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Background Many carcinogenic chemicals are still used or produced in several economic sectors. The aim of this study is to investigate differences in occupational exposure patterns to carcinogens by gender in Italy. Methods Information about the most common carcinogens recorded in the Italian occupational exposures database (SIREP) for the period 1996–2015 was retrieved. Descriptive statistics were calculated for exposure-related variables (carcinogenic agent, occupational group, economic activity sector, and workforce size). The chi-square(χ2) test was used to verify differences between genders, and logistic regression analysis was performed to evaluate the association between gender and risk of having higher exposure levels, after adjusting for age. Concurrent exposures to multiple carcinogens were investigated using the two-step cluster analysis. Results A total of 166,617 exposure measurements were selected for 40 different carcinogens. Exposed workers were only in a small proportion women (9%), and mostly aged 20–44 years (70%) in both genders. Women were more likely to be exposed than men to higher levels for several carcinogens even after correction for age at exposure, and the exposure level was significantly (p

Objective: The aim of this study is to evaluate the long-term outcome of granulosa cell tumour (GCT) of the ovary in a large series of patients treated in MITO centres (Multicentre Italian Trials in Ovarian Cancer) and to define prognostic parameters for relapse and survival. Methods: A retrospective multi-institutional review of patients with GCTs of the ovary treated or referred to MITO centres was conducted. Surgical outcome, intraoperative and pathological findings and follow-up data were analysed. Kaplan–Meier and Cox proportional hazards analyses were used to determine the predictors for survival and recurrence. Results: A total of 97 patients with primary GCT of the ovary were identified. The median follow-up period was 88 months (range 6–498). Of these, 33 patients had at least one episode of disease recurrence, with a median time to recurrence of 53 months (range 9–332). Also, 47% of recurrences occurred after 5 years from initial diagnosis. At multivariate analysis, age and stage were independent poor prognostic indicators for survival; surgical treatment outside MITO centres and incomplete surgical staging retained significant predictive value for recurrence in both univariate and multivariate analyses. Conclusions: This study confirms the generally favourable prognosis of GCTs of the ovary, with 5-year overall survival approaching 97%. Nevertheless, prognosis after 20 years was significantly poorer, with 20-year survival rate of 66.8% and a global mortality of 30–35. These findings support the need for lifelong follow-up even in early-stage GCT.

The presence of interval sentinel lymph nodes in melanoma is documented in several studies, but controversies still exist about the management of these lymph nodes. In this study, an immunohistochemical evaluation of tumor cell proliferation and neo-angiogenesis has been performed with the aim of establishing a correlation between these two parameters between positive and negative interval sentinel lymph nodes. This retrospective study reviewed data of 23 patients diagnosed with melanoma. Bioptic specimens of interval sentinel lymph node were retrieved, and immunohistochemical reactions on tissue sections were performed using Ki67 as a marker of proliferation and CD31 as a blood vessel marker for the study of angiogenesis. The entire stained tissue sections for each case were digitized using Aperio Scanscope Cs whole-slide scanning platform and stored as high-resolution images. Image analysis was carried out on three selected fields of equal area using IHC Nuclear and Microvessel analysis algorithms to determine positive Ki67 nuclei and vessel number. Patients were divided into positive and negative interval sentinel lymph node groups, and the positive interval sentinel lymph node group was further divided into interval positive with micrometastasis and interval positive with macrometastasis subgroups. The analysis revealed a significant difference between positive and negative interval sentinel lymph nodes in the percentage of Ki67-positive nuclei and mean vessel number suggestive of an increased cellular proliferation and angiogenesis in positive interval sentinel lymph nodes. Further analysis in the interval positive lymph node group showed a significant difference between micro- and macrometastasis subgroups in the percentage of Ki67-positive nuclei and mean vessel number. Percentage of Ki67-positive nuclei was increased in the macrometastasis subgroup, while mean vessel number was increased in the micrometastasis subgroup. The results of this study suggest that the correlation between tumor cell proliferation and neo-angiogenesis in interval sentinel lymph nodes in melanoma could be used as a good predictive marker to distinguish interval positive sentinel lymph nodes with micrometastasis from interval positive lymph nodes with macrometastasis subgroups.

Recurrent miscarriage (RM) is defined as 3 or more miscarriages before 20 weeks’ pregnancy. In recent years, interest has been focused on chronic endometritis (CE), a subtle inflammation thought to be associated with RM. We aimed to evaluate the relationships between CE and RM. The records of 360 women with unexplained RM were retrospectively analyzed. Data from hysteroscopy, endometrial histology, endometrial culture, and polymerase chain reaction for chlamydia, performed before and after antibiotic treatment for CE, were analyzed. The occurrence of successful pregnancies within 1 year after treatment was also evaluated. Results showed that 208 (57.8%) women with RM showed CE at hysteroscopy; 190 (91.3%), positive at hysteroscopy, were also positive at histology, and 142 (68.3%) had positive cultures. Common bacteria were found in 110 (77.5%) patients. Mycoplasma and Ureaplasma were found in 36 (25.3%) patients and Chlamydia in 18 patients (12.7%). In 102 (71%) women, antibiogram-based antibiotic treatment normalized hysteroscopy, histology, and cultures (group 1); while in 40 (28.2%) patients, CE was still present at hysteroscopy (group 2). In 16 of the 66 patients positive at hysteroscopy, but not at cultures, the hysteroscopy becomes normal (group 3) after a Centers for Disease Control and Prevention-based therapy; while in 50 women, CE was still present (group 4). One year after treatment, group 1 showed a significantly higher number of pregnancies (78.4%) compared to group 2 (17.5%; P < .001) and group 4 (15.3%; P = .005). The CE is frequent in women with RM. Antibiotic treatment seems to be associated with an improved reproductive outcome.

