Minding the Bathwater: Fertility and Reproductive Toxicity in the Age of Immuno-Oncology.

Immune checkpoint inhibition has resulted in significant efficacy across many cancer types, including melanoma. Melanoma is the second most common cancer among those of reproductive age, yet the reproductive toxicities of adjuvant and first-line immunotherapy are largely unknown.The normal innate and adaptive immune systems play a vital role in reproductive organ homeostasis of men and women and are essential for implantation, fertility, and a successful pregnancy. The programmed cell death-1 receptor/programmed cell death receptor ligand-1 (PD-1/PD-L1) pathway is essential in several aspects of fertility and pregnancy. Recent studies have largely focused on the role of the PD-1/PD-L1 pathway in fetomaternal tolerance, highlighting the importance of intact immune regulation in promoting a successful pregnancy.In this review, we describe a case of a reproductive-aged female with stage IIIC melanoma who sought guidance on family planning after pembrolizumab therapy. We discuss the known fertility-related toxicities of immune checkpoint inhibitors, the potential targets for reproductive toxicity in males and nonpregnant females, and the implications of anti-PD-1 therapy in relation to fetomaternal tolerance. Informed decision making will benefit from data and consensus.

Poor reproducibility of percentage of normally shaped sperm using the World Health Organization Fifth Edition strict grading criteria.

Objective: To determine the reproducibility of the World Health Organization Fifth Edition (WHO5) strict grading methodology by comparing the percentage of morphologically normal sperm (PNS) recorded by the core laboratory with results obtained at the fertility centers participating in a multisite clinical trial. Design: Secondary cohort analysis of data from the Males, Antioxidants, and Infertility trial. Setting: Fertility centers. Patients: Semen values of 171 men participating in a multicenter, double-blind, randomized, placebo-controlled trial evaluating the effect of antioxidants on male fertility. Interventions: Not applicable. Main Outcome Measures: Strict morphology expressed as PNS as determined at each fertility center and the core central laboratory for the same semen sample. Results: No correlation was found in the PNS values for the same semen sample between the core laboratory and fertility center laboratories either as a group or by individual site. Interobserver agreement was similarly low (κ = 0.05 and 0.15) between the core and fertility laboratories as a group for strict morphology, categorized by the WHO5 lower reference limits of 4% and 0, respectively. Moderate agreement was found between the core and 2 individual fertility laboratories for the cutoff value of 0 (κ = 0.42 and 0.57). The remainder of the comparisons demonstrated poor to fair agreement. Conclusions: Strict morphology grading using the WHO5 methodology demonstrated overall poor reproducibility among a cohort of experienced fertility laboratories. This lack of correlation and agreement in the PNS values calls into question the reproducibility, and thereby the potential applicability, of sperm strict morphology testing.

Impact of surgical volume and resident involvement on patency rates after vasectomy reversal-A 14-year experience in an open access system.

OBJECTIVE: Evaluate the influence of fellowship training, resident participation, reconstruction type, and patient factors on outcomes after vasectomy reversals in a high volume, open access system. METHODS: Retrospective review of all vasectomy reversals performed at a single institution from January 1, 2002 to December 31, 2016 was conducted. Patient and spouse demographics, patient tobacco use and comorbidities, surgeon training and case volume, resident participation, reconstruction type, and postoperative patency were collected and analyzed. RESULTS: Five hundred and twenty-six vasectomy reversals were performed during the study period. Follow-up was available in 80.6% of the cohort and overall patency, regardless of reconstruction type was 88.7%. The mean time to reversal was 7.87 years (range of 0-34 years). The majority of cases included resident participation. Case volume was high with faculty and residents logging a mean of 37.0 and 38.7 (median 18 and 37) cases respectively. Bilateral vasovasostomy was the most common reconstruction type (83%) and demonstrated a significantly better patency rate (89%) than all other reconstructions (p=0.0008). Overall patency and patency by reconstruction type were not statistically different among faculty surgeons and were not impacted by fertility fellowship training, resident participation or post-graduate year. Multivariate analysis demonstrated that increased time to reversal and repeat reconstructions had a negative impact on patency (p=0.0023 and p=0.043, respectively). CONCLUSIONS: Surgeons with a high volume of vasectomy reversals have outcomes consistent with contemporary series regardless of fellowship training in fertility. Patency was better for bilateral vasovasostomies. Patency was not negatively impacted by tobacco use, comorbidities, resident participation, or post-graduate year.

Addressing Barriers to Fertility Preservation for Cancer Patients: The Role of Oncofertility Patient Navigation.

