Association between brominated flame retardants and risk of endocrine-related cancer: A systematic review and meta-analysis.

BACKGROUND: The incidence of endocrine-related cancer, which includes tumors in major endocrine glands such as the breast, thyroid, pituitary, and prostate, has been increasing year by year. Various studies have indicated that brominated flame retardants (BFRs) are neurotoxic, endocrine-toxic, reproductive-toxic, and even carcinogenic. However, the epidemiological relationship between BFR exposure and endocrine-related cancer risk remains unclear. METHODS: We searched the PubMed, Google Scholar, and Web of Science databases for articles evaluating the association between BFR exposure and endocrine-related cancer risk. The odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were used to assess the association. Statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. Begg's test was performed to evaluate the publication bias. RESULTS: We collected 15 studies, including 6 nested case-control and 9 case-control studies, with 3468 cases and 4187 controls. These studies assessed the risk of breast cancer, thyroid cancer, and endocrine-related cancers in relation to BFR levels. Our findings indicate a significant association between BFR exposure in adipose tissue and an increased risk of breast cancer. However, this association was not observed for thyroid cancer. Generally, BFR exposure appears to elevate the risk of endocrine-related cancers, with a notable increase in risk linked to higher levels of BDE-28, a specific polybrominated diphenyl ether congener. CONCLUSIONS: In conclusion, although this meta-analysis has several limitations, our results suggest that BFR exposure is a significant risk factor for breast cancer, and low-brominated BDE-28 exposure could significantly increase the risk of endocrine-related cancers. Further research is essential to clarify the potential causal relationships between BFRs and endocrine-related cancers, and their carcinogenic mechanisms.

Characteristics of 1270 Chinese sibling pairs with cancer.

BACKGROUND: Previous research found that the cancer history of an individual's sibling may be a better indicator than that of the parents. We aim to provide recommendations for opportunistic screening for individuals whose sibling had been diagnosed with cancer. METHODS: During the physical examination in Cancer Hospital, Chinese Academy of Medical Sciences, 43,300 people were asked if they have at least two siblings who developed cancer. RESULTS: A total of 1270 sibling-pairs from 766 families developed cancer, including 367 pairs of brothers (Bro-pairs), 368 pairs of sisters (Sis-pairs), and 535 pairs of brother-and-sister (BroSis-pairs). The mean ages at diagnosis of cancer for the three groups were from 58 to 62 years. More than half of Bro-pairs (55.3%) or Sis-pairs (51.1%) had cancer from the same systemic origin, and more than a quarter of Bro-pairs (28.1%) and Sis-pairs (37.2%) developed the same type of cancer. However, only 36.0% of BroSis-pairs developed cancers from the same systemic origin, and 18.9% developed the same type of cancer. In Bro-pairs and BroSis-pairs, lung cancer and digestive system cancer were the most common cancers, while in Sis-pairs, breast cancer, lung cancer, cervical cancer, liver cancer and thyroid cancer were the most common ones. CONCLUSIONS: If an individual's sibling is diagnosed with cancer, the individual should consider participating in opportunistic screening annually, especially for lung cancer and digestive system cancers for both sexes. For sisters, breast cancer, cervical cancer and thyroid cancer should be screened early. Additionally, genetic services are essential for individuals who have siblings with cancer.

Hereditary Endocrine Tumors and Associated Syndromes: A Narrative Review for Endocrinologists and Endocrine Surgeons.

OBJECTIVE: Hereditary endocrine tumors (HET) were among the first group of tumors where predisposition syndromes were recognized. The utility of genetic awareness is having the capacity to treat at an earlier stage, screen for other manifestations and initiate family cascade testing. The aim of this narrative review is to describe the most common hereditary syndromes associated with frequently encountered endocrine tumors, with an emphasis on screening and surveillance. METHODS: A MEDLINE search of articles for relevance to endocrine tumors and hereditary syndromes was performed. RESULTS: The most common hereditary syndromes associated with frequently encountered endocrine tumors are described in terms of prevalence, genotype, phenotype, penetrance of malignancy, surgical management, screening, and surveillance. CONCLUSION: Medical practitioners involved in the care of patients with endocrine tumors should have an index of suspicion for an underlying hereditary syndrome. Interdisciplinary care is integral to successful, long-term management of such patients and affected family members.

