Vitamin D deficiency: a potential risk factor for cancer in obesity?

Obesity is considered an abnormal or excessive accumulation of adipose tissue, due to a prolonged positive energy balance that arises when energy intake is greater than energy expenditure, leading to an increased risk for the individual health and for the development of metabolic chronic diseases including several different types of cancer. Vitamin D deficiency is a metabolic alteration, which is often associated with the obesity condition. Vitamin D is a liposoluble vitamin, which plays a pivotal role in calcium-phosphate metabolism but extraskeletal effects have also been described. Among these, it plays an important role also in adipocyte physiology and glucose metabolism, typically dysregulated in subjects affected by obesity. Moreover, it is now recognized that Vitamin D also influences the processes of cell proliferation, differentiation, adhesion potentially leading to carcinogenesis. Indeed, data indicate a potential link between vitamin D levels and cancer, and higher vitamin D concentrations have been associated with a lower risk of developing different kinds of tumors, including breast, colon, lymphoma, lung, and prostate cancers. Thus, this review will revise the literature regarding this issue investigating and highlighting the potential mechanism of action, which might lead to new therapeutical options.

Sex differences in carcinoid syndrome: A gap to be closed.

The incidence of neuroendocrine neoplasms and related carcinoid syndrome (CS) has markedly increased over the last decades and women seem to be more at risk than men for developing CS. Nevertheless, very few studies have investigated sex differences in clinical presentation and outcomes of CS. However, as per other tumours, sex might be relevant in influencing tumour localization, delay in diagnosis, clinical outcomes, prognosis and overall survival in CS. The present review was aimed at evaluating sex differences in CS, as they emerge from an extensive search of the recent literature. It emerged that CS occurs more frequently in female than in male patients with NENs and women seem to have a better prognosis and a slight advantage in overall survival and response to therapy. Moreover, the disease likely impacts differently the quality of life of men and women, with different psychological and social consequences. Nevertheless, sex differences, even if partially known, are deeply underestimated in clinical practice and data from clinical trials are lacking. There is urgent need to increase our understanding of the sex-related differences of CS, in order to define tailored strategies of management of the disease, improving both the quality of life and the prognosis of affected patients.

Biliary Stone Disease in Patients with Neuroendocrine Tumors Treated with Somatostatin Analogs: A Multicenter Study.

BACKGROUND: Somatostatin analogs (SSAs) are the mainstay of neuroendocrine tumor (NET) treatment. Biliary stone disease is reported as a common side effect of SSAs, with a frequency ranging from 10% to 63%. Studies on SSA-treated patients for acromegaly report an increased incidence of biliary stone disease compared with the general population, whereas data on patients with NETs are few. Guidelines are based on weak evidence, thus resulting in conflicting recommendations. The aim of the study is to evaluate biliary stone disease incidence, complications, and risk factors in a large population of SSA-treated patients with NETs. MATERIALS AND METHODS: A retrospective analysis of a prospectively collected database was performed. Patients with a diagnosis of NET in seven dedicated centers from 1995 to 2017 were included at the time of SSA start. RESULTS: A total of 754 SSA-treated patients were evaluated. Patients with history of cholecystectomy or with known biliary stone disease were excluded; 478 patients were included. Among them, 118 patients (24.7%) received prophylactic ursodeoxycholic acid (UDCA). During the study period, 129 patients (27.0%) developed biliary stone disease; of them, 36 (27.9%) developed biliary complications. On multivariate analysis, primary gastrointestinal (GI)-NET (hazard ratio [HR] 1.76) and related surgery (HR 1.58) were independent risk factors for biliary stone disease. CONCLUSION: We report a high incidence of biliary stone disease particularly in GI-NET or GI surgery. UDCA prophylaxis does not seem to have a protective role. Our data suggest that all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy; no conclusion could be drawn on the indication of prophylactic cholecystectomy in patients with primary pancreatic or thoracic NET for whom abdominal surgery is not planned. IMPLICATIONS FOR PRACTICE: The results of this study confirm an increased rate of gallstones development and related complications in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs (SSAs). NETs of the gastrointestinal (GI) tract and related surgery are independent risk factors for biliary stone disease development. Therefore, all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy. Data on other subgroups are not exhaustive, and management also evaluating additional clinical features (life expectancy, surgical and anesthesiological risks) should be considered. Prophylactic treatment with ursodeoxycholic acid does not seem to be a protective factor for SSA-related biliary stone disease.

VENUS BY BOTTICELLI AND HER PITUITARY ADENOMA.

