Dyslipidemia, lipid-lowering agents and neuroendocrine neoplasms: new horizons.

PURPOSE: Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies originating from cells with a neuroendocrine phenotype. The complex relationship between lipid metabolism and cancer is gaining interest and a potential anti-cancer effect of lipid lowering agents is being considered. This review aims to discuss the current understanding and treatment of dyslipidaemia in NENs, focusing on the role of lipid lowering agents, including new therapeutic approaches, and future perspectives as possible tool in cancer prevention and tumor-growth control. METHODS: We performed an electronic-based search using PubMed updated until December 2023, summarizing the available evidence both in basic and clinical research about lipid lowering agents in NENs. RESULTS: Dyslipidemia is an important aspect to be considered in NENs management, although randomized studies specifically addressing this topic are lacking, unlike other cancer types. Available data mainly regard statins, and in vitro studies have demonstrated direct antitumor effects, including antiproliferative effects in some cancers, supporting possible pleiotropic effects also in NENs, but data remain conflicting. Ezetimibe, omega 3-fatty acids, fibrates and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) may enhance the regulation of lipid homeostasis, as demonstrated in other cancers. CONCLUSIONS: Targeting dyslipidemia in NENs should be part of the multidisciplinary management and an integrated approach may be the best option for both metabolic and tumor control. Whether lipid lowering agents may directly contribute to tumor control remains to be confirmed with specific studies, focusing on association with other metabolic risk, disease stage and primary site.

Osteoporosis and dermatoporosis: a review on the role of vitamin D.

Osteoporosis (OP) and Dermatoporosis (DP) are expressions of the aging process at the skin and bone levels, respectively. Both conditions are associated with increased morbidity for elderly people, and this requires necessary interventions. They share many common risk factors; among these, vitamin D (VD) deficiency appears to have a role. VD is involved in either disease with many mechanisms, among which immunomodulation. VD deficiency has been linked to OP because it inhibits the body's capacity to absorb calcium and maintain optimal bone health. Available evidence suggests that proper vitaminosis D also appears to be vital in preventing skin age-related issues. DP is often seen in elderly individuals, particularly those with long-term sun exposure and a history of chronic sun damage. VD deficiency can be linked to DP, since its involvement in collagen production, epidermal barrier function, inflammation regulation, wound healing, and sun protection. Aim of this review is to summarize the most updated existing evidence on the role of VD in the development of fragility syndromes such as DP and OP and the possible benefits of VD supplementation as a simple and harmful weapon against aging.

Visceral Obesity and Cytokeratin-18 Antigens as Early Biomarkers of Liver Damage.

Visceral obesity is linked to the progression of fatty liver to nonalcoholic steatohepatitis (NASH). Cytokeratin-18 (CK18) epitopes M30 (CK18M30) and M65 (CK18M65) represent accurate markers for detecting NASH. The aim of this study was to evaluate the association of CK18M30 and CK18M65 levels with anthropometric and metabolic characteristics, liver stiffness, and liver indices of steatosis and fibrosis in a cohort of subjects with visceral obesity; in this cross-sectional study, transient elastography (TE-Fibroscan®), anthropometric measurements, metabolic parameters, High Sensitivity C-Reactive Protein (hsCRP), and CK18M30 and CK18M65 levels (Apoptosense ELISA, PEVIVA, Germany) were evaluated. Fatty Liver Index (FLI), Fibrosis 4 (FIB-4), and Aspartate transaminase (AST)-platelet ratio index (APRI) were calculated; among 48 subjects, 47.2% presented metabolic syndrome, 93.8% hepatic steatosis, 60.4% high liver stiffness, and 14.6% hypertransminasemia, while FIB-4 and APRI were normal. CK18M30 and CK18M65 levels were significantly correlated with waist circumference, AST, ALT, HoMA-IR, liver stiffness, and APRI (p < 0.001). Subjects with CK18 fragments above the median values showed significantly higher waist circumference, HbA1c, AST, ALT, HoMA-IR, FLI, and APRI compared to those with values below the median; CK18M30 and CK18M65 levels correlated well with anthropometric and metabolic characteristics, representing good biomarkers for early identification of NASH in subjects with visceral obesity.

Treatment of Hydatid Liver Cyst With Double Percutaneous Aspiration and Ethanol Injection Under Ultrasound Guidance: 6.5-Year Median Follow-up Analysis.

