Regenerative medicine and register studies related to bladder exstrophy

Abstract: Bladder exstrophy is a rare congenital malformation affecting both boys and girls. The malformation involves the bladder, the urethra, genitalia, and pelvis. The child presents with a defect of the lower abdominal wall exposing an open bladder. In this thesis, the field of regenerative medicine is explored with the aim of improving the surgical treatment of malformations where there is a lack of tissue, such as bladder exstrophy when a bladder conduit is sometimes needed for bladder catheterization. The thesis also includes register studies for further understanding of the prevalence, morbidities, the quality of life, and risk factors associated with bladder exstrophy. Studies I and II were conducted in a porcine animal model with the aim of constructing a functional autologous bladder conduit to be used for catheterization. Both studies were aimed at using regenerative medicine techniques with minimal ex vivo handling. Bladder tissue was obtained and minced for autologous tissue transplantation in order to analyze the regenerative capacity of the mucosa, the urothelium, and the muscle, the detrusor. Animals were housed up to five weeks post transplantation. In Study I, functional bladder emptying tests were performed by catheterization through the neo-regenerated conduit and CT scans were used for anatomical evaluation. In Study II, detrusor muscle expansion was studied in vitro and in vivo for evaluation of the regenerative capacity after mincing. In conclusion, bladder wall mincing techniques could be a valuable tool for autologous tissue expansion, which can be prepared at the operating table as a one-step surgical procedure. Study III was conducted as a matched case-control study using Swedish national populationbased registers. One-hundred-and-twenty cases of bladder exstrophy were identified between 1973 and 2011. The prevalence was 3:100 000, which was stable over time. In contrast to other publications, an equal male-to-female ratio was found. Birth descriptive data were comparable to those of controls, and bladder exstrophy occurred most often without any other major associated malformations. Congenital inguinal hernia and undescended testis were, however, more prevalent than in the general population. The only potentially associated maternal risk factor was advanced maternal age. Study IV was conducted as a matched cohort study between 1952 and 2011. We used Swedish national population–based registers to assess morbidity, mortality, and such social parameters as partnership, fertility, and education. One-hundred-and-eighty cases were identified for analyses of morbidity and mortality and 124 of these cases were individuals over 18 years of age and thus were available for further social analyses. The incidences of bladder cancer and psychiatric disorders were comparable to those of the general Swedish population. Mortality was low. Sensory neurogenic hearing disorders indicated a possible genetic association in a few cases. No differences concerning partnership could be established, but significantly fewer cases conceived biological children. The educational level was high overall, with male cases reaching a slightly lower level, and females a higher level ofthe highest level of education compared to controls