Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas ...through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene.
Purpose of Review
The aim of this review is to sum up the state of the art of urachal carcinoma (UC) in order to easily guide clinicians.
Recent Findings
UC is a rare and aggressive disease with ...consequent few data about diagnosis and treatment. Dates are mainly based on retrospective trial and case reports with limited prospective trial. Clinical presentation is not specific, often with urinary symptoms. Diagnosis is mainly based on CT scan and MRI, useful to evaluate local invasion and nodal status and to detect the presence of distant metastases. Therefore, biopsy is needed to obtain histological confirmation. Surgery is the gold standard for localized disease, while different chemotherapy schemes have been used in metastatic setting.
Summary
Novel findings based on mutational analysis of the tumor include the use of biological treatment, such as cetuximab, and immunotherapy, such as atezolizumab, with satisfactory responses, suggesting that personalized treatment could be the most suitable option for UC.
Active and Environmental Tobacco Smoke (ETS) are a global cause of death. Osteoporosis (Op) is the most common metabolic bone disorder worldwide, impacting on mortality and disability, with high ...health and welfare costs. Active smoking is a known risk factor for Op, but there is few information regarding Op and ETS in men.
The study aim is to evaluate the association between smoking habits and Op in community-dwelling men that have been subjected to Dual-X-ray Absorptiometry and completed a questionnaire about their own and cohabiter's smoking habits.
We performed a cross-sectional study based on administrative data. This study is part of the SIMON protocol. The binary logistic regression analysis was used to estimate the role of ETS on the risk of Op, adjusting for age, body mass index (BMI), type 2 diabetes mellitus (T2DM) and eGFR.
Four hundred sixteen men were selected and, based on questionnaire replies, 167 were classified as current smokers (CS), 93 as passive smokers (PS) and 156 as never smokers (NS). NS showed a lower prevalence of past fragility fracture, radiological features of osteoporosis and hypovitaminosis D compared to PS and CS (p < 0.05). NS showed a lower prevalence of Op compared to PS and CS, also after correction for age, BMI, T2DM and eGFR (p < 0.05).
The study results demonstrate that PS and CS have a higher risk of Op, fragility fractures and vitamin D deficiency compared to NS.
En France, des dizaines de milliers d’enfants et d’adolescents sont en surpoids. La majorité n’a qu’un excès de quelques kg, mais un petit nombre rentre dans la définition de « superobésité », ce qui ...correspond à un IMC de 50 à l’âge adulte. Les défauts métaboliques ne sont pas le problème principal de ces adolescents. Progressivement désocialisés, ils ne forment plus aucun projet d’avenir, et n’imaginent pas pouvoir se sortir un jour de leur état. De 1995 à 2010 nous avons pris en charge une grande cohorte d’enfants obèses : plus de 90 % ne purent stabiliser leur poids, ni améliorer de façon perceptible les conséquences de l’obésité. En 2010, nous avons tiré les conséquences de nos échecs, en décidant de consacrer notre effort à la très grande obésité. Après une expérience de pose d’anneaux gastriques, nous avons abandonné cette technique pour concentrer notre offre de soins sur un programme de sleeve gastrectomie par trocart unique. Indications : prédiction d’un poids supérieur à 120 kg à 16–18 ans, échec de la prise en charge classique. Procédure : parcours d’un an avec consultations et hospitalisations de jour. Détection des complications. Décision finale selon une procédure RCP. À trois années de la mise en place du programme, notre unité assure maintenant une trentaine d’interventions par an. Les résultats ont été brillants, sans complications à ce jour et surtout la perception par tous les patients d’une amélioration de la qualité de vie. L’évidence d’une obésité massive, résistante, évoluant rapidement à l’adolescence, est devenue notre indication.
