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Cristina et al.                                                                                                                                                               Urological application of platelet rich fibrin

           bladder biopsy is a search for urothelial carcinoma/  of PRF. Questionnaires score showed a significant
           carcinoma  in situ of the bladder, which may be    improvement of patients’ symptomatology during the
           confused with IC [26] .                            follow-up. Our patients presented improvement in
                                                              quality of life and symptoms especially regarding the
           We enrolled patients according to their typical and   mental health. Both the mental and the physical health
           highly disabling symptoms. Once we excluded the    increased significantly and remained stable after 28
           presence of bladder cancer, the aim of this study   days and 3 months. PGI-I and SF-36 questionnaires
           was to test the safety and the efficacy of endovesical   can provide an overall appraisal of a patients’ condition
           instillation of PRF to stimulate tissue regeneration   and they are practical for clinical use by their simplicity
           and control the clinical symptoms. Because         in administration and interpretability. The interstitial
           standardized treatment for IC does not exist, patients   cystitis symptom index has been designed to capture
           usually try many kinds of procedures such as many   the most important voiding and pain symptoms and to
           drugs (pentosan polysulphate, antidepressants);    assess how problematic patients find them. Almost no
           endovesical instillation of hyaluronic acid or Bacillus   IC patients score less than 6 while almost no controls
           Calmette-Guerin; sacral neuromodulation or surgery   score as high as 6. In our study, the symptom index
           (laser ablation of ulceration, cystectomy, bladder   was higher than 6 for both patients and this value is
           augmentation). Instillation therapy has a direct   comparable to the score of O’Leary et al. . No further
                                                                                                  [11]
           action on the urothelium and sub-urotheliium to    clinical improvements were seen after the first weeks
           restore the normal bladder lining. Endovesical fibrin   after PRF instillation. This may justify revaluation
           glue has been succesfully used also for refractory   during the follow-up for new endovesical treatments
           hemorrhagic cystitis occurred after unrelated marrow,   even though they presented partial or no response.
           cord blood, and haploidentical hematopoietic       PRF is an autologous blood component and it is safe
           stem cell transplantation [27] . Campus Bio-Medico
           University (Urology and Hematology Departments)    and biocompatible. Patients treated with PRF did not
           has already conducted, as coordinating center of   present any immediately or long term side effects.
           Rome Transplanta Network in 2009, a study on 35    The small series represents the major limitation of the
           patients affected by severe hemorrhagic cystitis after   study. Further cases are needed to achieve stronger
           allogeneic hematopoietic stem cell transplantation.   results.
           All 35 patients showed clinical response and pain
           resolution. In this new study, we treated patients   In conclusion, PRF is an autologous component
           affected by IC and we demonstrated that the typical   that promotes angiogenesis, tissue growth and
           urothelium coating involution can be successfully   repair through multiple growth factors. It is safe and
           helped by PRF that promotes angiogenesis, tissue   biocompatible; it is widely applied in different clinical
           growth and repair through multiple growth factors as   scenarios to promote the tissue regeneration. Our
           showed for transplanted patients.                  preliminary data show that patients affected by IC who
                                                              underwent endovesical application of PRF over the
           A significant number of patients with ulcerative IC   damaged urothelium, present significant improvement
           show ulceration, severe inflammation, and granulation   in clinical symptoms and quality of life. Further studies
           tissue [28] . The inflammatory infiltrates are usually   are needed to obtain more data.
           superficial, and restricted to the lamina propria [29] . The
           lamina propria is edematous, with stromal hemorrhage   DECLARATIONS
           and congested venules. In these patients, the rupture
           of the bladder mucosa subsequently resulted in     Authors’ contributions
           reparative granulation tissue [30] . Hemorrhage is present   Study conception and design: F. Cristina
           in 90% of nonulcerative IC. While generally localized,   PRF production: M.C. Tirindelli
           the hemorrhage may extend into the urothelium [25]  and   Data collection: A. Nicotera
           causes the mucosal rupture. Usually inflammation is   Analysis and interpretation of data: T. Petitti
           mild, but edema and vascular congestion are frequently   Drafting of manuscript: M. Buscarini
           seen. In both cases (ulcerative and non-ulcerative IC)   Critical revision: G. Avvisati
           the urothelium is particularly fragile. Baseline symptom
           assessment and regular symptom level reassessment   Financial support and sponsorship
           are essential to document efficacy of single and   None.
           combined treatments  [31] . We used different types
           of questionnaires to compare the entity of patients’   Conflicts of interest
           discomfort before and after the endoscopic application   There are no conflicts of interest.

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