Specificities of small cell neuroendocrine prostate cancer: Adverse prognostic value of TTF1 expression

ObjectivesTo determine whether small cell neuroendocrine prostate cancers (NEPCa) emerging after anti-androgen treatments are different from the rarest cases diagnosed de novo, and to identify effective predictive markers.Material and methodsThe expression of neuroendocrine markers, androgen receptor (AR) and androgen-regulated genes, as well as markers of aggressiveness, were analyzed by immunohistochemistry on a tissue microarray containing samples of 30 sNEPCa, either pure or admixed with conventional PCa, and including 14 cases diagnosed de novo and 16 cases subsequent to prior androgen deprivation.ResultsChromogranin A is a better marker of NE differentiation than synaptophysin in post-treatment NEPCa, with 94% and 44% of positive tumors, respectively, while both markers are equally expressed in de novo cases. Despite the acquisition of a NE phenotype, more than half of NEPCa expressed AR and the androgen-regulated gene NKX3.1, more frequently in cases admixed with conventional PCa. TTF1 staining, present in half of NEPCa, was associated with loss of androgen-regulated genes and with markers of aggressiveness, including increased proliferation, Zeb1 expression and PTEN loss. In multivariate analysis, only TTF1 expression was significantly associated with shorter overall survival.ConclusionThese results suggest the persistence of androgen signaling in a number of NEPCa cases, and the interest of TTF1 staining as a predictive biomarker.     

Modified Fasting Compared to True Fasting Improves Blood Glucose Levels and Subjective Experiences of Hunger,Food Cravings and Mental Fatigue,But Not Cognitive Function: Results of an Acute Randomised Cross-Over Trial

Recent dietary trends have prompted growing support for a variety of fasting paradigms involving extreme restriction or nil-caloric intake on fasting days. Some studies indicate that fasting may negatively influence factors including cognitive function through inducing fatigue, which may prove problematic in the context of completing a range of cognitively demanding activities required by daily obligations such as work. This randomised within-subjects cross-over trial explored the effects of true fasting (i.e., nil-caloric intake) versus modified fasting, the latter of which involved two sub-conditions: (1) extended distribution (three small meals distributed across the day; 522 kcal total); and (2) bulking (two meals eaten early in the day; 512 kcal total) over a period of 7.5 h on a single day with a 7-day washout period between conditions. Participants were n = 17 females (Body Mass Index (BMI) Mean (M) = 25.80, Standard Deviation (SD) = 2.30) aged 21–49 years. Outcomes included cognitive function, subjective mental fatigue, satiety, food cravings and blood glucose. Results showed that there were no differences in cognitive test performance between conditions;however, both modified fasting sub-conditions had improved blood glucose levels, cravings, hunger and fullness compared to true fasting. Moreover, subjective mental fatigue was significantly reduced in the modified fasting conditions relative to true fasting. Overall, results indicated that the subjective experience of true fasting and modified fasting is different, but that cognition does not appear to be impaired.     

A Comparison of Sugar Intake between Individuals with High and Low Trait Anxiety: Results from the NutriNet-Santé Study

(1) Background: Dietary carbohydrates are likely correlated with mental health in general, and with anxiety in particular. Our aim was to investigate the cross-sectional relationship between trait anxiety and carbohydrate (especially sugar) intake in a large sample derived from the general French population. (2) Methods: The analyses included 20,231 non-diabetic adults enrolled in the NutriNet-Santé e-cohort, who had completed the trait anxiety subscale of the Spielberger State-Trait Anxiety Inventory (T-STAI, 2013–2016) and who were subsequently divided into high and low trait anxiety groups (T-STAI cut-off of 40 points). Sugar-rich food and macronutrient intake was calculated from ≥3 self-administered 24-h dietary records. The association between trait anxiety and carbohydrate intake was evaluated by ANCOVA according to age category (<45 and ≥45 years). (3) Results: In the full sample, 7942 (39.3%) individuals fell into the high trait anxiety category. They were more likely to be women (82.2% versus 69.2%; p < 0.0001) and younger (mean age 51.6 versus 55.1 years; p < 0.0001) compared to the low trait anxiety group. In fully-adjusted models, high-anxiety individuals aged under 45 years had significantly higher mean consumption of added simple sugars (43.9 versus 42.3 g/d; p < 0.0007), whereas those aged over 45 years with high trait anxiety had significantly lower mean consumption of fruit (214.0 versus 219.5 g/d; p < 0.02) compared to their low-anxiety counterparts. (4) Conclusions: This cross-sectional study revealed modest age-specific associations between anxiety status and sugar intake among adults. Prospective studies with representative samples are needed to explore potential bi-directionality of the observed associations.     