[Primary urological cancers in a context of limited resources: Epidemiology and treatment]. / Les cancers urologiques primitifs dans un contexte de ressources limitées : épidémiologie et traitement.

OBJECTIVES: To describe the epidemiological, clinical and therapeutic aspects of primary urological cancers in semi-urban areas in Burkina Faso. PATIENTS AND METHOD: A descriptive study was conducted over the period from 1 January 2008 to 31 December 2017 in the General Surgery Department of the Tenkodogo Regional Hospital, located in the east of Burkina Faso. All patients over 15 years of age who were diagnosed with primary urological cancer were included. RESULTS: A total of 160 patients were included. One hundred and thirty-one patients were male (81.9%). The sex ratio was 4.5. The average age of the patients was 58.9 years (standard deviation: 18 years). We found 73 cases of prostate cancers (45.6%), 53 bladder cancers (33.1%), 17 kidney cancers (10.6%), 11 testicular cancers (6.9%) and 6 cancers of the male external genitalia (3.7%). The histological types of prostate cancer were adenocarcinoma (88%) and neuroendocrine carcinoma (12%). Thirty-seven prostate cancers (50.7%) were diagnosed at the T3 stage and 12 others (16.4%) at the T4 stage. Prostate cancer treatment was only medical in 23 patients; surgical treatment was indicated in 50 other patients. The 5-year survival was 85%. Sixteen patients (30.2%) had metastatic bladder cancer at the time of diagnosis. The treatment of vesical cancers has been palliative in 50 cases.

[Endocrine tumours in Stockholm - increasing general incidence]. / Incidensökning av endokrina tumörer - Kraftig ökning av diagnostiserade tumörer i sköldkörtel, bisköldkörtel och binjure i stockholm mellan 1992 och 2017.

In recent years, a significantly increased incidence of endocrine tumours has been observed worldwide, not least papillary thyroid cancer - with improved diagnostics and various biological factors being two possible causes of the upsurge. In this material from the Karolinska University Hospital, to date the largest tertiary endocrine surgery unit in the Nordic region, we see a near five-fold increase in the number of diagnosed thyroid cases and a distinct rise in the incidence of tumour cases in the thyroid, parathyroid and adrenal glands. The increase can only partly be explained by an accommodation of patients to tertiary units and should therefore be considered as a true increase in incidence across the Swedish population. Our findings therefore verify the international reports regarding a surge in endocrine tumours and highlight the need for efficient patient care - from diagnosis to treatment.

Linking obesity-induced leptin-signaling pathways to common endocrine-related cancers in women.

Obesity is related to many major diseases and cancers. Women have higher rates of obesity and obesity is linked to commonly occurring cancers in women. However, there is a lack of knowledge of the unique mechanism(s) involved in each type of cancer. The objective of this review is to highlight the need for novel experimental approaches and a better understanding of the common and unique pathways to resolve controversies regarding the role of obesity in cancer. In women, there is a link between hormones and obesity-associated genes in cancer development. Leptin is an obesity-associated gene that has been studied extensively in cancers; however, whether the defect is in the leptin gene or in its signaling pathways remains unclear. Both leptin and its receptor have been positively correlated with cancer progression in some endocrine-related cancers in women. This review offers an up-to-date and cohesive review of both upstream and downstream pathways of leptin signaling in cancer and a comprehensive picture of cancer pathogenesis in light of current evidence of leptin effects in several major types of cancer. This work is intended to aid in the design of better therapeutic strategies for obese/overweight women with cancer.

Dietary Intake of Omega-3 fatty acids and Endocrine-related Gynecological Cancer: A Meta-Analysis of Observational Studies.

