Outcomes and Risk Factors for Complications of Laser Ablation for Thyroid Nodules: A Multicenter Study on 1531 Patients.

BACKGROUND: Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity. PATIENTS: Clinical records of 1534 consecutive laser-treated nodules in 1531 patients from eight Italian thyroid referral centers were assessed. Inclusion criteria were as follows: solid or mixed nodules with fluid component up to 40%; benign cytological findings; and normal thyroid function. METHODS: LAT was performed with a fixed-power protocol, whereas the number of applicators and illumination times were different according to target size. From one to three illuminations with pullback technique and with a total energy delivery based on the nodule volume were performed during the same session. Patients were evaluated during LAT, within 30 days, and 12 months after the procedure. RESULTS: Total number of treatments was 1837; 1280 (83%) of nodules had a single LAT session. Mean nodule volume decreased from 27 ± 24 mL at baseline to 8 ± 8 mL 12 months after treatment (P < .001). Mean nodule volume reduction was 72% ± 11% (range 48%-96%). This figure was significantly greater in mixed nodules (79% ± 7%; range 70%-92%) because they were drained immediately before laser illumination. Symptoms improved from 49% to 10% of cases (P < .001) and evidence of cosmetic signs from 86% to 8% of cases (P < .001). Seventeen complications (0.9%) were registered. Eight patients (0.5%) experienced transitory voice changes that completely resolved at the ear-nose-throat examination within 2-84 days. Nine minor complications (0.5%) were reported. No changes in thyroid function or autoimmunity were observed. CONCLUSIONS: Real practice confirmed LAT as a clinically effective, reproducible, and rapid outpatient procedure. Treatments were well tolerated and risk of major complications was very low.

Foot bone mass and analysis of calcium metabolism in diabetic patients affected by severe neuropathy.

AIM: Charcot neuro osteoarthropathy (NAC) is a devastating foot complication which is associated to peripheral neuropathy. The aim of this study was to investigate the changes in foot bone mass in patients with peripheral neuropathy and to correlate this with calcium metabolism in diabetes. METHODS: The study included three groups of patients enrolled consecutively: group 1 consisted of 28 diabetic patients, affected by both peripheral neuropathy and autonomic neuropathy as well as monolateral foot ulcer; group 2 consisted of 10 diabetic patients without neuropathy and without foot ulcerations; group 3 consisted of 10 healthy people. In all patients we studied calcium and bone metabolism and quantitative ultrasonography (QUS) of calcaneal bone was performed in both feet in each subject. Calcium and bone metabolism were assessed by the assay of serum parathyroid hormone (PTH), serum calcium, serum phosphorus, serum magnesium, serum bone alkaline phosphatase isoenzyme and urinary excretion of deoxypyridinoline DPD. RESULTS: In patients with neuropathic ulceration, QUS showed a decrease in bone density in the affected foot: mean T score in the normal foot was -0.54+/-0,26 (mean+/-ESM) while mean T score in the foot with the ulcer was -1.23+/-0.31 (mean+/-ESM) (P=0.004). In diabetic patients without neuropathy the authors did not find any difference in T score between the two feet. Moreover, the T score in the feet in these patients didn't show any differences in comparison to the T score of the healthy foot in neuropathic patients. The T-score in the feet of normal subjects didn't show any difference in respect to the healthy feet in diabetic patients. No difference of serum parameters of calcium metabolism was seen among the groups, while, among the parameters of bone metabolism, B-ALP was elevated in patients with foot ulcer. CONCLUSION: These data suggest that bone demineralization is associated to peripheral neuropathy with foot ulceration. MOC can represent a way to personalized therapy of patients who are prone to fractures and to the development of NAC.

Radioiodine ablation of post-surgical thyroid remnants after preparation with recombinant human TSH: why, how and when.

AIMS: The use of recombinant human TSH (rhTSH) represents one of the most exciting innovations in the field of differentiated thyroid cancer (DTC) management, but the use of rhTSH for radioiodine post-surgical thyroid remnant ablation is still controversial. The aim of this review is to provide the reader with an analysis of the literature regarding the use of rhTSH for the radioiodine ablation of post-surgical thyroid remnants. METHODS: We performed a literature search of the most relevant papers in the PubMed database. FINDINGS AND CONCLUSIONS: To date, five prospective studies have been published regarding this topic and there is strong evidence of the effectiveness of rhTSH, at least when high doses of 131I are used. Vice-versa, data regarding the outcome of ablation using low doses (30 mCi) are quite different in the studies published. So the problem of the amount of 131I to be administered and the influence of iodine intake is still open. In fact, the results of some studies suggest that 131I uptake could be particularly dependent on iodine intake during the euthyroid state and when low doses of 131I are used. This could be the reason for the reduced radioiodine uptake observed in other studies. However, also when rhTSH stimulation had produced a reduced iodine uptake, this was at least partially compensated for by an increased half-time in thyroid cells. So rhTSH stimulation appears to have pathophysiological bases which all lead to a powerful destructive effect by 131I on thyroid cells. All the data in the literature appear concordant that rhTSH is safe and associated to a good quality of life and the problem of costs appears negligible when compared to the benefits for the patient. In most cases, the use of rhTSH, for radioiodine ablation of post-surgical thyroid remnants can represent the best therapeutic option that we can offer to the patient.

