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Simple Summary: Pancreatic cancer is one of the most lethal digestive cancers and is becoming more common over the decades. The analysis of prognostic factors for survival could help to evaluate the existing treatments and find better treatment options. Our retrospective study analyzed data from 2117 patients issued from a digestive tumor registry. Age, surgery, chemotherapy, radiotherapy, and metastasis location are prognostic factors correlated with overall survival. Although this study is retrospective, our data were collected across multiple sites and reflect the outcomes of the management of patients with pancreatic cancer over a long period. Pancreatic cancer is associated with high mortality rates, and most cases are diagnosed at advanced stages. This study aimed to evaluate the prognostic factors for survival in pancreatic adenocarcinoma. Data from the Finistere registry of digestive database were used in this analysis. This retrospective population-based study included 2117 patients with pancreatic adenocarcinoma diagnosed between 2005 and 2019. Cox regression was used to assess the impact of different prognostic factors. The overall median age was 74 (IQR 65.0–81.0). The majority of pancreatic adenocarcinoma 1120 (52.90%) occurred in the head of the pancreas. The type of surgical resection correlated with age (pancreaticoduodenectomy performed in 13.39% of patients aged under 65 years and only 1.49% of patients aged ≥ 80 years). For the entire cohort, 1-year mortality rate after diagnosis was 77.81%. Chemotherapy was associated with better survival for both operated (HR 0.17 95% CI 0.22; 0.64 p < 0.001) and unoperated patients (HR 0.41 95% CI 0.27; 0.61 p < 0.001). Palliative radiotherapy was associated with improved survival (HR 0.69 95% CI 0.56; 0.85 p < 0.001). Among operated patients, the presence of lung metastases (median 34.06; CI 20.06; 34.66) was associated with better survival compared with liver metastases (median 21.10; CI 18.10; 28.96), peritoneal carcinomatosis (median 11.00; CI 8.53; 14.63), or distant metastases (median 15.16; CI 12.66; 18.13) (p = 0.0001). Age, curative surgery, positive lymph nodes, chemotherapy, and palliative radiotherapy were corelated with overall survival. Surgical resection is the only potentially curative treatment, but less than a quarter of patients were eligible. [ABSTRACT FROM AUTHOR]

Simple Summary: In addition to the age and comorbidities of elderly patients, the presence of a metastatic disease makes the choice of therapeutic options difficult. Our retrospective study aimed to determine the predictive factors for survival in patients aged 80 years and older with metastatic colon cancer. We analyzed data of 1115 patients issued from four digestive tumor registries. Comorbidity burden, metastasis location, chemotherapy, and curative surgery of primary tumors and metastases are prognostic factors correlated with overall survival. Although this study is retrospective, our data were collected across multiple sites and reflect the outcomes of the management of elderly patients with metastatic colon cancer. Oncological strategies in the elderly population are debated. The objective of this study was to determine the predictive factors of survival in patients aged 80 years and older with metastatic colon cancer. Data from four digestive tumour registry databases were used in this analysis. This population-based retrospective study included 1115 patients aged 80 years and older with stage IV colon adenocarcinoma diagnosed between 2007 and 2016. Cox regression was used to assess the impact of different prognostic factors. Age was significantly correlated with the surgical treatment (p < 0.001) but not with overall survival. Patients with a low comorbidity burden had better survival than patients with higher comorbidities scores (9.4 (0–123) versus 7.9 (0–115) months) (p = 0.03). Surgery was more common for proximal colon cancer (p < 0.001), but the location of the primary lesion was not correlated with improved survival (p = 0.07). Patients with lung metastases had a better prognosis than those with liver metastases (HR 0.56 95% CI 0.40, 0.77 p < 0.001); multiple organ involvement had the worst survival (HR 1.32 95% CI 1.15, 1.51 p < 0.001). Chemotherapy was associated with improved survival for both operated (HR 0.45 95% CI 0.35, 0.58 p < 0.001) and non-operated patients (HR 0.41 95% CI 0.34, 0.50 p < 0.001). The majority of patients receiving adjuvant treatment had a low comorbidity burden. In our study, the location of metastases but not the primary tumor location had an impact on overall survival. Low comorbidity burden, curative surgery, and chemotherapy had a significant advantage for elderly patients with metastatic colon cancer. [ABSTRACT FROM AUTHOR]

