New tools for assessing the individual risk of metastasis in renal cell carcinoma.

Localized renal cell carcinoma (RCC) progresses to metastatic disease in 20-40 % after surgical resection. Affected patients might benefit from adjuvant treatment and have to be reliably identified for treatment indication. However, existing molecular markers and classification nomograms lack sufficient validity for clinical application so far. Therefore, in order to improve diagnostic tools for the identification of patients at risk, we tested invasiveness and the capability to activate vascular endothelium of primary RCC cells as tumor specific functional parameters. As a parameter for cell invasiveness the ability of RCC cells to break-down transepithelial electrical resistance (TEER) of an epithelial cell monolayer was tested. Loss of resistance, calculated as invasivity index, resembled the degree of cell invasiveness. In addition, secretion of Von Willebrand Factor by endothelial cells incubated with RCC cell supernatant was measured as a surrogate marker for endothelial cell activation. TEER-assay results matched clinical status of disease in 9 out of 12 cases. Metastatic tumors and less differentiated tumors had a significant increase of invasivity index (p = 0.007; p = 0.034). Endothelial cell activation and clinical outcome matched in 5 out of 9 samples. In addition, tumor cell induced endothelial cell activation significantly correlated to the pathologic T classification status of RCC tumors (p = 0.009). Taken together, our study validated endothelial cell activation analysis and cell invasiveness as solitary prognostic markers for tumor dissemination. TEER-analysis has proven to be a useful functional assay giving highly relevant individual information on functional tumor cell characteristics that add to pathologic evaluation.

Chronic pain has a negative impact on sexuality in testis cancer survivors.

Testis cancer is a disease that directly affects a man's sense of masculinity and involves treatments compromising sexual function. The aim of this study was to investigate the prevalence of sexual dysfunction and the influence of chronic pain on sexuality in long-term testis cancer survivors. Thus, we examined 539 patients after they had one testis removed because of a testicular germ cell tumor. Having completed oncologic therapy, all patients received a detailed questionnaire asking about the occurrence and clinical presentation of testis pain before and after orchiectomy. In addition, items from the abridged International Index of Erectile Function and Brief Sexual Function Inventory were used to gain precise information on individual sexual function. Overall, 34.5% of our testicular cancer survivors complained of reduced sexual desire, and sexual activity was reduced in 41.6%. Erectile dysfunction was present in up to 31.5% of patients. In 24.4%, the ability to maintain an erection during intercourse was impaired. Ejaculatory disorders (premature, delayed, retrograde, or anejaculation) occurred in 84.9% of our testis cancer survivors. A total of 32.4% of our participants experienced a reduced intensity of orgasm, and 95.4% experienced reduced overall sexual satisfaction. There was a significant correlation between the occurrence of chronic pain symptoms and the relative frequency and intensity of erectile dysfunction, inability to maintain an erection, ejaculation disorders, and reduced intensity of orgasm. In conclusion, chronic pain has a negative impact on sexuality in testis cancer survivors.

Bilateral histological evaluation of exocrine testicular function in men with obstructive azoospermia: condition of spermatogenesis and andrological implications?

BACKGROUND: The aim of this study was to investigate whether there is a need for diagnostic biopsies in men with obstructive azoospermia (OA). METHODS: Sixty-three adult men with OA due to vasectomy, bilateral inflammation or bilateral aplasia of the vas deferens were included in the study. We determined testicular volume, sexual hormone levels and testicular histologies of right and left testes (236 biopsies from 118 testes) during diagnostic and therapeutic infertility surgery (microsurgical vasal reconstruction or testicular/epididymal sperm extraction). Spermatogenesis was histologically classified according to the Holstein score from 0 (Sertoli cell-only, complete absence of germ cells) to 10 (100% of tubules with elongated spermatids). RESULTS: All patients (mean age 34 ± 5 years) had low glucosidase levels (5.4 ± 4.2 mU/ejaculate), normal serum FSH levels (4.6 ± 2.5 mU/ml) and normal testicular volumes (right 21 ± 8 ml; left 19 ± 6 ml). Median histological score for right and left testis was 9. There were eight patients with score differences ≥ 3 between right and left testis (14% of men), showing that even in men with OA, there may be differences in spermatogenic activity between both sides. In all of these patients, normal spermatogenesis was found in the larger testis. Testicular histology (spermatogenesis score) was positively correlated with testicular volume and negatively correlated with FSH levels. CONCLUSIONS: Patients with OA may not need to be biopsied for diagnostic purposes. Our data support the use of unilateral therapeutic biopsy in men with OA and that the larger testicle should be operated on when there is a significant difference in size.

