Trends in thyroid function testing, neck ultrasound, thyroid fine needle aspiration, and thyroidectomies in North-eastern Italy.

PURPOSE: Evidence of an increased diagnostic pressure on thyroid has emerged over the past decades. This study aimed to provide estimates of a wide spectrum of surveillance indicators for thyroid dysfunctions and diseases in Italy. METHODS: A population-based study was conducted in North-eastern Italy, including 11.7 million residents (20% of the total Italian population). Prescriptions for TSH testing, neck ultrasound or thyroid fine needle aspiration (FNA), surgical procedures, and drugs for hypo- or hyperthyroidism were extracted from regional health databases. Proportions and rates of selected examinations were calculated from 2010 to 2017, overall and by sex, calendar years, age, and region. RESULTS: Between 2010 and 2017 in North-eastern Italy, 24.5% of women and 9.8% of men received at least one TSH test yearly. In 2017, 7.1% of women and 1.5% of men were prescribed drugs for thyroid dysfunction, 94.6% of whom for hypothyroidism. Neck ultrasound examinations were performed yearly in 6.9% of women and 4.6% of men, with a nearly two-fold variation between areas. Thyroid FNA and thyroidectomies were three-fold more frequent in women (394 and 85 per 100,000) than in men (128 and 29 per 100,000) with a marked variation between areas. Both procedures decreased consistently after 2013. CONCLUSIONS: The results of this population-based study describe recent variations over time and between surrounding areas of indicators of 'diagnostic pressure' on thyroid in North-eastern Italy. These results emphasize the need to harmonize practices and to reduce some procedures (e.g., neck ultrasound and total thyroidectomies) in certain areas.

Clinical presentation and outcome of non-AIDS defining cancers, in HIV-infected patients in the ART-era: the Italian Cooperative Group on AIDS and tumors activity.

The advent of antiretroviral therapy (ART) has markedly extended the survival rates of patients with human immunodeficiency virus (HIV), leading to suppression even though not eradication of HIV. In HIV infected patients, cancer has become a growing problem, representing the first cause of death. A large number of worldwide studies have shown that HIV infection raises the risk of many non-AIDS defining cancers (NADCs), including squamous cell carcinoma of the anus (SCCA), testis cancer, lung cancer, cancer of the colon and rectum (CRC), skin (basal cell skin carcinoma and melanoma), Hodgkin disease (HD) and hepatocellular carcinoma (HCC). Generally in HIV positive patients NADCs are more aggressive and in advanced stage disease than in the general population. In the ART era, however, the outcome of HIV positive patients is more similar as in the general population. Only about lung cancer the outcome seems different between HIV positive and HIV negative patients. The aim of this article is to provide an up-date on NADCs within the activity of the Italian Cooperative Group on AIDS and Tumors (GICAT) to identify clinical prognostic and predicting factors in patients with HIV infection included in the GICAT.

Feasibility of intraperitoneal Trastuzumab treatment in a patient with peritoneal carcinomatosis from gastric cancer.

OBJECTIVES: This case report evaluates the feasibility and efficacy of intraperitoneal (IP) trastuzumab administration in gastric cancer (GC) patients with peritoneal carcinomatoses. METHODS: Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or disease recurrence in patients with GC. Recently, the role of HER2 overexpression in GC, occurring in about 20% of cases, is correlated with a worse prognosis. We report the case of 61-years old female, admitted to our Hospital after curative surgery for GC with over-expression of HER2. Seven months after the start of first line chemotherapy treatment a pleuro-peritoneal disease progression occurred, documented by cytological exam; according to HER2 status, we decided to treat the patient with IP trastuzumab administration. RESULTS: Between September and October 2012, the patient (ECOG performance status was 0), underwent to 6 cycles of IP trastuzumab. Trastuzumab was administered weekly at a dose of 150 mg for each cycle after paracentesis. The safety was good, no local complications (e.g. abdominal pain, peritonitis) occurred. The clinical revaluation evidenced a stable peritoneal disease. CONCLUSIONS: To our knowledge this is the first report on Trastuzumab use to treat IP metastases from GC, with acceptable toxicity and local disease control.

In vivo dosimetry with radiochromic films in low-voltage intraoperative radiotherapy of the breast.

