Preservação da fertilidade em homens jovens com câncer: conceitos atuais e o futuro

Over the past 40 years, the global profile of cancer is changing. Initially regarded as a disease of the rich countries, it is noted that currently most of its global burden comes from poor or developing countries. In recent decades cancer has become a public health problem worldwide, with alarming estimates for subsequent decades. In Brazil, the estimates for the year 2012 will be valid for the year 2013 and reveals the occurrence of approximately 518,510 new cases of cancer, including cases of non-melanoma skin. Are expected a total of 257,870 new cases for males. The great thing is that about 10% of these cases are in the age group below 45 years and 1% below 20 years of age. Although the current treatment of cancer has increased considerablysurvival rates at 5 years young patients, it is almost invariably associated with great risk of infertility, leading to significant negative impact in the lives of these young men. This review article discusses the most current concepts in preserving fertility in young men treated for cancer, the growth of this field within the oncology and urology and the future of this topic so relevant to our population. Even today there is a important disconnect between the world and medical practice guidelines, when it comes to fertility preservation in men with cancer of reproductive age.Nos últimos 40 anos, o perfil mundial do câncer vem mudando. Encarado inicialmente como uma doença dos países ricos, nota-se atualmente que a maior parte de seu ônus global provêm de países de poucos recursos ou em desenvolvimento. Nas últimas décadas o câncer se tornou um problema de saúde pública mundial, com estimativas alarmantes para as décadas subseqüentes. No Brasil, as estimativas para o ano de 2012 serão válidastambém para o ano de 2013 e revelam a ocorrência de aproximadamente 518.510 casos novos de câncer, incluindo os casos de pele não melanoma. São esperados um total de 257.870 casos novos para o sexo masculino. A grande questão é que cerca de 10% destes casos serão na faixa etária inferior a 45 anos e 1% abaixo de 20 anos de idade. Embora o tratamento atual do câncer tenha aumentadoconsideravelmente as taxas de sobrevida em 5 anos de pacientes jovens, ele quase que invariavelmente estará associado a enorme risco de infertilidade, levando a impacto negativo importante na vida destes jovens homens. Este artigo de revisão aborda os mais atuais conceitos em preservação de fertilidade em homens jovens tratados de câncer, o crescimento deste campo dentro da oncologia e da urologia e o futuro deste tema tão relevante para nossa população. Até hoje existe uma importante desconexão entre os guidelines mundiais e a prática médica, quando o assunto é preservação da fertilidade em homens com câncer em idade reprodutiva

Resultados oncológicos da nefrectomia radical laparoscópica no tratamento do carcinoma renal

PURPOSE: To report the 5-year oncological outcomes of patients undergoing laparoscopic radical nephrectomy for renal cancer compared to a cohort of patients undergoing open radical nephrectomy. METHODS: We retrospectively analyzed the data of 88 patients undergoing radical nephrectomy for renal cell carcinoma prior to January 2000. Of these, 45 patients underwent laparoscopic radical nephrectomy, and 43 patients underwent open radical nephrectomy. Inclusion criteria comprised clinically organ-confined tumors of 15 cm or less in size without concomitant lymphadenopathy or vena cava thrombus. Oncological follow-up data were obtained from charts, radiological reports, and phone calls to patients or their families, and were calculated from the date of surgery to the date of last appointment with physician or date of death. RESULTS: All laparoscopic procedures were completed without open conversion. On comparing the laparoscopic radical nephrectomy and open radical nephrectomy groups, mean tumor size was 5. 8 vs 6.2 cm (P = . 44), mean blood loss was 183 vs 461 mL (P = . 004), and mean operative time was 2.8 vs 3.7 hrs (P < . 001). Over a mean follow-up of 5 years in the laparoscopic radical nephrectomy group and 6 years in the open radical nephrectomy group, the overall survival was 81% vs 79% (P = . 47), and cancer-specific survival was 90% vs 92% (P = . 70) , respectively. CONCLUSIONS: Laparoscopic radical nephrectomy for renal cancer confers equivalent 5-year oncological outcomes to those of open surgery.OBJETIVO: Relatar os resultados oncológicos após 5 anos de seguimento em pacientes submetidos a nefrectomia radical laparoscópica para tratamento do câncer renal, comparando esses com os resultados obtidos com um grupo de pacientes submetidos a nefrectomia radical aberta. MÉTODOS: Foram analisadas retrospectivamente as informações obtidas de 88 pacientes submetidos a nefrectomia radical para o tratamento do carcinoma renal realizadas previamente a Janeiro de 2000. Destes pacientes, 45 foram tratados com nefrectomia radical laparoscópica e 43 com nefrectomia radical aberta. Foram incluídos pacientes com tumores localizados com tamanho máximo de 15 cm, sem adenopatia ou sinal de envolvimento de veia renal na avaliação radiologica pré-operatória. As informações sobre o seguimento dos pacientes foram obtidas a partir de prontuários, laudos de exames radiológicos e ligações telefônicas para pacientes e/ou familiares. O seguimento foi calculado desde a data da cirurgia até a última consulta médica ou data de falecimento. RESULTADOS: Todos os procedimentos laparoscópicos foram realizados sem conversão para a técnica aberta. O tamanho médio tumoral foi de 5.8 e. 6.2 cm (P=0.44), perda sanguínea estimada de 183 e. 461 mL (P=0.004), e tempo operatório de 2.8 e. 3.7 horas (

