Is anastomotic biopsy necessary before radiotherapy after radical prostatectomy?

PURPOSE: External beam radiotherapy may be given after radical prostatectomy as adjuvant (immediate) or therapeutic (delayed) treatment, the latter in response to evidence of disease recurrence. In patients receiving delayed radiotherapy the necessity of a positive anastomotic biopsy before treatment remains unclear. We determined whether a positive anastomotic biopsy predicted the response to radiation in this setting. MATERIALS AND METHODS: We reviewed the records of 67 patients who received radiotherapy for biochemical or biopsy proved recurrent prostate cancer after radical prostatectomy. Patients underwent surgery at our institution or its affiliated hospitals, or were referred to our institution for radiotherapy. All patients had a negative metastatic evaluation before receiving radiotherapy. Biochemical failure after radiotherapy was defined as serum prostate specific antigen (PSA) 0.2 ng./dl. or greater on 2 or more consecutive occasions. Biochemical recurrence-free survival was calculated using the Kaplan-Meier method. Independent predictors of PSA failure after radiotherapy were identified using the multivariate Cox proportional hazards model. RESULTS: Of the 67 patients evaluated 33 and 34 received radiotherapy for biochemical failure and biopsy proved local recurrence, respectively. The 3-year recurrence-free survival rate was 49% in patients treated for biochemical failure and 39% in those with biopsy proved local recurrence. There was no significant difference in PSA-free survival in these 2 groups. Only pre-radiotherapy PSA 1 ng./dl. or greater (p = 0.02) and seminal vesicle invasion (p = 0.02) were significant independent predictors of biochemical failure. CONCLUSIONS: A positive anastomotic biopsy did not predict an improved outcome after radiotherapy following radical prostatectomy. Anastomotic biopsy was associated with a longer time to salvage radiotherapy. However, this delay did not translate into worse disease-free outcomes in patients who underwent anastomotic biopsy. High pre-radiotherapy PSA greater than 1 ng./ml. was the most significant predictor of biochemical failure after therapeutic radiotherapy. Decisions regarding local radiation therapy after radical prostatectomy may be made without documenting recurrent local disease.

Is intracytoplasmic sperm injection safe? Current status and future concerns.

In vitro fertilization with intracytoplasmic sperm injection (ICSI) has revolutionized the treatment of patients with severe forms of male infertility. However, because ICSI has been performed for only 10 years, long-term outcomes and risks to offspring remain largely unknown. The fact that ICSI can potentially bypass natural selection barriers to genetic disease transmission has brought a sobering but important impetus to recent research on the risks and outcomes of ICSI. Several studies were done recently to examine specific risks to children born following ICSI. Because of rapid advances in the ICSI procedure itself, studies evaluating the safety of using immature sperm forms from the testis (spermatids, spermatocytes) also have been undertaken. This review summarizes recent studies examining the risks and long-term outcomes to date of in vitro fertilization with ICSI.

Increased frequency of mutations in DNA from infertile men with meiotic arrest.

In diverse organisms from yeast to mice, mutations in numerous genes required for DNA repair may lead to defects in meiosis. Although it is likely that meiosis is conserved throughout evolution, little is known about the genetics of meiosis in humans even though meiotic arrest associated with azoospermia is common. In this work, we compared the sequence fidelity of a polymorphic marker amplified from DNA of two groups of patients: those with testis biopsy suggesting meiotic arrest and those with normal spermatogenesis who were obstructed. We demonstrated that mutations are more common in DNA from testicular tissue derived from men with meiotic arrest than in DNA from testicular tissue derived from men with normal spermatogenesis and physical obstruction (P < 0.05). No mutations were observed in blood tissue from either group of men. This suggests the possibility that defects in genes required in DNA repair could contribute to meiotic arrest in men just as has been observed in other organisms.

Management of a positive surgical margin after radical prostatectomy: decision analysis.