The GMO90+ project was designed to identify biomarkers of exposure or health effects in Wistar Han RCC rats exposed in their diet to 2 genetically modified plants (GMP) and assess additional information with the use of metabolomic and transcriptomic techniques. Rats were fed for 6-months with 8 maize-based diets at 33% that comprised either MON810 (11% and 33%) or NK603 grains (11% and 33% with or without glyphosate treatment) or their corresponding near-isogenic controls. Extensive chemical and targeted analyses undertaken to assess each diet demonstrated that they could be used for the feeding trial. Rats were necropsied after 3 and 6 months. Based on the Organization for Economic Cooperation and Development test guideline 408, the parameters tested showed a limited number of significant differences in pairwise comparisons, very few concerning GMP versus non-GMP. In such cases, no biological relevance could be established owing to the absence of difference in biologically linked variables, dose-response effects, or clinical disorders. No alteration of the reproduction function and kidney physiology was found. Metabolomics analyses on fluids (blood, urine) were performed after 3, 4.5, and 6 months. Transcriptomics analyses on organs (liver, kidney) were performed after 3 and 6 months. Again, among the significant differences in pairwise comparisons, no GMP effect was observed in contrast to that of maize variety and culture site. Indeed, based on transcriptomic and metabolomic data, we could differentiate MON- to NK-based diets. In conclusion, using this experimental design, no biomarkers of adverse health effect could be attributed to the consumption of GMP diets in comparison with the consumption of their near-isogenic non-GMP controls. [ABSTRACT FROM AUTHOR]

Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The fetal testes are essential for canonical androgen production, but little is known about the synthesis of backdoor androgens, despite their known critical role in masculinization. In this study, we have measured plasma and tissue levels of endogenous steroids in second trimester human fetuses using multidimensional and high-resolution mass spectrometry. Results show that androsterone is the principal backdoor androgen in the male fetal circulation and that DHT is undetectable (<1 ng/mL), while in female fetuses, there are significantly lower levels of androsterone and testosterone. In the male, intermediates in the backdoor pathway are found primarily in the placenta and fetal liver, with significant androsterone levels also in the fetal adrenal. Backdoor intermediates, including androsterone, are only present at very low levels in the fetal testes. This is consistent with transcript levels of enzymes involved in the alternate pathway (steroid 5α-reductase type 1 [SRD5A1], aldo-keto reductase type 1C2 [AKR1C2], aldo-keto reductase type 1C4 [AKR1C4], cytochrome P450 17A1 [CYP17A1]), as measured by quantitative PCR (qPCR). These data identify androsterone as the predominant backdoor androgen in the human fetus and show that circulating levels are sex dependent, but also that there is little de novo synthesis in the testis. Instead, the data indicate that placental progesterone acts as substrate for synthesis of backdoor androgens, which occurs across several tissues. Masculinization of the human fetus depends, therefore, on testosterone and androsterone synthesis by both the fetal testes and nongonadal tissues, leading to DHT formation at the genital tubercle. Our findings also provide a solid basis to explain why placental insufficiency is associated with disorders of sex development in humans. [ABSTRACT FROM AUTHOR]

Body mass index is a known breast cancer risk factor due to, among other mechanisms, adipose-derived hormones. We developed a method for steroid hormone profiling in adipose tissue to evaluate healthy tissue around the tumor and define new biomarkers for cancer development. A semi-automated sample preparation method based on gel permeation chromatography and subsequent derivatization with trimethylsilyl (TMS) is presented. Progestagens and androgens were determined by GC-EI-MS/MS (LOQ 0.5 to 10 ng/g lipids). For estrogen measurement, a highly sensitive GC-APCI-MS/MS method was developed to reach the required lower limits of detection (0.05 to 0.1 ng/g lipids in matrix, 100-200 fg on column for pure standards). The combination of the two methods allows the screening of 27 androgens and progestagens and 4 estrogens from a single sample. Good accuracies and repeatabilities were achieved for each compound class at their respective limit of detection. The method was applied to determine steroid hormone profiles in adipose tissue of 51 patients, collected both at proximity and distant to the tumor. Out of the 31 tested steroid hormones, 14 compounds were detected in human samples. Pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone (DHEA), and androstendione accounted together for 80% of the observed steroid hormone profiles, whereas the estrogens accounted for only 1%. These profiles did not differ based on sampling location, except for ß-estradiol; steroid hormone conversions from androgens to estrogens that potentially take place in adipose or tumoral tissue might not be detectable due a factor 100 difference in concentration of for example DHEA and ß-estradiol. [ABSTRACT FROM AUTHOR]

Humans are significantly exposed to phthalates via food packaging, cosmetics and medical devices such as tubings and catheters. Testicular Leydig cells (LCs) are suggested to be among the main targets of phthalate toxicity in the body. However, their sensitivity to phthalates is species-dependent. This paper describes the response of the LCs from different species (mouse, rat and human) to phthalate exposure in different experimental paradigms (in vivo, ex vivo and in vitro), with particular focus on mechanisms of phthalate action on LC steroidogenesis. A comprehensive analysis of the impact of phthalate diesters and phthalate monoesters on LCs in different stages of their development is presented and possible mechanisms of phthalates action are discussed. Finally novel, not yet fully elucidated sites of action of phthalate monoesters on the backdoor pathway of 5α-dihydrotestosterone biosynthesis in immature mouse LCs and their effects on steroidogenesis and redox state in adult mouse LCs are reported. [ABSTRACT FROM AUTHOR]

