Ultrasound-guided percutaneous irreversible electroporation of hepatic and abdominal tumors not eligible for surgery or thermal ablation: a western report on safety and efficacy.

PURPOSE: To report our first results on sixteen patients affected by liver and abdominal malignant tumors, unfit for surgery or thermal ablation, treated with US-guided percutaneous irreversible electroporation (IRE). METHODS: From June 2014 to December 2016, all patients meeting the inclusion criteria (malignant hepatic or abdominal tumors not eligible for resection or thermal ablation) and not meeting the exclusion criteria (heart arrhythmia, pro-hemorrhagic hematological alterations, tumor size > 8 cm, presence of a biliary metallic stent) referred to our institutions were prospectively enrolled to undergo percutaneous US-guided irreversible electroporation (IRE). Sixteen patients (age range 59-68 years, mean 63; 7 females) with 18 tumors (diameter range 1.3-7.5 cm) fulfilled the inclusion criteria and were included in the study. Data concerning efficacy (tested by a 1-week CEUS and a 4-week enhanced CT and/or enhanced MRI) and safety were recorded during a 18-month follow up. RESULTS: All patients completed a 35-50-min procedure without complications. One patient with 6 cm Klatskin tumor also underwent a second session for 1 month. A 1-week CEUS and a 4-week e-CT and/or e-MRI arterial phase contrast enhancement analysis showed an overall reduction of arterial flow with confirmation of unenhanced lesions for seven nodules. After 1-18 months of follow up, no major complications were recorded and no tumor-related death occurred. The lesions of two patients disappeared 3 and 6 months after their treatment, respectively. CONCLUSIONS: IRE is a promising ablation modality in the treatment of malignant hepatic and abdominal tumors unsuitable for resection or thermal ablation.

Thyroid diseases in women with breast cancer.

AIM: Several studies have been undertaken to investigate a possible link between breast cancer and thyroid diseases, notably thyroid carcinoma and autoimmune thyroid diseases, but the issue remains unresolved. The aim of this study is to evaluate, in thyropathic women with and without breast cancer, the following effects: the distribution of different thyroid diseases, the breast-cancer-related prevalence of anti-thyroperoxidase and anti-thyroglobulin antibodies and the role in thyroid pathology of breast-cancer post-surgery therapy with tamoxifene. MATERIALS AND METHODS: One-hundred-ninety thyropathic women with breast cancer (BC group) were recruited, and compared with a control group (C group) of one-hundred-ninety thyropathic women without breast cancer. RESULTS: Nodular disease is the most frequent pathology in both groups. The difference in the incidence of thyroid carcinoma is also not statistically significant. The biochemical increase in the positivity of autoantibodies in BC-group patients is confirmed, but there is no statistically significant difference in the rate of clinical autoimmune diseases between the two groups. No difference in the frequency of any particular thyroid disease is found between those patients who underwent post-operative tamoxifene therapy and those who did not. CONCLUSION: It can be concluded, on the basis of these results, that it is advisable to reduce the clinical weight of the issue. A routine thyroid screening is recommended in women with BC for the management of chronic comorbidities, as would be for women in the general population having the same age and coming from the same iodine-intake area.

Medical treatment of hyperthyroidism: state of the art.

Methimazole (MMI) and propylthiouracil (PTU) are the main antithyroid drugs used for hyperthyroidism. They inhibit the synthesis of thyroid hormone at various levels and are used as the primary treatment for hyperthyroidism or as a preparation before radioiodine therapy or thyroidectomy. MMI is the drug of choice because of its widespread availability, longer half-life and small number of severe side effects. Drugs of second choice are potassium perchlorate, beta blockers, iodine, lithium carbonate and glucocorticoids. Rituximab, a monoclonal antibody directed against human CD20, was recently proposed as a biological therapy for cases of Graves' disease unresponsive to traditional drugs.

Diagnostic accuracy of rhTSH test with neck ultrasonography in differentiated thyroid cancer follow-up.

Serum thyroglobulin levels measurement after injection of recombinant human thyrotropin (rh-TSH) represents the most important advance in the follow-up of patients with differentiated thyroid cancer, obtaining TSH elevation without L-thyroxine withdrawal, avoiding marked hypothyroidism symptoms. During a 4-yr period (2004-2008), 66 consecutive patients with DTC (59 papillary and 7 follicular carcinomas) were examined after rh-TSH Tg test and neck ultrasonography. In all patients basal Tg was <0.25 ng/ml. In twelve (18.5%) examined patients rh-TSH Tg was >0.25 ng/ml, and in seven (58.3%) of these was demonstrated persistent or recurrent disease. These data indicate that rhTSH-Tg>0.25 ng/ml should be considered diagnostic for persistent or recurrent disease and suggests further exams (neck ultrasonography, whole body scan or cytology) to localize the disease. Furthermore, neck ultrasonography has demonstrated high accuracy in detecting lymph nodal metastases and should be always combined with rh-TSH test.

[Antithyroid drugs therapy]. / Terapia con farmaci antitiroidei.

