Kunj R. Sheth

Improved fertility preservation care for male patients with cancer after establishment of formalized oncofertility program

PURPOSE Survival to reproductive age among men with cancer has steadily increased and yet cancer therapy and cancer itself may carry the risk of infertility. Since 2006, we have used a formalized fertility preservation program with expedited fertility care at our institution. We assessed the impact of this program by comparing the frequency of sperm cryopreservation and patient characteristics before and after its implementation. MATERIALS AND METHODS Men 18 to 55 years old diagnosed with cancer at our institution from 2002 to 2010 were included in our study. We retrospectively reviewed patient charts to identify those who were offered and subsequently used fertility preservation services before and after program formalization. RESULTS From 2002 to 2010 at our institution 4,818 men 18 to 55 years old were diagnosed with cancer, of whom 411 were offered fertility preservation consultation and 249 underwent sperm cryopreservation. Since program implementation, the annual number of men receiving fertility preservation consultation and undergoing sperm cryopreservation increased by 2.4 and 2.7-fold, respectively, while the total number diagnosed with cancer remained fairly constant. Upon substratifying patients into the more conventional reproductive age range of 18 to 40 years 23.4% of all men with cancer in this group were offered consultation before formalization vs 43.3% after formalization (p <0.05). The overall sperm use and discard rates were 8.4% and 14.8%, respectively. CONCLUSIONS A formalized institutional fertility preservation program significantly increased the overall number and percent of male patients with cancer who received fertility preservation consultation and pursued sperm cryopreservation. These increases were seen in men with all types of cancer and across all demographics assessed at our institution.

Vasectomy demographics and postvasectomy desire for future children: Results from a contemporary national survey

OBJECTIVE To describe the longitudinal demographics and family planning attitudes of vasectomized men with the use of the National Survey for Family Growth (NSFG). DESIGN Retrospective cohort analysis of the NSFG with the use of national projections and multivariable regressions. SETTING In-home survey. PATIENT(S) The NSFG sampled 10,403 men aged 15-45 years from 2006 to 2010 regarding family planning attitudes. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Vasectomy and desire for children. RESULT(S) There were 3,646,339 (6.6%) vasectomized men aged 18-45 years in the U.S. On multivariable regression the following factors increased the odds of having a vasectomy: currently married (odds ratio [OR] 7.814), previously married (OR 5.865), and increased age (OR 1.122) and income (OR 1.003). The odds of having a vasectomy increased with number of children. The following factors decreased the odds of having a vasectomy: immigrant status (OR 0.186), African American (OR 0.226), Hispanic (OR 0.543), Catholic (OR 0.549), and other non-Protestant religion (OR 0.109). Surprisingly, an estimated 714,682 (19.6%) vasectomized men in the U.S. desire future children. Men practicing a religion (OR 8.575-15.843) were more likely than atheists to desire children after vasectomy. 71,886 (2.0%) vasectomized men reported having a vasectomy reversal. CONCLUSION(S) This study highlights the importance of preoperative counseling for permanency of vasectomy and reveals an opportunity to counsel couples about vasectomy versus tubal ligation.

Diagnosing Testicular Torsion before Urological Consultation and Imaging: Validation of the TWIST Score

PURPOSE The TWIST (Testicular Workup for Ischemia and Suspected Torsion) score uses urological history and physical examination to assess risk of testis torsion. Parameters include testis swelling (2 points), hard testis (2), absent cremasteric reflex (1), nausea/vomiting (1) and high riding testis (1). While TWIST has been validated when scored by urologists, its diagnostic accuracy among nonurological providers is unknown. We assessed the usefulness of the TWIST score when determined by nonurological nonphysician providers, mirroring emergency room evaluation of acute scrotal pain. MATERIALS AND METHODS Children with unilateral acute scrotum were prospectively enrolled in a National Institutes of Health clinical trial. After undergoing basic history and physical examination training, emergency medical technicians calculated TWIST score and determined Tanner stage per pictorial diagram. Clinical torsion was confirmed by surgical exploration. All data were captured into REDCap™ and ROC curves were used to evaluate the diagnostic usefulness of TWIST. RESULTS Of 128 patients (mean age 11.3 years) 44 (13.0 years) had torsion. TWIST score cutoff values of 0 and 6 derived from ROC analysis identified 31 high, 57 intermediate and 40 low risk cases (positive predictive value 93.5%, negative predictive value 100%). CONCLUSIONS TWIST score assessed by nonurologists, such as emergency medical technicians, is accurate. Low risk patients do not require ultrasound to rule out torsion. High risk patients can proceed directly to surgery, with more than 50% avoiding ultrasound. In the future emergency medical technicians and/or emergency room triage personnel may be able to calculate TWIST score to guide radiological evaluation and immediate surgical intervention at initial assessment long before urological consultation.

