RARE MALIGNANT FEMALE ADNEXAL TUMOR OF WOLFFIAN ORIGIN (FATWO) WITH MULTIPLE RELAPSES AND CHEMOTHERAPY REGIMENS.

CONTEXT: Female adnexal tumors of probable Wolffian origin (FATWO) represent very rare borderline ovarian tumors with low malignant potential. Only 15 cases of malignant FATWO are described in the current literature, among which, only 5 are reported as being recurrent. OBJECTIVE: Due to the rare presentation of the recurrence of the malignant FATWO and the few cases reported in the scientific database, there are no clear therapy recommendations. This paper should help practitioners to choose the best therapy approach. DESIGN: This paper presents the 6th case of malignant recurrent FATWO and will compare all the cases available in the literature. SUBJECTS AND METHODS: We present a review of the literature comparing the therapeutic approaches and outcomes of all the five cases of recurrent malignant FATWOs. Also, we introduce the case of a stage III Wolffian origin adnexal tumor with multiple recurrences appeared after 6 years of disease free interval. RESULTS: Our case presents the longest survival reported in the literature and underwent most surgical procedures of the recurrences and more than 4 lines of chemotherapy regimens. CONCLUSIONS: This paper shows possible therapeutic approaches to be used as example by the practitioners according to the drug availability in their centers.

A systematic approach on the frequency of cleft lip/palate in pediatric patients with leukemia.

PURPOSE: The purpose of this study was to reveal the frequency between cleft lip/palate and leukemia in pediatric patients by a systematic analysis of the current literature. MATERIALS AND METHODS: Electronic search on three database (PubMed, Web of Science, Cochrane) was carried out using the following keywords: cleft lip, cleft palate, facial cleft, oral cleft, orofacial cleft, leukemia, acute myeloid leukemia, acute lymphocytic leukemia, lymphoma. Studies published until March 2020 reporting an association between leukemia and cleft lip/palate (CL/P) were included in our research. RESULTS: Five articles (2 case-controls, 3 cohorts), met the inclusion criteria. Case-control studies involved 268 patients with acute lymphocytic leukemia (ALL) and 177 patients with acute myeloid leukemia (AML), of which 9 patients had CL/P. The cohorts studies involved 10 patients with ALL, of which 6 patients with CL/P, 2 patients with cleft palate and 1 patient with cleft lip and palate. CONCLUSION: This research was able to indicate a limited evidence of the association between CL/P and leukemia. In order to draw a clear conclusion, studies with larger cohorts are needed to establish this correlation.

FOLLICULAR THYROID CARCINOMA - CLINICAL AND DIAGNOSTIC FINDINGS IN A 20-YEAR FOLLOW UP STUDY.

CONTEXT: Follicular thyroid carcinomas (FTC) represent 6-10 % of all thyroid carcinomas; the evolution of FTC is quite controversial, partly due to frequent changes of the histopathological definition (minimally invasive-MIFTC or widely invasive carcinoma-WIFTC) and treatment strategies adjustments. OBJECTIVE: This research aims to examine the diagnostic procedure, therapeutic attitude and survival rates of patients with FTC, over a period of 16 years in the same institution, with a follow-up of at least 4 years, by analyzing correlations between histology subtype, treatments and the rate of recurrent disease. SUBJECTS AND METHODS: We have studied 5891 patients with thyroid carcinomas who have undergone surgical or oncological treatment within the institution, between 1st January 2000 - 31st December 2015; among them we found 133 patients (2.25%) with "pure" follicular thyroid carcinoma: 114 (86%) women and 19 (14%) men, with a female-male ratio of 6:1. The age of the patients ranged from 10 to 76 years, with an average of 47.8 years. Statistical analysis was done comparing differences among groups of MIFTC and WIFTC. RESULTS: There was an unexpected high percentage of WIFTC and also an increased number of biochemically persistent and/or recurrent disease in patients with MIFTC. A stronger correlation was observed with the tumour dimensions, rather than with the histopathological subtype. CONCLUSIONS: This research observed that overall survival was associated with tumour size rather than histopathological subtype and there is an important need to perform further studies to assess the effectiveness of treatment strategies.

Life satisfaction is a protective factor against the onset of Type 2 diabetes in men but not in women: findings from the MONICA/KORA cohort study.