BACKGROUND: Infertility is a common late effect for cancer survivors. Whereas assisted reproductive technology has made it possible for survivors to take steps to preserve fertility before starting treatment, only a minority of patients proceed with preservation. Patient-, provider-, health system-, and societal-level barriers to fertility preservation (FP) exist. Oncofertility patient navigation is a valuable resource for addressing FP barriers. OBJECTIVES: To highlight the critical role of oncofertility patient navigation in addressing barriers to FP within an academic oncofertility program. METHODS: The role of the oncofertility patient navigator in reducing FP barriers, promoting informed decision-making, and ensuring program sustainability is described. Program metrics illustrating the impact of oncofertility patient navigation on referrals for FP counseling and access to FP in the last year also are provided. DISCUSSION: The oncofertility program at our academic adult and pediatric medical centers aims to facilitate rapid referral to fertility counseling and preservation services for postpubertal cancer patients. The patient navigator is integral to the success of the program. The navigator ensures that patients are: (1) well-informed about the potential impact of cancer on fertility and FP options, (2) aware of available resources (eg, financial) for pursuing FP, (3) able to access FP services if desired, and (4) well supported in making an informed FP decision. The inclusion of the patient navigator has led to an almost 2-fold increase in referrals for FP counseling in the past year over the historic annual average. CONCLUSIONS: Our institution's oncofertility program, with patient navigation at the core, provides a potential model for increasing patient access to oncofertility care and promoting program sustainability. Oncofertility patient navigation is a valuable resource for providing patients and families with education and support regarding FP decision-making, as well as addressing the multilevel barriers to FP.

An unusual presentation: renal tuberculosis.

Genitourinary tuberculosis (TB) is the second most common form of extrapulmonary TB after peripheral lymphadenopathy. We report the case of a 44-year-old woman referred for hydronephrosis discovered on ultrasound performed due to flank pain. Contrast computed tomography (CT) scan demonstrated a well-circumscribed cystic mass with enhancing septations at the inferior pole of the right kidney, concerning for malignancy. Following extirpative surgery, she was diagnosed with renal TB.

Could Nonenhanced Computer Tomography Suffice as the Imaging Study of Choice for the Screening of Asymptomatic Microscopic Hematuria?

OBJECTIVE: To compare the diagnostic accuracy of the noncontrast and contrast-enhanced phases of computed tomographic urography for detection of upper urinary tract findings in adults undergoing initial evaluation of newly diagnosed asymptomatic microscopic hematuria to determine if less-intensive noncontrast imaging has the potential to become a suitable imaging alternative in the work-up of this common condition. MATERIALS AND METHODS: Retrospective review from 2010-2015 for adults who underwent computed tomographic urography for initial evaluation of asymptomatic microscopic hematuria. Three nonblinded physicians independently categorized the upper urinary tract findings described in the computed tomography reports into one of three groups: normal, benign, or suspicious for malignancy. The noncontrast images of a randomized portion of the studies categorized as normal and all studies categorized as suspicious and benign were submitted to two blinded radiologists who independently classified each study into one of the aforementioned categories. RESULTS: The noncontrast images for 475 subjects were blindly reviewed. When compared to the computed tomographic urography reports, the negative predictive values of noncontrast images were 97.25% and 94.92% for radiologist 1 and radiologist 2, respectively, with an associated specificity of 88.6% and 97.95%. Of the 5 true upper tract malignancies, both blinded radiologists correctly identified 4 of the 5. CONCLUSION: Contrast imaging added little diagnostic value when compared with noncontrast imaging for most subjects undergoing initial evaluation for asymptomatic microscopic hematuria. Less-intensive imaging with nonenhanced computed tomography could reduce the nontrivial risks associated with multiphasic contrast imaging but further work is necessary to identify risk-stratifying criteria.

Hexaminolevulinate Blue-Light Cystoscopy in a Patient with Metastatic Melanoma of the Bladder.

BACKGROUND: Although bladder cancer is one of the most frequently diagnosed tumors worldwide, metastatic melanoma of the bladder is a rare occurrence with only 29 cases reported in the literature. CASE PRESENTATION: We present the case of a 60-year-old male with a medical history significant for metastatic melanoma, who was referred to the urology department for gross hematuria. Transurethral resection of bladder tumor (TURBT) was performed with the assistance of hexaminolevulinate acid (HAL) with blue-light cystoscopy (BLC). Subsequent histopathologic analysis of the specimen confirmed a diagnosis of metastatic melanoma of the bladder. To our knowledge, this is the first reported case of metastatic bladder melanoma diagnosed with the assistance of HAL-BLC in a patient undergoing a TURBT. CONCLUSION: Although HAL-BLC is only indicated for use in the cystoscopic detection of papillary nonmuscle invasive bladder cancer, it may aid in the detection of nonconventional bladder pathologies, such as melanoma.

