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The relationship between hypoxia and cavernosal brosis has been documented in at least two in vitro studies [9,57] It is thought that hypoxia induces TGF- 1 expression that in turn accelerates collage-
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Radical Pelvic Surgery-Associated Sexual Dysfunction nization of the corpus cavernosum smooth muscle, while at the same time decreasing the level of PGE1, which may help protect from brosis Since hypoxia of cavernous tissue is related to the blood supply, and the greatest blood supply occurs at time of erection, any neural damage that results in ED may expose the cavernous tissues to longer periods of hypoxia Leungwattanakij et al demonstrated in a cavernous neurotomy rat model that sharp neural injury resulted in an increase in hypoxia inducible factor-1 (HIF-1 ) and TGF- 1 as well as increase in cavernous tissue collagen synthesis [8] In a landmark study, Montorsi et al based a study on the assumption that the events of nocturnal erection supply the cavernous bodies with oxygenation that might protect them from developing brotic changes during the transient period of erectile dysfunction following nerve-sparing radical prostatectomy [58] In their study they treated patients with three times per week intracavernosal injections of alprostadil In this prospective study, 30 patients were enrolled, all potent, and all had nerve-sparing RP Fifteen received three injections per week for 15 weeks; twelve completed the treatment Despite the small sample size, the difference between treatment and control group was statistically signi cant (Treatment group, 67% had erections good enough for intercourse; control group, 20%, P < 001) However, this is to date the only evidence-based medicine for the role of penile rehabilitation with intracavernosal injections after radical prostatectomy; because of the small sample size used combined with the invasiveness of the treatment, there is a need for a larger con rmatory study A single human randomized, placebo-controlled study has been conducted examining the role of nightly sildena l for six months following RP [59] This analysis demonstrated the ability of this regimen to increase the rate of preservation of preoperative erectile function (based on validated inventory assessments) at 48 weeks in the sildena l arm compared to the placebo arm (27% vs 4%, respectively) In another non-controlled study, Schwartz et al gave either 50 mg or 100 mg of sildena l on alternate nights for six months after RP [60] Patients had a percutaneous biopsy before RP and after six months of sildena l treatment Comparing the smooth muscle content of the post-treatment biopsy to the pre-
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operative biopsy, no change was demonstrated in the 50 mg group, but an increase in smooth muscle content was noted in the 100 mg group In an animal study, Donohue et al used doses of 10 mg/kg and 20 mg/kg of sildena l, given at induction of anesthesia and continued daily, which results in trough serum levels comparable to levels obtained with 50 mg and 100 mg tablets, respectively, in man [61] Daily subcutaneous sildena l administration at both doses showed an improvement in the mean ICP/MAP ratio compared to control The control group demonstrated improvement in erectile function over time, with the ICP/MAP ratio rising from 18 6% at three days to 31 9% at 10 days, remaining relatively unchanged at 28 days (32 5%) The 10 mg/kg group showed higher ICP/MAP ratios at all time points compared to control, but these changes were not statistically signi cant Further improvement in a doseand time-dependent manner was demonstrated by the 20 mg/kg group, with maximal improvement shown at 28 days with an ICP/MAP ratio of 45 6% (P = 001) noted Mean sham ICP/MAP ratios were 70% Thus, there exists human and animal evidence that ICI and regular sildena l (and possible PDE5 inhibitors in general) use may translate into greater preservation of erectile function In the absence of a large, multi-center, randomized controlled trial assessing the utility of a formal penile rehab regimen, this approach to post-RP care remains investigational To date, there has been no formal analysis of what represents the optimal rehabilitation program and thus giving the reader formal guidelines is dif cult Figure 171 represents the approach at MSKCC, although this is not to say that this is the only approach The algorithm is based on the animal and human data at this time that there is probably a value to erections, that there is probably an adjunctive value to regular PDE5 inhibitor use
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