ABSTRACT
Infertility in couples is a common problem, with both female and male factors contributing to similar extents. Severe, congenital disorders affecting fertility are, however, rare. While folliculogenesis and spermatogenesis are generally orchestrated via different mechanisms, some genetic anomalies can impair both female and male gametogenesis. Minichromosome maintenance complex component 9 (MCM9) is involved in DNA repair and mutations of the MCM9 gene have been previously reported in females with premature ovarian insufficiency (POI). MCM9 is also an emerging cancer risk gene. We performed next-generation and Sanger sequencing of fertility and related genes and hormonal and imaging studies in a kindred whose members had POI and disordered spermatogenesis. We identified a homozygous pathogenic MCM9 variant, c.394C>T (p.Arg132*) in three sisters affected by POI due to ovarian dysgenesis and their brother who had normal pubertal development but suffered from non-obstructive azoospermia. Testicular biopsy revealed Sertoli cell-only testicular histopathology. No evidence of early onset cancer was found in the homozygotic family members, but they were all young (<30 years) at the time of the study. In the male patient the homozygous MCM9 variant led to normal pubertal development and hormonal levels but caused a Sertoli-cell-only syndrome with non-obstructive azoospermia. In the homozygous females studied, the clinical, hormonal, and gonadal phenotypes revealed ovarian dysgenesis consistent with previous reports. Active screening for potential colorectal and other cancer risks in the homozygotic MCM9 subjects has been instigated.
ABSTRACT
BACKGROUND: Prostate-specific membrane antigen (PSMA) ligand PET/CT has already provided promising results in prostate cancer (PC) imaging, yet simple and reproductible reporting criteria are still lacking. This study aimed at retrospectively evaluating interobserver agreement of [68Ga]Ga-PSMA-11 PET/CT images interpretation according to PC molecular imaging standardized evaluation (PROMISE) criteria and reproducibility of PSMA reporting and data systems (RADS). METHODS: Forty-three patients with newly diagnosed, histologically proven intermediate- or high-risk PC, eligible for radical prostatectomy and who underwent [68Ga]Ga-PSMA-11 PET/CT before surgery were retrospectively included. Three nuclear medicine physicians (2 experienced and 1 resident) independently reviewed PET/CT images. Interpretation of [68Ga]Ga-PSMA-11 PET/CT images was based on PROMISE criteria including miTNM staging and lesions miPSMA expression score visual estimation and PSMA-RADS version 1.0 for a given scan. Readers' agreement was measured using Krippendorff's coefficients RESULTS: Agreement between observers was almost perfect (coefficient ≥ 0.81) for miM; it was substantial (coefficient ≥ 0.61) for the following criteria: miT, miN, PSMA-RADS, and miPSMA expression score of primary PC lesion and metastases. However, agreement was moderate (coefficient = 0.41-0.60) for miPSMA score of positive lymph nodes and for detection of PC primary lesion. CONCLUSION: Visual interpretation of [68Ga]Ga-PSMA-11 PET/CT images in patients with newly diagnosed PC in a clinical setting leads to at least substantial agreement for PROMISE criteria and PSMA-RADS classification except for PC primary lesion detection and for miPSMA expression scoring of positive lymph nodes that might have been hampered by the interindividual variability of reference organs PSMA expression.
ABSTRACT
OBJECTIVE: To assess the outcomes of patients following a first-line systematic endourologic procedure used to treat ureteroenteric anastomotic strictures (UEAS). MATERIALS AND METHODS: All data from patients treated using a first-line endourologic approach for UEAS between 2010 and 2015 were reviewed retrospectively. The following data were analyzed: age, type of urinary diversion, initial symptoms, surgical endoscopic approach (antegrade or retrograde), pre- and postoperative creatinine levels, and postoperative complications and outcomes. Follow-up visits occurred at 6 weeks, 3 months, and 6 months postoperatively, and at least annually thereafter. RESULTS: A total of 27 patients (median age: 62.5 years) were included. Overall, 28 UEAS were treated endoscopically (ileal conduit: n = 25; neobladder: n = 3). Most UEAS developed following radical cystectomy for bladder cancer (n = 19). Overall, the endoscopic approach was successful in 20 cases (71.4%). The UEAS length was >1 cm in 21 cases (75%). All UEAS of <1 cm were treated successfully (n = 7). There were three grade II and five grade III complications. The median follow-up period was 25 months. The median creatinine levels before surgery and at last follow-up were 1.3 mg/dL and 0.9 mg/dL, respectively. CONCLUSION: An endourologic procedure is a reasonable option for first-line treatment for UEAS and has promising functional outcomes and limited morbidity.
