Ex Vivo Radiation Leads to Opposing Neurite Growth in Whole Ganglia vs Dissociated Cultured Pelvic Neurons

BackgroundProstatic radiation therapy (RT) often causes erectile dysfunction (ED) and the mechanisms governing RT-induced ED are unclear with a lack of therapeutic strategies.AimTo determine the effects of ex vivo RT on major pelvic ganglion (MPG) neuron survival, and neurite growth in whole vs dissociated culture.MethodsMPGs were removed and irradiated (0 or 8 Gy) from male Sprague Dawley rats. For dissociated culture, MPG neurons were digested in collagenase/dispase and cultured on coverslips. Immunofluorescent staining for beta-tubulin III (TUBB3; neuron marker), neuronal nitric oxide synthase (nNOS; nitrergic marker), tyrosine hydroxylase (TH; sympathetic marker), and terminal deoxynucleotidyl transferase dUTP nick end labeling assessed neurite length, branching, autonomic neuron density, and apoptosis. For whole organ culture, MPGs were grown in Matrigel. Gene expression of apoptotic markers (caspase 1, 3), TUBB3, nNOS, TH, and Schwann cells (Sox10, Krox20, glial fibrillary acid protein) was measured in whole organ cultured MPGs by quantitative polymerase chain reaction.OutcomesAfter 72 hours, neurite length, branching, autonomic neuron density, and apoptosis were assessed, and gene expression was measured.ResultsRT increased apoptosis in dissociated neurons measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (P < .001) and whole MPG culture via upregulation of caspase 3 gene expression (P < .05). Nitrergic neurons were markedly decreased in irradiated dissociated culture (P < .05), while nNOS gene expression was upregulated in irradiated whole organ culture (P < .05). The proportion of dissociated sympathetic neurons and whole organ TH gene expression remained unchanged after RT. Interestingly, RT dissociated neurites were 22% shorter than controls, while RT whole organ neurites were 15% longer than controls (P < .01). MPG Schwann cells markers (Sox10, Krox20) were elevated after RT in whole organ culture.Clinical TranslationProstatic RT leads to increased neuronal cell death and less erectogenic nitrergic neurons contributing to ED.Strengths & LimitationsThe advantages of dissociated neuron culture include distinct neurites which are easily measured for apoptosis, length/branching, and specific neuron types. In contrast, whole MPG culture is advantageous as it contains all the supporting cells present in vivo.ConclusionThe 2 different culture methods demonstrated opposing neurite growth after RT indicating the importance of supporting cell network to promote pelvic neuron neuritogenesis and survival following RT.Randolph JT, Pak ES, Koontz BF, et al. Ex Vivo Radiation Leads to Opposing Neurite Growth in Whole Ganglia vs Dissociated Cultured Pelvic Neurons. J Sex Med 2020;17:1423–1433.     

Exosome Released From Schwann Cells May Be Involved in Microenergy Acoustic Pulse–Associated Cavernous Nerve Regeneration

BackgroundNeurogenic erectile dysfunction (ED) is often refractory to treatment because of insufficient functional nerve recovery after injury or insult. Noninvasive mechano-biological intervention, such as microenergy acoustic pulse (MAP), low-intensity pulsed ultrasound, and low-intensity extracorporeal shockwave treatment, is an optimal approach to stimulate nerve regeneration.AimTo establish a new model in vitro to simulate nerve injury in neurogenic ED and to explore the mechanisms of MAP in vitro.MethodsSprague-Dawley rats were used to isolate Schwann cells (SCs), major pelvic ganglion (MPG), and cavernous nerve with MPG (CN/MPG). SCs were then treated with MAP (0.033 mJ/mm², 1 Hz, 100 pulses), and SC exosomes were isolated. The MPG and CN/MPG were treated with MAP (0.033 mJ/mm², 1 Hz) at different dosages (25, 50, 100, 200, or 300 pulses) or exosomes derived from MAP-treated SCs in vitro.OutcomesNeurite growth from the MPG fragments and CN was photographed and measured. Expression of neurotropic factors (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) was checked.ResultsNeurite outgrowth from MPG and CN/MPG was enhanced by MAP in a dosage response manner, peaking at 100 pulses. MAP promoted SC proliferation, neurotropic factor (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) expression, and exosome secretion. SC-derived exosomes significantly enhanced neurite outgrowth from MPG in vitro.Clinical ImplicationsMAP may have utility in the treatment of neurogenic ED by SC-derived exosomes.Strength & LimitationsWe confirmed that MAP enhances penile nerve regeneration through exsomes. Limitations of this study include that our study did not explore the exact mechanisms of how MAP increases SC exosome secretion nor whether MAP modulates the content of exosomes.ConclusionThis study revealed that neurite outgrowth from MPG was enhanced by MAP and by SC-derived exosomes which were isolated after MAP treatment. Our findings indicate that one mechanism by which MAP induces nerve regeneration is by stimulation of SCs to secrete exosomes.Peng D, Reed-Maldonado AB, Zhou F, et al. Exosome Released From Schwann Cells May Be Involved in Microenergy Acoustic Pulse–Associated Cavernous Nerve Regeneration. J Sex Med 2020;17:1618–1628.     

Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth

Background

Erectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated.

Vasa Nervorum in Rat Major Pelvic Ganglion are Innervated by Nitrergic Nerve Fibers

IntroductionThe vasa nervorum comprises a network of small diameter blood vessels that provide blood supply to nerves and ganglia. The cell bodies of autonomic nerves innervating the urogenital organs are housed in the major pelvic ganglia (MPG) in rats. The vasa nervorum of rat MPG have not been characterized previously, and it is not known whether these blood vessels are innervated by neuronal nitric oxide synthase (nNOS) containing nitrergic nerves.AimTo characterize the blood vessels in and around the rat MPG and to assess their nitrergic innervation.Main Outcome MeasuresCharacterization of small blood vessels in and around the rat MPG and expression of nNOS in nerve fibers around those blood vessels.MethodsMPG were obtained from healthy Sprague Dawley rats, fixed in paraformaldehyde, frozen and sectioned using a cryostat. The blood vessels and their nitrergic innervation were assessed with immunohistochemistry using antibodies against alpha‐smooth muscle actin (smooth muscle marker), CD31 (endothelial marker), collagen IV (basal membrane marker) and nNOS. The immunofluorescence was imaged using a laser scanning confocal microscope.ResultsThe neuronal cell bodies were contained within a capsule in the MPG. Blood vessels were observed within the capsule of the MPG as well as outside the capsule. The blood vessels inside the capsule were CD31‐positive capillaries with no smooth muscle staining. Outside the capsule capillaries, arterioles and venules were observed. The extra‐capsular arterioles and venules, but not the capillaries were innervated by nNOS‐positive nerve fibers.ConclusionsThis study, to our knowledge, is the first to demonstrate the blood vessel distribution pattern and their nitrergic innervation in the rat MPG. While similar studies in human pelvic plexus are warranted, these results suggest that the blood flow in the MPG may be regulated by nitrergic nerve fibers and reveal a reciprocal relationship between nerves and blood vessels. Beetson KA, Smith SF, Muneer A, Cameron NE, Cotter MA, and Cellek S. Vasa nervorum in rat major pelvic ganglion are innervated by nitrergic nerve fibers. J Sex Med 2013;10:2967–2974.     

M1 Macrophages Are Predominantly Recruited to the Major Pelvic Ganglion of the Rat Following Cavernous Nerve Injury