Thyroid papillary cancers: microcarcinoma and carcinoma, incidental cancers and non-incidental cancers - are they different diseases?

OBJECTIVE: Tumour size represents a much-debated prognostic factor in papillary cancer, and the necessity to perform a fine-needle aspiration (FNA) on small nodules is a frequent matter of discussion. We compared some prognostic histological features for various sizes of papillary cancers (PCs) and, with regard to these prognostic features, we compared non-incidental with incidental PCs. We also considered the possibility that ultrasonography could detect nodules harbouring the most aggressive cancers. DESIGN AND PATIENTS: We have studied patients with a histological diagnosis of PC from 1999 to 2003. FNA was performed on all nodules > 1.0 cm and on hypoechoic nodules with irregular margins or microcalcification when the size was < 1.0 cm (3321 FNAs in total). We were able to consider several different types of patients: those with PC diagnosed by FNA before surgery; those with large goitre and PC of small size diagnosed after histological examination and in whom a careful examination of the presurgical ultrasonography could show a distinct highly suspicious nodule that was not subjected to FNA, and patients with real incidental PC (that is, those with nodular goitre who correctly underwent FNA on suspicious nodules but in whom thyroid cancer was discovered only at histological examination). We considered two groups of patients with PC. Group 1 PCs were diagnosed before surgery with FNA (128 cases); in this group we also considered the two cases that were not correctly diagnosed before surgery. Group 2 real incidental PCs (12 cases) were found in goitres at histological examination after thyroidectomy for goitre (282 thyroidectomies). Group 1 was divided into three subgroups according to the maximum size of the PC at histological examination: (a) 44 PCs with maximum size < 10 mm, (b) 47 PCs with maximum size between 10 mm and 20 mm, and (c) 39 PCs with maximum size 20 mm. In all subgroups 1 as well as in group 2, the following four histological features were considered separately: multifocality, extracapsular extension, lymph-node involvement and its extent, and special aggressive features (dedifferentiation and/or insular aspects, tall and columnar variants). RESULTS: In subgroups 1a, 1b and 1c the results were, respectively: multifocality 56.8, 57.4 and 51.2%; extracapsular extension 27.2, 23.4 and 46.3% (P = 0.01, subgroups 1a and 1b vs. subgroup 1c); lymph-node metastasis 13.5, 23.3 and 46.1% (P = 0.003 subgroup 1a vs. 1c; P = 0.04, subgroup 1b vs. 1c); special aggressive features 11.3, 25.5 and 28.2% (P = ns). Group 2 showed one case of multifocality (8.3%) in a patient with prior exposure to radiotherapy in childhood, while no case was found of extracapsular invasion or lymph-node involvement, and only one patient had a PC with features of dedifferentiation. CONCLUSIONS: Non-incidental cancer, apart from multifocality, showed a classical progression for all prognostic factors from microcarcinoma to larger cancers. However, real incidental PC seemed to be different from non-incidental PC microcarcinoma regarding the main prognostic features. We conclude that ultrasonography is useful not only in terms of revealing the presence of cancer but also in identifying the most aggressive cancers.

Thyroid nodules with microfollicular findings reported on fine-needle aspiration: invariably surgical treatment?