Methimazole and Propylthiouracil are the cornerstones in the management of Graves' disease. Their primary effect is to inhibit thyroid hormone synthesis at different steps, i.e. in thyroid gland and in peripheral tissues. Antithyroid drugs can be used as the primary treatment for hyperthyroidism (long term therapy: 1-2 years) or as preparative therapy before radioiodine treatment or surgery (short term therapy: weeks or months). Generally, the starting dose of methimazole is 10-30 mg, as single daily dose, while that of PTU is 100-300 mg every 6 hours. Methimazole is the drug of choice, because major side effects are less common, it can be used as single dose, it's less expensive and more available. As far as the treatment of hyperthyroidism in pregnancy, MMI and PTU have same therapeutic efficacy and are both safe for the fetus, having similar placental transfer kinetics. The use of methimazole can be associated with aplasia cutis and choanal/esophageal atresia, while there are no data supporting the association between congenital anomalies and PTU. For this reason the latter is the drug of choice in the treatment of hyperthryroidism in pregnancy. Both thionamides are present in breast milk, but there are no controindications for their use during lactation.

Trend in thyroid carcinoma size, age at diagnosis, and histology in a retrospective study of 500 cases diagnosed over 20 years.

Recently, the Italian Network of Cancer Registries analyzed 5101 cases of thyroid carcinoma showing a reduction of mortality rate of 4%/year. This prompts us to evaluate the temporal trend in tumor size, age at diagnosis, and histology in a retrospective analysis of 500 thyroid cancers diagnosed over 20 years. Thyroid cancers were divided in two groups. The first included 193 cases diagnosed from 1985 to 1994, and the second 307 from 1995 to 2004. The size of all tumors was significantly reduced from 30 +/- 1.4mm in the first group to 15 +/- 0.8mm in the second group. In particular, papillary thyroid carcinoma (PTC) size decreased from 28 +/- 1.2mm to 14 +/- 0.8mm and follicular carcinoma from 40 +/- 6.3mm to 17 +/- 4.5 mm. Age at diagnosis of all carcinomas increased significantly from 40 +/- 1.3 years in the first group to 48 +/- 0.9 years in the second group. Analysis of the histological types revealed a significant increase of PTC rate in the second decade from 82% to 92% and a concomitant reduction of anaplastic thyroid carcinoma (ATC) from 3.7% to 1.0%. Moreover, a significant increase of micro-PTC rate, from 7.3% to 36.4%, was observed. In conclusion, it may be speculated that the above mentioned decreased mortality rate for thyroid carcinoma could be related to the significant reduction with time of cancer size, to the progressive increase of PTC rate and to the reduction of ATC rate. These data, if confirmed in other series, underscore the importance of evaluating thyroid nodules smaller than 10mm and corroborate recent findings suggesting that age be reconsidered as an independent prognostic factor for differentiated thyroid cancers.

A novel biweekly pancreatic cancer treatment schedule with gemcitabine, 5-fluorouracil and folinic acid.

Pancreatic adenocarcinoma is a common disease considered to be poorly responsive to antiblastic treatment. Recent clinical and preclinical results suggest that a combined treatment of gemcitabine (GEM), 5-flurouracil (5-FU) and folinic acid (FA) offers a clinical benefit in patients with advanced pancreas adenocarcinoma. The aim of this phase II clinical trial was to evaluate the antitumour activity and toxicity of a novel biweekly schedule of this combination in patients with pancreatic adenocarcinoma. A total of 42 patients received a 30 min infusion of FA (100 mg m(-2)) and 5-FU (400 mg m(-2)) (FUFA) on days 1-3, and GEM 1000 mg m(-2) on day 1 every 15 days. We observed 13 objective responses (two complete, 11 partial) and 23 stable diseases. The median time to progression was 9.75 months (95% Confidence Interval (CI), 6.88-12.62) and the median overall survival was 13.10 months (95% CI 9.64-16.56). There were seven cases of each grade III gastroenteric and haematological toxicity. The GEM plus FUFA combination appears to be well tolerated and very active in patients with pancreatic carcinoma.

Localization and expression of thyroid hormone receptors normal and neoplastic human thyroid.

The aim of this study was to investigate the regional expression of thyroid hormone nuclear receptor forms (TR(alpha) and TR(beta)) and isoform (TR(alpha1) and TR(beta2)) mRNAs in normal and neoplastic (benignant and malignant) human thyroid tissue. Tumor specimens from patients with thyroid carcinomas (papillary: 5 cases; follicular: 5 cases; anaplastic: 2 cases), thyroid follicular adenomas (7 cases) and tissue from normal thyroid glands (12 cases) were analyzed by in situ hybridization and semiquantitative RT-PCR for the expression of TR(alpha1) and beta, as well as for the isoform alpha2 that does not bind the hormone. In normal tissues, TR(alpha2) was expressed at lower levels compared to TR(alpha1) (alpha1/alpha2 = 4.3). In papillary and follicular carcinomas, the expression of TR(alpha1) and TR(beta) did not change as compared with normal thyroid tissue and adenomas (0.87 +/- 0.15 SD vs 0.89 +/- 0.17 densitometric units, DU, and 0.15 +/- 0.02 vs 0.14 +/- 0.03 DU, respectively). However, the expression of TR(alpha2) was significantly higher in differentiated carcinomas compared to normal thyroid tissue and adenomas (0.47 +/- 0.05 vs 0.20 +/- 0.05 DU, p < 0.05) with alpha1/alpha2 = 1.4. In anaplastic carcinoma all TRs were absent. We concluded that both normal and pathological thyroid tissues, with the exception of anaplastic carcinoma, express all TRs in thyreocites and that differentiated thyroid carcinomas are associated in enhancing the expression of TR(alpha2) mRNA.

