The potential impact of the fetal genotype on maternal blood pressure during pregnancy.

The heritability of pregnancy-induced hypertension (encompassing both gestational hypertension and preeclampsia) is around 0.47, suggesting that there is a genetic component to its development. However, the maternal genetic risk variants discovered so far only account for a small proportion of the heritability. Other genetic variants that may affect maternal blood pressure in pregnancy arise from the fetal genome, for example wild-type pregnant mice carrying offspring with Cdkn1c or Stox1 disrupted develop hypertension and proteinuria. In humans, there is a higher risk for preeclampsia in women carrying fetuses with Beckwith-Wiedemann syndrome (including those fetuses with CDKN1C mutations) and a lower risk for women carrying babies with trisomy 21. Other risk may be associated with imprinted fetal growth genes and genes that are highly expressed in the placenta such as GCM1. This article reviews the current state of knowledge linking the fetal genotype with maternal blood pressure in pregnancy.MRCThis is the Author Accepted Manuscript of Petry CJ, Beardsall K, Dunger DB. "The potential impact of the fetal genotype on maternal blood pressure during pregnancy". published in the Journal of Hypertension. The published version is available at http://dx.doi.org/10.1097/HJH.000000000000021

Mikroszatellita-instabilitás előfordulása, intratumoralis heterogenitása, prognosztikus és prediktív potenciálja primer colorectalis carcinomák és párosított májáttéteik sebészi kezelését követően

Absztrakt Bevezetés: A vastagbéldaganatokra jellemző genetikai instabilitás megnyilvánulhat több úton: kromoszomális instabilitás, mikroszatellita-instabilitás, illetve „CpG-island methylator phenotype”. Ezek pontosabb karakterizálásával a rendelkezésre álló kezelések elviekben optimalizálhatók lehetnek. Célkitűzés: A szerzők a mikroszatellita-instabilitás előfordulását, heterogenitását, prognosztikus és prediktív potenciálját vizsgálták 122 primer colontumor szisztematikusan szelektált régióiban és 69 párosított májmetasztázisban. Módszer: Szöveti multiblokkok kialakítása után az MLH1, MSH2, MSH6 és PMS2 kifejeződését vizsgálták immunhisztokémiai módszerrel. Eredmények: A betegek 11,5%-a (14/122) rendelkezett mikroszatellita-instabil fenotípusú daganattal. A különböző tumorrégiók fehérjekifejeződésében nem volt jelentős különbség. A primer tumor–májmetasztázis párok esetében 20,2%-ban a kettő más mismatch repair státusba volt sorolható. A relapsusmentes és teljes túlélést tekintve a mismatch repair státus nem volt prognosztikus. Az 5-fluorouracil-, oxaliplatin-, irinotecan-, bevacizumab-, cetuximab-, panitumumabterápia hatékonyságát tekintve mismatch repair státus nem volt prediktív a progressziómentes és teljes túlélés adatai alapján. Következtetések: A prognosztikus faktorok pontosabb meghatározása nagyobb esetszámú, pontosan szelektált vizsgálat keretében hatékonyabbá teheti a kezelés megválasztását. Orv. Hetil., 2015, 156(36), 1460–1471

Characterization of sebaceous and non-sebaceous cutaneous manifestations in patients with lynch syndrome: a systematic review.

A subset of patients with Lynch Syndrome demonstrates cutaneous manifestations of the disorder. Characterization of these Lynch-related skin lesions could help in early recognition of patients with Lynch Syndrome. A broad search of the literature on OVID Medline and Embase was carried out to capture papers reporting cutaneous manifestations in Lynch Syndrome patients. The results were uploaded into Mendeley reference management software. The PRISMA workflow was used in the literature selection process. In this systematic review, data were collected from 961 cases from 413 studies, including 380 molecularly confirmed Lynch Syndrome cases. The main skin lesions were: Sebaceous adenomas (43%), sebaceous carcinomas (27%), keratoacanthomas (16%), sebaceomas (13%), squamous cell carcinomas (23%), and basal cell carcinomas (10%). MSH2 variants were the most common underlying genotype (72%). Assessment of mismatch repair by immunohistochemistry, microsatellite instability analysis, or both were performed on 328 skin lesions from 220 (58%) molecularly confirmed cases. In those skin lesions, 95% of Immunohistochemistry and 90% of the microsatellite instability test results were concordant with the underlying genotype. Sebaceous skin lesions are well-recognised phenotypic features of Lynch Syndrome. Our results show that squamous and basal cell carcinomas are relatively common in patients with Lynch syndrome; however, available evidence cannot confirm that Lynch syndrome is causal. Immunohistochemistry and/or microsatellite instability testing of skin tumours in patients with a family history of Lynch Syndrome-associated cancers may be a useful approach in identifying patients requiring referral to Clinical Genetics and/or consideration of germline genetic testing for Lynch Syndrome

Mismatch repair protein expression defects in endometrioid endometrial adenocarcinoma

