Indication for radioiodine remnant ablation in differentiated thyroid cancer patients: does 2018 Italian consensus change anything?

PURPOSE: We speculated that radioiodine remnant ablation (RRA) could be performed less frequently in differentiated thyroid cancer (DTC) patients, if the recommendations of the 2018 Italian Consensus (ITA) were applied in clinical practice. Therefore, we compared the ITA indications for RRA with the recommendations by the 2015 American Thyroid Association guidelines (ATA). METHODS: We retrospectively evaluated 380 consecutive DTC patients treated with surgery and RRA, followed at the Section of Endocrinology, University of Siena, Italy from January 2006 to December 2019. RESULTS: Using ITA a significant increase of DTC patients classified as low or high risk and a significant decrease of patients defined at intermediate risk were observed (p < 0.0001). Consequently, the percentage of patients without routinary indication for RRA (47.4%, versus 38.2%, p < 0.0001) and those with a definite indication for RRA (8.2 versus 1.8%, p < 0.0001) was significantly higher compared to ATA. Moreover, using ITA the percentage of patients with a selective use of RRA was lower in comparison to ATA (44.7% versus 60%, p < 0.0001). Nevertheless, the prevalence of distant metastases, at post-ablative whole body scan, in patients without indication for RRA, was not different using either ATA or ITA (2.1% and 1.1% respectively, p = 0.37). CONCLUSION: The use of ITA Consensus, in clinical practice, increases significantly the number of patients for whom RRA is not routinely indicated in comparison to ATA guidelines but without differences in delaying the diagnosis of distant metastatic disease.

Should familial disease be considered as a negative prognostic factor in micropapillary thyroid carcinoma?

PURPOSE: An increased aggressiveness of familial papillary thyroid carcinoma (FPTC) compared with sporadic form has been reported. On the contrary, the biological behavior of familial microPTC (FmPTC) is still debated. To assess if familial diseases should be considered as a negative prognostic factor in mPTC, the clinical presentation and outcome of FmPTC and sporadic mPTC (SmPTC) were compared. METHODS: We retrospectively analyzed 291 mPTC (SmPTC n = 248, FmPTC n = 43) patients followed for a median follow-up of 8.3 years. FmPTC was defined as the presence of PTC in two or more first-degree relatives, after excluding hereditary syndromes associated with PTC. RESULTS: FmPTC patients had more frequently bilateral tumor (32.6% versus 16.5%, p = 0.01) and lymph node metastases at diagnosis (30.2% versus 14.9%, p = 0.02). At the first follow-up, FmPTC patients had a higher rate of structural disease and a lower rate of remission compared to SmPTC (p = 0.01). Also in a multivariate model, using a "CHAID tree-building algorithm", familial disease correlated with a worse clinical presentation and outcome of mPTC patients. Familial disease was associated with a higher rate of intermediate risk patients in non incidental mPTC and with a higher rate of structural incomplete response in mPTC without lymph node metastases (p = 0.01). CONCLUSIONS: Like in macroPTC, the familial form of the diseases has been shown to be a negative prognostic factor also in mPTC, therefore, it should be highly regarded in the management of mPTC patients.

MicroRNA expression profile of thyroid nodules in fine-needle aspiration cytology: a confirmatory series.

INTRODUCTION: MiRNAs are small endogenous non-coding RNAs implicated with gene expression regulation. Changes in miRNA levels have been reported in thyroid cancer. Fine-needle aspiration cytology (FNAC) is the most reliable tool for differential diagnosis of thyroid nodules. METHODS: We have analyzed 174 FNAC from 168 patients with thyroid nodules for expression levels of 11 miRNAs (miRNA197; -187; -181b-3p; -181b-5p; -224; -181a; 146b; -221; -222; -155 and miRNA183) known to be up-regulated in cancer tissues compared to benign lesions. Expression of miRNAs was analyzed in FNA samples calculating the fold change of miRNA expression relative to normal thyroid tissue after normalization to an endogenous control. RESULTS: In FNAC, miRNA expression was confirmed to be higher in malignant or suspicious for malignancy nodules compared to benign, only for miRNA146b, -222 and -221 (fold change expression ≥ 5). CONCLUSION: In this study, we confirmed that a limited set of miRNAs can be used for the differential diagnosis of thyroid nodules.

