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.

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.

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.

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.

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.

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.

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.

Increased prevalence of tricuspid regurgitation in patients with prolactinomas chronically treated with cabergoline.

BACKGROUND: Cabergoline, a dopamine receptor-2 agonist used to treat prolactinomas, was associated with increased risk of cardiac valve disease in Parkinson's disease. OBJECTIVE: Our objective was to evaluate prevalence of cardiac valve regurgitation in cabergoline-treated patients with prolactinomas. DESIGN AND SETTING: An observational, case-control study was conducted at a university hospital. PATIENTS: Fifty treated patients (44 women and six men) and 50 sex- and age-matched control subjects participated; 20 de novo patients were also studied. INTERVENTION: In the treated patients, the last cabergoline dose was 1.3 +/- 1.3 mg/wk (<1 mg/wk in 44%, 1-3 mg/wk in 46%, and >3 mg/wk in 10%). Treatment duration was 12-60 months in 32% and more than 60 months in 68%. The cumulative (milligrams x months of treatment) dose of cabergoline ranged from 32-1938 mg (median 280 mg). MEASUREMENTS: Valve regurgitation was assessed according to the recommendations of the American Society of Echocardiography. RESULTS: In de novo patients, treated patients, and controls, the prevalence of mild regurgitation of mitral (35, 22, and 12%, P = 0.085), aortic (0, 4, and 2%, P = 0.59), tricuspid (55, 30, and 42%, P = 0.13) or pulmonic (20, 12, and 6%, P = 0.22) valves was similar. Conversely, the prevalence of moderate tricuspid regurgitation was higher in the treated patients (54%) than in de novo patients (0%) and controls (18%, P < 0.0001). Moderate tricuspid regurgitation was more frequent in patients receiving a cumulative dose above the median (72%) than in those receiving a lower dose (36%, P = 0.023). A higher systolic (P = 0.03) and diastolic blood pressure (P < 0.0001) was found in patients with than in those without moderate tricuspid regurgitation. CONCLUSION: Moderate tricuspid regurgitation is more frequent in patients taking cabergoline (at higher cumulative doses) than in de novo patients and control subjects, but the clinical significance of this finding has not been established. A complete echocardiographic assessment is indicated in patients treated long term with cabergoline, particularly in those requiring elevated doses.

Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia.

BACKGROUND: Whether the withdrawal of treatment in patients with nontumoral hyperprolactinemia, microprolactinomas, or macroprolactinomas is safe and effective has been unclear. We performed an observational, prospective study of cabergoline (a dopamine-receptor agonist) withdrawal in such patients. METHODS: The study population included 200 patients--25 patients with nontumoral hyperprolactinemia, 105 with microprolactinomas, and 70 with macroprolactinomas. Withdrawal of cabergoline was considered if prolactin levels were normal, magnetic resonance imaging (MRI) showed no tumor (or tumor reduction of 50 percent or more, with the tumor at a distance of more than 5 mm from the optic chiasm, and no invasion of the cavernous sinuses or other critical areas), and if follow-up after withdrawal could be continued for at least 24 months. RESULTS: Recurrence rates two to five years after the withdrawal of cabergoline were 24 percent in patients with nontumoral hyperprolactinemia, 31 percent in patients with microprolactinomas, and 36 percent in patients; with macroprolactinomas. Renewed tumor growth did not occur in any patient; in 10 female patients (22 percent) and 7 male patients (39 percent) with recurrent hyperprolactinemia, gonadal dysfunction redeveloped. In all diagnostic groups, prolactin levels at the time of recurrence were significantly lower than at diagnosis (P<0.001). The Kaplan-Meier estimated rate of recurrence at five years was higher among patients with macroprolactinomas and those with microprolactinomas who had small remnant tumors visible on MRI at the time of treatment withdrawal than among patients whose MRI scans showed no evidence of tumor at the time of withdrawal (patients with macroprolactinomas, 78 percent vs. 33 percent, P=0.001; patients with microprolactinomas, 42 percent vs. 26 percent, P=0.02). CONCLUSIONS: Cabergoline can be safely withdrawn in patients with normalized prolactin levels and no evidence of tumor. However, because the length of follow-up in our study was insufficient to rule out a delayed increase in the size of the tumor, we suggest that patients be closely monitored, particularly those with macroprolactinomas, in whom renewed growth of the tumor may compromise vision.

Contrast-enhanced sonography in the characterization of small hepatocellular carcinomas in cirrhotic patients: comparison with contrast-enhanced ultrafast magnetic resonance imaging.

AIM: To evaluate the role of low mechanical index (MI) contrast-enhanced sonography (CEUS) for the characterization of small hepatocellular carcinomas (HCC) in cirrhotic patients by comparing the results to ultrafast dynamic gadolinium-enhanced magnetic resonance imaging (MRI) studies. MATERIALS AND METHODS: Between September 2003 and June 2004, 73 patients (49 male and 24 female; mean age, 63 years; age range, 40-84 years) with a single liver nodule (< or =30 mm) were selected to enter into the study. CEUS and MRI studies were performed in all patients on consecutive days. All lesions were histologically confirmed after both imaging studies. CEUS was performed at low MI after i.v. administration of the contrast agent SonoVue. The enhancement pattern related to tumor hypervascularity was analyzed. The Chi-square test was used for statistical analysis. RESULTS: HCCs < or =10 mm (11 cases): On CEUS, 3/11 HCCs were hypervascular, while 8/11 were not visible (sensitivity, 27.3%; specificity, 100%; positive predictive value, 100%; negative predictive value, 55.6%). MRI studies showed a typical pattern in eight HCCs (sensitivity, 72.7%; specificity, 90.0%; positive predictive value, 88.9%; negative predictive value, 75.0%). HCCs 11-30 mm (37 cases): On CEUS, 34/37 (91.9%) HCCs were hypervascular, 2/37 avascular, and 1/37 not visible (sensitivity, 91.9%; specificity, 93.3%; positive predictive value, 97.1%; negative predictive value, 82.4%). MRI studies showed a typical pattern in 35/37 HCCs (sensitivity, 94.6%; specificity, 86.7%; positive predictive value, 94.6%; negative predictive value, 86.7%). The overall concordance between CEUS and MRI results was 75.0%. CONCLUSION: CEUS is a promising technique for the characterization of small HCCs in cirrhotic patients. It could be complementary to conventional sonography in evaluating focal liver lesions larger than 10 mm.