Study Question: Do sex and maternal smoking effects on human fetal anogenital distance (AGD) persist in a larger study and how do these data integrate with the wider literature on perinatal human AGD, especially with respect to sex differences?Summary Answer: Second trimester sex differences in AGD are broadly consistent with neonatal and infant measures of AGD and maternal cigarette smoking is associated with a temporary increase in male AGD in the absence of changes in circulating testosterone.What Is Known Already: AGD is a biomarker of fetal androgen exposure, a reduced AGD in males being associated with cryptorchidism, hypospadias and reduced penile length. Normative fetal AGD data remain partial and windows of sensitivity of human fetal AGD to disruption are not known.Study Design, Size, Duration: The effects of fetal sex and maternal cigarette smoking on the second trimester (11-21 weeks of gestation) human fetal AGD were studied, along with measurement of testosterone and testicular transcripts associated with apoptosis and proliferation.Participants/materials, Setting Methods: AGD, measured from the centre of the anus to the posterior/caudal root of penis/clitoris (AGD(app)) was determined in 56 female and 70 male morphologically normal fetuses. These data were integrated with current literature on perinatal AGD in humans.Main Results and the Role Of Chance: At 11-13 weeks of gestation male fetal AGD(app) was 61% (P< 0.001) longer than in females, increasing to 70% at 17-21 weeks. This sexual dimorphism was independent of growth characteristics (fetal weight, length, gonad weight). We confirmed that at 14-16 weeks of gestation male fetal AGD(app) was increased 28% (P < 0.05) by in utero cigarette smoke exposure. Testosterone levels were not affected by smoking. To develop normative data, our findings have been integrated with available data from in vivo ultrasound scans and neonatal studies. Inter-study variations in male/female AGD differences lead to the conclusion that normalization and standardization approaches should be developed to enable confidence in comparing data from different perinatal AGD studies.Limitations, Reasons For Caution: Sex differences, and a smoking-dependent increase in male fetal AGD at 14-16 weeks, identified in a preliminary study, were confirmed with a larger number of fetuses. However, human fetal AGD should, be re-assessed once much larger numbers of fetuses have been studied and this should be integrated with more detailed analysis of maternal lifestyle. Direct study of human fetal genital tissues is required for further mechanistic insights.Wider Implications Of the Findings: Fetal exposure to cigarette smoke chemicals is known to lead to reduced fertility in men and women. Integration of our data into the perinatal human AGD literature shows that more work needs to be done to enable reliable inter-study comparisons.Study Funding/competing Interests: The study was supported by grants from the Chief Scientist Office (Scottish Executive, CZG/1/109 & CZG/4/742), NHS Grampian Endowments (08/02), the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 212885 and the Medical Research Council, UK (MR/L010011/1). The authors declare they have no competing interests, be it financial, personal or professional. [ABSTRACT FROM AUTHOR]

The efficiency of the administration of recombinant bovine growth hormone (rbGH) to enhance fish growth has been widely reported in the literature. Although its use is probable and has been described in several countries, rbGH is prohibited in the European Union (Council Decisions 1994/936/EC, 1999/879/EC). In this context, an analytical strategy was optimised in order to identify rbGH-treated fish. Currently, one of the most difficult challenges for the detection of rbGH in fish is probably the choice of the matrix and the corresponding available quantity for analysis. Therefore, based on a previous efficient protocol developed for mammalian species, a method was adapted for very limited serum volume (50 µl) and was successfully implemented to analyse serum collected from seven trout treated with rbGH. The detection of rbGH was possible from the very first day after administration and the hormone could easily be identified at least for 1 month with levels in the range 5–10 µg ml−1. The limits of detection (LODs) estimated around 0.5 µg ml−1rbGH in fish serum are far below observed concentrations in incurred samples and therefore attest to the relevance of the developed protocol. [ABSTRACT FROM PUBLISHER]

Oxolinic acid, flumequine, oxytetracycline, and florfenicol are antibiotics commonly used in farming. Because an important percentage of these antibiotics given to fish and cattle ends up, directly or indirectly, in the freshwater environment, suitable tools for the monitoring of these antibiotics are needed. A French river was chosen because of the location of four fish farms and a sewage plant on its main course. First, a passive monitoring program involving water, sediment, and autochthonous bryophytes was performed at 25 sampling sites tested once every three months for one year. Second, an active monitoring method was performed using moss bags for a one-month exposure period, both upstream and downstream of each potential source of antibiotics. Sediment and bryophyte samples, but not water samples, were found to be useful for monitoring environmental contamination by oxolinic acid, flumequine, oxytetracycline, and florfenicol. Sediments and bryophytes also appeared to be complementary media for dating the river's contamination by antibiotics. Data collected by both active and passive monitoring methods confirmed contamination of the river, mainly by flumequine and oxytetracycline, attributable to fish farming but also to terrestrial animal farming and perhaps human pharmaceuticals. [ABSTRACT FROM AUTHOR]