current state in terms of liver and heart iron overload as well as of liver and heart related morbidity and mortality in a large cohort of thalassemia patients. Myocardial iron loading was present in 28.9% patients, which was severe in 3.2%. Liver iron was normal in 9.3% and severe in 15%. The rate of cardiac deaths started to decrease between 2000 and 2003 and dropped significantly afterwards. The prescription of combination therapy soon after the hospital admission for decompensated heart failure was associated with a decrease in the short-term mortality. In 111 adult patients who underwent liver elastometry, 14 HCVRNA positive subjects and 2 HCVRNA negative, had stiffness values suggestive of cirrhosis. No cases of hepatocarcinoma were reported. Liver "iron free foci" occurred in a HCV negative patient and the occurrence of a malignant epithelioid hemangioendothelioma led to liver transplantation in another. The study suggests that a subset of patients continues to develop progressive hemosiderosis that may lead to cardiac disease and death. Beyond its key role in preventing myocardial iron overload, liver iron chelation is essential for hampering the onset of hepatic tumors, which may not be limited to hepatocarcinoma.

Kaposiform lymphangiomatosis: a distinct aggressive lymphatic anomaly.

OBJECTIVE: To describe the clinical and imaging characteristics of a new lymphatic disorder with a unique histological pattern and poor prognosis. STUDY DESIGN: An observational, retrospective study identified and characterized 20 patients with distinct lymphatic histopathology referred to the Vascular Anomalies Center at Boston Children's Hospital between 1995 and 2011. RESULTS: The median age at onset was 6.5 years (range, birth to 44 years). Clinical and radiologic findings suggested a generalized process. The most common presentations were respiratory symptoms (50%), hemostatic abnormalities (50%), and an enlarging, palpable mass (35%). All patients had mediastinal involvement; 19 patients developed pericardial (70%) and/or pleural effusions (85%). Extrathoracic disease manifested in bone and spleen and less frequently in abdominal viscera, peritoneum, integument, and extremities. Despite aggressive procedural and medical therapies, the 5-year survival was 51% and the overall survival was 34%. Mean interval between diagnosis and death was 2.75 years (range, 1-6.5 years). CONCLUSIONS: We describe a clinicopathologically distinct lymphatic anomaly. We propose the term kaposiform lymphangiomatosis (KLA) because of characteristic clusters or sheets of spindled lymphatic endothelial cells accompanying malformed lymphatic channels. The intrathoracic component is most commonly implicated in morbidity and mortality; however, extrathoracic disease is frequent, indicating that KLA is not restricted to pulmonary lymphatics. The mortality rate of KLA is high despite aggressive multimodal therapy.

Does histology predict outcome for malignant vascular tumors of the liver?

BACKGROUND AND OBJECTIVES: Malignant vascular tumors (MVT) of the liver are uncommon and poorly understood. We hypothesized that tumor histology is a predominant factor associated with survival in these tumors. METHODS: Patients with malignant histopathologic diagnoses of hepatic angiosarcoma (AS), hemangioendothelioma (HE) and its epithelioid variant (EHE), or hemangiopericytoma (HP) were identified using the SEER database (1973-2007). Overall survival (OS) was studied with Kaplan-Meier curves. RESULTS: We included 297 patients with MVT (207 AS, 28 HE, 56 EHE, 6 HP). All tumors demonstrated metastatic potential, although EHE and AS had the highest rate of regional or distant metastases (75% each). Patients with AS had the shortest median OS (1 month), however, those undergoing surgery had improved survival (6 months). Three patients with AS underwent liver transplant and lived for 11, 21, and 91 months each. Patients with EHE had the longest overall median survival of 75 months (30-183, P < 0.001). Surgical resection and transplant did not demonstrate an improvement in OS of patients with EHE in multivariable models. CONCLUSIONS: Histology is an important factor in determining survival for patients with hepatic MVT. Patients with EHE have the longest OS, whereas patients with AS have shorter survival but may benefit from surgery.

Radiation therapy for hemangioendothelioma: the university of Florida experience.