PURPOSE: Previous observational epidemiological studies have reported inconsistent findings on the association between dietary intake of omega-3 fatty acids and endocrine-related gynecological cancer such as ovarian cancer and endometrial cancer. This study aimed to investigate this association using a meta-analysis of observational studies. MATERIALS AND METHODS: We searched PubMed, EMBASE, and Cochrane library by using key words related with the topic in April 2017. The pooled odd ratios (pORs), relative risks (pRRs), or hazard ratios (pHRs) with 95% confidence intervals (CIs) were calculated based on the random-effects model. Also, we performed subgroup meta-analysis by methodological quality, types of cancer, study design, and omega-3 fatty acids. RESULTS: A total of ten observational studies with six case-control and four cohort studies were included in the final meta-analysis. In the meta-analysis of all the studies, dietary intake of total omega-3 fatty acids was not significantly associated with the risk of endometrial and ovarian cancers (pOR/HR, 0.87; 95% CI, 0.73-1.04; I2=67.2%) (highest versus lowest intake). In the subgroup meta-analysis by type of study, there was no significant association between them in cohort studies (pHR, 1.03; 95% CI, 0.63-1.67, I2=81.9%), whereas its reduced risk was observed in case-control studies (pOR, 0.81; 95% CI, 0.67 to 0.98, I2=55.7%). CONCLUSION: The current meta-analysis of observational studies suggests that there is no higher level of evidence to support the protective effect of dietary omega-3 fatty acids on endocrine-related gynecological cancer. Further prospective studies should be conducted to confirm the association.

Germline variants in familial pituitary tumour syndrome genes are common in young patients and families with additional endocrine tumours.

OBJECTIVE: Familial pituitary tumour syndromes (FPTS) account for 5% of pituitary adenomas. Multi-gene analysis via next-generation sequencing (NGS) may unveil greater prevalence and inform clinical care. We aimed to identify germline variants in selected patients with pituitary adenomas using a targeted NGS panel. DESIGN: We undertook a nationwide cross-sectional study of patients with pituitary adenomas with onset ≤40 years of age and/or other personal/family history of endocrine neoplasia. A custom NGS panel was performed on germline DNA to interrogate eight FPTS genes. Genome data were analysed via a custom bioinformatic pipeline, and validation was performed by Sanger sequencing. Multiplex ligation-dependent probe amplification (MLPA) was performed in cases with heightened suspicion for MEN1, CDKN1B and AIP mutations. The main outcomes were frequency and pathogenicity of rare variants in AIP, CDKN1B, MEN1, PRKAR1A, SDHA, SDHB, SDHC and SDHD. RESULTS: Forty-four patients with pituitary tumours, 14 of whom had a personal history of other endocrine tumours and/or a family history of pituitary or other endocrine tumours, were referred from endocrine tertiary-referral centres across Australia. Eleven patients (25%) had a rare variant across the eight FPTS genes tested: AIP (p.A299V, p.R106C, p.F269F, p.R304X, p.K156K, p.R271W), MEN1 (p.R176Q), SDHB (p.A2V, p.S8S), SDHC (p.E110Q) and SDHD (p.G12S), with two patients harbouring dual variants. Variants were classified as pathogenic or of uncertain significance in 9/44 patients (20%). No deletions/duplications were identified in MEN1, CDKN1B or AIP. CONCLUSIONS: A high yield of rare variants in genes implicated in FPTS can be found in selected patients using an NGS panel. It may also identify individuals harbouring more than one rare variant.

Endocrine neoplasms in familial syndromes of hyperparathyroidism.

Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential.

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.

Lithium treatment and cancer incidence in bipolar disorder.