Autoimmune thyroid diseases are more common in patients with prolactinomas: a retrospective case-control study in an Italian cohort.

BACKGROUND: Prolactin may exert immunological effects. Over the years, a higher prevalence of autoimmune thyroid diseases (ATD) has been reported in patients with prolactinomas (PRLs) in areas with sufficient iodine intake. PURPOSE: The aim of our study was to evaluate the prevalence of ATD [Graves' disease (GD) and chronic autoimmune thyroiditis (AIT)] in a retrospective cohort of Italian patients with PRLs compared to a sex-matched control group, represented by subjects with non-functioning pituitary adenoma (NFPA) or empty sella (ES). MATERIALS AND METHODS: We enrolled 149 patients (108 F/41 M) with PRLs (110 micro/39 macro) and 143 subjects (100 F/43 M) with NFPA (n = 96, 56 micro/40 macro) or ES (n = 47), with normal serum prolactin. Neck ultrasound and thyroid function tests (anti-thyroid antibodies, TSH, FT3 and FT4) were performed in all patients. RESULTS: In PRLs, median serum prolactin was significantly higher (98.3 vs. 8.9 ng/ml, p ≤ 0.0001), while age was lower (34 vs. 46 years, p ≤ 0.001) compared to controls. The prevalence of ATD was 13.4% (20/149) in PRLs (1 GD and 19 AIT) compared to 6.3% (9/143) in the controls (p = 0.042). At the multivariate analysis, serum prolactin was the only independent factor predicting ATD. Thyroid volume (12.5 ± 5.9 ml vs. 12.8 ± 10 ml, p = 0.47) and the presence of uni- or multinodular goiter (29.5% vs. 35%, p = 0.35) did not differ between PRLs and control groups. CONCLUSIONS: Our data in an area with mild iodine deficiency confirm a higher prevalence of ATD in patients with prolactinomas.

Small papillary thyroid carcinoma with minimal extrathyroidal extension should be managed as ATA low-risk tumor.

PURPOSE: According to American Thyroid Association (ATA) guideline, papillary thyroid cancer (PTC) with minimal extrathyroidal extension (mETE) is classified at "intermediate risk" of persistent/recurrent disease. However, the impact of mETE per se on patients' outcome is not fully understood. The aim of our study was to evaluate the prognostic significance of mETE in patients with PTC not submitted to therapeutic or prophylactic lymph node dissection, according to tumor size and other prognostic factors. PATIENTS AND METHODS: We retrospectively evaluated a total of 514 PTC patients: 127 (24.7%) had mETE (pT3Nx) and 387 (75.3%) had negative margins (pT1-2Nx). At a median follow-up of 9.1 years, patients were divided in two groups: patients with "good outcome" (no evidence of disease) and patients with "poor outcome" (persistent structural disease or recurrent disease or tumor-related death). RESULTS: The rate of patients with "poor outcome" was significantly higher in patients with mETE compared with patients with negative margins (11.8 versus 5.1%; OR 2.4576, 95% CI 1.2178-4.9594, p = 0.01). However, mETE was significantly associated with poor outcome only in patients with tumors larger than 1.5 cm. CONCLUSIONS: mETE is an unfavorable prognostic factor in tumors larger than 1.5 cm, suggesting that, in the absence of other unfavorable characteristics, smaller tumors with mETE should be classified and managed as "low risk" tumors.

[For an ethics of medical-assisted reproduction]. / Per un'etica della procreazione medico-assistita.

The principal problems to the bioethic of reproduction are exposed. A distinction must be done between the therapy of sterility and the processes for artificial reproduction. The first treatments do not need special rules, being under the laws regarding the medical profession. The second on the contrary need a legal regulation by the Parliament in order to avoid the manipulation of human life at its origin. More attention to values and less emphasis to technical problems is now required.

Bone mass density in post-menopausal women.