Electrocardiographic abnormalities as potential contributors to premature mortality in patients with mental illness in a psychiatric day treatment program.

OBJECTIVE: Because patients with mental illness can die prematurely, we sought to determine if undetected cardiovascular disease might be present in a psychiatric day treatment population. METHOD: We studied 96 patients in a day treatment program seen between February 2011 and August 2012. Data were obtained through an electronic medical record database. Electrocardiographic diagnoses were assigned by 1 investigator (M.L.). Medications were categorized into classes, and problem lists revealed comorbid diagnoses. Fisher exact test (2-tailed) and analysis of variance were used to compare findings between patient groups. Electrocardiogram (ECG) findings were the primary outcome measure. RESULTS: Ninety-two ECGs were performed in 37 patients. Of these 37 patients, 70% were women, 65% were 50 years of age or younger, and 54% were people of color. ECGs were performed mainly for chest pain/dyspnea (46%) and overdose/altered mental status (27%). Of these 37 patients, 20 (54%) had abnormal ECGs, 7 (19%) had borderline findings, and 10 (27%) had normal studies. When compared with the larger group of 59 patients without ECG testing, those with abnormal ECGs were more likely to be older (mean age = 47 vs 37 years, P < .001) and have more comorbid conditions (mean no. = 10.0 vs 3.8, P < .0001). The most common abnormalities were conduction disorders (prolonged QRS ≥ 105 ms, or prolonged QTc ≥ 450 ms in men or ≥ 460 ms in women), coronary artery disease, and arrhythmias. CONCLUSIONS: In psychiatric outpatients who underwent ECG testing, mainly for chest pain or altered mental status, over 50% had concerning findings. Older patients with multiple comorbidities were at higher risk of having abnormal ECGs. Generalizability of these findings depends on validation in larger samples in multiple settings.

Epidemiology of nephrolithiasis in personnel returning from Operation Iraqi Freedom.

OBJECTIVES: To examine the epidemiology of urolithiasis in personnel returning from deployment to Southwest Asia. METHODS: A survey-based study of personnel returning from deployment to Southwest Asia was performed. The demographics were compared between the personnel reporting a history of urolithiasis during or within the first 90 days of returning from deployment and the personnel without a history of reported urolithiasis. RESULTS: A total of 10,180 personnel were demobilized and 6153 surveys were received during a 9-month period, for a survey response rate of 60%. Of the personnel returning survey, 1% reported urolithiasis during their deployment. The personnel who reported urolithiasis were slightly older than those who did not (32.6 vs 29 years old, P < .00038). The odds of reporting urolithiasis during deployment were 30.9 times greater for personnel with a history of stone disease and 2.4 times greater for those with a family history of stone disease. No difference was found in the rates of urolithiasis with regard to sex or race. Also, no strong evidence for an association between the rates of reported urolithiasis and seasonal variations in temperature in Southwest Asia was found. CONCLUSIONS: The rate of reported urolithiasis among deployed personnel was lower than that in the general population. The personnel who reported urolithiasis during deployment were slightly older. A personal history or family history of stone disease was significant predictors of urolithiasis in this deployed population.

Effect of flexible cystoscopy on serum prostate-specific antigen values.

OBJECTIVES: To determine the effect of flexible cystoscopy on the total, free, and percent-free prostate-specific antigen (PSA) values in male volunteers. Flexible cystoscopy is the standard method of evaluation of the bladder and urethra. PSA measurement is currently used in conjunction with the digital rectal examination to detect and guide management of prostate cancer. Thus, we must understand the effect of flexible cystoscopy on serum PSA levels. METHODS: Healthy men who were undergoing flexible cystoscopy and provided informed consent were enrolled in the study. The volunteers had blood taken for PSA measurement before cystoscopy and 1 and 24 hours after. The mean PSA values were compared using the paired t test. RESULTS: A total of 40 volunteers (age 22-82 years) enrolled in the study. Statistically significant increases in the total, free, and percent-free PSA values were noted at 1 and 24 hours after cystoscopy. The differences of 0.113 and 0.112 ng/mL (P < .05) in the mean total PSA level at 1 and 24 hours after cystoscopy were not clinically significant. The interassay variability was 0.053 ng/mL, with a standard deviation of 0.150 ng/mL. The standard deviation of 0150 ng/mL was greater than the 0.113- and 0.112-ng/mL differences seen in the total PSA values at 1 and 24 hours after cystoscopy. CONCLUSIONS: Statistically significant differences were noted in the total, free, and percent-free PSA levels before and after cystoscopy. Although these small differences achieved statistical significance, none were clinically significant. We have concluded that the serum PSA values are not affected by diagnostic flexible cystoscopy.