PURPOSE: We created and tested a decision analysis model to help determine the preferred management of a positive surgical margin(s) after radical prostatectomy. MATERIALS AND METHODS: We constructed a decision tree modeling surveillance versus immediate prophylactic adjuvant radiation in patients with a positive surgical margin(s) after radical prostatectomy. Literature and institution based estimates were determined for certain factors, including the probability of undetectable prostate specific antigen (PSA) in patients followed expectantly postoperatively and those treated with immediate adjuvant radiotherapy, complications of radiotherapy after prostatectomy and probability of undetectable PSA in those treated with therapeutic radiation for detectable PSA postoperatively. A panel of experts assigned utilities to the various outcomes. Sensitivity analysis was performed to determine threshold values required to change the model outcome. RESULTS: Using average probability estimates from a literature review the decision model recommended initial surveillance. Sensitivity analysis demonstrated that the model depended on the probability of disease recurrence in men followed expectantly after surgery as well as the efficacy of therapeutic radiation. We tested the decision model again for patient groups based on tumor grade, pathological stage, preoperative PSA and number of positive margins. The model recommended initial radiation for patients with low to intermediate grade disease, no evidence of seminal vesicle invasion and multiple positive margins. CONCLUSIONS: The results of our decision analysis imply that immediate radiation may be appropriate for patients with a positive surgical margin(s) and a high likelihood of recurrent local rather than distant disease. This model may be useful to physicians and patients who use individual probability estimates and utility values to determine the preferred course of management after surgery.

Imaging for recurrent prostate cancer.

Multiple imaging modalities are available to evaluate recurrent prostate cancer following primary treatment with RP, RT, or cryo-surgery. These tests must be used in close conjunction with clinical parameters, such as the characteristics of the tumor itself (grade, stage) as well as specific PSA characteristics that can help predict the sites of probable recurrence. Figure 19 represents an algorithm of how patients can be monitored for recurrence according to their mode of primary treatment. As more treatments become available for recurrent prostate cancer, it will be necessary to monitor disease response with many of the imaging modalities discussed in this article.

Compound genetic factors as a cause of male infertility: case report.

A 40 year old healthy Chinese male with primary infertility was seen in a university male infertility and genetic counselling clinic. He presented with congenital bilateral absence of the vas deferens (CBAVD) and the finding of testis atrophy. Fine needle aspiration mapping of the testis identified and localized sperm production within the testicles for in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Careful evaluation of testicular cytology revealed late maturation arrest of spermatogenesis. Cystic fibrosis gene mutation analysis revealed heterozygosity for the 5T variant within the polypyrimidine tract of intron 8. Cytogenetic analysis revealed a pericentric inversion of chromosome 6 with break points at p12 and q21 [46,XY,inv(6)(p12q21)]. This case illustrates that spermatogenesis is not necessarily normal with congenital bilateral absence of the vas deferens. Compound genetic defects may coexist and underlie male infertility.

Genetic causes of male infertility: current concepts.

Infertile men with severe spermatogenic defects and low or no sperm counts have a significantly higher rate of genetic abnormalities than fertile men. The fact that intracytoplasmic sperm injection can potentially bypass natural selection barriers to genetic disease transmission has brought a sobering but important impetus to recent research in the area of genetic infertility. Recent studies have focused on examining the prevalence of certain genetic defects in infertile men, analyzing the molecular basis of infertility in genetic disorders, and detecting new causes of genetic infertility. Several novel research findings deserve mention for their potential impact on genetic infertility. It has been demonstrated that elongated and round spermatids can be successfully injected into human oocytes and viable births obtained. Likewise, significant advances have been made in the arena of interspecies germ cell transplantation. Of some concern is the finding of a relationship between faulty DNA repair and infertility in men with severe testis failure. This review summarizes the recent genetic advances in these areas of male genetic infertility.

Radiotherapy after radical prostatectomy: treatment outcomes and failure patterns.

