Role of metformin and other metabolic drugs in the prevention and therapy of endocrine-related cancers.

Metabolic syndrome is associated with chronic diseases, including type 2 diabetes, cardiovascular diseases, and cancer. This review summarizes the current evidence on the antitumor effects of some relevant drugs currently used to manage metabolic-related pathologies (i.e. insulin and its analogs, metformin, statins, etc.) in endocrine-related cancers including breast cancer, prostate cancer, pituitary cancer, ovarian cancer, and neuroendocrine neoplasms. Although current evidence does not provide a clear antitumor role of several of these drugs, metformin seems to be a promising chemopreventive and adjuvant agent in cancer management, modulating tumor cell metabolism and microenvironment, through both AMP-activated protein kinase-dependent and -independent mechanisms. Moreover, its combination with statins might represent a promising therapeutic strategy to tackle the progression of endocrine-related tumors. However, further studies are needed to endorse the clinical relevance of these drugs as adjuvants for cancer chemotherapy.

Italian cancer figures--Report 2015: The burden of rare cancers in Italy.

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population.

Association of environmental chemicals & estrogen metabolites in children.

BACKGROUND: The prevalence of pediatric hormonal disorders and hormonally-sensitive cancers are rising. Chemicals including bisphenol A (BPA), phthalates, parabens, 4-nonylphenol (4NP) and triclosan have been linked to disruption of endocrine pathways and altered hormonal status in both animal and human studies. Additionally, changes in estrogen metabolism have been associated with pediatric endocrine disorders and linked to estrogen-dependent cancers. The main objective of the study was to measure the presence of these environmental chemicals in prepubescent children and assess the relationship between chemical metabolites and estrogen metabolism. METHODS: 50 subjects (25 male, 25 female) were recruited from the principal investigator's existing patient population at his pediatric primary care office. The first 5 boys and 5 girls in each age group (4 through 8 years old inclusive) who presented for annual examinations were included, as long as they were Tanner Stage I (prepubertal) on physical exam, without diagnosis of hormonally-related condition and/or cancer and able to give a urine sample. Urine samples were collected in glass containers for analysis of chemical and estrogen metabolites. Study kits and lab analysis were provided by Genova Diagnostics (Duluth, GA). Summary statistics for the concentrations of each chemical metabolite as well as estrogen metabolites were computed (minimum, maximum, median and inter-quartile range) for males only, for females only and for all subjects. Comparisons between groups (e.g. males v. females) were assessed using the nonparametric Wilcoxon test, since the data was skewed. The correlation between concentrations of chemical metabolites and estrogen metabolites in prepubescent children were examined by the Spearman's correlation coefficient (ρ). RESULTS: 100 % of subjects had detectable levels of at least five chemicals [corrected] in their urine, and 74 % had detectable levels of eight or more chemicals. 28 % of subjects had measurable levels of 4NP. No associations were found between the urine levels of chemicals and estrogen metabolites. CONCLUSIONS: Endocrine disrupting environmental chemicals were detected in all children in the study, with measurable levels of 4NP in nearly 1/3 of subjects. This is the first known published study of 4NP levels in American children. No associations were found between the urine levels of chemicals tested and estrogen metabolites. The presence of multiple chemicals in a majority of children's urine coupled with increasing prevalence of pediatric hormonal disorders warrants further research to elucidate potential causal mechanisms in pre- and post-pubertal children.

Recomendaciones para la determinación de biomarcadores en tumores endocrinos gastroenteropancreáticos. Consenso nacional de la Sociedad Española de Anatomía Patológica y de la Sociedad Española de Oncología Médica / Guidelines for biomarker testing in gastroenteropancreatic endocrine tumours. A national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

La incidencia de los tumores neuroendocrinos en la población caucásica oscila entre 2,5 y 5 casos nuevos anuales por cada 100.000 habitantes. Los tumores neuroendocrinos gastroenteropancreáticos difieren considerablemente entre sí, tanto en su composición hormonal, como en los síndromes que producen, así como en su comportamiento biológico. Esta notable complejidad y heterogeneidad clínica, junto con su conocida dificultad para predecir su comportamiento a partir de características patológicas, han quedado reflejadas en las múltiples clasificaciones que se han realizado a lo largo del tiempo. En este artículo se revisan los principales biomarcadores tisulares y clínicos, y se ofrecen recomendaciones para su uso en la práctica médica. El documento obedece a un consenso fruto de la colaboración entre la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Anatomía Patológica (SEAP) (AU)