IntroductionNeurogenic erectile dysfunction is a common sequela of radical prostatectomy. The etiology involves injury to the autonomic cavernous nerves, which arise from the major pelvic ganglion (MPG), and subsequent neuroinflammation, which leads to recruitment of macrophages to the injury site. Currently, two macrophage phenotypes are known: neurotoxic M1 macrophages and neuroprotective M2 macrophages.AimTo examine whether bilateral cavernous nerve injury (BCNI) in a rat model of erectile dysfunction would increase recruitment of neurotoxic M1 macrophages to the MPG.MethodsMale Sprague-Dawley rats underwent BCNI and the MPG was harvested at various time points after injury. The corpora cavernosa was used to evaluate tissue myographic responses to electrical field stimulation ex vivo. Quantitative real-time polymerase chain reaction was used to examine the gene expression of global macrophage markers, M1 macrophage markers, M2 macrophage markers, and cytokines and chemokines in the MPG. Mathematical calculation of the M1/M2 index was used to quantify macrophage changes temporally. Western blot of MPG tissues was used to evaluate the protein amount of M1 and M2 macrophage markers quantitatively. Immunohistochemistry staining of MPGs for CD68, CD86, and CD206 was used to characterize M1 and M2 macrophage infiltration.Main Outcome MeasuresCorpora cavernosa responsiveness ex vivo; gene (quantitative real-time polymerase chain reaction) and protein (western blot) expressions of M1 and M2 markers, cytokines, and chemokines; and immunohistochemical localization of M1 and M2 macrophages.ResultsBCNI impaired the corporal parasympathetic-mediated relaxation response to electrical field stimulation and enhanced the contraction response to electrical field stimulation. Gene expression of proinflammatory (Il1b, Il16, Tnfa, Tgfb, Ccl2, Ccr2) and anti-inflammatory (Il10) cytokines was upregulated in the MPG 48 hours after injury. M1 markers (CD86, inducible nitric oxide synthase, interleukin-1β) and M2 markers (CD206, arginase-1, interleukin-10) were increased after BCNI in the MPG, with the M1/M2 index above 1.0 indicating that more M1 than M2 macrophages were recruited to the MPG. Protein expression of the M1 macrophage marker (inducible nitric oxide synthase) was increased in MPGs after BCNI. However, the protein amount of M2 macrophage markers (arginase-1) remained unchanged. Immunohistochemical characterization demonstrated predominant increases in M1 (CD68⁺CD86⁺) macrophages in the MPG after BCNI.ConclusionThese results suggest that an increase in M1 macrophage infiltration of the MPG after BCNI is associated with impaired neurogenically mediated erectile tissue physiology ex vivo and thus has significant implications for cavernous nerve axonal repair. Future studies are needed to demonstrate that inhibition of M1 macrophage recruitment prevents erectile dysfunction after CNI.     

Pelvic insufficiency fractures in patients with cervical and endometrial cancer treated with postoperative pelvic radiation

ObjectiveThere is an increased awareness of pelvic insufficiency fractures (PIF) as a potential morbidity of pelvic radiotherapy (RT). The purpose of this study was to determine the incidence of PIF and assess prognostic factors, including intensity-modulated RT (IMRT), in gynecologic oncology patients treated with postoperative pelvic RT.MethodsWe performed a retrospective review of all patients with endometrial or cervical carcinoma who received postoperative pelvic RT at our institution during 2000–2008. Patients who received definitive or palliative RT were excluded.ResultsA total of 222 patients were identified, of whom 11 (5%) developed PIF at a median time of 11.5 months (range, 5.5–87.3 months) from RT completion. The 5-year actuarial rate was 5.1% (95% CI 3.3–6.9). In patients with osteoporosis, the 5-year rate was 15.6% compared with 2.9% for those without (P = 0.01). Similarly, patients who were on prior hormone-replacement therapy (HRT) had a higher rate (14.8% vs 4.1%, P = 0.009). The median body-mass index (BMI) for patients who developed PIF was significantly lower than those who didn't (25.9 vs 27.2, P = 0.016). The rate of PIF was 4.9% whether patients received IMRT or conventional RT.ConclusionsThe 5-year risk of PIF for postoperative pelvic RT in cervical and endometrial cancer is 5.1%. Women with history of osteoporosis, prior HRT, or low BMI need to be counseled about the risk of PIF. The use of IMRT did not decrease PIF, but further studies are needed to determine if a dose/volume relationship exists between RT and PIF.     

Increased Level of Tumor Necrosis Factor-Alpha (TNF-α) Leads to Downregulation of Nitrergic Neurons Following Bilateral Cavernous Nerve Injury and Modulates Penile Smooth Tone