Objectives: Ochratoxin A (OA) is a ubiquitous mycotoxin that can contaminate foods, drinks, and animal feeds worldwide. Humans and animals can therefore absorb this toxin via the gastrointestinal tract after ingestion of contaminated products. OA is known to exert toxic effects, particularly on the renal system, and the International Agency for Research on Cancer (IARC) classified it as a ''possible human carcinogen'' (Group 2B). The measurement of OA serum levels is an effective method of evaluating internal doses. Inhala- tion of airborne OA can represent a source of addi- tional exposure. We determined the levels of serum OA in workers exposed to airborne dust originating from the handling or processing of contaminated foods. Methods: We carried out area and personal sampling for airborne OA determination in three industries where coffee, cocoa beans, and spices, foods highly susceptible to contamination, were being processed. OA levels in the serum of six healthy workers employed in these factories were measured in samples collected at the end of the work shift. Results: Airborne OA measured in the three industries, both by personal and area sampling, ranged from

Collection of an endometrial specimen for investigating infectious agents in the endometrial cavity is an invasive technique that is at times difficult and painful. In order to avoid the need for endometrial sampling in the cases of suspected or evident endometrial pathology, the aim of this study is to investigate the reliability of cervical cultures for detecting infectious agents present at the endometrial level, comparing the results between cervical cultures and endometrial cultures in women with clinical signs of endometrial inflammation.In a prospective diagnostic study, in the period from January 2009 to October 2010, we enrolled 404 women referred to the Department of Obstetrics and Gynecology for diagnostic hysteroscopy. All the patients underwent cervical and endometrial sampling. Cultures for common bacteria, Neisseria gonorrhoeae, yeast, and Ureaplasma urealyticum were performed.The most frequent infectious agents detected at the endometrial level were common bacteria, which accounted for 69% of all cases. In particular, streptococci were found in 27% of cases, and bacteria from intestinal flora (Enterococcus faecalis and Escherichia coli) was recovered in 31% of cases. U. urealyticum was detected in 10% and Mycoplasma in only one patient (0.2% of cases). No cases of N. gonorrhoeae were found.Cervical culture has a low concordance with endometrial culture. In fact in only 33% of cases was the microorganism found in the cervix the same as that found in the endometrium. These results infer that an endometrial culture is a useful investigative tool for determining the microorganisms in endometrial pathology.

Neonatal gastroesophageal reflux (GER) is primarily due to a transient motility disorder and characterized by a prevalence of weakly acid refluxes. Drug management, where necessary, must set out to reduce the number of refluxes besides correct their acidity. Prokinetics could be of assistance in this respect, though the evidence in favor of their efficacy and safety is still far from sufficient. In this randomized controlled study, the action of domperidone, a prokinetic antidopaminergic drug with little effect on the central nervous system, was evaluated in newborns with symptomatic GER.Combined multichannel intraluminal impedance and pH measuring for 24 h was carried out in 13 newborns receiving 0.3 mg per kg domperidone per os at the eighth and the sixteenth hour, and 13 controls. Each newborn was compared to the control nearest in postconceptional age.GER episodes per hour increased significantly compared to the baseline in the domperidone group (4.06+/-1.16 vs 2.8+/-1.42; P=0.001) and were shorter (16.68+/-4.49 vs 20.18+/-7.83 s; P=0.043), whereas there were no differences in the maximum proximal extent reached by the refluxes (3.37+/-0.45 vs 3.34+/-0.94 channels; P=0.894) and their pH (4.72+/-0.69 vs 4.60+/-1.17; P=0.634).This paradoxical increase in the number of GER episodes could be the expression of a domperidone-induced amplification of the motor incoordination of the neonatal gastroesophageal tract. Doubt is thus cast on the efficacy of prokinetics in this age bracket, especially in view of their adverse effects as described in the literature.