PURPOSE: Although hydatid liver cyst (HLC) is a benign disease, treatment is recommended to avoid life-threatening complications. There are several treatment options for HLC: "wait-and-watch," medical or surgical or percutaneous treatment. The purpose of this study was to assess the long-term effectiveness of an alternative of the traditional percutaneous PAIR procedure, called double percutaneous aspiration and ethanol injection (D-PAI). MATERIALS AND METHODS: This prospective, non-randomized study was conducted from 1988 to 2019 using DPAI procedure characterized by no reaspiration of the ethanol injected to replace the aspirated fluid and repetition of the procedure after 3-7 days. RESULTS: Two hundred and three patients with 290 HLCs underwent D-PAI. Two hundred and two HLC (160 patients) were univesicular cysts and 88 (43 patient) were multivesicular. Seventeen patients underwent one D-PAI session, 15 patients two sessions, and 18 up to four sessions. The follow-up ranged 0.9-21 years (median 6.5 years). On ultrasound, 188 cysts (64.8%) disappeared; 57 cysts (19.7%) became solid (inactive) and 45 (15.5%) showed a small inactive residual component. Parasitologic cure was very high. The overall response to D-PAI was higher than 90% considering also the procedures carried out after the first D-PAI at the time of recurrence. One patient died for anaphylactic shock. The hospital stay ranged 1-3 days. Smaller cysts (< 5 cm) healed sooner than larger cysts (p < 0.001). CONCLUSIONS: Long-term analysis showed that D-PAI is a safe and effective option in percutaneous treatment of viable HLC, except for CE2/CE3b in which the recurrences can be observed. This inexpensive and simple procedure can be applied everywhere and especially in developing countries.

Effect of Octreotide Long-Acting Release on Tregs and MDSC Cells in Neuroendocrine Tumour Patients: A Pivotal Prospective Study.

Octreotide long-acting repeatable (LAR) is largely used to treat functional and/or metastatic neuroendocrine neoplasms (NENs). Its effect in controlling carcinoid syndrome and partially reduce tumour burden is attributable to the ability of octreotide to bind somatostatin receptors (SSTRs) on the tumour and metastasis, regulating growth hormone secretion and cell growth. Notably, SSTRs are also expressed, at different levels, on Tregs. Tregs, together with myeloid-derived suppressor cells (MDSCs), are key components in the anti-tumour immunoregulation. This is the first prospective study aimed to explore the impact of Octreotide (OCT) LAR on the immune system, with a particular focus on Tregs and MDSC cells. Here, we show that circulating Tregs are elevated in NENs patients compared to healthy donors and that treatment with OCT LAR significantly decrease the level of total Tregs and of the three functional Tregs populations: nTregs, eTregs and non-Tregs. Furthermore, OCT LAR treatment induces a functional impairment of the remaining circulating Tregs, significantly decreasing the expression of PD1, CTLA4 and ENTPD1. A trend in circulating MDSC cells is reported in patients treated with OCT LAR. The results reported here suggest that the effect of OCT LAR on Tregs could tip the balance of the patients' immune-system towards a durable anti-tumour immunosurveillance with consequent long-term control of the NENs disease.

Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors.

Patients affected by gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP-NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP-NET, focusing on vitamin D and its role in GEP-NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis.

Prognostic impact of tumour burden in stage IV neuroendocrine neoplasia: A comparison between pancreatic and gastrointestinal localizations.

BACKGROUND: Although prognosis of NENs is affected by several features including tumour burden, the specific role of this factor in pancreatic NENs (PanNENs) and gastrointestinal NENs (GI NENs) is not well established. AIM: To compare the prognostic role of tumour burden in PanNENs and GI NENs. PATIENTS AND METHODS: This study was a retrospective analysis of stage IV PanNENs and GI NENs. Tumours were classified based on liver tumour volume (<25% or >25%). Overall survival as assessed by Kaplan-Meier curves, and Cox proportional hazards method was used to perform risk factor analysis. RESULTS: The analysis included 300 patients, including 166 panNENs (55.3%) and 134 GI NENs (44.7%). A total of 158 patients (52.7%) had G2 tumours, 107 had G1 tumours (35.7%), and 35 had G3 tumours (11.6%). Tumour liver involvement >25% was observed in 187 patients (62.3%): 106 PanNENs (56.7%), and 81 GI NENs (43.3%) (p = 0.551). Bone metastases were present in 45 patients (15%): 22 PanNENs (13.2%) and 23 GI NENs (17.1%) (p = 0.416). Characteristics of the PanNENs, including: grading (G2 vs G1, HR = 3.7; G3 vs G1, HR = 16.40), liver involvement > 25% (HR = 3.09), and bone metastases (HR = 2.27) were independent predictors for poor survival, whereas the only significant risk factor in GI NENs was grading (G2 vs G1, HR = 4.36; G3 vs G1, HR = 8.60). CONCLUSIONS: PanNENs and GI NENs have different risk profiles. Liver tumour volume and the presence of bone metastases significantly affect survival in patients with PanNENs but has no impact on the clinical outcomes of GI NENs.