Objective: Simonetta Vespucci, considered the most beautiful woman of the Renaissance, is the inspiration and face of one of the most famous paintings of all times, "The Birth of Venus," by Botticelli. She died in 1476 at the age of 23 years. We postulate she suffered from a pituitary-secreting tumor progressing to pituitary apoplexy. The goals of this study were 3-fold: (i) verify that the subject depicted by Botticelli in different paintings represents the same woman; (ii) identify the facial traits affected by the progression of a growth hormone- and prolactin-secreting tumor; and (iii) confirm that the observed changes of the face traits observed in the portraits of Simonetta Vespucci are compatible with the facial traits changes identified earlier. Methods: Comparison among face traits was based on the analysis of the face regions measured by means of fiducial points and their distances, and after pose compensation based on three-dimensional head modelling. Results: In favor of the hypothesis that Simonetta suffered from a pituitary growth hormone- and prolactin-secreting tumor stands changes of her lineaments, a feature which becomes evident over the years and particularly manifest in the Allegorical Lady, where galactorrhea is depicted. Conclusion: We conclude that sufficient evidence is presented to suggest that Simonetta Vespucci, the Venus depicted by Botticelli, suffered from pituitary adenoma secreting prolactin and growth hormon with parasellar expansion. The current interpretation of the Venus strabism should be revisited according to this finding. Abbreviation: GH = growth hormone.

Heterogeneity of Duodenal Neuroendocrine Tumors: An Italian Multi-center Experience.

BACKGROUND: The optimal management of duodenal neuroendocrine neoplasms (dNENs) is unclear, and endoscopic resection is increasingly performed instead of surgery. METHODS: This is a retrospective analysis of patients with histologically confirmed diagnosis of dNENs, managed at five Italian tertiary referral Centers in Italy. RESULTS: From 2000 to 2017, 108 patients (69 males, 39 females, median age 59.5 years) were included in this study. Seventy-one patients had G1, 21 G2, 4 G3 dNENs (12 Ki-67 not available). Fifty-four patients showed metastases at diagnosis, and 20 patients developed metachronous metastases. Thirty patients had a functioning dNEN (14 metastatic). Fifty-seven patients had the dNEN surgically resected, 16 endoscopically, 23 metastatic, received medical therapy + surgery or endoscopy. Seven patients underwent liver-directed therapies, and one patient had PRRT. Median OS was 187 months. During a median follow-up of 76 months, 20 patients died (19 of disease-related causes). At Cox's multivariate proportional hazard regression, grading and age were the only variables independently related to OS. Median PFS was 170 months. Grading and staging at the initial diagnosis were independently related to PFS. No differences in terms of OS and PFS were observed between patients treated surgically or endoscopically. CONCLUSIONS: dNENs prognosis may be highly variable. These tumors can be metastatic in up to 50% of cases at the time of first diagnosis and can develop metastases thereafter. Functioning neoplasms express high metastatic potential. Nuclear imaging should be performed to exclude distant metastases in all dNENs. Endoscopy and surgery play a primary role in the management of the disease. Further prospective studies are needed.

Beyond Weight Loss: Added Benefits Could Guide the Choice of Anti-Obesity Medications.

PURPOSE OF REVIEW: To highlight the added benefits of approved and upcoming, centrally-acting, anti-obesity drugs, focusing not only on the most common metabolic and cardiovascular effects but also on their less explored clinical benefits and drawbacks, in order to provide clinicians with a tool for more comprehensive, pharmacological management of obesity. RECENT FINDINGS: Obesity is increasingly prevalent worldwide and has become a challenge for healthcare systems and societies. Reduced life expectancy and cardiometabolic complications are some of the consequences of this complex disease. Recent insights into the pathophysiology of obesity have led to the development of several promising pharmacologic targets, so that even more effective drugs are on the horizon. The perspective of having a wider range of treatments increases the chance to personalize therapy. This primarily has the potential to take advantage of the long-term use of anti-obesity medication for safe, effective and sustainable weight loss, and to concomitantly address obesity complications/comorbidities when already established. The evolving scenario of the availability of anti-obesity drugs and the increasing knowledge of their added effects on obesity complications will allow clinicians to move into a new era of precision medicine.

The Effects of Radioligand Therapy on Quality of Life and Sexual Function in Patients with Neuroendocrine Neoplasms.

Peptide receptor radionuclide therapy (PRRT), also called radioligand therapy, is an effective antitumoral treatment in patients with neuroendocrine neoplasm (NEN). It improves the patient's health-related quality of life (HRQoL), which is evaluated by self-assessment questionnaires. The aim of this narrative review was to report the current knowledge on the changes of HRQoL and sexual function in patients with NEN treated with PRRT. We conducted a literature search of the PubMed, Embase, and APA PsycInfo databases. We selected 15 studies (12 for HRQoL and three for sexual function). After treatment with PRRT, patients with NEN experienced a significant improvement in their global health status, disease-related worries, social and emotional functioning, and cancer-related symptoms such as fatigue and diarrhea. Other symptoms, such as nausea/vomiting, dyspnea, and constipation, as well as the economic impact, were unchanged by radioligand therapy. Data on sexual function were not equally promising; only a few studies investigated this issue by using appropriate questionnaires in patients treated with radioligand therapy. Therefore, additional studies are needed to draw a conclusion about the benefits from PRRT on sexual function.