Summary evidence on the effects of varicocele treatment to improve natural fertility in subfertile men

The objective of this review was to summarize the evidence concerning the benefit of varicocele treatment to improve natural fertility in subfertile males. We also analyzed the effect of varicocele treatment on conventional semen parameters and sperm functional tests. An electronic search to collect the data was performed using the PubMed/MEDLINE databases until July 2015. Data pooled from a variety of study designs indicate that varicocelectomy improves semen parameters in the majority of the treated men with clinical varicocele and abnormal semen parameters regardless of the chosen surgical method. Surgical varicocele repair was beneficial not only for alleviating oxidative stress-associated infertility but also to improve sperm nuclear DNA integrity. However, given the low magnitude of the effect size in sperm DNA integrity, further research is needed to elucidate its clinical significance. Conflicting results on the effect of varicocele treatment on natural fertility seem to be due to heterogeneous study designs and, more importantly, patient selection criteria. When these issues are controlled, current evidence indicates that treatment of subclinical varicocele is not warranted, as it does not seem to improve fertility. On the contrary, fair evidence indicates that varicocele treatment should be offered to infertile patients with palpable varicocele and abnormal semen parameters. This evidence supports the current guidelines issued by the American Urological Association and European Association of Urology, which state that varicocele treatment should be offered to male partners of infertile couples presenting for evaluation with clinical varicocele and semen parameters alterations

Clinical relevance of oxidative stress and sperm chromatin damage in male infertility: an evidence based analysis

Oxidative stress (OS) in the reproductive tract is now a real entity and concern due to the potential harmful effects of high levels of reactive oxygen species (ROS) on sperm number, motility, quality, and function including damage to sperm nuclear DNA. Evaluation of OS related damage to non-functional sperm is highly relevant as intracytoplasmic sperm injection (ICSI) technique, an effective therapy for severe male factor infertility, bypasses the majority of reproductive tract deficiencies. Despite the controversial findings in the existing literature, there is now enough evidence to show that sperm DNA damage is detrimental to reproductive outcomes. In addition, spermatozoa of infertile men are suggested to carry more DNA damage than do the spermatozoa from fertile men. Besides impairment of fertility such damage is likely to increase the transmission of genetic diseases during the assisted reproductive procedures. Standardization of protocols to assess reactive oxygen species and DNA damage is very important in introducing these tests in such clinical practice. Thus evaluation of seminal ROS levels and extent of sperm DNA damage especially in an infertile male may help develop new therapeutic strategies and improve success of assisted reproductive techniques (ART)