PURPOSE: EBT2 radiochromic films were studied and used for in vivo dosimetry in targeted intraoperative radiotherapy (TARGIT), a technique in which the Intrabeam system (Carl Zeiss, Oberkochen, Germany) is used to perform intraoperative partial breast irradiation with x-rays of 50 kV(p). METHODS: The energy of the radiation emitted by the Intrabeam with the different spherical applicators, under 1 and 2 cm of solid water, and under the tungsten impregnated rubber used for shielding of the heart in TARGIT of the breast, was characterized with measurements of half-value layer (HVL). The stability of response of EBT2 was verified inside this range of energies. EBT2 films were calibrated using the red and green channels of the absorption spectrum in the 0-20 Gy dose range delivered by the Intrabeam x-rays. The dependence of film response on temperature during irradiation was measured. For in vivo dosimetry, pieces of radiochromic films wrapped in sterile envelopes were inserted after breast conserving surgery and before TARGIT into the excision cavity, on the skin and on the shielded pectoralis fascia for treatments of the left breast. RESULTS: HVLs of the Intrabeam in TARGIT of the breast correspond to effective energies of 20.7-36.3 keV. The response of EBT2 was constant inside this range of energies. We measured the dose to the target tissue and to organs at risk in 23 patients and obtained an average dose of 13.52 ± 1.21 Gy to the target tissue. Dose to the skin in close proximity to the applicator was 2.22 ± 0.97 Gy, 0.29 ± 0.17 Gy at 5-10 cm from the applicator, and 0.08 ± 0.07 Gy at more than 10 cm from the applicator. Dose to the pectoral muscle for left breast treatment was 0.57 ± 0.23 Gy. CONCLUSIONS: Our results show that EBT2 films are accurate at the beam energies, dose range, and irradiation temperature found in TARGIT and that in vivo dosimetry in TARGIT with EBT2 films wrapped in sterile envelopes is a feasible procedure. Measured dose to the organs at risk indicates that the technique is safe from side effects to the skin and the heart.

Somatostatin receptor scintigraphy versus chromogranin A assay in the management of patients with neuroendocrine tumors of different types: clinical role.

BACKGROUND: Current diagnosis and staging of neuroendocrine tumors (NETs) are significantly improved by the introduction of the chromogranin A (CgA) assay in plasma or serum as a tumor marker, and by the use of somatostatin receptor scintigraphy (SRS) for tumor localization. However, the clinical role of CgA assay compared with SRS in the management of NETs has not been well elucidated. PATIENTS AND METHODS: Sixty-three consecutive patients with a histological diagnosis of NET underwent plasma CgA assay and SRS for tumor staging (23 cases), evaluation of tumor response (18 cases) and evaluation of tumor recurrence on follow-up (22 cases). Twenty-one patients had well-differentiated neuroendocrine tumors (WDNETs: 18 gastroenteropancreatic tumors and three lung NETs); 22 patients had well-differentiated neuroendocrine carcinomas (WDNECs: 17 gastroenteropancreatic carcinomas, two lung neuroendocrine carcinomas and three neuroendocrine carcinomas of unknown origin) and 20 patients had poorly differentiated neuroendocrine carcinomas (PDNECs: 14 extra-pulmonary small-cell carcinomas and six Merkel cell carcinomas). Almost all (58 of 63) NETs were non-functioning. The quantitative determination of CgA was performed in plasma using an enzyme immunoassay with a cut-off value fixed at 34 U/l. Scintigraphies with indium 111-DTPA-octreotide ((111)In-pentetreotide) included whole-body images and single photon emission computed tomography (SPECT) scans of the chest and abdomen. RESULTS: SRS results were compared with CgA findings and final clinical data. The overall sensitivity of SRS and CgA, based on the final clinical data, was 77% and 55%, respectively, whereas the specificity of both SRS and CgA was 94%. Concerning tumor type, SRS accuracy was 95% for WDNETs, 86% for WDNECs and 60% for PDNECs; CgA accuracy was 76% for WDNETs, 68% for WDNECs and 50% for PDNECs. With regard to disease extent, SRS sensitivity was 100% for limited disease and 72% for advanced disease; CgA sensitivity was 43% for limited disease and 57% for advanced disease. CONCLUSIONS: In our NET series, SRS proved to be more sensitive than CgA, with equivalent specificity. Tumor differentiation influences the sensitivity of SRS and CgA analysis. In addition, the plasma CgA level is related to tumor secretory activity. Nevertheless both SRS and CgA should be considered useful tools in the diagnostic work-up of NET patients.

Pharmacokinetics of vinorelbine in patients with liver metastases.

BACKGROUND: The main elimination pathway of vinorelbine is hepatic metabolism, and the clearance of vinorelbine could be reduced in patients with liver metastases. OBJECTIVES: To study the pharmacokinetics of vinorelbine in patients who have advanced breast cancer with or without liver metastases and to study the relationship between hepatic function and vinorelbine clearance. PATIENTS AND METHODS: We studied 29 patients with advanced breast cancer: 19 with liver metastases and 10 control patients with extrahepatic metastases (mean age, 61 years; age range, 38 to 81 years). The vinorelbine dose was 30 mg/m2 as a short intravenous infusion; the dose was reduced by 50% in patients with bilirubin > 2 mg/dl. Patients were classified by ultrasonographic estimation of the liver volume replaced by tumor (%LVRT). Standard liver function tests and a monoethylglycinexylidide test (a quantitative liver function test based on lidocaine metabolite formation) were performed. Vinorelbine was assayed in plasma by HPLC with fluorescence detection. Vinorelbine determination was impossible in two patients with more than 75% LVRT because of interferences. Pharmacokinetic parameters were calculated with a noncompartimental method and compared by means of the Kruskal-Wallis test. RESULTS: A lower vinorelbine clearance rate was observed in the five patients with more than 75% LVRT (22.9 L/hr/m2) compared with the 10 patients with no liver metastases (48.0 L/hr/m2) and the 12 patients with 25% to 75% LVRT (45.3 L/hr/m2). Terminal elimination half-life and apparent volume of distribution were not significantly different among groups. The monoethylglycinexylidide test had a significant correlation with vinorelbine clearance. (r2 = 0.70; p = 10(-4). CONCLUSIONS: These results support vinorelbine dose reduction in patients with severe liver failure but not in patients with moderate secondary liver involvement. The monoethylglycinexylidide test may prove to be useful for vinorelbine dose individualization.