Agricultural exposure and risk of bladder cancer in the AGRIculture and CANcer cohort

Purpose

Literature on agricultural activities and bladder cancer risk is scarce. However, farmers can be subjected to carcinogenic exposure (e.g. arsenic, previously used as a pesticide in France). This study aimed at assessing the role of a large range of agricultural activities and tasks on bladder cancer risk.

Methods

The study population was the AGRIculture and CANcer cohort, a large prospective cohort of individuals affiliated to the agricultural health insurance scheme (MSA) in France. Incident bladder cancers were identified by cancer registries from enrolment (2005–2007) to 2009. Data on agricultural exposure during professional lifetime (5 animals, 13 crops, specific tasks) were obtained from the enrolment questionnaire. Associations between bladder cancer and agricultural exposure were analysed using a Cox model, adjusted for gender and smoking history.

Results

Among the 148,051 farm owners and workers included in this analysis, 179 incident bladder cancers were identified. We observed an elevated risk among field-grown vegetable workers [HR 1.89, 95% CI (1.20–2.99)], with an exposure–response relationship with duration of work [≥30 years: HR 2.54, 95% CI (1.11–5.83), p-trend = 0.02], and higher risk among women [HR 3.82, 95% CI (1.58–9.25), p-interaction = 0.05]. Non-significantly increased risks were also observed in greenhouse farmers (HR = 1.95), pea sowing (HR = 1.84), rape sowing (HR = 1.64); several tasks involving pesticide use, especially seed treatment (HR = 1.24); and in activities and tasks potentially exposing to arsenic compounds via pesticide use (HR = 1.49) or re-entry tasks (HR = 1.63).

Conclusions

Our analyses raise the question of a possible link between agricultural activity, especially field-grown vegetables, and greenhouse cultivation and bladder cancer.

     

The testicular biopsy and spermatogenesis disturbance of infertile patients with bilateral varicocele

In this article we describe the examination and the results obtained in 221 patients subjected to surgical intervention, i.e. microsurgical bilateral varicocele or to the conventional Ivanisevich technique and systematic multiple and bilateral testicular biopsy at the scrotal examination. Testicular biopsy (TB) has been executed according to the microsurgical protocol in a standard way; in each of the testicles two different quadrants. Upper-internal and lower-external quadrants were used to establish the qualitative mean index. According to concentration of spermatozoa per milliliter of the sperm the patients were classified into 5 different biological groups: I group--azoospermia or extreme oligozoospermia 93 patients, II--severe oligozoospermia 43 patients, III--moderate oligozoospermia 23, IV--relative oligozoospermia 18, and V group--normozoospermia 44 patients. The results of testicular biopsies have been evaluated according to the biological group. In the group with azoospermia and the extreme oligozoospermia the TB has determined the degree of the spermatogenesis derangement in 92 cases, in the majority of cases--50 MA (maturation arrest) + SCOS (Sertoli Cell Only Syndrome) + tubular fibrosis. In many cases hypospermatogenesis is accompanied with MA, SCOS or testicular fibrosis. In this group the semen analysis generally demonstrates different variations of oligospermia. Incidence of maturation arrest was observed in 32 cases of total 221. Among the MA there are 7 cases of early stage spermatocyte I, MA spermatocyte II in 21 patients and MA spermatide (late arrest) in 4 cases. SCOS was observed in 20 patients. All the patients have secretory azoospermia. SCOS is also observed together with other disorders of spermatogenesis. Tubular and peritubular fibrose atrophy was observed in 5 cases. These are the patients with the antecedent criptorchidia.