Bone Metastases in Neuroendocrine Neoplasms: From Pathogenesis to Clinical Management.

Bone represents a common site of metastases for several solid tumors. However, the ability of neuroendocrine neoplasms (NENs) to localize to bone has always been considered a rare and late event. Thanks to the improvement of therapeutic options, which results in longer survival, and of imaging techniques, particularly after the introduction of positron emission tomography (PET) with gallium peptides, the diagnosis of bone metastases (BMs) in NENs is increasing. The onset of BMs can be associated with severe skeletal complications that impair the patient's quality of life. Moreover, BMs negatively affect the prognosis of NEN patients, bringing out the lack of curative treatment options for advanced NENs. The current knowledge on BMs in gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) NENs is still scant and is derived from a few retrospective studies and case reports. This review aims to perform a critical analysis of the evidence regarding the role of BMs in GEP- and BP-NENs, focusing on the molecular mechanisms underlining the development of BMs, as well as clinical presentation, diagnosis, and treatment of BMs, in an attempt to provide suggestions that can be used in clinical practice.

Safety and Activity of Metronomic Temozolomide in Second-Line Treatment of Advanced Neuroendocrine Neoplasms.

BACKGROUND: Platinum-based chemotherapy is the mainstay of front-line treatment of patients affected by pluri-metastatic intermediate/high grade NeuroEndocrine Neoplasms (NENs). However, there are no standard second-line treatments at disease progression. Previous clinical experiences have evidenced that temozolomide (TMZ), an oral analog of dacarbazine, is active against NENs at standard doses of 150 to 200 mg/mq per day on days 1 to 5 of a 28-day cycle, even if a significant treatment-related toxicity is reported. METHODS: Metastatic NENs patients were treated at the ENETS (European NeuroEndocrine Tumor Society) center of excellence of Naples (Italy), from 2014 to 2017 with a second-line alternative metronomic schedule of TMZ, 75 mg/m2 per os "one week on/one week off". Toxicity was graded with NCI-CTC criteria v4.0; objective responses with RECIST v1.1 and performance status (PS) according to ECOG. RESULTS: Twenty-six consecutive patients were treated. Median age was 65.5 years. The predominant primary organs were pancreas and lung. Grading was G2 in 11 patients, G3 in 15. More than half of patients had a PS 2 (15 vs. 11 with PS 1). The median time-on-temozolomide therapy was 12.2 months (95% CI: 11.4-19.6). No G3/G4 toxicities were registered. Complete response was obtained in 1 patient, partial response in 4, stable disease in 19 (disease control rate: 92.3%), and progressive disease in 2. The median overall survival from TMZ start was 28.3 months. PS improved in 73% of patients. CONCLUSIONS: Metronomic TMZ is a suitable treatment for G2 and G3 NENs particularly in PS 2 patients. Prospective and larger trials are needed to confirm these results.

Therapeutic sequences in patients with grade 1-2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group.

PURPOSE: Many different treatments are suggested by guidelines to treat grade 1-2 (G1-G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1-G2 NET. METHODS: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. RESULTS: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1-G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). CONCLUSIONS: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1-G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy.

Sorafenib Combined with Radio-frequency Ablation Compared with Sorafenib Alone in Treatment of Hepatocellular Carcinoma Invading Portal Vein: A Western Randomized Controlled Trial.

