Wayland Hsiao

Successful Treatment of Postchemotherapy Azoospermia With Microsurgical Testicular Sperm Extraction: The Weill Cornell Experience

UNLABELLED PURPOSE; Advances in chemotherapy have led to greater longevity and paternity may be an important consideration for postchemotherapy survivors of childhood cancers. While traditionally considered sterile, men who are azoospermic after chemotherapy can be treated with microdissection testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). PATIENTS AND METHODS Oncologic data, pretreatment hormone profiles, testicular histology, and outcomes of microdissection TESE-ICSI were reviewed. ICSI was performed in a programmed in vitro fertilization cycle using fresh spermatozoa. Embryos were transferred into the uterine cavity on the third day after microinjection. RESULTS Eighty-four microdissection TESE procedures were performed in 73 patients. The mean time elapsed since chemotherapy was 18.6 years (range, 1 to 34 years). Spermatozoa were retrieved in 37% of patients and in 42.9% of overall procedures. A 57.1% fertilization rate (per injected oocyte) was achieved with ICSI allowing a 50% clinical pregnancy rate with a live birth rate of 42% overall. There were 15 deliveries, with a total of 20 children born. Hypospermatogenesis seen on preoperative biopsy was associated with 100% sperm retrieval while exposure to alkylating agents resulted in a significantly lower sperm retrieval rate. Patients with testicular cancer had the highest sperm retrieval rates while patients previously treated for sarcoma had the lowest retrieval rates. CONCLUSION To our knowledge, this represents the largest series of postchemotherapy microdissection TESE-ICSI to date. Sperm were retrieved in 37% of patients despite a prevalence of Sertoli cell-only pattern on preoperative biopsy. Although prechemotherapy sperm cryopreservation is recommended, treatment with microdissection TESE and ICSI are effective treatment options for many azoospermic men after chemotherapy.

Extensive Inguinal Lymphadenectomy Improves Overall 5-Year Survival in Penile Cancer Patients: Results From the Surveillance, Epidemiology, and End Results Program

European Urological Association guidelines recommend potentially curative inguinal lymphadenectomy for certain cases of penile cancer such as grade 3 and pT2‐4 lesions, among others. Anecdotally, the authors have noticed that few patients undergo inguinal lymphadenectomy. Therefore, they assessed the frequency of inguinal lymphadenectomy and the impact of dissection extent on survival using the Surveillance, Epidemiology, and End Results (SEER) database.

Older Age Is Associated With Similar Improvements in Semen Parameters and Testosterone After Subinguinal Microsurgical Varicocelectomy

PURPOSE It is generally accepted that men with clinically palpable varicocele are at high risk for a progressive decrease in fertility and testosterone levels with time. Varicocelectomy is thought to improve testicular function or at least halt the accelerated decrease in testicular function associated with varicocele. Substantial controversy exists as to whether varicocelectomy is effective in older men, possibly due to irreversible testicular damage or limited potential for recovery from varicocele induced damage. MATERIALS AND METHODS We retrospectively reviewed the records of men who underwent microsurgical subinguinal varicocelectomy, as done by a single surgeon. Demographics, patient questionnaires, operative notes, charts, testosterone and semen analysis were reviewed. Patients were divided into 3 groups based on age at surgery, including less than 30, 30 to 39 and 40 years or greater. RESULTS A total of 272 men met study inclusion criteria. In all 3 age groups we noted similar testosterone and baseline semen analysis parameters. There were significant increases in sperm concentration and total sperm count in all age groups. When analysis was restricted to men with baseline testosterone 400 ng/dl or less, there was a mean 110, 133 and 136 ng/dl increase in 21 men who were 40 years old or older, in 30 who were 30 to 39 years old and in 21 who were younger than 30 years, respectively. CONCLUSIONS Microsurgical varicocelectomy resulted in significant increases in sperm concentration, total sperm count and testosterone in all age groups studied, including men in the fifth and sixth decades of life. Microsurgical varicocelectomy should be offered to older men for infertility and/or hypogonadism.

Indications and strategies for fertility preservation in men.

Fertility preservation is feasible in the majority of men. Herein, we review the reproductive toxicities of commonly encountered clinical threats to male fertility, including cancer, radiotherapy, chemotherapy, surgery, and nonmalignant diseases treated with immunosuppression. Other scenarios, in which fertility preservation may be considered, such as Klinefelter syndrome, acute testicular injury, and sudden unexpected death, are also discussed. We provide an algorithmic approach to fertility preservation in men, and review strategies for sperm acquisition in cases of ejaculatory dysfunction and azoospermia. Lastly, emerging options for fertility preservation in prepubertal boys are discussed.