BackgroundErectile dysfunction (ED) after injury to peripheral cavernous nerve (CN) is partly a result of inflammation in pelvic ganglia, suggesting that ED may be prevented by inhibiting neuroinflammation.AimThe aim of this study is to examine temporal changes of TNF-α, after bilateral CN injury (BCNI), to evaluate effect of exogenous TNF-α on neurite outgrowth from major pelvic ganglion (MPG), and to investigate effect of TNF-α signal inhibition to evaluate effects of TNF-α on penile tone with TNF-α receptor knockout mice (TNFRKO).MethodsSeventy Sprague-Dawley rats were randomized to undergo BCNI or sham surgery. Sham rats’ MPGs were harvested after 48 hours, whereas BCNI groups’ MPGs were at 6, 12, 24, 48 hours, 7, or 14 days after surgery. qPCR was used to evaluate gene expression of markers for neuroinflammation in MPGs. Western blot was performed to evaluate TNF-α protein amount in MPGs. MPGs were harvested from healthy rats and cultured in Matrigel with TNF-α. Neurite outgrowth from MPGs was measured after 3 days, and TH and nNOS immunofluorescence was assessed. Wild type (WT) and TNFRKO mice were used to examine effect of TNF-α inhibition on smooth muscle function after BCNI. MPGs were harvested 48 hours after sham or BCNI surgery to evaluate gene expression of nNOS and TH.OutcomesGene expression of TNF-α signaling pathway, Schwann cell and macrophage markers, protein expression of TNF-α in MPGs, and penile smooth muscle function to electrical field stimulation (EFS) were evaluated.ResultsBCNI increased gene and protein expression of TNF-α in MPGs. Exogenous TNF-α inhibited MPG neurite outgrowth. MPGs cultured with TNF-α had decreased gene expression of nNOS (P < .05). MPGs cultured with TNF-α had shorter nNOS+ neurites than TH+ neurites (P < .01). Gene expression of nNOS was enhanced in TNFRKO mice compared to WT mice (P < .01). WT mice showed enhanced smooth muscle contraction of penises of WT mice was enhanced to EFS, compared to TNFKO (P < .01). Penile smooth-muscle relaxation to EFS was greater in TNFKO mice compared to WT (P < .01).Clinical TranslationTNF-α inhibition may prevent ED after prostatectomy.Strength/LimitationsTNF-α inhibition might prevent loss of nitrergic nerve apoptosis after BCNI and preserve corporal smooth muscle function but further investigation is required to evaluate protein expression of nNOS in MPGs of TNFKO mice.ConclusionsTNF-α inhibited neurite outgrowth from MPGs by downregulating gene expression of nNOS and TNFRKO mice showed enhanced gene expression of nNOS and enhanced penile smooth-muscle relaxation.Matsui H, Sopko NA, Campbell JD, et al. Increased Level of Tumor Necrosis Factor-Alpha (TNF-α) Leads to Downregulation of Nitrergic Neurons Following Bilateral Cavernous Nerve Injury and Modulates Penile Smooth Tone. J Sex Med 2021;18:1181–1190.     

Role of MR imaging in surgical planning and prediction of successful surgical repair of pelvic organ prolapse

ObjectiveTo determine the role of magnetic resonance imaging (MRI) in surgical planning for females with pelvic organ prolapsed (POP) and to determine the clinical utility of MR imaging in predicting successful surgical repair.MethodsFifteen patients with different varieties of pelvic floor dysfunction and 15 nulliparous females as control subjects were studied by magnetic resonance imaging (static and dynamic). Intraoperative findings related to POP were correlated to MRI findings. In the symptomatic patients, magnetic resonance imaging was repeated within 6–12 months after surgery.ResultsPreoperative MRI and operative findings showed a significant correlation in all types of prolapse, except rectocele. On the other hand preoperative pelvic examination and operative findings were significantly correlated for cystocele, rectocele and vaginal cuff prolapse (r = 0.75, P < 0.008). Preoperative magnetic resonance imaging added information that changed the management in 40% of symptomatic women. Postoperative magnetic resonance imaging showed normal pelvic floor in asymptomatic patients (n = 13). Abnormal imaging findings were found in patients with persistent postoperative or de novo complaints (n = 2).ConclusionMagnetic resonance imaging can accurately localize pelvic floor defects, evaluate success or failure of surgical procedures, predict the need for more extensive reconstruction, and identify complications.     

