The importance of the urologist in male oncology fertility preservation.

OBJECTIVES: To demonstrate that surgical sperm retrieval (SSR) and spermatogonial stem cell retrieval (SSCR) in an oncological context are safe and successful. PATIENTS AND METHODS: This a retrospective study in a tertiary hospital in the UK. Patients requiring fertility preservation from December 2017 to January 2020 were included. Data were analysed with Microsoft Excel 2016 and the Statistical Package for the Social Sciences (version 20). RESULTS: Among 1264 patients referred to the Reproductive Medical Unit at the University College of London Hospitals for cryopreservation prior to gonadotoxic treatment, 39 chose to go forward with SSR/SSCR because they presented as azoo-/cryptozoospermic or an inability to masturbate/ejaculate. Interventions were testicular sperm extraction (23 patients) or aspiration (one), electroejaculation (one), and testicular wedge biopsy for SSCR (14). The median (range) age was 15.0 (10-65) years and the median testosterone level was 4.4 nmoL/L. Primary diagnoses were sarcoma in 11 patients, leukaemia in nine, lymphoma in eight, testicular tumour in five, other oncological haematological entities in two, other solid cancers in two, while two patients had non-oncological haematological diseases. SSR/SSCR could be offered within 7.5 days on average. Chemotherapy could follow within 2 days from SSR/SSCR, and bone marrow transplant occurred within 19.5 days (all expressed as medians). The success rate for SSR was 68.0% (at least one vial/straw collected). The mean (SD) Johnsen score of testicular biopsies was 5.23 (2.25) with a trend towards positive correlation with SSR success (P = 0.07). However, age, hormonal profile and type of cancer did not predict SSR outcome. CONCLUSION: We show that SSR and SSCR in an oncological context are valid treatment options with a high success rate for patients in which sperm cryopreservation from semen is impossible. By providing an effective pathway, fertility preservation is possible with minimal delay to oncological treatment.

Stimulation of Leydig and Sertoli Cellular Secretory Function by Anti-Oestrogens: Clomiphene.

Leydig and Sertoli cells are essential for the testicular homeostasis. Clinically, the testicular homeostasis is impaired in hypogonadal and subfertile men. Therapeutically, the selective oestrogen receptor modulator clomiphene citrate (CC) is frequently used to treat these patients. In men, the mechanism of action of CC has long been thought to be limited to inhibition of the retro-control by oestrogen on the pituitary gland. However, oestrogen receptors are also expressed in the testis. Therefore, we will explore in this review the systemic effects as well as its action on reproductive function. We will describe in particular the possible effects of CC on the secretory functions of Leydig and Sertoli cells and their implication on the testicular microenvironment. CC is a costeffective and relatively safe off-label treatment for young hypogonadal men actively trying for a child or subfertile men with low testosterone with a positive effect on sperm concentration. Nevertheless, its effects on the oestrogen receptors and other signalling pathways at the testicular level remain poorly investigated. Further research, including combined treatment, could allow improving sperm morphology and sperm motility which do not seem to be significantly enhanced by CC alone.

[About the indications to urodynamic studies and to a prior antibioprophylaxy]. / Indications à un bilan urodynamique et à une antibioprophylaxie avant celui-ci.

In this review article, we refer to recent publications dealing with the indication to pressure-volume and pressure-flow studies using cystometry as well as the indication for antibioprophylaxis prior to these examinations. We conclude that despite various indications these examinations must be reserved for complex cases after exhaustive preliminary evaluation. Moreover, in case of complex urinary incontinence or neurogenic bladder videocystomanometry is recommended for a correct and complete diagnosis. In addition, antibiotic prophylaxis is no longer considered as necessary before these examinations, including for neurological patients.