AIM: To compare in a randomized controlled trial (RCT) 3-year survival of cirrhotic patients with hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombus (PVTT) treated with sorafenib plus percutaneous radiofrequency ablation (RFA) of both intraparenchymal HCC and PVTT (combination Group) or sorafenib alone (sorafenib-alone Group). PATIENTS AND METHODS: Ninety-nine consecutive Child A cirrhotics were randomized to receive RFA of both HCC and main portal vein tumor thrombus (MPVTT) plus sorafenib (n=49) or sorafenib alone (n=50). RESULTS: One-, 2- and 3-year survival rates were 60%, 35% and 26%, respectively, in the combination group and 37% and 0 % at 1- and 2-year, respectively, in the sorafenib alone group. At multivariate analysis, the combination of RFA of both HCC and MPVTT was the only factor predicting survival. CONCLUSION: Use of RFA of both HCC and MPVTT plus sorafenib significantly increases 3-year survival compared to sorafenib alone.

Hepatic arterial embolization in patients with neuroendocrine tumors.

Liver metastases occur in 46-93% of patients with neuroendocrine neoplasms (NENs). Presence and extension of liver metastases are considered important prognostic factors, as they may significantly impair the patient's quality of life, because of either tumor bulk or hormonal hypersecretion. Therapies for NEN liver metastases include surgical resection, liver transplantation, chemotherapy and biotherapy. Surgery is the gold standard for curative therapy, but in most of NEN patients with liver metastases, when surgery can not be applied, minimally invasive therapeutic approaches are adopted. They include trans-arterial embolization (TAE), trans-arterial chemoembolization (TACE), radiofrequency thermal ablation and new emerging techniques.TAE is based on selective infusion of particles in the branch of the hepatic artery supplying the tumor lesions. The goal of TAE is to occlude tumor blood vessels resulting in ischemia and necrosis. Many reports have shown that TAE can reduce tumor size and hormone output, resulting in palliation of symptoms without the use of cytotoxic drugs, resulting in better tolerability. This review will focus on TAE performance and safety in NEN patients with liver metastases.

Transarterial embolization (TAE) is equally effective and slightly safer than transarterial chemoembolization (TACE) to manage liver metastases in neuroendocrine tumors.

Liver metastases from neuroendocrine tumor (NET) can be treated by transarterial embolization (TAE) or transarterial chemoembolization (TACE). The goal of TAE and TACE is to reduce blood flow to the tumor resulting in tumor ischemia and necrosis. In this retrospective study, the effectiveness and safety of TAE-TACE in the treatment of liver metastases in patients with NET was compared. Thirty patients with a histologically confirmed gastro-entero-pancreatic NET with liver metastases were retrospectively investigated. Seventeen patients underwent TAE, while 13 patients underwent TACE. Tumor response, degree of devascularization in treated lesions, and progression free survival (PFS) were evaluated in the whole population and then separately in TAE and TACE subgroups. In all patients treated with TAE and TACE, there was a significant size reduction of lesions as compared to baseline. Per lesion reduction was 2.2 ± 1.4 versus 3.3 ± 1.5 cm for TAE (p < 0.001) and 2.2 ± 1.5 versus 3.4 ± 1.7 cm for TACE (p < 0.001). In the whole population, the median PFS for all patients was 36 months (16.2-55.7 CI), without significant difference between TAE and TACE. In no patient did adverse events grade 3 and 4 as well as TAE/TACE-related death occurred, while the post-embolization syndrome occurred in 41 % of patients treated with TAE and 61 % of those treated with TACE. TAE and TACE are both effective in NET patients with liver metastases. TAE should be preferred to TACE in light of its similar anti-tumor effects and slightly better toxicity profile.

Results of a single-center observational 10-year survey study on recurrence of hyperprolactinemia after pregnancy and lactation.

CONTEXT: The current survey study investigated the recurrence rate of hyperprolactinemia after cabergoline (CAB)-induced pregnancy and after lactation as well as safety of CAB exposure during early gestation. PATIENTS AND METHODS: From 1997-2008, 143 pregnancies were recorded in 91 patients with hyperprolactinemia (age 30.4 ± 4.7 yr, 76 microadenomas, 10 macroadenomas, and five nontumoral hyperprolactinemia). CAB therapy was discontinued within wk 6 of gestation in all. Pregnancies were monitored until delivery or termination, during and after lactation, twice yearly up to 60 months. The incidence of abortions, premature delivery, and fetal malformations was also analyzed. RESULTS: Pregnancies resulted in 13 (9.1%) spontaneous abortions and 126 (88.1%) live births. No neonatal malformations and/or abnormalities were recorded. In 29 of 91 patients (three with macroadenomas), treatment with CAB had to be restarted within 6 months after lactation because of hyperprolactinemia recurrence, whereas in 68% of cases, no additional therapy was required up to 60 months. No tumor mass enlargement was observed. All patients but three were breastfeeding, 35 (38.5%) for less than 2 months and 56 (61.5%) for 2-6 months. Three months after cessation of lactation and 60 months after pregnancy, no difference in prolactin levels was found between patients nursing for less than 2 months and 2-6 months. CONCLUSIONS: Fetal exposure to CAB at conception does not induce any increased risk of miscarriage or malformations. Pregnancy is associated with normalization of prolactin levels in 68% of patients. Breastfeeding does not increase the recurrence rate of hyperprolactinemia.