[Acute hepatitis in a patient with adult onset Still disease]. / Epatite acuta in paziente con malattia di Still dell'adulto.

Liver abnormalities in the course of Adult Onset Still's Disease (AOSD), both in form of hepatomegaly and elevation of hepatic enzymes, have been reported in up to three-quarts of the affected patients. These abnormalities may reflect disease activity or may be induced by drugs. Only in a few of this patients a liver biopsy was performed. However liver histology has shown, generally, non specific abnormalities or even normal pictures. We have recently observed a 47-year-old woman with a febrile illness started five months before, who after pertinent investigation was diagnosed as AOSD (according to criteria of Yamaguchi et al.). Apart from laboratory findings characteristic of an inflammatory disease, in absence of drug therapies the biochemical data showed raised levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and aminoglutamil transferase. Serological tests for either viral hepatitis viruses (HAV, HBV, HCV) or other viruses were negative. Ultrasonographic examination of gallbladder and bile ducts did not find gallstones or other abnormalities. A liver biopsy was performed, which histopathologic examination showed moderate fatty methamorphosis with focal areas of hepatocellular swelling with minimal necrosis, mild Kuppfer cell hyperplasia, portal and sinusoidal infiltrates of mononuclear cells. This picture consisted with the diagnosis of an acute unspecific reactive hepatitis.

[Thyroid myopathy in an aged woman]. / Miopatia tiroidea in una donna in età senile.

The case is reported of an old woman with a myopathy syndrome. Upon differential diagnosis this myopathy was attributed to hypothyroidism. Treatment with low doses of L-thyroxine lead to complete remission of the clinical and serologic syndrome.

Haemodynamic effects of nisoldipine by oral route.

The aim of this study is to investigate the acute haemodynamic effect of orally administered nisoldipine. Eight patients with stable angina and normal overall ventricular function were submitted to cardiac catheterization and angiography before and one hour after administration of nisoldipine 20 mg per os. Cardiac output increased, peripheral resistance decreased and aortic compliance increased, determining a marked decrease in overall peripheral impedance. Left ventricular ejection fraction hardly increased and contractility did not vary. Left ventricular end diastolic pressure decreased, owing to a decrease in left ventricular wall stiffness. Thus nisoldipine acts as a peripheral dilating agent, decreasing arteriolar tone and, possible, venous tone, and increasing left ventricular muscle distensibility.

[IgG paraproteinemia and arthritis. Description of a clinical case]. / IgG paraproteinemia ed artrite. Descrizione di un caso clinico.

The case is reported of a patient with monoclonal gammopathy of undetermined significance (M.G.U.S.) in whom suddenly an acute polyarthritis appeared. Upon differential diagnosis, this arthropathy was attributed to the precipitation of paraprotein-containing complexes within the synovial fluid leading to an inflammatory articular reaction. Treatment with low doses of methylprednisolone lead to complete remission of this arthritis.

Natural and post-surgical history of mitral stenosis and mitral stenosis and insufficiency: an observational study.

Natural and post-surgical history has been investigated in 410 pts with mitral stenosis and 209 pts with mixed mitral stenosis and regurgitation. They had undergone cardiac catheterization in the years 1968-1980. Hemodynamic data and clinical status (NYHA class) have been statistically analyzed in order to obtain prognostically useful parameters. In mitral stenosis peak pulmonary artery pressure is the most important parameter for natural history, whereas cardiac index is the leading parameter in the operated patients. Commissurotomy has a very low surgical mortality, largely due to the better conditions of the patients undergoing this type of conservative surgery. Results are similar in mixed mitral stenosis and regurgitation. Surgery markedly improves survival in comparable patients. Therefore, intervention seems to be indicated especially in patients with elevated pulmonary artery pressure, because they can get the maximum advantage at a minimal risk.

[Cold agglutinins in a cardiosurgical patient: a successfully operated case]. / Agglutinine da freddo nel paziente cardiochirurgico: su un caso clinico operato con successo.

A technique is described for providing myocardial protection with cold cardioplegia in a patient with cold autoagglutinins. The operation was done in normothermia and the coronary system was perfused with a normothermic (+37 degrees C) NaCl 0,9% solution to remove the blood before in it introducing the cold (+4 degrees C) cardioplegic solution. With this technique, the patient underwent an uneventful operation to relieve right ventricular-outflow stenosis operation.