Dans cet article de synthèse, nous nous référons aux publications récentes traitant de l'indication aux études pression-volume et pression-débit par cystomanométrie ainsi qu'à l'indication à une antibioprophylaxie avant ces examens. Nous concluons à des indications diverses mais réservées à des cas complexes après évaluation préalable exhaustive. De plus, en cas d'incontinence urinaire complexe ou en présence d'une vessie neurogène une vidéocystomanométrie est recommandée pour un diagnostic correct et complet. Par ailleurs, l'antibioprophylaxie n'est plus considérée comme nécessaire avant ces examens, y compris pour les patients neurologiques.

Is there a need for smooth muscle cell transplantation in urethral reconstruction?

BACKGROUND: Hypospadias and urethral strictures are conditions requiring additional tissue for reconstruction. Due to a limited source of tissue, autologous skin and oral mucosa are frequently used. However, long-term follow-up studies demonstrated significant complications and diminished quality of life. Recently, a variety of tubular biodegradable biomaterials have been used. Cell seeding seems to be important to improve the host acceptance and neovascularization. OBJECTIVE: To compare in vivo performance of smooth muscle cell (SMC)-seeded and unseeded tubular collagen-based scaffolds in a rabbit urethral reconstruction model. MATERIALS AND METHODS: Sixteen New Zealand rabbits underwent an open-bladder biopsy for SMC harvesting. The SMCs were cultured for 3 weeks and labeled with ethynyldeoxyuridine (EdU). A 1-cm-length tubular collagen-based 0.5 wt% scaffold was seeded and cultured with SMCs and implantation in a rabbit model. Eight rabbits received SMC-seeded scaffolds for a 1-cm-length circumferential urethral repair, situated 1.5 cm from the meatus. After 1 and 3 months, four rabbits underwent a urethrography and were sacrificed. The penises underwent hematoxylin and eosin, immunohistochemistry, and EdU fluorescence staining. In the control group eight rabbits received acellular scaffolds. RESULTS: The SMC-seeded group presented one stricture at 1 month and one fistula at 3 months. Three strictures were present in the unseeded group at 1 month and one at 3 months. In the seeded group, more SMC expression and neovascularization was observed, and less mononuclear and giant cells could be found. All scaffolds showed luminal urothelial cell revetment. The detection of EdU-labeled SMCs revealed SMC transplantation survival. CONCLUSION: SMC-seeded tubular collagen scaffolds improved urethral regeneration in this rabbit model. Such constructs may be valuable for repair of severe urethral diseases.

Osteosarcoma metastasis causing ileo-ileal intussusception.

Osteosarcoma metastasis causing intussusception is a very rare entity, with a pejorative prognosis. Based on a case, we performed a literature review in order to better assess this situation. We conclude that, in patients with a history of osteosarcoma lung metastasis, echographic and/or computed tomography scan evidence of a small bowel obstruction with intussusception should lead to an open surgical procedure if the laparoscopic approach does not allow to accurately explore and resect the lesion, in order to prevent misdiagnosis and to avoid further delay in the management.

In-vivo performance of high-density collagen gel tubes for urethral regeneration in a rabbit model.

Congenital malformations or injuries of the urethra can be treated using existing autologous tissue, but these procedures are sometimes associated with severe complications. Therefore, tissue engineering may be advantageous for generating urethral grafts. We evaluated engineered high-density collagen gel tubes as urethral grafts in 16 male New Zealand white rabbits. The constructs were either acellular or seeded with autologous smooth muscle cells, isolated from an open bladder biopsy. After the formation of a urethral defect by excision, the tissue-engineered grafts were interposed between the remaining urethral ends. No catheter was placed postoperatively. The animals were evaluated at 1 or 3 months by contrast urethrography and histological examination. Comparing the graft caliber to the control urethra at 3 months, a larger caliber was found in the cell-seeded grafts (96.6% of the normal caliber) than in the acellular grafts (42.3%). Histology of acellular and cell-seeded grafts did not show any sign of inflammation, and spontaneous regrowth of urothelium could be demonstrated in all grafts. Urethral fistulae, sometimes associated with stenosis, were observed, which might be prevented by urethral catheter application. High-density collagen gel tubes may be clinically useful as an effective treatment of congenital and acquired urethral pathologies.