OBJECTIVE: To assess whether fine-needle aspiration (FNA) can be a diagnostic procedure for identification of malignant thyroid nodules when the smear reveals the cytologic (microfollicular) finding of "follicular neoplasm" (FN). METHODS: We reviewed a group of 79 patients with FN who underwent surgical treatment and evaluated the possible significance of the cytologic features of anisokaryosis, amount of colloid, and nuclear overlapping (NO). We excluded from the study those patients with FN who had other highly suspicious cytologic features, such as sporadic grooves and sporadic pseudonucleoli. RESULTS: In our series of 79 patients with FN at FNA, we found anisokaryosis in 49.4%, scant or no colloid in 31.6%, and NO in 5.1%. Thyroid cancer (TC)--follicular cancer or follicular variant of papillary cancer--was found in six patients (7.6%): four patients (10.2%) with anisokaryosis and two patients (5.0%) without anisokaryosis (P<0.5; chi2 test). All the patients with malignant lesions had scant or no colloid in the smears, and four of them were those with NO. Therefore, TC was found in 24.0% of nodules with scant or no colloid versus 0.0% of nodules with abundant colloid (P<0.001; chi2 test), and TC was found in 100% of nodules with NO versus 2.6% of nodules without NO (P<0.001; chi2 test). CONCLUSION: Because of the high prevalence of thyroid nodules and the frequency of FN at FNA, the number of unnecessary interventions may be very high. FNA cannot be diagnostic in FN because invasion of the tumor capsule and blood vessels can be evidenced only at histologic examination. Although it is common opinion that microfollicular nodules should be surgically treated, simple cytologic features can help select patients at low risk who can be monitored and reassessed clinically and by FNA. Patients with high-risk cytologic features such as NO should be advised that a total thyroidectomy may be necessary.

Training general practitioners in flexible sigmoidoscopy to screen for colorectal cancer.

BACKGROUND: A screening programme to detect polyps or early carcinoma would significantly reduce the mortality and morbidity of colorectal cancer (CRC). The aims of the present study were to evaluate: (i) the feasibility of training general practitioners in flexible sigmoidoscopy (FS) for CRC screening; (ii) the acceptability of screening by faecal occult blood testing (FOBT) and FS in asymptomatic standard risk Australians aged over 50 years; and (iii) the yield of such screening. METHODS: Subjects were recruited by general practitioner (GP) referral, newspaper advertisement or by a direct approach to retirement villages. Participants were mailed a FOBT kit and a prescreening questionnaire. Flexible sigmoidoscopy was performed by a GP supervised by an experienced endoscopist. Subjects then completed a second questionnaire. General practitioners were assessed after 50 unassisted procedures. RESULTS: A total of 264 individuals contacted the study coordinator; 169 were screened. Screening was accepted well by the participants. Fifteen per cent of subjects had polyps and 4% had a positive FOBT. Training in FS was adversely affected by the availability of resources. Three GPs completed 50 unassisted procedures over a 15-month period, but none were able to reliably assess the distal bowel. CONCLUSIONS: Although the three trainees and their supervisors did not consider that the GPs were adequately trained after 50 unassisted procedures, training was adversely affected by limited resources within the Victorian public hospital system. Screening by FOBT and FS was considered to be acceptable by the patients undergoing these procedures. Existing facilities are not adequate if GPs are to be trained in FS as part of a national CRC screening program.

Verapamil acute administration: a new dynamic test in hyperprolactinemic states.

We studied the effect of acute administration of the calcium-channel blocker verapamil (VER) in 27 patients with tumoral hyperprolactinemia ([THPRL] prolactinomas and pseudoprolactinomas). We also studied the effect of VER in seven patients with idiopathic hyperprolactinemia (IHPRL) and a small group of patients with normal prolactin (PRL) levels and minimal incidental anomalies shown by magnetic resonance imaging (MRI). The study was performed on 2 separate days: on the first day, all subjects received VER, and on the second they received placebo. Acute administration of VER evoked a remarkable increase in serum PRL in IHPRL (as in normal healthy subjects used as controls), but no response was shown in THPRL, with no overlap between the two conditions. Acute administration of VER stimulated PRL secretion in patients with minimal incidental lesions shown by MRI; however, this increase was smaller in patients whose PRL level consistently reached the upper-normal limit. Although the meaning of such minimal anomalies shown by MRI is unknown, this could suggest that the test is precociously altered. To further elucidate the action of VER on lactotropes, we investigated the effect of VER given intravenously (IV) and compared different oral formulations in healthy subjects. Our data show that the VER test is effective in distinguishing between THPRL and IHPRL, but unfortunately, like other tests, it is not able to individualize patients in whom THPRL is the result of diminished dopaminergic tone (pseudoprolactinoma). From a pathophysiological point of view, calcium influx would appear less important in PRL regulation in chronic disorders of PRL secretion. VER given IV did not stimulate PRL release in normal subjects. This suggests that IV administration could produce a peak with an inadequate duration or that oral formulations may act also by metabolites formed on first-pass metabolism in the liver.

[Incidence and onset of arterial hypertension and diabetic retinopathy in a population of subjects with diabetes mellitus]. / Considerazioni sulla incidenza e l'insorgenza dell'ipertensione arteriosa e retinopatia diabetica in una popolazione di soggetti affetti da diabete mellito.

The authors noticed a 50% increase in the incidence of arterial hypertension in diabetic subjects compared with non diabetic ones. Females are more affected in both types of diabetes mellitus and during the first ten years after onset of NIDDM. Diabetic retinopathy is more frequent in IDDM. In hypertensive diabetic females retinopathy is twice as frequent as in non-hypertensive female patients.