OBJECTIVES: To investigate whether there is an increased risk of cancer associated with lithium treatment in patients with bipolar disorder compared to the general population. METHODS: A nationwide Swedish register study of incidence rate ratios (IRRs) of total cancer and site-specific cancer in the 50-84-year age range was carried out in patients with bipolar disorder (n = 5,442) with and without lithium treatment from July 2005 to December 2009 compared to the general population using linked information from The Swedish Cancer Register, The National Patient Register, and The Drug Prescription Register. RESULTS: The overall cancer risk was not increased in patients with bipolar disorder. There was no difference in risk of unspecified cancer, neither in patients with lithium treatment compared to the general population [IRR = 1.04, 95% confidence interval (CI): 0.89-1.23] nor in patients with bipolar disorder without lithium treatment compared to the general population (IRR = 1.03, 95% CI: 0.89-1.19). The cancer risk was significantly increased in patients with bipolar disorder without lithium treatment in the digestive organs (IRR = 1.47, 95% CI: 1.12-1.93), in the respiratory system and intrathoracic organs (IRR = 1.72, 95% CI: 1.11-2.66), and in the endocrine glands and related structures (IRR = 2.60, 95% CI: 1.24-5.47), but in patients with bipolar disorder with lithium treatment, there was no significantly increased cancer risk compared to the general population. CONCLUSIONS: Bipolar disorder was not associated with increased cancer incidence and neither was lithium treatment in these patients. Specifically, there was an increased risk of respiratory, gastrointestinal, and endocrine cancer in patients with bipolar disorder without lithium treatment.

Venous thromboembolism and risk of cancer in patients with diabetes mellitus.

AIM: Venous thromboembolism (VTE) has long been regarded as a marker of underlying malignancy in the general population. Patients with diabetes mellitus are at increased risk of developing VTE, but it is unclear whether VTE in diabetes patients is also a harbinger of occult cancer. METHODS: From Danish medical health databases, we identified all diabetes patients (N=8783) with a first-time diagnosis of VTE during 1978-2011. We followed the patients until a first-time diagnosis of cancer, emigration, death, or study end, whichever came first. We calculated one-year absolute cancer risk and overall and site-specific standardized incidence ratios (SIRs) for cancer based on national cancer incidence. RESULTS: During the total study period 878 cancers were observed. The one-year absolute cancer risk was 4.1% and the corresponding SIR was 3.28 (95% confidence interval [CI]: 2.94-3.64). The highest SIRs were observed for cancers of the gallbladder and biliary tract (SIR 13.59; 6.77-24.31), the pancreas (SIR 10.16; 6.85-14.50), the ovary (SIR 9.85; 5.63-16.00), and the liver (SIR 9.39; 4.30-17.84). After the first year of follow-up, the overall cancer SIR associated with VTE and diabetes decreased to 1.05 (95% CI: 0.97-1.15). CONCLUSIONS: VTE may be a marker of underlying cancer in patients with diabetes mellitus.

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.

Neuroendocrine tumor imaging with 68Ga-DOTA-NOC: physiologic and benign variants.

OBJECTIVE: Imaging with (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotide analogs has become an important modality in patients with neuroendocrine tumors (NETs). In addition to high uptake in NET lesions, prominent physiologic radiotracer activity has been reported in the pituitary gland, pancreas, adrenal glands, liver, and spleen, and faint activity has been reported in the thyroid and gastrointestinal tract. This article describes previously unknown sites of 68Ga-DOTA-1-NaI3-octreotide (NOC) uptake unrelated to NETs. MATERIALS AND METHODS: One hundred eighty-two patients (96 female and 86 male patients; age range, 4-89 years) with documented (n=156) or suspected (n=26) NETs underwent 207 68Ga-DOTA-NOC PET/CT studies. Studies were retrospectively reviewed for the presence, intensity, and localization of foci of increased uptake that were further correlated with findings on additional imaging studies and clinical follow-up for a period of 4-32 months. RESULTS: Uptake of 68Ga-DOTA-NOC not identified as NET or known physiologic activity was detected in 297 sites with confirmation in 149 of 207 studies (72%). The most common location of non-NET-related 68Ga-DOTA-NOC-avid sites was in small lymph nodes, followed by prostate, uterus, breasts, lungs, brown fat, musculoskeletal system, and other sites, including oropharynx, pineal body, thymus, aortic plaque, genitalia, surgical bed, and subcutaneous granuloma. Intensity of uptake in non-NET-related 68Ga-DOTA-NOC-avid sites ranged in maximum standardized uptake value from 0.8 to 10.5. CONCLUSION: Previously unreported benign sites of 68Ga-DOTA-NOC uptake were found in the majority of studies, suggesting the presence of somatostatin receptors in physiologic variants or processes with no evidence of tumor. Knowledge of increased tracer uptake in non-NET-related sites is important for accurate interpretation and for avoiding potential pitfalls of 68Ga-DOTA-NOC PET/CT.