Percutaneous needle aspiration of multiple pyogenic abscesses of the liver: 13-year single-center experience.

OBJECTIVE: The aim of this study was to report 13 years of experience in the management of multiple pyogenic liver abscesses with only percutaneous needle aspiration of the abscess cavities under sonographic guidance. MATERIALS AND METHODS: From December 1991 to October 2004, 39 consecutively registered patients (29 men and 10 women; age range, 37-82 years; mean age, 64 years) with 118 pyogenic liver abscesses were treated with sonographically guided percutaneous needle aspiration at our institution. The number of pyogenic liver abscesses per patient ranged from two to 15 (mean, 3.0). RESULTS: Eighty-seven percutaneous needle aspirations were performed on 39 patients with 118 pyogenic liver abscesses (range, 1-4 aspirations per patient; mean, 2.2 aspirations per patient). Because they were close to another aspirated abscess in the right lobe of the liver, 31 (26.3%) of 118 abscesses were aspirated without removal of the needle from the liver. Thirty-six (92.3%) of 39 patients were treated with a single aspiration of an abscess in a single session. The other three patients needed two aspiration sessions. No patient needed imaging-guided percutaneous catheter drainage or open surgical drainage. Complete reconstitution of liver parenchyma occurred within a maximum of 80 days. No abscesses recurred during the follow-up period, which ranged from 7 to 42 months (mean, 18 months). CONCLUSION: Percutaneous needle aspiration of multiple pyogenic abscesses under sonographic guidance is a safe, effective, and low-cost procedure. In our experience, percutaneous needle aspiration was acceptable to patients. Our data suggest that a trial of percutaneous needle aspiration should always be undertaken before catheter drainage or surgery.

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.

Prolactin and prostate hypertrophy: a pilot observational, prospective, case-control study in men with prolactinoma.

In experimental models, prolactin (PRL) displays independent hypertrophic effects on the prostate. To investigate whether hyperprolactinemia is associated with prostate enlargement in humans, we designed this open, prospective, case-control study enrolling 20 men with prolactinoma (aged 34 +/- 10 yr) and 20 age-matched healthy men. The endocrine profile and prostate transrectal ultrasonography were performed before and after 12 and 24 months of cabergoline treatment in the patients and at study entry and after 24 months in the controls. The patients had lower serum testosterone, dihydrotestosterone (DHT), and IGF-I levels and prostate volume (15.4 +/- 3.5 vs. 19.6 +/- 5.1 ml; P < 0.001) and higher PRL levels and prostate-specific antigen density than controls. There was no difference in prostate and transitional zone volumes between patients with normoandrogenemia (n = 8) or hypoandrogenemia (n = 12). After 12 and 24 months of treatment, PRL, testosterone, and DHT levels were normal in all cases, as were IGF-I and IGF-binding protein-3 levels. After 24 months, prostate volume was comparable to that in controls (21.7 +/- 4.5 vs. 22.5 +/- 4.7 ml). There were no changes in prostate structure throughout the study period in either the patients or the controls. In conclusion, in young men with prolactinoma PRL excess is unlikely to have effects on the prostate per se, because it is accompanied by low testosterone and DHT levels that produce the major effects.

Dopamine receptor agonists for treating prolactinomas.

Prolactinomas are the most common hormone-secreting pituitary tumours and cause infertility and gonadal and sexual dysfunction in both sexes. The approach to prolactinomas has changed in the last 25 years thanks to the availability of dopaminergic drugs characterised by a potent prolactin-inhibitory effect, a tumour shrinking effect associated with a satisfactory tolerability. In more recent years, cabergoline 1-[(6-allelylergolin-8beta-yl)carbonyl]-1-[3-(dimethylamino) propyl]-3-ethyl-urea an ergoline derivative with potent, selective and long-lasting inhibitory activity on prolactin release, has been used to suppress prolactin secretion in women with hyperprolactinaemia. Cabergoline was shown to be significantly more effective than bromocriptine in inducing a complete biochemical response and clinical efficacy and was better tolerated than bromocriptine in the majority of patients. Notable tumour shrinkage until tumour disappearance was observed during cabergoline treatment in most patients with macroprolactinoma and it was also proven effective in patients resistant to or with a poor response to bromocriptine. In view of the limited data on cabergoline-associated pregnancies and the long half-life of the drug, it is currently recommended that women hoping to become pregnant, once ovulatory cycles have been established, should discontinue cabergoline therapy 1 month before they intend to conceive. However, no data concerning negative effects on pregnancy or offspring have been reported. The great efficacy of this compound together with its excellent tolerability makes this drug the current treatment of choice for the majority of patients with hyperprolactinaemic disorders.

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.