OBJECTIVES: The benefit of radiotherapy (RT) for unresectable hemangioendotheliomas or patients with a high risk of local recurrence is unclear. This single-institution report describes the long-term effectiveness of RT for hemangioendothelioma. METHODS: From 1976 to 2009, 14 patients with nonmetastatic hemangioendothelioma were treated with RT at our institution. Median patient age was 45 years (range, 20 to 71 y). Nine patients had hemangioendothelioma of the extremities and 5 had spinal tumors. Eleven tumors originated from bone. Most tumors (n=12) were ≤5 cm in diameter. Nine patients had multifocal tumors. Four patients underwent surgery and postoperative RT, whereas 10 had RT alone. All 4 operative patients had microscopic negative margins. Median RT dose was 52.2 Gy (range, 45 to 60 Gy) for RT alone and 62.2 Gy (range, 60 to 64.8 Gy) for postoperative patients. Seven patients received 1.5-2 Gy once daily and 7 patients received 1.2 Gy twice daily. The median follow-up was 10.3 years (range, 0.1 to 28.0 y). RESULTS: The 10-year local control, cause-specific survival, and overall survival rates were 100%, 86%, and 73%, respectively. Two patients experienced a distant metastasis and died within 3 months of starting definitive RT. Three patients died of intercurrent illness at a median of 10.5 years after treatment. Nine patients had no evidence of disease at most recent follow-up. No patients experienced greater than grade 1 acute or late toxicity from RT. CONCLUSIONS: With no local recurrences and minimal risk of toxicity, our data suggest that RT can effectively manage this disease and radical surgery compromising function or cosmesis may be safely avoided with moderate-dose RT.

[Paediatric malignant liver tumours]. / Tumeurs malignes primitives du foie de l'enfant.

Tumours and pseudotumours of the liver are a heterogeneous group of neoplasm including 60% of malignant tumours. Malignant liver tumours account for less than 2% of the lesions in children and vary considerably in incidence throughout the paediatric age range, with hepatoblastoma, rhabdoid tumour of the liver, hemangioendothelioma, biliary tract rhabdomysosarcoma and mesenchymal hamartoma in the first two years of life and hepatocellular carcinoma, focal nodular hyperplasia, and undifferentiated sarcoma in older children and adolescents. Treatment of malignant epithelial tumours is based on the surgical resection of the tumour associated with pre- and postoperative chemotherapy including cisplatinum. Modalities of the treatment are adapted to risk factors. Survival rates at three years are over 80% for localised hepatoblastoma whereas they are less than 30% in hepatocellular carcinomas. The role of targeted therapies still has to be defined.

Successful treatment of kaposiform hemangioendothelioma and tufted angioma with vincristine.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare, locally aggressive vascular tumors. Although currently classified as separate entities, they are becoming increasingly recognized as a spectrum of the same pathology. There is a well-recognized association with Kasabach-Merritt phenomenon KHE and TA are considered neoplasms of intermediate malignancy because of infiltrative growth, local aggressiveness, and variable prognosis. To date, definitive treatment for these vascular tumors has had limited success. AIM: To evaluate the safety, efficacy, and role of vincristine in the treatment of KHE and TA. METHODS: Case review of patient files and pathology reports at The Children's Hospital at Westmead from 1995 to 2009. RESULTS: Twelve cases with KHE or TA were identified. Seven cases were treated with vincristine. The survival rate in the vincristine group was 100%. Mean age of diagnosis was 30 months (range birth to 9 y). 6 patients were female (85.7%). Mean time of the follow-up was 4 years (range 4 mo to 8 y). Out of the 7 cases treated with vincristine, 3 patients had associated Kasabach-Merritt phenomenon (43%). Complete resolution, regression in size, and improvement in analgesia were found in 1 case (14%), 3 cases (43%) and 2 cases (29%), respectively. Vincristine related side effects occurred in 2 cases (29%). CONCLUSIONS: Vincristine is an effective treatment option for KHE/TA. It is associated with a low side effect profile and should be considered as the first-line agent.

Factors predicting survival in childhood malignant and intermediate vascular tumors : retrospective analysis of the Polish and German cooperative paediatric soft tissue sarcoma study groups and review of the literature.