AIMS: To investigate the association of high life satisfaction with incident Type 2 diabetes separately in men and women. METHODS: A longitudinal analysis was conducted among the 7107 participants (3664 men, 51.5%; 3443 women, 48.5%) aged 25-74 years (mean ± sd age 47.8 ±13.7 years) of two population-based MONICA/KORA surveys conducted in 1989-1995 and followed up until 2009. Life satisfaction was assessed using a one-item instrument with a six-order response level, which was dichotomized into high vs medium or low. Sex-specific hazard ratios were estimated using Cox proportional hazards models. RESULTS: Crude incidence rates for Type 2 diabetes per 10 000 person-years were lower in participants with high than in those with medium or low life satisfaction (men: 57 vs 73; women: 37 vs 48). In men with high life satisfaction, there was a 27% risk reduction in incident Type 2 diabetes (hazard ratio 0.73, 95% CI 0.56-0.94; P=0.02) in a model adjusted for sociodemographic, behavioural and clinical risk factors. The association lost statistical significance after further adjusting for depressed mood (hazard ratio 0.79, 95% CI 0.61-1.03). Life satisfaction was not significantly associated with incident Type 2 diabetes in women. CONCLUSION: Life satisfaction may be a valuable asset in assessing risk of Type 2 diabetes, especially in men, and in the development of more effective prevention strategies to deter onset of diabetes. More research is needed to investigate the underlying potential causal pathways that may link life satisfaction to the development of Type 2 diabetes.

CIRCULATING TUMOR CELLS IN MINIMALLY INVASIVE FOLLICULAR THYROID CARCINOMA AND BENIGN THYROID TUMORS WITH A FOLLICULAR PATTERN: PILOT EXPERIENCE.

PURPOSE: Minimally invasive follicular thyroid carcinomas (MIFCs) are uncommon; literature offers limited guidance on their natural history and management. Starting January 2015 we measured circulating tumor cells (CTCs) in patients with MIFC (n=22) or benign thyroid tumors with follicular features (n=4). METHODS: In a retrospective analysis, we assessed detectability of and serial changes in CTC, compared demographic/clinical differences between CTC-positive versus CTC-negative subgroups using Student's t-test, and examined correlations between CTC status and serum thyroglobulin using Spearman's test. CTCs were quantitated via immunomagnetic separation/microscopic inspection. RESULTS: Thirteen patients (50%: 12/22 MIFC, 1/4 benign tumor) were initially CTC-positive; 3 remained CTC-positive in ≥1 subsequent measurement. CTC-positive patients had larger tumors and more frequent multifocality and vascular invasion versus CTC-negative patients (n=13). However, no tested variable differed significantly between the subgroups. After 17.2±10.5 months, neither subgroup showed evidence of disease. Significant correlation was absent (p ≥ 0.263) between CTC and Tg negativity (r = 0.243; n=13 evaluable) or initial CTC positivity and Tg positivity (r = -0.418; n=9 evaluable). CONCLUSIONS: In the studied settings, CTC measurement is feasible, has unclear clinical/outcome implications, but may provide different information versus thyroglobulin testing. Lengthier assessment is warranted in larger series.

Iodine status and thyroid nodules in females: a comparison of Cyprus and Romania.

OBJECTIVES: The increased comparative prevalence rates of thyroid cancer in Cyprus (>EU average) led us to conduct this study on possible risk factors of thyroid nodules. Romania served as a reference with a comparative thyroid cancer prevalence < EU average. This study aimed to assess the association between urinary iodine (UI) and thyroid nodules in adult females (n = 208) from Cyprus and Romania. STUDY DESIGN: A case-control study (n = 208). METHODS: Cases were females with ultrasound-confirmed thyroid nodules and controls with confirmed absence of nodules. In both countries, subjects underwent ultrasound medical examinations, completed a questionnaire and offered a spot urine sample. RESULTS: Median UI level in Cyprus was 94 µg/L, whereas 32% of the Cypriot UI was < 50 µg/L, classifying the population as mildly iodine deficient. In Romania, both cases and controls were iodine sufficient. No significant differences (P > 0.05) in serum free thyroxin (fT4) and thyroid stimulating hormone (TSH) levels were found between cases and controls. Cases had lower median TSH levels compared with controls (1.4 mIU/L and 1.7 mIU/L, P = 0.060), but serum TSH and free thyroxin levels were within normal range. Albeit non-significant, participants with inadequate UI (<100 µg/L) had increased risk for thyroid nodules (odds ratio = 1.40, 95% confidence interval = 0.70, 2.81, P = 0.346), using multiple logistic regression after adjusting for age, body mass index, education, country and serum TSH. CONCLUSIONS: This was the first study to quantify UI levels in Cyprus. While the Romanian iodine fortification programme reflected onto its UI levels, a representative assessment of iodine status in Cyprus will address the necessity of an iodine fortification programme.