Childhood and adolescent obesity has been defined as a planetary epidemic by WHO “globesity”. The obesogenic environment, defined as a life environment promoting a high-energy intake and a sedentary ...lifestyle, significantly contributes to the genesis and the diffusion of the globesity. In the last decades, several authors and working groups tried to develop methodological instruments in order to guarantee a reliable analysis of an obesogenic environment. Their efforts have led to the production of a relatively large number of questionnaires with different characteristics. The general aim of these questionnaires is to identify the factors that significantly contribute to the creation of an obesogenic environment around children and adolescents. As a result of this work, a number of studies were carried out using such questionnaires. Aim of this review is to evaluate ad hoc questionnaires useful to identify and analyze obesogenic environment.
The search was carried out in February–March 2017 using the PubMed-Medline and Scopus databases (time interval: the last 10 years). After the selection and verification phases, a total of 14 studies were selected and therefore included in the present review.
The questionnaires constructed and validated to analyze multiple constitutive elements of an obesogenic environment at the same time are complex and must be administered by qualified and trained staff. On the other hand, when two or more questionnaires are used to analyze different factors, the questionnaires used are generally shorter, self-administered, and generally easier to understand and interpret.
•An obesogenic environment is an environment promoting high energy intake and sedentary behavior.•The primary and secondary prevention of childhood obesity is linked to the identification of the factors promoting an obesogenic environment.•The obesogenic environment is generally analyzed using ad hoc questionnaires.•Internet is among the factors that may promote an obesogenic environment but also is a potential powerful instrument for primary and secondary prevention of childhood obesity.
Background/aim
To study the characteristics of interleukin 6 (IL6), soluble form of interleukin 6 receptor (sILR)/IL6 complex in obese children and adolescents and its relationship with insulin ...resistance (IR).
Subjects and methods
66 obese children and adolescents 34 boys, mean age 10.3 ± 2.9 years,
z
-score of body mass index (BMI) 4.76 ± 1.36 and 24 non-obese healthy sex- and age-matched controls. Fasting levels of glucose, insulin, IL6, sIL6, sgp130 were measured. IR was assessed by homeostasis model assessment of IR (HOMA-IR).
Results
Obese subjects showed increased levels of insulin and IL-6 and higher HOMA-IR compared to controls (117.67 ± 50.9 vs. 62.42 ± 29.4 pmol/L, 2.73 ± 0.98 vs. 1.07 ± 0.41 pg/ml and 4.03 ± 2.16 vs. 1.83 ± 1.05 for insulin, IL-6 and HOMA-IR, respectively,
p
< 0.01 in all cases). sIL-6R levels were significantly lower in obese subjects (34.7 ± 14.2 vs. 55.6 ± 15.2 ng/ml in controls,
p
= 0.005), whereas sgp130 levels were not significantly different. In obese subjects, IL-6 directly correlated with
z
-score BMI (
r
= 0.481,
p
= 0.009) and with waist-to-height ratio (
r
= 0.494,
p
= 0.007), while sIL6-R was inversely related to HOMA-IR (
r
= −0.522,
p
= 0.002). Insulin resistant subjects showed higher levels of IL6 and lower levels of sIL6R (3.31 ± 0.72 vs. 2.25 ± 0.64 pg/ml,
p
= 0.020 and 25.3 ± 9.3 vs. 42.5 ± 10.4 ng/ml,
p
= 0.013, respectively).
Conclusions
In obese children and adolescents, IR is associated with elevated levels of IL-6 and diminished values of sIL-6R.
Background. Metabolic syndrome (MetS) and nephrolithiasis (NL) are quite common disorders. While some of the components of MetS have been proposed as precursors of NL in population studies, no data ...are available about the possible association between NL and MetS as such. The primary objective of the study was to evaluate the relationship between MetS and NL. The secondary outcome was to examine the relationship between MetS single constitutive elements and NL considering the strict correlation occurring among these factors. Methods. We studied 2132 Caucasian inpatients of the ‘Spinelli’ Hospital in southern Italy (males/females = 0.95; mean age 63.8 ± 15.8 years; body mass index 26.1 ± 3.9 kg/m2). The MetS diagnosis was performed according to the Heart Association/National Heart, Lung, and Blood Institute criteria. The presence of NL was assessed by ultrasound examination of the kidneys and upper urinary tract. Results. Seven hundred twenty-five subjects (34.0%) had a positive diagnosis of MetS. Two hundred twenty subjects (10.3%) had echographic evidence of NL, while 199 subjects reported a past history of NL (9.3%). The presence of MetS, as well as the male sex, and the occurrence of a previous episode of NL (in male subjects only) were each independently related to echographic evidence of NL. Among the individual components of MetS, high blood pressure and abdominal obesity (in female individuals only) were also independently related to echographic evidence of NL. Conclusions. MetS is significantly associated with echographic evidence of NL. A gender-related difference in the clinical expression of NL was also observed.