The use of thallium-201 in the preoperative detection of breast cancer: an adjunct to mammography and ultrasonography.

Thallium-201 breast scans were performed preoperatively in 72 female patients with breast abnormalities detected by mammography and/or ultrasonography (7.5-13 MHz), in order to differentiate benign from malignant breast disease. Informed consent was obtained from each patient. Scintigraphy consisted of anterior and oblique planar images of the affected breast and axilla at 10 min and 3 h following the injection of 201Tl chloride (110 MBq). All 201Tl scans were interpreted without prior knowledge of surgery data. Pathological features of breast malignancies, such as tumour size, axillary lymph node metastases, tumour grading, lymphatic vascular channel invasion and receptor status, were analysed for their association with 201Tl uptake by tumour cells. A total of 76 breast lesions were assessed in the study. On final histological diagnosis, there were 56 malignant tumours, 14 benign nodules (9 fibroadenomas, two cases of adenosis, two cases of focal fibrosis and one case of epitheliosis) and six atypical lesions (atypical ductal or lobular hyperplasia). Thallium scintigraphy was shown to have high accuracy (92%) in detecting breast cancer, better than mammography (74%) and ultrasonography (84%). Almost all (51/56) breast cancers showed greater 201Tl activity than surrounding normal breast tissue while there was no significant increase in 201Tl activity above background in all but one (19/20) case of non-malignant disease. 201Tl activity within breast tumours, calculated as tumour/background (T/B) ratio, ranged between 1.2 and 2.5 with a mean value of 1.45. In our experience the concentration of thallium in the breast cancer seems to be primarily dependent on vascularity and tumour size rather than tumour grading, lymphatic/vascular invasion or receptor status. 201Tl scan sensitivity was 97% for malignant lesions larger than 1.5 cm (n = 35) and 80% for lesions of 1.5 cm or less (n = 21); however, five of the eight breast cancers smaller than 1.0 cm were also detectable by 201Tl scintigraphy, compared with five out of seven by mammography. Thallium scintigraphy would not be useful in evaluating the axilla for lymph node metastases (sensitivity 27%, specificity 77%).

Usefulness of immunoscintigraphy in the follow-up of surgically treated gastrointestinal carcinomas using 111In-labelled anti-CEA monoclonal antibodies.

Twenty-five patients treated surgically for gastrointestinal carcinomas (16 rectum-sigmoid colon, 6 colon, 3 stomach) were investigated by immunoscintigraphy (IS) using 111In-labelled anti-CEA antibody (mouse monoclonal F023C5) F(ab')2 fragments in order to visualize questionable abdominopelvic recurrences (excluding the liver). Fifteen (60%) patients showed a rise in serum CEA levels above 5 ng/ml. Planar scans and emission computed tomographic (ECT) imaging were carried out without reference to the results of computed tomographic (CT) scans and gastrointestinal endoscopic examinations done 1-2 weeks before IS. Final diagnoses were based on biopsies and autopsies (13 cases) or on follow-up findings over at least 2 years (12 cases). Sixteen patients had a final diagnosis of recurrent malignant disease in the extrahepatic abdomen or pelvis. Of these, six were correctly diagnosed by both IS and conventional diagnostic procedures, six by IS only and two by conventional methods only. Two tumour recurrences remained undetected by both diagnostic approaches. However, five tumour recurrences were detected by IS more than 4 months earlier than by any other diagnostic procedures performed during clinical follow-up. Of the nine disease-free patients (disregarding the liver) three were correctly identified by both IS and the other diagnostic methods, four by IS only and two by conventional diagnostic procedures only. Overall sensitivity (75%) and specificity (89%) of 111In-IS were higher than figures obtained using CT scanning and endoscopy (50% and 78% respectively). True positive IS was observed in 6/15 (40%) CEA seropositive patients and in 6/10 (60%) CEA seronegative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Echocardiographic and color Doppler diagnosis in congenital aneurysm of the mitral-aortic intervalvular fibrous tissue]. / Diagnosi ecocardiografica e color Doppler di aneurisma congenito del tessuto fibroso intervalvolare mitro-aortico.

We describe the case of a 12-years-old boy, who had an echocardiogram for sports fitness. The echocardiographic image showed a small probably congenital aneurysm of the mitral-aortic intervalvular fibrosa. The diagnosis of this rare anomaly was made possible by the combination of bidimensional echocardiographic and Color Doppler information.