BACKGROUND: The rarity of malignant and intermediate vascular tumors in children means that little is known about their clinical course, optimal treatment, and variables predicting survival. METHODS: A total of 32 children with malignant vascular tumors (14 angiosarcomas [AS], 5 epithelioid hemangioendotheliomas, and 13 intermediate vascular tumors, including other hemangioendotheliomas plus adult-type hemangiopericytomas), registered in the German and Polish Paediatric Soft Tissue Sarcomas Study Groups, were treated following the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, -86, -91, and -96 protocols. RESULTS: Male sex, AS histology, tumor size >5 cm, and T2 invasiveness were independent predictors of inferior 5-year overall survival, while AS histology and T2 invasiveness were predictors of inferior 5-year event-free survival. AS histology was the most important negative prognostic factor for overall survival and event-free survival. Completeness of primary tumor excision was a good prognostic factor for survival in univariate, but not multivariate, analysis. Local therapy (radiotherapy and delayed surgery) were provided to the minority of patients (28% and 38%, respectively) late in the course of disease (after a mean of 9 and 6 months, respectively) and did not prevent local relapses. Response to systemic treatment was poor (44%) and did not prevent local and distant relapses. CONCLUSIONS: The clinical course and outcome in childhood epithelioid HE seems to be similar to intravascular tumors and less aggressive than AS. RTX and delayed surgery should be performed more frequently and earlier in the disease course. An urgent need for modification of systemic therapy is needed because of the development of many metastatic and/or combined relapses and poor response to classic chemotherapy. The problem of effective therapy for childhood AS is the most appaling: 13 of 14 patients died of progression despite multimodal treatment.

Treatment of hepatic epithelioid hemangioendothelioma: a single-institution experience with 25 cases.

OBJECTIVE: To examine treatment of hepatic epithelioid hemangioendothelioma (EHE), a rare vascular tumor with a variable course. Treatment modalities at our institution include liver resection, transplantation, and catheter-based therapies. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURES: Retrospective review of 25 patients treated for hepatic EHE (1976-2007). We examined treatment modality, overall survival, complications, and clinicopathologic characteristics. RESULTS: Of the 25 patients treated for hepatic EHE, 17 underwent liver transplantation (LT); 4, transcatheter arterial chemoembolization (TACE); 2, resection; and 2, TACE followed by LT. Twelve patients (48%) were male. The median age at diagnosis was 38 years (range, 9 months to 72 years). Mean overall survival was 167 (95% confidence interval [CI], 123-212) months, with 172 (124-220) months in the LT group and 83 (54-112) months in the TACE group. The 2 patients in the resection group remain alive after 19 and 71 months. The 2 patients treated with TACE followed by LT died after 13 and 113 months. Extrahepatic disease was identified as a predictor of outcome. Patients with extrahepatic disease treated with TACE fared better than those treated with surgical approaches (mean survival, 83.0 [95% CI, 54.2-111.8] vs 38.8 [23.7-53.8] months; P = .12). CONCLUSIONS: Hepatic EHE is a rare tumor that can be treated with surgical or nonsurgical approaches. In our experience, LT is used for patients with advanced local disease, whereas TACE is the primary modality when extrahepatic disease or comorbid conditions prohibiting LT are present. To our knowledge, this is the largest single-institution experience describing the various therapeutic modalities in the treatment of hepatic EHE.

Long-term outcomes following liver transplantation for hepatic hemangioendothelioma: the UNOS experience from 1987 to 2005.

INTRODUCTION: Hepatic hemangioendothelioma (HEH) is a vascular neoplasm with intermediate malignant potential. Outcomes after liver transplantation have only been reported as small, single-institution experiences. The purpose of this study was to evaluate patient and allograft survivals after liver transplantation in a large, multi-institutional cohort of patients with HEH. METHODS: Using the United Network for Organ Sharing (UNOS) database, we identified 110 patients with a diagnosis of HEH who underwent 126 transplants between 1987 and 2005. Patient and allograft survivals were calculated using Kaplan-Meier survival curves. Log rank tests were used to determine the influence of study variables on outcomes. RESULTS: Of the 110 transplanted patients, 75 patients (68%) were female, 80 patients (73%) were Caucasian, and the median age was 36 years old (23%<4 y.o., 71%>18 y.o.). The 30-day posttransplant mortality rate was 2.4%. At a median patient follow-up interval of 24 months, 1- and 5-year patient and allograft survivals were 80% and 64%, and 70% and 55%, respectively. Pretransplant medical status, but not age, was found to statistically correlate with patient survival. CONCLUSION: These data indicate that survivals after transplantation for HEH are favorable. Given the propensity for recurrence after resection, these data support consideration of liver transplantation for all patients with significant intrahepatic tumor burden.

Infantile hepatic hemangioendothelioma: clinical presentation and treatment.