Exercise is Associated with Better Erectile Function in Men Under 40 as Evaluated by the International Index of Erectile Function

INTRODUCTION Studies have shown an association between erectile dysfunction and sedentary lifestyle in middle-aged men, with a direct correlation between increased physical activity and improved erectile function. Whether or not this relationship is present in young, healthy men has yet to be demonstrated. AIM The aim of this study was to assess the association between physical activity and erectile function in young, healthy men. MAIN OUTCOME MEASURES The primary end points for our study were: (i) differences in baseline scores of greater than one point per question for the International Index of Erectile Function (IIEF); (ii) differences in baseline scores of greater than one point per question for each domain of the IIEF; (iii) exercise energy expenditure; and (iv) predictors of dysfunction as seen on the IIEF. METHODS The participants were men between the ages of 18 and 40 years old at an academic urology practice. Patients self-administered the Paffenbarger Physical Activity Questionnaire and the IIEF. Patients were stratified by physical activity into two groups: a sedentary group (≤1,400 calories/week) and an active group (>1,400 calories/week). Men presenting for the primary reason of erectile dysfunction or Peyronies disease were excluded. RESULTS Seventy-eight patients had complete information in this study: 27 patients (34.6%) in the sedentary group (≤1,400 kcal/week) and 51 patients (65.4%) in the active group (>1,400 kcal/week). Sedentary lifestyle was associated with increased dysfunction in the following domains of the IIEF: erectile function (44.4% vs. 21.6%, P = 0.04), orgasm function (44.4% vs. 17.7%, P = 0.01), intercourse satisfaction (59.3% vs. 35.3%, P = 0.04), and overall satisfaction (63.0% vs. 35.3%, P = 0.02). There was a trend toward more dysfunction in the sedentary group for total score on the IIEF (44.4% vs. 23.5%, P = 0.057), while sexual desire domain scores were similar in both groups (51.9% vs. 41.2%, P = 0.37). CONCLUSIONS We have demonstrated that increased physical activity is associated with better sexual function measured by a validated questionnaire in a young, healthy population. Further studies are needed on the long-term effects of exercise, or lack thereof, on erectile function as these men age.

Outcomes of the management of post-chemotherapy retroperitoneal lymph node dissection-associated anejaculation

Study Type – Outcomes (cohort)

Stage IV Prostate Cancer: Survival Differences in Clinical T4, Nodal and Metastatic Disease

PURPOSE In the prostate specific antigen era most prostate cancer presents at an early stage. However, a significant number of patients have advanced disease, including those with stage IV disease. Assignment to stage IV prostate cancer may occur by different modes, namely as T4N0M0 vs N1 vs M1 disease. We hypothesize that patients with clinical T4 disease have better outcomes than those with N1 or M1 disease. MATERIALS AND METHODS A total of 17 SEER registries were queried from 1995 through 2003. Multivariate and univariate analyses examined overall survival and prostate cancer specific survival across subcategories of stage IV disease while controlling for various patient and disease related characteristics. RESULTS There were 615 patients with cT4N0M0 disease, 3,189 with TxN1M0 and 10,893 with TxNxM1 who met the study inclusion criteria. Survival differences were observed between cT4N0M0 and M1 cancer, between N1 and M1 disease, and were most pronounced in younger patients (age 50 years or younger), gradually narrowing with increasing patient age. Factors that demonstrated significant association with poor survival included higher tumor grade, unknown tumor grade and absence of a spouse. CONCLUSIONS Staging systems based on American Joint Committee on Cancer/TNM staging enables the grouping of patients into homogenous categories for treatment selection and prognostication. However, our data suggest that not all stage IV prostate cancers behave similarly. The difference in survival among locally advanced (T4), node positive and distantly metastatic stage IV prostate cancer appears to be dependent on patient age.