[Incidence and type of dyslipidemia in a diabetic population]. / Indagine sull'incidenza ed il tipo della dislipidemia in una popolazione diabetica.

The incidence of dyslipidemia in the diabetic patients tested was found to be twofold compared to the non diabetic population. The percentage was found to be higher in Fredrikson class IIb, unchanged in class IIa and diminished in class IVF.

[Autoimmune hypophysitis. Review of the literature and a case report]. / L'ipofisite autoimmune. Rassegna della letteratura e descrizione di un caso.

Lymphoid hypophysitis is a rare disease (fewer than 30 cases) which is associated with lymphocytic infiltration of the pituitary gland with complete or partial hypopituitarism, pituitary mass, and occurrence exclusively in women, often during pregnancy or in the postpartum period. The majority of the women had autoimmune endocrine and not endocrine disorders and in some cases antipituitary antibodies were present. For these reasons an autoimmune cause has been suggested. We report a patient in menopause with chronic thyroiditis and anti nuclear, anti smooth muscle and anti mitochondrial autoantibodies who developed a panhypopituitarism with an empty sella. This case is the third observation of a possible autoimmune atrophy of the pituitary.

Enhanced accessory cell function by alveolar macrophages from patients infected with the human immunodeficiency virus: potential role for depletion of CD4+ cells in the lung.

Mononuclear phagocytes, including alveolar macrophages (AM), can be infected by the human immunodeficiency virus (HIV). Acting as accessory cells (AC), AM could infect CD4 lymphocytes through cell-to-cell contact and by inducing T cell proliferation, which increases lymphocyte susceptibility to infection. Using normal allogeneic T cells as responders, AM from infected individuals demonstrated an enhanced ability to stimulate a Con A and pokeweed mitogen lymphocyte proliferation assay compared with normal AM. Exogenous IL 1 enhanced the stimulation of a mitogen response by normal AM, but not from HIV-positive individuals, suggesting increased levels of this cytokine may explain the observed enhancement. However, increased IL 1 secretion by AM from HIV-infected patients could not be demonstrated, either in a bioassay or antigenically using an ELISA for IL-1 beta. Syncytia formation was observed when AM from asymptomatic HIV-positive individuals were cultured with normal T cells, suggesting viral transmission was occurring. Finally, in individual patients the stimulation of a mitogen response was inversely correlated with the CD4/CD8 ratio and total CD4 count, suggesting that enhanced AC function and CD4 cell depletion may be related in vivo. These findings indicate that enhanced AM accessory cell function is seen in HIV-infected individuals and could be a potential mechanism for CD4 cell depletion in the lung.

Mycobacterium avium-Mycobacterium intracellulare infection limited to the skin and lymph nodes in patients with AIDS.

Three patients with AIDS who were taking 3'-azido-3'-deoxythymidine (AZT) developed cutaneous abscesses from which Mycobacterium avium-Mycobacterium intracellulare was isolated. Culture of multiple blood samples and bone marrow aspirate from all three patients revealed that the infection was not disseminated. This is a rare form of presentation for this infection in AIDS patients. We speculate that the antiviral drug AZT was responsible for the localization of disease.

Ciprofloxacin for methicillin-resistant Staphylococcus aureus infections.

Thirty-seven patients with methicillin-resistant Staphylococcus aureus infections and/or colonization were treated with oral ciprofloxacin (750 mg twice a day). Clinical cure or improvement of infections occurred in 91% of the patients, and bacteriologic cure occurred in 60%. Ciprofloxacin therapy suppressed methicillin-resistant S. aureus colonization in 55% of the patients. Ciprofloxacin-resistant strains emerged in 6 of the 37 patients.

Pseudomonas testosteroni infections: eighteen recent cases and a review of the literature.

Pseudomonas testosteroni has been largely overlooked as a potential pathogen in humans. Ten cases of infection due to P. testosteroni were identified at a single metropolitan hospital in Texas during a three-year period. The organism was most often found in association with anatomic abnormalities of the gastrointestinal tract (six of 10 cases); perforation of the appendix was the commonest abnormality (five cases). The infections were more often polymicrobial (seven cases) than monomicrobial (three cases) and usually involved other organisms that, like P. testosteroni, are of colonic origin. Eight additional cases of infection involving P. testosteroni were reported by other hospitals in Texas during the same period. The organism was isolated from the peritoneal cavity in five of these cases. The results of these surveys suggest that infections of humans with P. testosteroni, while not common, are not as rare as might be predicted on the basis of the number of cases reported in the literature.