The annual incidence of neuroendocrine tumours in the Caucasian population ran- ges from 2.5 to 5 new cases per 100,000 inhabitants. Gastroenteropancreatic neuroendocrine tumours vary considerably in their hormonal composition, the syndromes they cause and their biological behaviour. This high complexity and clinical heterogeneity, together with the well- known difficulty of predicting their behaviour from their pathological features, are reflected in the many classifications that have been formulated over the years. This article reviews the main tissue and clinical biomarkers and makes recommendations for their use in medical prac- tice. This document represents a consensus reached jointly by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) (AU)

Endocrinological cancers and the internet.

Endocrine cancers are some of the commonest forms of cancer getting mention as early as in old papyruses of Egypt. Our current knowledge about this cluster of cancer has grown immensely with improved survival rates. In the era of specialization and super specialization, we started peeking into these conditions more elaborately and beyond microscopically. The growing awareness demanded categorization of information into disease basics like molecular pathology of initiation and progression; advanced diagnostics; new therapeutic options; patient awareness and involvement in clinical trials. Recent advances in genomics and hereditary counseling have delineated pre-disease forecasting possibilities. With advanced diagnostics and therapeutic modalities, we saw an increase in cancer survivors demanding extra care and moral support. Throughout these developments, we went through a boost in global information communications, the main thrust being the Internet. Networking of computers globally generated a platform that created a ripple of knowledge far and wide. The purpose of this review is to investigate how the Internet is supporting the growth and development of the field of endocrine cancer, and present and future scope of the Internet as a tool for professionals involved in this area. The information furnished here were collected from cited references as well as all websites mentioned in the tables.

[Relationship between toxic effects of potassium bromate and endocrine glands]. / Powiazania pomiedzy toksycznymi efektami bromianu potasowego a gruczolami wydzielania wewnetrznego.

Potassium bromate (KBrO(3)) is a compound belonging to Group 2B of carcinogens (a possible human carcinogen). This agent was used as a food additive in flour treatment, as a component of cold-wave hair lotions, and is still used in barley processing. Additionally, KBrO(3) is formed as an oxyhalide by-product during water ozonation. KBrO(3) induces oxidative stress and may contribute to neoplasia in endocrine glands. It has been demonstrated that KBrO(3) triggers thyroid follicular cell tumors in rats. It has been revealed in our in vivo and in vitro studies that KBrO(3) significantly increases lipid peroxidation in rat and porcine thyroid. KBrO(3) also induces mesotheliomas which may secrete hormones or similar substances, such as parathyroid hormone related protein, phosphatonins or melanocyte stimulating hormone. In our experimental studies we demonstrated that antioxidants, such as pineal hormone - melatonin, indole-3-propionic acid (IPA) (a compound chemically and physically similar to melatonin) and antythyroid drug - propylthiouracil (PTU), produce distinct protective effects against lipid peroxidation due to KBrO(3) in the thyroid in vivo. KBrO(3) is a prooxidant which may induce neoplasia in endocrine glands and cause hormonal disturbances, however its damaging effects may be neutralized by hormones, mainly melatonin.

Hormonal approaches to the chemoprevention of endocrine-dependent tumors.

The estrogen dependency of human breast cancer has been successfully exploited in the treatment of early and advanced diseases and provides a unique opportunity for chemoprevention of this common malignancy. Preliminary results with the antiestrogens Tamoxifen and Raloxifene show an encouraging reduction in the incidence of breast cancer. Alternative approaches include the use of highly selective and non-toxic aromatase inhibitors and, in premenopausal women, the use of LHRH agonists in conjunction with the administration of small doses of estrogen and progesterone. The rationale for these chemopreventive strategies and their possible limitations are briefly discussed.