A collagen-poly(lactic acid-co-ɛ-caprolactone) hybrid scaffold for bladder tissue regeneration.

Scaffold materials should favor cell attachment and proliferation, and provide designable 3D structures with appropriate mechanical strength. Collagen matrices have proven to be beneficial scaffolds for tissue regeneration. However, apart from small intestinal submucosa, they offer a limited mechanical strength even if crosslinking can enhance their mechanical properties. A more cell-friendly way to increase material strength is to combine synthetic polymer meshes with plastic compressed collagen gels. This work describes the potential of plastic compressed collagen-poly(lactic acid-co-ɛ-caprolactone) (PLAC) hybrids as scaffolds for bladder tissue regeneration. Human bladder smooth muscle and urothelial cells were cultured on and inside collagen-PLAC hybrids in vitro. Scaffolds were analyzed by electron microscopy, histology, immunohistochemistry, and AlamarBlue assay. Both cell types proliferated in and on the hybrid, forming dense cell layers on top after two weeks. Furthermore, hybrids were implanted subcutaneously in the backs of nude mice. Host cell infiltration, scaffold degradation, and the presence of the seeded bladder cells were analyzed. Hybrids showed a lower inflammatory reaction in vivo than PLAC meshes alone, and first signs of polymer degradation were visible at six months. Collagen-PLAC hybrids have potential for bladder tissue regeneration, as they show efficient cell seeding, proliferation, and good mechanical properties.

High-density collagen gel tubes as a matrix for primary human bladder smooth muscle cells.

Tissue-engineered grafts for the urinary tract are being investigated for the potential treatment of several urologic diseases. These grafts, predominantly tubular-shaped, usually require in vitro culture prior to implantation to allow cell engraftment on initially cell-free scaffolds. We have developed a method to produce tubular-shaped collagen scaffolds based on plastic compression. Our approach produces a ready cell-seeded graft that does not need further in vitro culture prior to implantation. The tubular collagen scaffolds were in particular investigated for their structural, mechanical and biological properties. The resulting construct showed an especially high collagen density, and was characterized by favorable mechanical properties assessed by axial extension and radial dilation. Young modulus in particular was greater than non-compressed collagen tubes. Seeding densities affected proliferation rate of primary human bladder smooth muscle cells. An optimal seeding density of 10(6) cells per construct resulted in a 25-fold increase in Alamar blue-based fluorescence after 2 wk in culture. These high-density collagen gel tubes, ready seeded with smooth muscle cells could be further seeded with urothelial cells, drastically shortening the production time of graft for urinary tract regeneration.

In vivo study of an injectable poly(acrylonitrile)-based hydrogel paste as a bulking agent for the treatment of urinary incontinence.

Urinary incontinence can be treated by endoscopic injection of bulking agents, however, no optimal therapeutic effect has been achieved upon this treatment yet. In the present study, the development of a injectable poly(acrylonitrile) hydrogel paste is described, and its efficacy and histological behavior, once injected into the submucosal space of the minipig bladder, are evaluated. A device was developed to mix poly(acrylonitrile) hydrogel powder with glycerin, used as carrier, prior to injection into the submucosal space of the bladder. Several paste deposits, depending on the size of the bladder, were injected per animal. The implants were harvested at days 7, 14, 21, 28, 84 and 168 and analyzed morphologically and by histology. The persistence of the implants was demonstrated. However, at later time points the implants were split up and surrounded by granulomatous tissue, which was gradually replaced by histiocytes and adipocytes. Transitory focal urothelial metaplasia was observed only at day 7 and moderate foreign body reaction was detected predominantly between the second and fifth week. This study demonstrated the feasibility to develop an injectable paste of poly(acrylonitrile) hydrogel thought to provide the expected bulking effect, necessary for the treatment of urinary incontinence.