The TERE1 protein interacts with mitochondrial TBL2: Regulation of trans‐membrane potential, ROS/RNS and SXR target genes

We originally discovered TERE1 as a potential tumor suppressor protein based upon reduced expression in bladder and prostate cancer specimens and growth inhibition of tumor cell lines/xenografts upon ectopic expression. Analysis of TERE1 (aka UBIAD1) has shown it is a prenyltransferase enzyme in the natural bio‐synthetic pathways for both vitamin K‐2 and COQ10 production and exhibits multiple subcellular localizations including mitochondria, endoplasmic reticulum, and golgi. Vitamin K‐2 is involved in mitochondrial electron transport, SXR nuclear hormone receptor signaling and redox cycling: together these functions may form the basis for tumor suppressor function. To gain further insight into mechanisms of growth suppression and enzymatic regulation of TERE1 we isolated TERE1 associated proteins and identified the WD40 repeat, mitochondrial protein TBL2. We examined whether disease specific mutations in TERE1 affected interactions with TBL2 and the role of each protein in altering mitochondrial function, ROS/RNS production and SXR target gene regulation. Biochemical binding assays demonstrated a direct, high affinity interaction between TERE1 and TBL2 proteins; TERE1 was localized to both mitochondrial and non‐mitochondrial membranes whereas TBL2 was predominantly mitochondrial; multiple independent single amino acid substitutions in TERE1 which cause a human hereditary corneal disease reduced binding to TBL2 strongly suggesting the relevance of this interaction. Ectopic TERE1 expression elevated mitochondrial trans‐membrane potential, oxidative stress, NO production, and activated SXR targets. A TERE1‐TBL2 complex likely functions in oxidative/nitrosative stress, lipid metabolism, and SXR signaling pathways in its role as a tumor suppressor. J. Cell. Biochem. 114: 2170–2187, 2013.

Increased Low Density Lipoprotein and Increased Likelihood of Positive Prostate Biopsy in Black Americans

PURPOSE Differences in prostate cancer incidence, grade and stage at diagnosis, and survival in black vs nonblack men are well documented. Recent studies indicate that lipids may have a role in oncogenesis, including that of prostate cancer. We investigated the relationship between circulating lipids in black and nonblack patients, and newly diagnosed prostate cancer. MATERIALS AND METHODS The study population included consecutive patients who underwent prostate biopsy for increased prostate specific antigen and/or abnormal digital rectal examination at Atlanta Veterans Affairs Medical Center. Age, race, prostate specific antigen, prostate volume, body mass index, family history, high and low density lipoprotein, triglyceride and cholesterol lowering medications were included in data analysis. RESULTS A total of 1,775 men with complete information were included in data analysis. A total of 521 black and 451 white men had positive biopsies. Using 100 mg/dl or less as the referent the adjusted OR reflecting the association of low density lipoprotein and prostate cancer diagnosis in black men was 1.49 (95% CI 1.04-2.13, p = 0.031), 1.51 (95% CI 0.96-2.39, p = 0.076) and 3.24 (95% CI 1.59-6.92, p = 0.002) for low density lipoprotein greater than 100 to 130, greater than 130 to 160 and greater than 160 mg/dl, respectively. Corresponding results in nonblack men showed no significant association. CONCLUSIONS Increased serum low density lipoprotein is associated with an increased likelihood of prostate cancer diagnosis in black men but not in nonblack men. This association is strongest in the highest low density lipoprotein risk category. The reasons for the racial differences are unknown but may include genetic, dietary or other environmental factors.

Nomograms to Predict Patency After Microsurgical Vasectomy Reversal

PURPOSE After undergoing vasectomy up to 6% of men will elect to undergo vasectomy reversal. For these men paternity can be achieved with vasectomy reversal or surgical sperm retrieval coupled with assisted reproduction. Nevertheless, it remains difficult for surgeons to accurately counsel men on the chance of patency after vasectomy reversal. MATERIALS AND METHODS A retrospective review was conducted of 548 patients who underwent microsurgical vasectomy reversal. Surgery was considered successful if sperm concentration was 100,000 or more sperm per ml, total count was 100,000 or more sperm per ejaculate, motile sperm were present and there was no evidence of subsequent failure. A multivariate logistic regression model was constructed to calculate the probability of having a successful vasectomy reversal and nomograms for patency were generated from this model. RESULTS A total of 548 patients met the inclusion criteria for this study. Mean followup was 1.8 ± 0.10 years. Mean patient age was 43.4 ± 0.3 years and mean duration of obstruction was 10.4 ± 0.2 years. Two nomograms to predict patency were generated, one for preoperative counseling and a second for postoperative counseling. The factors with the largest effect on patency were average testicular volume and obstruction duration. The factor with the least effect was the presence of sperm granuloma. The concordance index for the preoperative and the postoperative nomograms was 0.64 and 0.66, respectively. CONCLUSIONS To our knowledge this represents the first use of nomograms to predict the likelihood of patency after microsurgical vasectomy reversal. These nomograms may prove useful to guide further treatment decisions.