Prevalence of Endometriosis and Peritoneal Pockets in Women with Infertility and/or Pelvic Pain

ObjectiveTo evaluate the prevalence of endometriosis and peritoneal pockets and to analyze whether these pockets are associated with pain.MethodsAnalysis of prospectively registered data of all women undergoing laparoscopy for infertility or pelvic pain between 1988 and 2011 at KU Leuven University Hospital.ResultsOf 4497 women, 191 had 238 pockets, with a prevalence of 4.7% in women with infertility only, 4.9% in women with infertility and pelvic pain, and 3.5% in women with pelvic pain only (P = 0.045 for all infertility vs. pelvic pain only). Prevalence did not vary by age. Pockets were associated with endometriosis (P < 0.0001), which was found in 77% of women with pockets. Among women with infertility only, the prevalence of endometriosis was higher in women with pockets (P = 0.0001) than in women without. The prevalence of endometriosis was similar in women with infertility and pelvic pain or pelvic pain only. Pelvic pain as an indication for surgery was associated simultaneously (through logistic regression) with endometriosis (P < 0.0001) and pockets (P = 0.040). Pelvic pain severity was associated simultaneously with pockets (P = 0.0026) and the severity of subtle (P = 0.001), typical (P = 0.030), cystic ovarian (P = 0.051), and deep endometriosis (P < 0.0001). Pelvic pain severity was not associated with endometriosis in the pockets or the diameter or location of pockets.ConclusionsThe prevalence of pockets was low, at between 3.5% and 5%. Women with infertility only and pockets had more endometriosis than women without. Severe pelvic pain and pelvic pain as an indication for surgery were associated with the presence of pockets as well as the presence and severity of endometriosis.     

Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth In Vitro

Background

Previously, we found that the neuropeptide galanin was strongly upregulated soon after bilateral cavernous nerve injury (BCNI) and that galanin and its receptors were expressed in nitrergic erectile innervation. Galanin has been observed to exert neuroregenerative effects in dorsal root ganglion neurons, but evidence for these effects in the major pelvic ganglion (MPG) after BCNI is lacking.

Prevalence and Predictors of Climacturia and Associated Patient/Partner Bother in Patients With History of Definitive Therapy for Prostate Cancer

BackgroundClimacturia is an under-reported complication of definitive therapy for prostate cancer (PCa) - that is, radical prostatectomy (RP) and/or radiation therapy (RT).AimWe sought to identify the prevalence and predictors of climacturia and associated patient/partner bother in patients with and without prior PCa treatment.MethodsWe analyzed a database of patients who presented to our Men's Health clinic and filled out a questionnaire related to sexual function and pertinent medical histories. The prevalence of climacturia and associated patient/partner bother in patients with/without prior RP/RT was calculated. Univariable and multivariable logistic regressions were performed to identify predictors associated with climacturia and patient/partner bother.OutcomesThe primary outcomes were the prevalence and predictors of climacturia and associated patient/partner bother in patients with/without history of definitive PCa treatment.ResultsAmong 1,117 patients able to achieve orgasm, 192 patients (17%) had prior history of definitive therapy for PCa (RP alone = 139 [72%]; RT alone = 22 [11%]; RP + RT = 31 [16%]). Climacturia was reported by 39%, 14%, 52%, and 2.4% of patients with history of RP alone, RT alone, RP + RT, and neither RP nor RT, respectively (P < .05 between all groups). 33 to 45 percent of patients with climacturia noted significant patient/partner bother. Factors significantly associated with climacturia were prior RP, prior RT, history of other prostate surgery, and erectile dysfunction, although erectile dysfunction was not significant on multivariable analysis. Significant reduction in climacturia prevalence was noted for patients who were ≥1 year out from RP, compared with patients who were <1 year out.Among patients with prior RP/RT, stress urinary incontinence was associated with increased risk of climacturia, whereas diabetes was associated with decreased risk. No factors were associated with patient/partner bother. Among patients with prior RP, nerve-sparing technique did not predict presence of climacturia but was associated with reduced patient/partner bother.Clinical translationGiven significant prevalence of climacturia and associated patient/partner bother, patients should be counseled on the risk of climacturia before undergoing RP/RT.Strengths and limitationsStrengths include the large study population and the focus on both RP and RT. Limitations include the facts that this is a single-institution study that primarily relies on patients’ subjective reporting and that the study population may not represent the general population.ConclusionsClimacturia affects a significant proportion of patients with history of RP/RT for PCa, and many patients and their partners find this bothersome.Jimbo M, Alom M, Pfeifer ZD, et al. Prevalence and Predictors of Climacturia and Associated Patient/Partner Bother in Patients With History of Definitive Therapy for Prostate Cancer. J Sex Med 2020;17:1126–1132.     