Radiofrequency ablation for intrahepatic cholangiocarcinoma: retrospective analysis of a single centre experience.

PURPOSE: To evaluate the usefulness and safety of radiofrequency ablation for primary and recurrent intrahepatic cholangiocarcinoma (ICC) in our single centre experience. MATERIALS AND METHODS: Ten patients with ICC refusing or not eligible for surgery underwent radiofrequency ablation for their tumor. The ICC was primary in 9 cases and recurrent, after 2 previous resections, in 1 patient. Radiofrequency ablation was performed percutaneously under ultrasound guidance using a 15G perfused electrode. Technical success of the procedure was assessed by contrast-enhanced ultrasound (CEUS). Technical effectiveness was evaluated by CEUS and contrast enhanced CT 1 month after the last course of a defined ablation protocol. Follow-up contrast enhanced CT or MRI were performed every 3-6 months. RESULTS: RFA was always technically successful and effective for ICC lesions ≤3.4 cm and ineffective for lesion ≥4 cm. After a median follow-up of 19.5 months (range 9-64 months), 8 patients were still alive while 2 had died due to tumor progression. The 1-, 3- and 5-year overall survival rate of all patients with ICC of our series were 100%, 83.3% and 83.3%. No major complication was observed. CONCLUSION: Radiofrequency ablation seems to be a safe and effective option for small (≤3.4 cm) ICC nodules. In addition it may be considered as a palliative treatment for larger tumors.

Characterization of dysplastic nodules, early hepatocellular carcinoma and progressed hepatocellular carcinoma in cirrhosis with contrast-enhanced ultrasound.

BACKGROUND: During the progression from low-grade dysplastic nodule (DN) to progressed hepatocellular carcinoma (HCC), intranodular portal tracts gradually disappear, while unpaired arteries develop increasingly. Contrast-enhanced ultrasound (CEUS) is highly accurate in depicting intranodular vascularity. This study evaluates the usefulness of CEUS in the characterization of DN, early HCC and progressed HCC in cirrhotic livers. MATERIALS AND METHODS: Forty consecutive patients with cirrhosis and a single hepatic nodule ≤2 cm underwent CEUS and subsequent ultrasound-guided biopsy of the nodule. Imaging and pathological findings of DN and HCC were compared. RESULTS: The homogeneous pattern of hypervascularization during the arterial phase identified progressed HCC with a sensitivity of 90.9% and a specificity of 100%, whereas the inhomogeneous and reticular pattern identified early HCC with a sensitivity of 85.7% and a specificity of 96.1%. CONCLUSION: DN, early HCC and progressed HCC can be accurately differentiated with CEUS on the basis of the vascularization pattern during the arterial phase.

Evolution of an aggressive prolactinoma into a growth hormone secreting pituitary tumor coincident with GNAS gene mutation.

CONTEXT: Mixed PRL- and GH-secreting pituitary adenomas are relatively common because somatotrophs and lactotrophs share the common somato-mammotroph progenitor lineage. Conversely, the occurrence of a prolactinoma evolving into clinically and biochemically active acromegaly is a rare phenomenon. OBJECTIVE AND RESULTS: We report a patient with a prolactinoma who after 15 yr of disease control by bromocriptine became resistant to dopaminergic drugs and due to the rapid tumor growth was submitted to four neurosurgeries and two stereotactic radiotherapies in the subsequent 5 yr. Unexpectedly, in the last 1.5 yr, after the fourth neurosurgery and second gamma-knife, she complained of signs and symptoms of acromegaly that was biochemically confirmed. Histological examination of the surgical specimens revealed high Ki67 and p53 and low D2 receptor expression. Although samples from the initial surgery were positive for prolactin and negative for GH, about 10% of GH-positive cells were detected in tissue from the last surgery, consistent with the observed clinical shift to acromegaly. Molecular screening failed to find mutations in RAS, TP53, and BRAF hot spots, whereas Arg201His mutation in GNAS gene (gsp oncogene), absent in the previous surgical materials, was detected in the tumor from the last surgery, which was found to be monoclonal. CONCLUSIONS: These observations suggest that 1)treatment of prolactinomas resistant to dopaminergic drugs is still a challenge, and 2) the appearance of gsp oncogene in a prolactinoma evolving into acromegaly might be the underlying mechanism of this rare transition, further confirming that this mutational change is associated with somatotroph growth and transformation.