Grade 3 Varicocele in Fertile Men: A Different Entity

Purpose: Although varicocele size has an inverse relationship with baseline semen parameters and a direct relationship with seminal reactive oxygen species in infertile patients, to our knowledge the effect of varicocele grade in fertile men is unknown. We evaluated the impact of varicocele grade on seminal parameters, testicular size and seminal reactive oxygen species in fertile men. Materials and Methods: We prospectively evaluated 194 men from July 2004 to April 2010. Of the men 156 were fertile and classified by presence of varicocele. A total of 38 infertile patients with varicocele as the only identifiable cause of infertility comprised the control group. Physical examination, semen parameters and seminal reactive oxygen species were compared between the groups. Results: Of 156 fertile men 43 (24.3%) had clinical varicocele, which was grade 1 to 3 in 22, 11 and 10, respectively. The remaining 113 men (72.7%) had no varicocele. Infertile men had smaller testes, decreased semen parameters and higher seminal reactive oxygen species than the fertile groups. Testicular size, reactive oxygen species and semen parameters did not differ between fertile men with vs without varicocele. Fertile men with varicocele grade 3 had higher seminal reactive oxygen species than those with lower grade varicocele. As varicocele grade increased, seminal reactive oxygen species increased and sperm concentration decreased. Conclusions: Although fertile men have more efficient defense mechanisms to protect against the consequences of varicocele on testicular function, these mechanisms may not be sufficient in those with varicocele grade 3. Further research is needed to clarify whether they are at increased risk for future infertility

Organ-Sparing Microsurgical Resection of Incidental Testicular Tumors Plus Microdissection for Sperm Extraction and Cryopreservation in Azoospermic Patients: Surgical Aspects and Technical Refinements

INTRODUCTION The management of nonpalpable testicular masses is a challenging task, and coexisting infertility can further complicate the treatment decisions. We present our technique for microsurgical organ-sparing resection of incidental nonpalpable testicular nodules combined with microdissection for testicular sperm extraction and tissue cryopreservation in azoospermic patients. TECHNICAL CONSIDERATIONS Five infertile patients with azoospermia presented with nonpalpable hypoechoic testicular masses that were detected by Ultrasonography and underwent organ-sparing surgery. The testis was delivered through an inguinal incision, and the blood circulation was interrupted with a vascular clamp placed on the spermatic cord. Sludged ice was used to prevent warm ischemia, and a temperature probe was used to control the temperature at 12 degrees-15 degrees C. Real-time reflex ultrasonography was used to locate the tumor, and a stereotaxic hook-shaped needle was inserted under ultrasound guidance. The needle was placed adjacent to the tumor to guide the microsurgical resection. The tunica albuginea was incised over the tumor, which was dissected and removed, along with the adjoining parenchymal tissue. Frozen section studies were performed and, if malignancy was confirmed, biopsies of the tumor cavity margins and remaining parenchyma were obtained to ensure the absence of residual tumor. Microdissection was performed for excision of selected enlarged tubules that were processed and cryopreserved. CONCLUSIONS We present a technique for microsurgical organ-sparing resection of testicular tumor and sperm extraction that can be used in selected infertile patients with azoospermia in whom incidental masses have been diagnosed by ultrasonography. This conservative approach should be especially considered for patients with a solitary testis or bilateral tumors. UROLOGY 73: 887-892, 2009. (C) 2009 Elsevier Inc

Oncological outcomes of laparoscopic radical nephrectomy for renal cancer

PURPOSE: To report the 5-year oncological outcomes of patients undergoing laparoscopic radical nephrectomy for renal cancer compared to a cohort of patients undergoing open radical nephrectomy. METHODS: We retrospectively analyzed the data of 88 patients undergoing radical nephrectomy for renal cell carcinoma prior to January 2000. Of these, 45 patients underwent laparoscopic radical nephrectomy, and 43 patients underwent open radical nephrectomy. Inclusion criteria comprised clinically organ-confined tumors of 15 cm or less in size without concomitant lymphadenopathy or vena cava thrombus. Oncological follow-up data were obtained from charts, radiological reports, and phone calls to patients or their families, and were calculated from the date of surgery to the date of last appointment with physician or date of death. RESULTS: All laparoscopic procedures were completed without open conversion. On comparing the laparoscopic radical nephrectomy and open radical nephrectomy groups, mean tumor size was 5. 8 vs 6.2 cm (P = . 44), mean blood loss was 183 vs 461 mL (P = . 004), and mean operative time was 2.8 vs 3.7 hrs (P OBJETIVO: Relatar os resultados oncológicos após 5 anos de seguimento em pacientes submetidos a nefrectomia radical laparoscópica para tratamento do câncer renal, comparando esses com os resultados obtidos com um grupo de pacientes submetidos a nefrectomia radical aberta. MÉTODOS: Foram analisadas retrospectivamente as informações obtidas de 88 pacientes submetidos a nefrectomia radical para o tratamento do carcinoma renal realizadas previamente a Janeiro de 2000. Destes pacientes, 45 foram tratados com nefrectomia radical laparoscópica e 43 com nefrectomia radical aberta. Foram incluídos pacientes com tumores localizados com tamanho máximo de 15 cm, sem adenopatia ou sinal de envolvimento de veia renal na avaliação radiologica pré-operatória. As informações sobre o seguimento dos pacientes foram obtidas a partir de prontuários, laudos de exames radiológicos e ligações telefônicas para pacientes e/ou familiares. O seguimento foi calculado desde a data da cirurgia até a última consulta médica ou data de falecimento. RESULTADOS: Todos os procedimentos laparoscópicos foram realizados sem conversão para a técnica aberta. O tamanho médio tumoral foi de 5.8 e. 6.2 cm (P=0.44), perda sanguínea estimada de 183 e. 461 mL (P=0.004), e tempo operatório de 2.8 e. 3.7 horas (P<0.001) , respectivamente para os grupos nefrectomia radical laparoscópica e nefrectomia radical aberta. O tempo de seguimento médio foi de 5 anos para o grupo nefrectomia radical laparoscópica e 6 anos para o grupo nefrectomia radical aberta. A sobrevida global após 5 anos foi de 81% e 79% (P=0.47), e a sobrevida específica para cancer foi de 90% e 92% (P=0.70), para os grupos nefrectomia radical laparoscópica e nefrectomia radical aberta respectivamente. CONCLUSÃO: A nefrectomia radical laparoscópica tem resultados oncológicos em 5 anos similares a técnica convencional aberta

