Diagnosis and Therapy of Female Genital Malformations (Part 2). Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/052, May 2019)

Objectives Female genital malformations may be present in the form of individual entities, they may involve neighboring organs or they may occur in the context of complex syndromes. Given the anatomical structures of the vulva, vagina, uterus and uterine appendages, the clinical picture of malformations varies greatly. Methods This S2k-guideline was developed by representative members from different medical specialties and professions as part of the guidelines program of the DGGG, SGGG and OEGGG. The recommendations and statements were developed and voted on using a structured consensus process with neutral moderation. Recommendations This guideline is the first comprehensive summary of female genital malformations from infancy to adulthood which covers clinical examinations, diagnostic workups and treatment options. Additional chapters have been included on complex urogenital malformations, vascular malformations, psychosomatic care, and tumor risk.

COT-6 Body mass index and height in relation to brain tumor risk in a Japanese population

Purpose: Because the prognosis of the malignant brain tumor including glioblastoma is extremely worse than other cancer, it is important to clarify the preventive factors of the brain tumor in the prospective cohort study. In the Japanese epidemiologic study of the brain tumor, the report of the prospective cohort study has not been accomplished. Therefore, we have reported the study in recent years from a multipurpose cohort study (Japan Public Health Center-based Prospective Study: JPHC study) that the national cancer center was mainly conducted. This prospective study investigated the association between height and BMI (Body mass index) and brain tumor risk in an Asian population, whose distribution of anthropometric data differs from Westerners. Methods: A total of 106,324 subjects (50,438 men and 55,886 women) enrolled in JPHC Study, was followed from 1990. We divided participants into 5 categories based on the distribution of BMI as <18.5, 18.5- <23, 23- <25, 25- <27.5, and >-27.5 Kg/m2. We used the Cox proportional hazards regression model and estimated brain tumor incidence by gender and tumor subtype, with adjustment for potential confounding variables; age, sex, pack-years of cigarette smoking, alcohol intake, coffee intake, green tea intake, past history of allergy and past history of diabetes mellitus.Results: During an average follow-up of 18.1 years, 157 incident cases of brain tumor were newly identified, included glioma (n=60), meningioma (n =51), lymphoma(n=9), schwannoma(n=3), pituitary adenoma(n=2), and others(n=32). Higher BMI was significantly positively associated with the risk of brain tumor. This positive association of BMI was stronger in men and for meningioma in subgroup analyses. In contrast, height showed no clear association with brain tumor risk. Conclusion: Higher BMI was associated with an increased risk of brain tumor, in particular of meningioma, and among men.Full article has been published annals of epidemiology.

Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population

Beckwith–Wiedemann Spectrum (BWSp) is the most common epigenetic childhood cancer predisposition disorder. BWSp is caused by (epi)genetic changes affecting the BWS critical region on chromosome 11p15. Clinically, BWSp represents complex molecular and phenotypic heterogeneity resulting in a range of presentations from Classic BWS to milder features. The previously reported tumor risk based on Classic BWS cohorts is 8–10% and routine tumor screening has been recommended. This work investigated the tumor risk and correlation with phenotype within a cohort of patients from Classic BWS to BWSp using a mixed-methods approach to explore phenotype and epigenotype profiles associated with tumor development through statistical analyses with post-hoc retrospective case series review. We demonstrated that tumor risk across BWSp differs from Classic BWS and that certain phenotypic features are associated with specific epigenetic causes; nephromegaly and/or hyperinsulinism appear associated with cancer in some patients. We also demonstrated that prenatal and perinatal factors that are not currently part of the BWSp classification may factor into tumor risk. Additionally, blood testing results are not necessarily synonymous with tissue testing results. Together, it appears that the current understanding from Classic BWS of (epi)genetics and phenotype correlations with tumors is not represented in the BWSp. Further study is needed in this complex population.

Association Between BoLA-DRB3.2 Polymorphism and Bovine Papillomavirus Infection for Bladder Tumor Risk in Podolica Cattle

Blood samples from 260 unrelated cattle (132 animals affected by papillomavirus-associated bladder tumors and 128 healthy) were genotyped using the classic polymerase chain reaction/restriction fragment length polymorphism method to screen MHC class II bovine leukocyte antigen-DRB3. 2 polymorphism. The DRB3*22 allele was significantly (p ≤ 0.01) detected in healthy cattle, thus appearing to have a negative association (protective effect) with virus infection of the urinary bladder known to represent a bladder tumor risk for cattle living free at pasture. Considering the two sequence alleles identified in animals carrying DRB3*22, DRB3*011:01 allele from samples of animals harboring the unexpressed bovine papillomaviruses (BPV)-2 E5 gene was characterized by amino acid residues believed to have a protective effect against BPV infection such as arginine at position 71 (R71) in pocket 4, histidine at position 11 (H11) in pocket 6, and both glutamine at position 9 (Q9) and serine at position 57 (S57) in pocket 9 of the antigen-binding groove. The DRB3*011:02v allele from affected animals was characterized by amino acids believed to be susceptibility residues such as lysine (K71), tyrosine (Y11), glutamic acid (E9), and aspartic acid (D57) in these pockets. These results suggest that animals harboring the DRB3*011:01 allele may have a lower risk of BPV infection and, consequently, a reduced risk of bladder tumors.