BACKGROUND/AIMS: Hepatic hemangioendotheliomas are rare tumors in childhood. We report our 10-years' experience in a tertiary health center. METHODS: This retrospective analysis included eight patients with infantile hepatic hemangioendothelioma. RESULTS: The median age at diagnosis was 24 days (age range: 1 to 70 days) and the female/male ratio was 5/3. The main symptoms were abdominal distention and respiratory distress. Cutaneous hemangiomas were present in four cases. Three infants had Kasabach-Merritt syndrome. Four cases had single hepatic tumors while the others had multiple. The tumor size ranged from 2 cm to 10 cm in diameter. These lesions were located equally in the right and left hepatic lobes, and three babies had bilobar involvement. Most of the multifocal hepatic tumors were associated with skin hemangiomas. Treatment options were assessed individually. Systemic prednisolone therapy (2 mg/kg/d) was commenced in six patients. Five patients responded to corticosteroids. One boy with Kasabach-Merritt syndrome did not respond to this therapy. Interferon-alpha (1 million units (MU)/m2/day) was started, and the daily dose of the drug was increased up to 10 MU/m2, administered 3 times per week, until clinical improvement was achieved. The response was very good and we observed only constitutional adverse symptoms. Two cases were operated; one died from intraoperative bleeding. Other patients were alive and well for 11 to 66 months. Overall survival was 87% in our series. CONCLUSIONS: The treatment approaches depend on the center's experience. A multidisciplinary approach is required for the best treatment option.

In vivo gene therapy with interleukin-12 inhibits primary vascular tumor growth and induces apoptosis in a mouse model.

Interleukin-12 is proposed to have anti-neoplastic activity on the basis of both its anti-angiogenic and immunologic effects. Gene gun therapy with interleukin-12 cDNA into the peritumoral area of immunocompetent 129/J mice with life-threatening primary vascular tumors reduced tumor volume 7.5-fold and almost tripled the duration of mouse survival, in contrast with luciferase-bombarded control mice. Epidermal expression of mouse interleukin-12 elevated tumoral and serum levels of interferon-gamma and tumor necrosis factor-alpha, increased the tumoral populations of T lymphocyte and natural killer cells, and induced tumor apoptosis. Gene transfer of interleukin-12 had little effect on tumor volumes and survival of tumor-bearing athymic nude mice, emphasizing the requirement for T cell directed cellular immunity. Peritumoral gene gun introduction of interleukin-12 may be a novel, cost-effective approach to limit the growth and associated mortality of life-threatening tumors.

Hepatic hemangioendothelioma: clinical experience and management strategy.

PURPOSE: This study sought to define management strategies based on clinical experience in treating infantile hepatic hemangioendothelioma. METHODS: A retrospective analysis of patients with hemangioendothelioma presenting to a tertiary liver transplantation center between 1989 and 1997 was performed. RESULTS: Thirteen patients (median age, 14 days) with hemangioendothelioma were identified. Congestive heart failure (P<.03) and abdominal mass (P<.081) were predictive of 5-month mortality rates. Ultrasonography and computerized axial tomography were the diagnostic modalities most commonly used. Treatment strategies consisted of medical management (steroids and alpha-interferon) and interventional modalities (hepatic artery ligation or embolization, resectional surgery, or orthotopic liver transplantation). Patients who underwent resectional surgery, with or without orthotopic liver transplantation, had a lower 5-month mortality rate (P<.02) and a greater 2-year survival rate (P<.003) than did those who underwent hepatic artery ligation or embolization. Early morbidity and mortality tended to be a consequence of the primary lesion, whereas late morbidity and mortality were reflective of the treatment modality used. CONCLUSIONS: In cases of failed medical management, resectional therapy should be used when possible. If partial hepatectomy is not technically achievable, hepatic artery embolization should be used either as definitive therapy or as a temporizing measure until orthotopic liver transplantation is possible.

Surgical treatment of malignant liver tumours.

Surgical resection is the mainstay of treatment for malignant liver tumours and offers the only chance of cure. Advances in radiological imaging, surgical technique and peri-operative management have enabled liver resection to be performed safely. Partial hepatectomy is indicated for the treatment of hepatocellular carcinoma and hepatic metastases from colorectal cancer. In addition, it may be utilized for selected patients with liver metastases from other primary tumours. Total hepatectomy with transplantation may be of benefit in some patients with unresectable neuroendocrine metastases or small hepatocellular carcinomas. The role of cryosurgery has not been precisely defined, and it needs to be compared with other palliative therapies such as ethanol injection and hepatic artery embolization.