Low Serum Testosterone Level Predisposes to Artificial Urinary Sphincter Cuff Erosion

OBJECTIVE To examine the association between decreased serum testosterone levels and artificial urinary sphincter (AUS) cuff erosion. MATERIALS AND METHODS We evaluated serum testosterone levels in 53 consecutive patients. Low testosterone was defined as <280 ng/dL and found in 30/53 patients (56.6%). Chi-square and Student t tests, Kaplan-Meier analysis, binary logistic regression, and Cox regression analysis were used to determine statistical significance. RESULTS Nearly all men with AUS cuff erosions had low serum testosterone (18/20, 90.0%) compared to those without erosions (12/33, 36.4%, P < .001). Mean time to erosion was 1.70 years (0.83-6.86); mean follow-up was 2.76 years (0.34-7.92). Low testosterone had a hazard ratio of 7.15 for erosion in a Cox regression analysis (95% confidence interval 1.64-31.17, P = .009) and Kaplan-Meier analysis demonstrated decreased erosion-free follow-up (log-rank P = .002). Low testosterone was the sole independent risk factor for erosion in a multivariable model including coronary artery disease and radiation (odds ratio 15.78; 95% confidence interval 2.77-89.92, P = .002). Notably, history of prior AUS, radiation, androgen ablation therapy, or concomitant penile implant did not confound risk of cuff erosion in men with low testosterone levels. CONCLUSION Men with low testosterone levels are at a significantly higher risk to experience AUS cuff erosion. Appropriate counseling before AUS implantation is warranted and it is unclear whether testosterone resupplementation will mitigate this risk.

Prognostic serum markers in patients with high-grade upper tract urothelial carcinoma

INTRODUCTION The role of preoperative serum-based markers in predicting survival outcomes of patients has been reported for several cancer types; however, their association with upper tract urothelial carcinoma (UTUC) prognosis is unclear. We evaluated the role of systemic serum-based markers in predicting adverse pathological features and survival outcomes in patients surgically treated for high-grade (HG) UTUC. METHODS We retrospectively reviewed all patients undergoing surgery for HG UTUC between June 2006 and July 2013 at our institution. Comprehensive clinicopathologic data and preoperative serum-based markers including hemoglobin, white blood cell count, platelet count, serum albumin, calcium, and liver function tests were recorded. Associations of serum markers with pathologic features and recurrence-free survival (RFS) were determined by logistic and Cox regression analyses, respectively. The concordance index for the oncologic outcomes model was determined. RESULTS In total, 101 patients were identified with a median follow-up of 18.5 months (range: 1-74mo). In all, 60% of patients had pT2 or less and 11% had nodal metastases. Preoperative elevated alkaline phosphatase (ALP) (≥116IU/l) was associated with multiple adverse pathologic features including advanced T stage, lymphovascular invasion, and histologic necrosis. On univariate analysis, serum markers independently associated with RFS included hemoglobin≤12.9 (hazards ratio [HR] = 2.51; 95% CI: 1.17-5.36, P = 0.018), albumin≤4g/dl (HR = 4.4; 95% CI: 2.04-9.30; P<0.0001), ALP≥116U/l (HR = 13.3; 95% CI: 5.3-33.52, P<0.0001), alanine transaminase≥27 (HR = 2.63, 95% CI: 1.11-6.21, P = 0.028), serum aspartate transaminase≥20 (HR = 2.21, 95% CI: 1.04-4.69, P = 0.038), and corrected calcium≥9.3 (HR = 2.45, 95% CI: 1.01-5.93, P = 0.047). The 2 strongest predictors, albumin and ALP, were combined to form an AA score (range: 0-2), which improved the baseline preoperative clinical model concordance index for prediction of RFS from 0.626 to 0.799. CONCLUSION In HG UTUC, elevated preoperative ALP was associated with adverse pathologic features. Additionally, elevated ALP and low albumin were independently associated with worse RFS and overall survival. These serum-based markers are often measured in the preoperative workup of UTUC, and thus they can be included in future prognostic models to risk stratify patients.