Objectives: Endometrioid endometrial carcinoma (EEC) is the sentinel cancer in over half female patients with heritable mismatch repair (MMR) mutations as part of Lynch syndrome. Immunohistochemical testing for tumoural MMR-protein expression is the primary screening test identifying cases potentially harbouring familial cancer syndrome-related mutations and is also a predictive biomarker for immune-checkpoint blockade response.Methods: Following Data Protection and Ethical clearance by the University of Malta, 200 EEC cases were retrospectively identified and categorized into three arms: 151 cases above age 50 at diagnosis, 49 cases at or below age 50 at diagnosis and 30 controls with benign endometrial tissue sampling. H&E case slides were re-examined by an independent pathologist to confirm the diagnosis and identify the block best representing the tumour. Four new slides per case were recut and immunohistochemistry performed for MLH1, PMS2, MSH2, and MSH6 proteins. Protein expression was analysed semiquantitatively using Allred scoring.Results: 31% of the overall EEC cases were deficient for one or more MMR-proteins. Dual loss of the MLH1-PMS2 protein heterodimer was the most common deficiency, occurring in 24.5% of cases. Loss of MSH2-MSH6 protein expression represented 3.2% of MMR-deficient cases. Well differentiated tumours had a 76.5% proficiency rate as opposed to grade 2/3 disease with 53.2% and 52.9% proficiency rate respectively. There was no significant difference in MMR status when age 50 was used as a hypothetical testing threshold. After correcting for tumour grade, MLH1 and PMS2 expression was shown to be negatively correlated with age-at-diagnosis while MSH6 expression was positively correlated.Conclusion: Reflex MMR proficiency testing of all EEC cases is advisable, as using age 50 as a testing threshold would have missed 82.3% of MMR deficient cases. Prospective evidence is required to clarify the role semi-quantitative scoring plays in MMR status interpretation and patient management in the ever-evolving field of targeted therapeutics.peer-reviewe

Klinička vrijednost transvaginalne ultrasonografije u usporedbi s histeroskopijom i histopatološkom analizom kod dijagnoze endometralnih abnormalnosti

The aim of our retrospective study was to compare the performance of transvaginal sonography in relation to histologic diagnosis of samples obtained by hysteroscopy through analysis of data collected over 16 years. Data on suspected formation of endometrial polyp or submucosal fibroid found on ultrasound examination were extracted. The study included a total of 3679 women examined during the 2000-2015 period. All women underwent ultrasound examination preoperatively for better planning the type and scope of operation to be performed. The study included only women with samples for histopathologic analysis collected during the operation. Ultrasound diagnosis of polyps compared with histology showed 89.6% sensitivity and 39.1% specificity. For submucosal myomas, sensitivity was 69.2% and specificity 91.3%. In conclusion, ultrasound is not reliable method for definitive diagnosis but it is an excellent orientation method.Cilj ovog retrospektivnog istraživanja je bila usporedba pouzdanosti transvaginalnog ultrazvuka u odnosu na histološki nalaz dobiven histeroskopijom kroz analizu podataka skupljenih tijekom 16 godina. Podatci o suspektnim endometralnim polipima i submukoznim miomima primijećenim na ultrazvučnom pregledu su izdvojeni. U istraživanje je uključeno 3679 žena pregledanih u razdoblju od 2000. do 2015. godine. Svim ženama je učinjen prijeoperacijski ultrazvučni pregled radi planiranja tipa i opsega zahvata. U istraživanje su uključene samo žene kojima je uzet histološki uzorak tijekom operacije. Ultrazvučno utvrđeni polipi u usporedbi s histološkim nalazom pokazali su osjetljivost od 89,6% i specifičnost od 39,1%. Za submukozne miome utvrđena je osjetljivost od 69,2% i specifičnost od 91,3%. Može se zaključiti kako je ultrazvuk nepouzdana metoda pri donošenju konačne dijagnoze, ali odlična orijentacijska metoda

Contemporary Gynecologic Practice

Gynecology is frequently changing due to extensive implementation of high technology in both, the diagnosis and management of gynecologic problems. General gynecologists, gynecologic endocrinologists, infertility specialists, gynecologic endoscopists, and gynecologic oncologists will find attractive, new information in this book

A Brief Description of Different Types of Cancers and Role of Some Herbs & Bioactive Compounds in Lung Cancer Management

Cancer immunotherapy has considerably raised patient survival rates and significantly improved patients\u27 quality of life in comparison to the gold standard of care, which includes chemotherapy, radiation therapy, and surgery. Immunotherapy has firmly established itself as a novel pillar of cancer care across the board, from the metastatic stage all the way through adjuvant and neoadjuvant treatment in a wide variety of cancer types. In this overview, the primary emphasis will be placed on the seminal moments in the history of cancer immunotherapy that prepared the way for the cutting-edge treatments that are available today. Cancer treatment that makes use of medicinal herbs and the phytocompounds that can be obtained from those herbs is becoming an increasingly attractive option. It has been demonstrated in a number of clinical studies that the use of herbal medicines in conjunction with conventional therapy can increase survival rates, immunological modulation, and quality of life (QOL) in patients who have cancer. In addition to this, we highlight the challenges and restrictions currently faced by cancer checkpoint immunotherapy as well as the cutting-edge research being conducted in the fields of individualized cancer vaccines, autoimmunity, the microbiome, the microenvironment of tumors, and metabolomics to find solutions to these problems. For hundreds of years, practitioners of traditional medicine have depended on treatments derived from plants. Many studies on their use have been carried out all over the world, and some of the findings have led to the development of medicines that are derived from plants. The global market for medicinal plant products is estimated to be worth more than one hundred billion dollars each year. This research investigates the role, contributions, and utility of medicinal plants in the context of the current strategic methods to disease prevention, notably lung cancer, which is a public health concern. The focus of this research is on the current strategic approaches to disease prevention