OBJECTIVES: To evaluate the effect of age, years since menopause and body weight on bone mass density (BMD) in 283 patients. METHODS: Bone mass density was assessed by bone computerized mineralometry at two sites of the forearm. RESULTS: The mean distal BMD and ultra BMD in the postmenopausal group were negatively correlated with age (P < 0.001, r = -0.48 and P < 0.001, r = -0.50, respectively) and years since menopause (P < 0.001, r = -0.32 and P < 0.001, r = -0.33, respectively). When body-mass index was regressed against distal and ultra distal BMD, positive correlations were found (P = 0.008 and P = 0.007). CONCLUSIONS: From our data, forearm computerized mineralometry seems to be a reliable method for the evaluation of the effects of age and body-mass index on bone mass.

The collagen skeleton of the human umbilical cord at term. A scanning electron microscopy study after 2N-NaOH maceration.

The organization of the collagen fibrils in the human umbilical cord at term is directly visualized by means of a scanning electron microscopy cell maceration method. This technique clearly reveals that there is a much more extensive collagen fibrillar architecture within the umbilical cord than that reported in the classical histological descriptions. The Wharton's jelly, in fact, appears as a spongy network of interlacing collagen fibres and small woven bundles apparently arranged at random and forming a continuous soft skeleton that encases the umbilical vessels. The collagen fibrillar network shows the presence of a wide system of interconnected cavities consisting of canalicular-like structures as well as cavernous and perivascular spaces. This system of cavities might play a mechanical role allowing the storing of the ground substance of the jelly and its diffusion during twisting or compression. Furthermore, it may have an important role facilitating the diffusion throughout the jelly of diffused materials (i.e. water and trophic metabolites) either from or to the umbilical vessels and the amniotic cavity, thus overcoming the lace of a proper vasculature with the jelly.

Ovarian development of the female child and adolescent: I. Morphology.

Ovarian morphology of 180 randomly selected females, aged 8-21, was investigated, utilizing standard sector scanning ultrasound techniques, at -1 year (1 year before menarche), year 0 (menarche) and years +1 to +8 (1-8 years postmenarche). According to strict morphologic criteria, seven ovarian patterns were recognized which varied in dominance with age in reference to menarche. Prior to menarche a multifollicular ovarian pattern (Type 1) dominates which after menarche is substituted by a predominantly active ovarian pattern (Type 5). Approximately 20% of postmenarcheal females do not develop this active pattern. In a relatively persistent percentage of females a microcystic (Type 2) ovarian pattern was recognized throughout all postmenarcheal years, suggestive of a normal transitional pattern from Type 1 to Type 5 ovaries. In contrast, multicystic (Type 3), hyperthecosis (Type 4), polycystic ("Mickey Mouse") (Type 6) and silent (Type 7) ovaries appear to represent abnormal ovarian developments. Based on percentage distributions, it is tempting to speculate that multicystic (Type 3) and/or hyperthecosis (Type 4) ovaries represent precursor ovaries to Type 6 (polycystic) ovaries. Confirmation of this hypothesis would have major clinical importance for the early diagnosis of the polycystic ovarian syndrome.

HLA sharing in couples with recurrent abortion.

To investigate the interactions between HLA region and recurrent abortion we examined the HLA-A and HLA-B antigen frequencies, the degree of HLA sharing, and the incidence of anti-HLA antibodies in 18 recurrent abortion and in 23 control couples. HLA antigens with low distribution (less than 25% of phenotype frequencies in the general population) represent 38.5% of the HLA antigens shared between recurrent abortion partners. No antibodies against partners' HLA antigens were detected in recurrent abortion women, while such antibodies were present in 39.1% of control women (p = 0.002).

[Investigations on herpes 1 and 2 infections]. / Indagini sull'infezione-malattia da herpes 1 e 2.

The authors carried out a research on diffusion of Herpes virus 1 and 2 investigating specific serous antibodies over a sample of 1660 women living in Roma and in the surrounding area aged between 14 and 40 years; 595 of them were suspected to have an Herpes infection. The results of this research confirmed an high frequency of Herpes 1 and 2 infection in the examined sample. In order to correlate better the outcomes obtained by the investigation on the suspected sample 102 vaginal smear, executed on women suspected to have a developed infection, have been examined. The issues confirmed that it's useful to execute cytoimmunologic research in so far as such method seems to give more certainty in infection and disease identification than seroconversion investigation.