EVALUATION OF CARDIOVASCULAR RISK AND MYOCARDIAL PERFUSION IN PATIENTS WITH RADICALLY TREATED DIFFERENTIATED THYROID CARCINOMA AND REPEATED EPISODES OF IATROGENIC HYPOTHYROIDISM.

CONTEXT: Patients with radically treated differentiated thyroid carcinoma (DTC) undergo multiple episodes of iatrogenously-acquired hypothyroidism for the oncological follow-up. In some patients, this elevates high-sensitive C-reactive protein (hsCRP), a cardiovascular risk biomarker. OBJECTIVE: We wanted to determine if there is any correlation between repeated hypothyroidism episodes, elevated hsCRP and an increased cardiovascular risk as stated through myocardial perfusion. DESIGN: Between July 2014-January 2015, we analyzed serological levels of hsCRP for identifying our patients' cardiovascular risk; we performed a myocardial perfusion scintigraphy to observe the alterations. SUBJECTS AND METHODS: We included 27 patients (n=27), mean age of 52±10: CI (95%),14 female, all disease- free after thyroidectomy, radioiodine ablation and chronic thyroid hormone treatment. We assigned the cardiovascular risk category for each patient according to hsCRP levels; all patients underwent a myocardial perfusion scintigraphy in order to determine the cardiac perfusion index (CPI). RESULTS: hsCRP has been higher in > 65 years old male patients with more than 5 thyroid hormone withholdings. hsCRP is significantly associated with CPI (p=0.001). Spearman's rank correlation indicates a strongly positive linear correlation between these two parameters (r=0.745). CONCLUSIONS: Repeated thyroid hormonal withdrawals in patients with DTC during the long-term follow-up elevated hsCRP at cardiovascular risk levels, having an impact on myocardial perfusion.

Highly-sensitive C-reactive protein, a biomarker of cardiovascular disease risk, in radically-treated differentiated thyroid carcinoma patients after repeated thyroid hormone withholding.

AIMS: In patients radically treated for differentiated thyroid carcinoma, we assessed the response of highly-sensitive C-reactive protein, an inflammatory biomarker for cardiovascular risk, after thyroid hormone withholding ("deprivation"), as well as factors potentially influencing this response. MATERIAL AND METHODS: We included 52 adults (mean age 45.6±14.0 years, 35 females) who were disease-free after total thyroidectomy, radioiodine ablation and chronic thyroid hormone therapy. They were lifelong non-smokers without apparent inflammatory comorbidity, cardiovascular history beyond pharmacotherapy-controlled hypertension, anti-dyslipidemic medication, or C-reactive protein >10 mg/L in any study measurement. The index deprivation lasted ≥2 weeks, elevating serum thyrotropin >40 mIU/L or ≥100 × the individual's suppressed level. We examined the relationship of age, number of prior deprivations, and gender with the magnitude of post-deprivation C-reactive protein concentration through multivariable statistical analyses using the F test on linear regression models. RESULTS: Post-deprivation, C-reactive protein reached intermediate cardiovascular risk levels (based on general population studies involving chronic elevation), 1-3 mg/L, in 44.2% of patients and high-risk levels, >3 mg/L, in another 17.3%. Mean C-reactive protein was 1.77±1.50 mg/L, differing significantly in females (2.12±1.66 mg/L) vs. males (1.05±0.69 mg/L, P <0.001). In multivariable analysis, patients ≤45 years old (odds ratio, 95% confidence interval 0.164 [0.049-0.548]) were less likely, and females, more likely (3.571 [1.062-12.009]) to have post-deprivation C-reactive protein ≥1 mg/L. CONCLUSIONS: Thyroid hormone withdrawal frequently elevated C-reactive protein to levels that when present chronically, were associated with increased cardiovascular risk in general population studies.