Phantom testis syndrome: prevalence, phenomenology and putative mechanisms.

Chronic phantom pain has been found in up to 78% of limb amputees and is a major complication of limb amputation. Less is known about phantom phenomena after the amputation of other, i.e. visceral, parts of the body. In a retrospective design, we identified 539 patients in whom one testis was removed between 1995 and 2005. The operative technique was a unilateral standard radical inguinal orchiectomy. The underlying pathology in all cases was a testicular germ cell tumour. All patients received a detailed questionnaire asking about the occurrence of phantom testis pain (pain felt in the removed testis), phantom testis sensations (non-painful sensations as if the removed testis was still intact) and hallucinations (illusionary perceptions on the removed testis). Furthermore, we asked about the occurrence and clinical presentation of pain before and after surgery and about pre-operative testicular pain. Out of 238 respondents, 125 patients (53%) reported any kind of phantom experience. The prevalence of phantom testis pain was 25% (60/238), non-painful phantom sensations 16% (37/238) and male gonad hallucinations 12% (28/238). Patients with phantom symptoms reported pre-operative pain in the removed testis more often than patients without phantom symptoms. This study presents first data on the clinical characteristics and possible mechanisms of the phantom testis syndrome after surgical removal of one testis.

Multiorgan failure 17 years after initial stone therapy: forgotten ureteral stent in a horseshoe kidney.

We report on the case of a 44-yr-old white man who was referred as an emergency from a local hospital to the medical intensive care unit (ICU) at our institution for progressive multiorgan failure of unknown cause. The CT scan of the abdomen showed a horseshoe kidney with extensive stone formation in both kidneys and the urinary bladder. A massively calcified double pigtail ureteral stent could also be seen in the left upper urinary tract. The stent had been placed prior to extracorporeal shock wave lithotripsy (ESWL) therapy 17 years previously. Three weeks later, after conservative treatment for heart failure and septic complications, the massively enlarged hydronephrotic left part of the horseshoe kidney was exposed and heminephroureterectomy was performed. Moreover, a right-sided pyelotomy was performed. Midline vesicotomy allowed extraction of the remaining bladder stone including the rest of the forgotten pigtail stent. The patient recovered rapidly after surgery and was discharged after 2 wk with all drains removed.

Update on the diagnostic safety for detection of testicular intraepithelial neoplasia (TIN).

Testicular intraepithelial neoplasia (TIN) of the testis is the noninvasive precursor of testicular germ cell tumours (GCT) and can be detected by a single random biopsy in 5% of patients with GCT in the contralateral testes. Although it is generally presumed that TIN is dispersed throughout the testis, we realize in about 60% of TIN bearing tissue close to testis tumours that its distribution is not homogenously diffuse, but may be focal. Thus we tested whether we can improve diagnostic safety in detecting TIN by increasing the number of biopsies. We could finally evaluate 295 men with proven testicular tumours. Three biopsies of contralateral testes were taken (each 5 mm length) from one surgical incision site and fixed in Bouin's solution or glutaraldehyde. TIN cells were histologically identified by their typical morphological characteristics and additionally by placental alkaline phophatase (PlAP) immunohistochemistry. Patients revealed testicular tumour without contralateral TIN in 271 cases and with contralateral TIN in 24 cases (8.1%). In 6 of these 24 men with contralateral TIN the cells could be detected in only one (n=5) or two (n=1) of the three specimen investigated. That means in these six patients TIN could have been missed if only one single random biopsy was taken. By increasing the number of biopsies (=increasing the number of investigated seminiferous tubules) the detection rate of contralateral TIN may be increased up to 8.1%. Thus we recommend multiple testicular biopsies to increase the diagnostic safety in detection of TIN. Biopsies may be taken from one randomly chosen surgical incision site.