Variants in KITLG predispose to testicular germ cell cancer independently from spermatogenic function

Epidemiological data suggest an association and a common pathogenetic link between male infertility and testicular germ cell tumor (TGCT) development. Genome-wide studies identified that TGCT susceptibility is associated with KITLG (c-KIT ligand), which regulates the formation of primordial germ cells, from which TGCT is believed to arise and spermatogenesis develops. In this study, we analyzed the link between KITLG, TGCT, and spermatogenic disruption by performing an association study between the KITLG markers rs995030 and rs4471514 and 426 TGCT cases and 614 controls with normal and abnormal sperm count. We found that TGCT risk was increased more than twofold per copy of the major G allele and A allele in KITLG rs995030 and rs4471514 (odds ratio (OR)=2.38, 95% confidence interval (95% CI)=1.81-3.12; OR=2.43, 95% CI=1.86-3.17 respectively), and homozygotes for the risk allele had a sevenfold increased risk of TGCT. KITLG markers were strongly associated with seminoma subtype (per allele risk increased more than threefold, homozygote risk increased by 13- to 16-fold) and weakly with nonseminoma. KITLG markers were not associated with sperm production, as no difference was observed in men with normozoospermia and azoo-oligozoospermia, both in controls and in TGCT cases. In conclusion, this study provides evidence that KITLG variants are involved in TGCT development and they represent an independent and strong specific risk factor for TGCT independently from spermatogenic function. A shared genetic cause and a common pathogenetic link between TGCT development and impairment of spermatogenesis are not evident from this study.     

Ocular manifestations in phakomatosis pigmentovascularis: Current concepts on pathogenesis,diagnosis, and management

Phakomatosis pigmentovascularis is a rare congenital multisystemic disease with variable manifestations where a vascular malformation of the skin is associated with a pigmentary nevus. Ocular involvement includes glaucoma, choroidal hemangioma, and pigmentary alterations that predispose to uveal melanoma. Diagnosis is made on clinical grounds, although recent advances in molecular genetics have better clarified the etiopathogenesis of the condition. The advent of improved imaging techniques such as enhanced depth imaging spectral domain optical coherence tomography has provided new insight into the ocular alterations, enabling better follow-up of patients. We review the ophthalmic manifestations of the disease with an update on etiopathogenesis and current management strategies.     

Minimal access anterior mediastinotomy

Anterior mediastinotomy and VATS are today the most common surgical approaches to obtain tissue diagnosis or to remove mediastinal lesions. However, both methods lead to inconveniences. This report demonstrates the advantages of a minimal access mediastinotomy to remove or diagnose mediastinal lesions.     

Association among Oral Health,Apical Periodontitis,CD14 Polymorphisms,and Coronary Heart Disease in Middle-aged Adults

Introduction

There is evidence to suggest that an association exists between oral infections and coronary heart disease (CHD). Subjects presenting lesions of endodontic origin (LEOs) or pulpal inflammation had an increased risk of developing CHD. However, findings concerning systemic manifestations of apical periodontitis (AP) remain controversial. An association between CD14 gene polymorphisms and atherosclerosis-associated diseases has been shown, but there are no data regarding an association between CD14 polymorphism and AP. This study evaluated associations between clinical oral health status, CD14 polymorphisms, and CHD.

Methods

A case-controlled clinical trial was designed to compare middle-aged adults with acute myocardial infarction or unstable angina (n = 51) within 12 months of the acute event defined as first manifestation with healthy controls (n = 49). Participants were matched for age, sex, and socioeconomic status. Indicators of oral disease and compliance were evaluated. CD14 polymorphisms were analyzed by restriction fragment length polymorphism–polymerase chain reaction.

Results

CHD subjects had a higher prevalence of oral diseases and lower compliance to oral preventive strategies than healthy controls. Multivariate analysis showed a positive association between missing teeth (odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.02–1.85), the number of LEOs (OR = 4.37; 95% CI, 1.69–11.28), chronic periodontitis (OR = 5.87; 95% CI, 1.17–29.4), and CHD. No statistically significant association emerged between the CD14 C(−260)T and the CD14 C(−159)T polymorphism, endodontic or periodontal disease, and CHD.

Conclusions

Chronic oral diseases may increase the risk of CHD and may be an unconventional risk factor for CHD.     

Long-term recovery of normal sexual function in testicular cancer survivors

Testicular cancer (TC) is the most common solid cancer in men between the third and fourth decade of life. Due to successful treatment approaches, TC survivors (TCSs) have long life expectancy, but with numerous potential long-term sequelae, including sexual dysfunction. We investigated predictors of long-term normal sexual function (SF) recovery in TCSs. Sociodemographic, medical, and psychometric data were analyzed in 143 Caucasian-European TCSs, who underwent orchiectomy at a single institution. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF). Statistical models tested the association between predictors (including age at surgery, body mass index, CCI, and adjuvant therapy: radiotherapy [RT], chemotherapy [CT], CT followed by retroperitoneal lymph node dissection [RPLND] and RPLND alone) and the long-term recovery of normal SF (defined as IIEF-erectile function [EF] ≥26, and sexual desire [SD], intercourse satisfaction [IS] orgasmic function [OF], and overall satisfaction [OS] domain scores in the upper tertiles). At a mean follow-up of 86 months, 35 (25.5%) TCSs had erectile dysfunction (ED), with 16 (11.2%) experiencing severe ED. Median time of EF recovery was 60, 60, and 70 months after CT, RT, and RPLND, respectively. Only adjuvant RT emerged as an independent predictor of nonrecovery of normal EF (HR: 0.55, P= 0.01). Neither adjuvant CT nor CT plus RPLND or RPLND alone significantly impaired the recovery of normal erections. Adjuvant therapy was not associated with impaired recovery of normal sexuality as a whole, considering the IIEF-SD, -OF, -IS, and OS domains.