OBJECTIVES: To define the optimal role for radiotherapy (RT) after radical prostatectomy (RP) and to characterize specific patterns of PSA failure in this setting. METHODS: The records of 105 patients who underwent RT after RP (69 received therapeutic RT because of an elevated prostate-specific antigen [PSA] level, 36 received immediate adjuvant RT) were reviewed. The median follow-up was 35 months after RT and 57 months after RP. Radiation success was defined as achievement and maintenance of a PSA less than 0.2 ng/mL. Preoperative, pathologic, and postoperative characteristics were examined for their ability to predict success after RT. Patterns of PSA recurrence after RT were also examined by determining the PSA nadir, PSA velocity, and timing of androgen-deprivation therapy. RESULTS: Of 105 patients, 47 experienced biochemical failure. Actuarial 3 and 5-year progression-free survival estimates for all patients were 55% and 43%, respectively. Significant favorable predictors of response to RT by multivariate analysis were preoperative PSA less than 20 ng/mL and the use of adjuvant RT. However, patients who received therapeutic RT with a pre-RT PSA less than 1.0 ng/mL demonstrated progression-free outcome equivalent to those who received adjuvant RT. Two distinct patterns of PSA failure were observed on the basis of PSA nadir after RT. Patients whose PSA failed to reach a nadir less than 0.2 ng/mL after RT had progression with a high PSA velocity (1.5 ng/mL/yr). Patients whose PSA reached a nadir less than 0.2 ng/mL but who subsequently had treatment failure progressed later with a lower PSA velocity (0.36 ng/ml/yr). CONCLUSIONS: RT is effective in select patients after RP. Given the low PSA velocity consistent with persistent local disease in nearly 50% of patients in whom RT failed, more effective local therapy is needed after RP in high-risk patients.

The mini-micro-epididymal sperm aspiration for sperm retrieval: a study of urological outcomes.

Epididymal sperm aspiration and in-vitro fertilization (IVF) with intracytoplasmic sperm injection is an established treatment for obstructive azoospermia. Sperm aspiration is performed with either an incision or percutaneously. To control costs, minimize morbidity and retain the advantages of both approaches, we developed a mini-incision technique for epididymal aspiration and here report sperm retrieval and procedure-related outcomes. Twenty-six consecutive patients with obstructive azoospermia underwent epididymal sperm retrieval through a 1 cm incision with local anaesthesia to provide spermatozoa for concurrent IVF cycles. The quality of retrieved spermatozoa, the quantity of spermatozoa cryopreserved as well as anaesthetic requirement, recovery time and patient satisfaction were evaluated. Fresh epididymal spermatozoa were retrieved in 25 of 26 (96%) patients. In one patient, testicular sperm extraction was necessary. Excess motile spermatozoa were cryopreserved in 24 of 26 (92%) patients; a mean total motile count of 4.8x10(6) motile spermatozoa were banked. The procedure was performed with 62% of patients receiving minimal i.v. sedation. Post-procedure recovery was rapid, with a median time to return to work of 2.0 days with a median of 2.0 pain pills taken. Procedure-related satisfaction was high. The mini-micro-epididymal sperm aspiration achieves the goals of reliable retrieval of abundant epididymal spermatozoa with a single, minimally morbid procedure. It appears to combine the advantages of the incision and percutaneous approaches.

Intestinal lactase: maturational excess expression of mRNA over enzyme protein.

The mechanism of decline of intestinal lactase during mammalian development remains uncertain. Despite a major loss of catalytic activity, lactase mRNA appears to persist at detectable concentrations in adult rats. We quantified lactase activity, total lactase protein, and lactase mRNA in rats aged 7, 11, 15, 18, 22, 30, and 60 days using the 7S ribosomal RNA as the developmental control. The active lactase fraction was 0.81 of total lactase for all age groups except 60-day-old animals, in which it declined to 0.60 (P = 0.004), indicating that conversion of active lactase to inactive species contributed to the lower activity in the adult. Northern blots revealed a single discrete 6.8-kb message at all ages. Although lactase activity and immunoprotein decreased coordinately to a minimum by day 30 (20% of the 7-day value), lactase mRNA doubled to a maximum at day 22 and was maintained at 7-day concentrations even in 60-day adults. The lactase mRNA-to-protein ratio was low at 7 days (0.19) but more than doubled (0.50) by 22 days, achieved a fivefold increase (1.0) by 30 days, and persisted at 0.77 in adults. The relative excess of lactase message during maturation suggests that translational or post-translational events may be paramount in the developmental regulation of lactase gene expression.