Relating economic conditions to vasectomy and vasectomy reversal frequencies: a multi-institutional study.

PURPOSE It was theorized that the use of permanent contraceptive methods may vary with economic conditions. We evaluated the relationship between vasectomy/vasectomy reversal frequencies at several large referral centers and national economic indicators during 2 recessions spanning 2001 to 2011. MATERIALS AND METHODS We performed an institutional review board approved, retrospective chart review to identify the number of vasectomies/vasectomy reversals per month at several large referral centers from January 2001 to July 2011. The rates of these procedures were pooled, correlated with national economic data and analyzed in a multivariate linear regression model. RESULTS A total of 4,599 vasectomies and 1,549 vasectomy reversals were performed at our institutions during the study period. The number of vasectomies per month positively correlated with the unemployment rate (r=0.556, p<0.001) and personal income per capita (r=0.276, p=0.002). The number of reversals per month negatively correlated with the unemployment rate (r=-0.399, p<0.001) and personal income per capita (r=-0.305, p<0.001). Neither vasectomy nor vasectomy reversal frequency significantly correlated with the inflation rate or the S&P 500®. Regression models confirmed that the unemployment rate explained more of the variance in vasectomy/vasectomy reversal frequencies than other indicators. CONCLUSIONS We noted a correlation between the number of vasectomies/vasectomy reversals performed at our institutions and national economic indicators. The strongest association was with the unemployment rate. This points to the importance of financial pressure on family planning decisions.

Improving Outcomes of Bulbomembranous Urethroplasty for Radiation-induced Urethral Strictures in Post-Urolume Era

OBJECTIVE To evaluate contemporary outcomes of excision and primary anastomosis (EPA) for the treatment of radiation-induced urethral strictures (RUS). PATIENTS AND METHODS A retrospective review of 72 patients undergoing EPA for RUS from 2007 to 2015 by a single surgeon was performed. We analyzed overall and long-term success rates of EPA urethroplasty and compared patient cohorts from two groups, 2007-2012 vs 2013-2015 (post-Urolume). RESULTS During the course of the study, we noted a near doubling of patient volume from the earlier (6.2 patients/year) to later (11.7 patients/year) cohorts. Among the 37 men treated from 2007 to 2012, we identified an EPA success rate of 70% compared with the improved 86% success rate in the subsequent cohort of 35 men treated from 2013 to 2015 (P = .07). Single dilation was successful in 50% of initial and 40% of subsequent cohort patients in the treatment of recurrence. Initial and subsequent cohorts varied only in regard to stricture length (mean 2.0 cm vs 3.0 cm in initial and subsequent cohorts, P = .001) and number treated with Urolume stent (initial 5 vs none in the later cohort, P = .03). Length of follow-up (median 50 [17-97] months for the initial and 22 [6-34] months for the later cohort) was not associated with recurrence. CONCLUSION Increasing numbers of RUS patients are presenting for urethral reconstruction in the post-Urolume era. With increasing experience, we improved success rates of EPA urethroplasty to over 85% despite increased stricture length.

Transscrotal Near Infrared Spectroscopy as a Diagnostic Test for Testis Torsion in Pediatric Acute Scrotum: A Prospective Comparison to Gold Standard Diagnostic Test Study