Hepatocellular carcinoma with cirrhosis: are patients with neoplastic main portal vein invasion eligible for percutaneous radiofrequency ablation of both the nodule and the portal venous tumor thrombus?

OBJECTIVE: The purpose of this study was to examine the results of percutaneous radiofrequency ablation of both medium-sized hepatocellular carcinoma (HCC) and the accompanying main portal venous tumor thrombus in patients with cirrhosis. SUBJECTS AND METHODS: From January 2005 to January 2008, among 1,837 consecutively registered patients with HCC seen at our institution, 412 had HCC and portal venous invasion; 27 of the 412 had a single HCC nodule accompanied by main portal venous tumor thrombus. Thirteen patients (10 men, three women; mean age, 70 years; range, 66-74 years) with 13 HCC nodules 3.7-5 cm in diameter extending into the main portal trunk underwent percutaneous radiofrequency ablation. Fourteen matched patients (10 men, four women; mean age, 69 years; range, 67-73 years) with 14 HCC nodules 3.6-4.8 cm in diameter extending into the main portal trunk refused radiofrequency ablation and composed the control group. Diagnosis of main portal venous tumor thrombus was made with fine-needle biopsy in all cases. Radiofrequency ablation was performed first on the main portal venous tumor thrombus and then on the HCC nodule. Efficacy of radiofrequency was defined as complete necrosis of HCC and complete recanalization of the main portal trunk and its branches. HCC necrosis was evaluated with enhanced CT. Recanalization of portal vessels was analyzed with color Doppler and contrast-enhanced ultrasound. Radiofrequency ablation was performed under ultrasound guidance with a perfused needle electrode. RESULTS: Complete necrosis of the HCC associated with complete recanalization of the main portal vein and its branches was achieved in 10 patients (efficacy, 77%). In the other three patients, necrosis of the HCC ranged from 70% to 90%, and recanalization of the main portal trunk was not complete. No major complications occurred. In three cases, mild to moderate ascites and increased aspartate aminotransferase and alanine aminotransferase levels were found. The follow-up periods ranged from 3 to 36 months among the treated patients and 2 to 10 months among the untreated patients. The cumulative survival rate was 77% 6, 12, and 36 months after procedure in the treated group and 43% and 0% 6 and 12 months after diagnosis in the untreated group (p < 0.0001). All 10 successfully treated patients were alive and the portal system was patent at the end of the follow-up period. All three untreated patients died of progressive disease within 5 months of diagnosis. CONCLUSION: Radiofrequency ablation can destroy both single intraparenchymal medium-sized HCCs and the accompanying main portal venous tumor thrombus with high efficacy and safety and a low rate of complications.

Sonography and clinical outcome of viable hydatid liver cysts treated with double percutaneous aspiration and ethanol injection as first-line therapy: efficacy and long-term follow-up.

OBJECTIVE: The objective of our study was to report our 19-year experience with sonography and the clinical outcome of viable hydatid liver cysts treated with double percutaneous aspiration and ethanol injection as first-line therapy. CONCLUSION: Viable hydatid liver cysts can be safely and successfully managed with double percutaneous aspiration and ethanol injection as first-line-therapy.

Percutaneous treatment of Hydatid Liver Cyst.

Percutaneous treatment of Hydatid Liver Cyst (HLC) with scolicidal agent under ultrasound guidance is now worldwide used after the advent of Percutaneous-Aspiration-Injection and Re-Aspiration (PAIR) and its modifications. Although HLC represent a benign disease, treatment has to be considered mandatory in symptomatic cysts and recommended in viable cysts because of the risk of severe complications. In this article, clinical indications, PAIR technique with results and complications are discussed. Finally, clinical flow-chart of active and inactive HLCs is reported. The present article is a review of some patents in the Hydatid liver cyst.