A surgical approach of severe obesity in adolescents De Filippo, G; Pourcher, G; Bougnères, P
Archives de pédiatrie : organe officiel de la Société française de pédiatrie,
07/2015, Volume:
22, Issue:
7
Journal Article
Simple nodular goiter and Hashimoto's thyroiditis are 2 frequent nonmalignant thyroid diseases. Tobacco smoking has detrimental effects on the endocrine system and in particular on thyroid function ...and morphology. The objective of this cross-sectional study, involving 1800 Caucasian adults from a geographical area with mild iodine deficiency, was to evaluate the relationship between tobacco smoking, smoking cessation, and the prevalence of simple nodular goiter and Hashimoto's thyroiditis. Thyroid status was evaluated by ultrasonic exploration of the neck, measurement of FT3, FT4, TSH, antibodies against thyroid peroxidase and thyroglobulin, and urinary iodine excretion. The fine-needle aspiration biopsy of significant nodules was also performed. Smoking habits were evaluated by a specific questionnaire and the calculation of number of pack years. Both current and previous smokers showed an increased risk of simple nodular goiter compared to never smokers after adjustment for potential confounders and known goitrogen factors. Interestingly, the simple nodular goiter risk was similar for never smokers and for previous smokers declaring a time since cessation of smoking for more than 69 months. Smoking habit was not associated to an increased risk of Hashimoto's thyroiditis.Smoking appears to be an independent risk factor for simple nodular goiter but not for Hashimoto's thyroiditis in an area with mild iodine deficiency. A prolonged withdrawal of smoking dramatically reduces the risk of simple nodular goiter occurrence.
We hypothesized that activating KRAS mutations and inactivation of the liver kinase B1 (LKB1) oncosuppressor can cooperate to sustain NSCLC aggressiveness. We also hypothesized that the growth ...advantage of KRAS/LKB1 co-mutated tumors could be balanced by higher sensitivity to metabolic stress conditions, such as metformin treatment, thus revealing new strategies to target this aggressive NSCLC subtype.
We retrospectively determined the frequency and prognostic value of KRAS/LKB1 co-mutations in tissue specimens from NSCLC patients enrolled in the TAILOR trial. We generated stable LKB1 knockdown and LKB1-overexpressing isogenic H1299 and A549 cell variants, respectively, to test the in vitro efficacy of metformin. We also investigated the effect of metformin on cisplatin-resistant CD133+ cells in NSCLC patient-derived xenografts.
We found a trend towards worse overall survival in patients with KRAS/LKB1 co-mutated tumors as compared to KRAS-mutated ones (hazard ratio: 2.02, 95% confidence interval: 0.94–4.35, p = 0.072). In preclinical experiments, metformin produced pro-apoptotic effects and enhanced cisplatin anticancer activity specifically in KRAS/LKB1 co-mutated patient-derived xenografts. Moreover, metformin prevented the development of acquired tumor resistance to 5 consecutive cycles of cisplatin treatment (75% response rate with metformin-cisplatin as compared to 0% response rate with cisplatin), while reducing CD133+ cells.
LKB1 mutations, especially when combined with KRAS mutations, may define a specific and more aggressive NSCLC subtype. Metformin synergizes with cisplatin against KRAS/LKB1 co-mutated tumors, and may prevent or delay the onset of resistance to cisplatin by targeting CD133+ cancer stem cells. This study lays the foundations for combining metformin with standard platinum-based chemotherapy in the treatment of KRAS/LKB1 co-mutated NSCLC.
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