Risk factors for operated carpal tunnel syndrome: a multicenter population-based case-control study.

BACKGROUND: Carpal tunnel syndrome (CTS) is a socially and economically relevant disease caused by compression or entrapment of the median nerve within the carpal tunnel. This population-based case-control study aims to investigate occupational/non-occupational risk factors for surgically treated CTS. METHODS: Cases (n = 220) aged 18-65 years were randomly drawn from 13 administrative databases of citizens who were surgically treated with carpal tunnel release during 2001. Controls (n = 356) were randomly sampled from National Health Service registry records and were frequency matched by age-gender-specific CTS hospitalization rates. RESULTS: At multivariate analysis, risk factors were blue-collar/housewife status, BMI > or = 30 kg/m2, sibling history of CTS and coexistence of trigger finger. Being relatively tall (cut-offs based on tertiles: women > or =165 cm; men > or =175 cm) was associated with lower risk. Blue-collar work was a moderate/strong risk factor in both sexes. Raised risks were apparent for combinations of biomechanical risk factors that included frequent repetitivity and sustained force. CONCLUSION: This study strongly underlines the relevance of biomechanical exposures in both non-industrial and industrial work as risk factors for surgically treated CTS.

[Occupational accidents among immigrant workers in the Fabriano areas]. / II fenomeno infortunistico nei lavoratori extracomunitari della zona territoriale n. 6 Fabriano.

BACKGROUND: The growing contribution of immigrant workers to the national economy particularly affects the trend of accidents at work. OBJECTIVES: The aim of this study was to describe the trend of work accidents in the Local Health Area No. 6 - Fabriano (Marche Region), during the period 2000-2003; to define the frequency for each job sector, age, gender, type of work, severity, month, day and week and time of day; to calculate the incidence rate for each year taken into consideration. METHODS: The sources of information used were: 1) The "New Informative Flows" database set up by Italian National Institute of Insurance for Occupational Injury (INAIL), Italian Superior Institute for Work Prevention and Safety (ISPESL) and Regional Governments, and the "EPIWORK software", for the total number of occupational accidents among immigrant workers. 2) The local Jobs and Training Centre of Fabriano. We used three different correction indexes to evaluate the number of hired workers so as to estimate the rate of accident incidence among immigrant workers. RESULTS: The total number of occupational accidents reached its peak in 2001 as a result of the rise in the number of employed people. After this date, the trend started to reverse and in 2002 an increase in the number of employed people--although smaller compared to the previous year--was accompanied by a reduction in the overall number of accidents, a reduction that became even more evident in 2003. Occupational accidents among immigrant workers gradually rose and peaked in 2002. The sectors with high rates of accidents were the mechanical engineering and metallurgic sectors and the construction industry. Accidents occurred mainly among young people (18 to 34years old). As for gender, there was a marked prevalence of men (83.3%) over women (16.7%). Most accidents had a prognosis of 8 to 30 days. The number ofoccupational accidents with a prognosis of 8 to 30 days fell progressively for workers in general but gradually rose for immigrant workers with a peak in 2001. The overall number of occupational accidents that caused permanent invalidity fell by 52.3% for the workforce in general, and by 25% among immigrant workers. CONCLUSIONS: This study shows that immigrant workers employed in the Fabriano area had a higher risk of accidents at work.

Maternal vitamin D levels during pregnancy and neonatal health: evidence to date and clinical implications.

Low maternal vitamin D levels during pregnancy have been associated with a plethora of adverse neonatal outcomes, including small for gestational age and preterm births, detrimental effect on offspring bone and teeth development, and risk of infectious diseases. Although most observational studies indicate a significant linear relationship between maternal 25-hydroxyvitamin D and the above outcomes, some randomized controlled trials to date are inconclusive, mostly due to differences in study design and supplementation regimen. The currently available results indicate that vitamin D supplementation during pregnancy reduces the risk of preterm birth, low birth weight, dental caries of infancy, and neonatal infectious diseases such as respiratory infections and sepsis. This narrative review aims to summarize available trial results regarding the effect of low maternal vitamin D levels during pregnancy, in conjunction with neonatal outcomes on the field, with a discourse on the appropriate clinical approach of this important issue.