Purpose: A rapid test for testicular torsion in children may obviate the delay for testicular ultrasound. In this study we assessed testicular tissue percent oxygen saturation (%StO2) measured by transscrotal near infrared spectroscopy as a diagnostic test for pediatric testicular torsion. Materials and Methods: This was a prospective comparison to a gold standard diagnostic test study that evaluated near infrared spectroscopy %StO2 readings to diagnose testicular torsion. The gold standard for torsion diagnosis was standard clinical care. From 2013 to 2015 males with acute scrotum for more than 1 month and who were less than 18 years old were recruited. Near infrared spectroscopy %StO2 readings were obtained for affected and unaffected testes. Near infrared spectroscopy &Dgr;%StO2 was calculated as unaffected minus affected reading. The utility of near infrared spectroscopy &Dgr;%StO2 to diagnose testis torsion was described with ROC curves. Results: Of 154 eligible patients 121 had near infrared spectroscopy readings. Median near infrared spectroscopy &Dgr;%StO2 in the 36 patients with torsion was 2.0 (IQR −4.2 to 9.8) vs −1.7 (IQR −8.7 to 2.0) in the 85 without torsion (p=0.004). AUC for near infrared spectroscopy as a diagnostic test was 0.66 (95% CI 0.55–0.78). Near infrared spectroscopy &Dgr;%StO2 of 20 or greater had a positive predictive value of 100% and a sensitivity of 22.2%. Tanner stage 3‐5 cases without scrotal edema or with pain for 12 hours or less had an AUC of 0.91 (95% CI 0.86–1.0) and 0.80 (95% CI 0.62–0.99), respectively. Conclusions: In all children near infrared spectroscopy readings had limited utility in diagnosing torsion. However, in Tanner 3‐5 cases without scrotal edema or with pain 12 hours or less, near infrared spectroscopy discriminated well between torsion and nontorsion.

Prospective Evaluation of Predictors of Testis Atrophy After Surgery for Testis Torsion in Children

OBJECTIVE To prospectively correlate pain duration, red scrotal skin, ultrasound appearance of testis, and intraoperative testis color to future testis atrophy after acute testicular torsion. METHODS Patients 2 months-18 years old with unilateral acute scrotum were consecutively enrolled in a National Institutes of Health transcutaneous near-infrared spectroscopy study, with a subgroup analysis of the true torsion group. Presence or absence of red scrotal skin, pain duration, testicular heterogeneity on preoperative ultrasound, and intraoperative testis color based on a novel visual chart 5 minutes after detorsion were recorded. All testes underwent orchiopexy regardless of appearance. Percent volume difference between normal and torsed testicles on follow-up ultrasound was compared between patients with and without risk factors. RESULTS Thirty of 56 patients who had surgical detorsion underwent scrotal ultrasound at a mean of 117 days after surgery. A color of black or hemorrhagic 5 minutes after detorsion, pain duration >12 hours, and heterogeneous parenchyma on preoperative ultrasound were associated with significant testis volume loss in follow-up compared with normal testis. All patients with a black or hemorrhagic testis had >80% volume loss. Erythematous scrotal skin was not significantly associated with smaller affected testis volume in follow-up. CONCLUSION Based on the high atrophy rate, orchiectomy can be considered for testes that are black or hemorrhagic 5 minutes after detorsion. Pain duration >12 hours and parenchymal heterogeneity on preoperative ultrasound were also associated with testis atrophy. Red scrotal skin was not a reliable predictor of atrophy and should not delay exploration.

The Adverse Survival Implications of Bland Thrombus in Renal Cell Carcinoma With Venous Tumor Thrombus

OBJECTIVE To characterize the presence of bland (nontumor) thrombus in advanced renal cell carcinoma and assess the impact of this finding on cancer-specific survival. METHODS A multi-institutional database of patients treated with nephrectomy with caval thrombectomy for locally-advanced renal tumors was assembled from 5 tertiary care medical centers. Using clinicopathologic variables including patient age, body mass index, Eastern Cooperative Oncology Group performance status, tumor stage, grade, nodal status and histology, and nearest-neighbor and multiple-matching propensity score matched cohorts of bland thrombus vs nonbland thrombus patients were assessed. Multivariable analysis for predictors of cancer-specific survival was performed. RESULTS From an initial cohort of 579 patients, 446 met inclusion criteria (174 with bland thrombus, 272 without). At baseline, patients with bland thrombus had significantly worse performance status, higher tumor stage, higher prevalence of regional nodal metastases and higher nuclear grade (P < .01 for all). In both nearest-neighbor and multiple-matching propensity score matched cohorts, the presence of bland thrombus presence was associated with inferior median cancer-specific survival (28.1 months vs 156.8 months, and 28.1 months vs 76.7 months, P < .001 for both). The presence of bland thrombus remained independently associated with an increased risk of cancer-specific mortality on multivariable analysis (hazard ratio 4.33, 95% confidence interval 2.79-6.73, P < .001). CONCLUSION Presence of bland thrombus is associated with adverse survival outcomes in patients treated surgically for renal tumors with venous tumor thrombus. These findings may have important implications in patient counseling, selection for surgery and inclusion in clinical trials.