Objectives: This study evaluates by comet assay the induction of early DNA damage in healthcare workers of an oncology hospital regularly handling antineoplastic drug mixtures. The aim was to identify a suitable biomarker of DNA damage by exposure to low levels of such drugs. Methods: We studied 12 day hospital nurses and 13 oncology ward nurses who performed up to 300 and up to 35 drug administrations per week, respectively, and five pharmacy employees who regularly prepared mixtures of antineoplastic agents. Thirty healthy subjects were selected as controls. For exposure evaluation, we performed environmental monitoring of 5-fluorouracil, cytarabine, gemcitabine, cyclophosphamide, and ifosfamide in selected work areas of pharmacy and day hospital units and biological monitoring of urine for the 5-fluorouracile metabolite, α-fluoro-β-alanine. We evaluated early DNA damage in lymphocytes and exfoliated buccal cells by comet assay measuring tail moment (TM) parameter that indirectly indicates the presence of DNA damage. Results: Environmental monitoring detected cyclophosphamide, 5-fluorouracil and ifosfamide, with higher levels of contamination in day hospital unit. The biological monitoring measured detectable levels of α-fluoro-β-alanine only in three nurses. Comet assay showed an increase on exfoliated buccal cells, even if not statistically significant, of mean TM with respect to controls in day hospital nurses (43.2 vs. 28.6, respectively) while ward nurses and pharmacy technicians did not show differences. Comet assay performed on lymphocytes did not show appreciable differences between exposed and controls. Conclusions: The employment of the sensitive comet assay, which is able to detect early the effects of a recent exposure to genotoxic substances, allowed us to find a slight DNA damage, only on exfoliated buccal cells of day hospital nurses, the group handling the highest amount of drugs during the administration process. This finding suggests that comet assay on exfoliated buccal cells could represent a useful tool to evaluate early and still repairable genotoxic effects of exposure to antineoplastic drug mixtures and then contribute to the improvement of the hospital safety practices.

Ret is a receptor-like tyrosine kinase involved in several neoplastic and developmental diseases affecting thyroid gland and tissues of neuroectodermal origin. Rearrangements of theret gene are observed in a sizeable fraction of human thyroid papillary carcinomas. «Gain of function» ofret has been shown to be caused by mutations associated with multiple endocrine neoplasia type 2A (MEN2A) or 2B (MEN2B) syndromes. Conversely, congenital megacolon or Hirschsprung’s disease (HSCR) is associated with «loss of function» ofret. Here, we show that glial cell line-derived neurotrophic factor (GDNF), a member of the TGFβ super-family, is able to stimulatein vivo tyrosine kinase activity of Ret. These effects were specific to GDNF, since neither other members of the TGFβ family nor other neurotrophins and unrelated growth factors exerted the same effects. Consistently, ectopic expression of Ret in NIH 3T3 cells rendered them responsive to the mitogenic action of GDNF. These results allow the conclusion that GDNF is a functional ligand for Ret and suggest that Ret-GDNF interaction plays an important role in the pathogenesis of diseases associated withret mutations.

Background Malignant mesothelioma is an aggressive and lethal tumour strongly associated with exposure to asbestos (mainly occupational). In Italy a large proportion of workers are protected from occupational diseases by public insurance and an epidemiological surveillance system for incident mesothelioma cases. Methods We set up an individual linkage between the Italian national mesothelioma register (ReNaM) and the Italian workers’ compensation authority (INAIL) archives. Logistic regression models were used to identify and test explanatory variables. Results We extracted 3270 mesothelioma cases with occupational origins from the ReNaM, matching them with 1625 subjects in INAIL (49.7%); 91.2% (1,482) of the claims received compensation. The risk of not seeking compensation is significantly higher for women and the elderly. Claims have increased significantly in recent years and there is a clear geographical gradient (northern and more developed regions having higher claims rates). The highest rates of compensation claims were after work known to involve asbestos. Conclusions Our data illustrate the importance of documentation and dissemination of all asbestos exposure modalities. Strategies focused on structural and systematic interaction between epidemiological surveillance and insurance systems are needed.

A case of cervical pregnancy with implantation of the fertilized ovum on the exocervix is described. This pregnancy was mistaken for an endometriotic lesion and treated by simple surgical excision. Discussion is centered on etiology, predisposing factors and management.

Background and aims: combined multichannel intraluminal impedance and pH-monitoring (MII/pH) is a new technique identifying refluxes irrespective of acidity and detecting their duration, proximal extent and pH. These features are important when studying gastroesophageal-reflux-disease (GERD) in infants, in which weakly acid refluxes are prevalent. Clinical application of MII/pH is uncommon yet, owing to lack of reference values and difficult interpretation of the variables obtained. Aim of the present study was to investigate the relationship between MII-pH results and clinical outcome on a sample of GERD infants. Methods: infants (age: 0-3 months) with GERD symptoms were studied with MII/pH and submitted to a follow-up consisting in clinical examinations and structured interviews to parents at 3-6-9-12-18-24-36 months to evaluate the presence of symptoms and the therapy effects. Results: 54 patients completed the follow-up (32M; age 33.69±21.78 days; weight 3465.13±791.08 gr.; length 52.08±3.55 cm). 22 and 15 patients were still symptomatic at the age of 6 and 9 months, without difference in MII/pH values between symptomatic and non symptomatic infants. The 12 infants that were still symptomatic at the age of 12 months showed a higher bolus exposure index (BEI) with respect to the healed patients (2.63±1.72% vs 1.72±1.05; p=0.029). Conclusions: MII-pH in first months of life could be useful to identify patients with high risk of presenting GER symptoms for more than 1 year. BEI is a pH independent variable with a significant relationship with symptoms duration. Our data highlight the clinical relevance of MII/pH-detected weakly acidic refluxes in GERD infant.