Use of subinguinal incision for microsurgical testicular biopsy during varicocelectomy in men with nonobstructive azoospermia

Objective: To describe a subinguinal technique of microsurgical testicular biopsy performed during subinguinal varicocelectomy in men with nonobstructive azoospermia. Design: Prospective clinical study. Setting: Andrology laboratory at tertiary care hospital. Male infertility section, department of urology, at tertiary care hospital. Patient(s): Ten azoospermic men with clinical varicocele. Intervention(s): Subinguinal microsurgical testicular biopsy and microsurgical varicocele repair. Main Outcome Measure(s): Safety, feasibility, and effectiveness of subinguinal testicular biopsy during varicocele repair. Result(s): All testes were easily delivered through the subinguinal incision, and testicular biopsies were successfully performed under microscopic view. After a median follow-up of 9 months, none of the patients had any discomfort, pain, or presented with testicular atrophy. No intraoperative or postoperative complications were observed. There was no incidence of wound infection or scrotal hematoma. Conclusion(s): The subinguinal approach is a safe and effective option for testicular biopsy during varicocele repair in men with nonobstructive azoospermia. This technique may be an attractive alternative to traditional biopsy because it obviates scrotal violation. (Fertil Steril (R) 2009;91:925-8. (c) 2009 by American Society for Reproductive Medicine.

Age-related increase of reactive oxygen species in neat semen in healthy fertile men

OBJECTIVES The effects of advancing paternal age on the male reproductive system are well known, but its effects on fecundity remain controversial. Although oxidative stress is associated with poor semen quality and function, a relationship with advancing male age has not been established. The objective of this study was to analyze the relationship between male age and seminal reactive oxygen species (ROS) levels in men presenting for voluntary sterilization. METHODS We prospectively evaluated 98 fertile men who were candidates for vasectomy. These were divided into 2 age groups: less than 40 years (n = 78) and 40 or more years (n = 20). We used 46 infertile patients as positive controls. Standard semen analysis, seminal leukocyte count and ROS levels were measured in all samples. Fertile men with leukocytospermia were excluded. RESULTS The mean age of the men was 35.1 +/- 5.6 years. Men 40 years and older had significantly higher ROS levels compared with younger men (P < 0.001). We observed a positive correlation between seminal ROS levels and age (r = 0.20; P = 0.040). In addition, ROS was negatively correlated with sperm concentration (r = -0-48; P < 0.001) and motility (r = -0.21; P = 0.030). CONCLUSIONS Reactive oxygen species levels are significant higher in seminal ejaculates of healthy fertile men older than 40 years. ROS levels in whole ejaculate are significantly correlated to age among fertile men. Because ROS are clearly implicated in the pathogenesis of male infertility, these data suggest that delayed fatherhood may reduce the chances of pregnancy as men become progressively less fertile with age