Endocrine tumours: epidemiology of malignant digestive neuroendocrine tumours.

Little is known about patients with malignant digestive neuroendocrine tumours (MD-NETs). Although their incidence is increasing, MD-NETs remain a rare cancer, representing 1% of digestive cancers. Most MD-NETs are well-differentiated. MD-NET poorly differentiated carcinomas account for 20% of cases on average. Anatomical localisation of MD-NETs varied according to geographic region. Stage at diagnosis and prognosis for patients with MD-NETs in the general population are considerably worse than often reported from small hospital case series. Prognosis varies with tumour differentiation, anatomic site and histological subtype. There are significant differences in survival from MD-NETs among European countries, independent of other prognostic factors. Early diagnosis is difficult; new therapeutic options appear to represent the best approach to improving prognosis.

Predicting the risk of multiple endocrine neoplasia type 1 for patients with commonly occurring endocrine tumors.

OBJECTIVE: Endocrine diseases that can be part of the rare inheritable syndrome multiple endocrine neoplasia type 1 (MEN1) commonly occur in the general population. Patients at risk for MEN1, and consequently their families, must be identified to prevent morbidity through periodic screening for the detection and treatment of manifestations in an early stage. The aim of the study was to develop a model for predicting MEN1 in individual patients with sporadically occurring endocrine tumors. DESIGN: Cross-sectional study. METHODS: In a nationwide study in The Netherlands, patients with sporadically occurring endocrine tumors in whom the referring physician suspected the MEN1 syndrome were identified between 1998 and 2011 (n=365). Logistic regression analysis with internal validation using bootstrapping and external validation with a cohort from Sweden was used. RESULTS: A MEN1 mutation was found in 15.9% of 365 patients. Recurrent primary hyperparathyroidism (pHPT; odds ratio (OR) 162.40); nonrecurrent pHPT (OR 25.78); pancreatic neuroendocrine tumors (pNETs) and duodenal NETs (OR 17.94); pituitary tumor (OR 4.71); NET of stomach, thymus, or bronchus (OR 25.84); positive family history of NET (OR 4.53); and age (OR 0.96) predicted MEN1. The c-statistic of the prediction model was 0.86 (95% confidence interval (95% CI) 0.81-0.90) in the derivation cohort and 0.77 (95% CI 0.66-0.88) in the validation cohort. CONCLUSION: With the prediction model, the risk of MEN1 can be calculated in patients suspected for MEN1 with sporadically occurring endocrine tumors.

Carcinoma of endocrine organs: results of the RARECARE project.

The rarity or the asymptomatic character of endocrine tumours results in a lack of epidemiological studies on their incidence and survival patterns. The aim of this study was to describe the incidence, prevalence and survival of endocrine tumours using a large database, which includes cancer patients diagnosed from 1978 to 2002, registered in 89 population-based cancer registries (CRs) with follow-up until 31st December 2003. These data give an unique overview of the burden of endocrine carcinomas in Europe. A list of tumour entities based on the third International Classification of Diseases for Oncology was provided by the project Surveillance of rare cancer in Europe (RARECARE) project. Over 33,594 cases of endocrine carcinomas were analysed in this study. Incidence rates increased with age and were highest in patients 65 years of age or older. In 2003, more than 315,000 persons in the EU (27 countries) were alive with a past diagnosis of a carcinoma of endocrine organs. The incidence of pituitary carcinoma equalled four per 1,000,000 person years and showed the strongest decline in survival with increasing age. Thyroid cancer showed the highest crude incidence rates (four per 100,000 person years) and was the only entity with a gender difference: (female-to-male ratio: 2:9). Parathyroid carcinoma was the rarest endocrine entity with two new cases per 10,000,000 person years. For adrenal carcinoma, the most remarkable observations were a higher survival for women compared to men (40% compared to 32%, respectively) and a particularly low relative survival of 24% in patients 65 years of age or older. More high quality studies on rare cancers, with additional information, e.g. on stage and therapeutic approach, are needed and may be of help in partly explaining the observed variation in survival.