Sacral Colpopexy Versus Transvaginal Mesh Colpopexy in Obese Patients

ObjectivesObesity can predispose women to pelvic organ prolapse and can also affect the success of pelvic organ prolapse surgery. The purpose of this study was to compare the postoperative anatomical outcomes following sacral colpopexy (SC) and transvaginal mesh colpopexy in a group of obese women with pelvic organ prolapse.MethodsWe conducted a retrospective cohort study of obese women who underwent SC (n = 56) or transvaginal mesh colpopexy (n = 35). Follow-up ranged from 6 to 12 months. Preoperative, perioperative, and postoperative variables were compared using Student t, Mann?Whitney U, and Fisher exact tests, and by analysis of covariance.ResultsThe women in the SC group had significantly higher mean apical vaginal measurements (P < 0.05), and significantly fewer stage II recurrences than women in the transvaginal mesh colpopexy group. There were no significant differences between the groups for other postoperative outcomes, including mesh erosion, recurrent prolapse symptoms, dyspareunia, and surgical satisfaction (P > 0.05).ConclusionIn these 91 obese patients with pelvic organ prolapse, SC resulted in better anatomical outcomes than transvaginal mesh colpopexy. However, the two procedures had similar outcomes with regard to recurrent symptoms and surgical satisfaction.     

Pelvic Floor Tenderness in the Etiology of Superficial Dyspareunia

ObjectiveTo calculate the prevalence of pelvic floor tenderness in the population of women with pelvic pain and to determine its implications for symptoms of pelvic pain.MethodsWe conducted a retrospective review of patients with pelvic pain at a tertiary referral centre. Pelvic floor tenderness was defined as levator ani tenderness on at least one side during single digit pelvic examination. The prevalence of pelvic floor tenderness in this cohort of women with pelvic pain was compared with the prevalence in a cohort of women without pain attending a gynaecology clinic. In the women with pelvic pain, multiple regression was performed to determine which variables were independently associated with pelvic floor tenderness.ResultsThe prevalence of pelvic floor tenderness was 40% (75/189) in the cohort with pelvic pain, significantly greater than the prevalence of 13% (4/32) in the cohort without pain (OR 4.61; 95% CI 1.55 to 13.7, P = 0.005). On multiple logistic regression, superficial dyspareunia (OR 4.45; 95% CI 1.86 to 10.7, P = 0.001), abdominal wall pain (OR 4.04; 95% CI 1.44 to 11.3, P = 0.005), and bladder base tenderness (OR 4.65; 95% CI 1.87 to 11.6, P = 0.001) were independently associated with pelvic floor tenderness. Pelvic floor tenderness was similarly present in women with or without underlying endometriosis.ConclusionPelvic floor tenderness is common in women with pelvic pain, with or without endometriosis, and is a contributor to superficial dyspareunia. Pelvic floor tenderness was also associated with abdominal wall pain and bladder base tenderness, suggesting that nervous system sensitization is involved in the etiology of pelvic floor tenderness.     

La parturition de Lucy,chemin vers l’extinction ?

ObjectivesTo compare pelvic cavities in australopithecines, modern humans and non-hominid primates in order to discuss the obstetrical mechanisms in australopithecinesMaterial and methodsBony pelves from fossil material (Australopithecus afarensis AL 288-1, Australopithecus africanus Sts14, Australopithecus Stw 431 and Mh2), 133 modern humans (82 adult females and 51 adult males) and 67 anthropoid primates (36 gorilla, 26 Pan troglodytes, 5 Pongo pygmaeus) were reconstructed and compared (shape and morphometric analysis) using 16 pelvimetric mesasurements.ResultsPelves of australopithecines were characterized by lower anteroposterior (AP) and transverse (TRV) diameters in inlet pelvis than in other species. Index (AP/TRV) of pelvic inlet, midpelvis and pelvic outlet in the australopithecines were the lowest (< 100) and the pelvic shape was platypelloid. A logarithmic factorial analysis showed that the pelvic morphology of australopithecines was different from humans and non-hominid primates but nearer the humans.Discussion and conclusionIn contrast with apes where obstetrical mechanics seem to be easier, and because of platypelloidy, mechanism of birth in australopithecines was as difficult as in modern homo sapiens. Birth without cesarean was probably possible in an asynclitic TRV orientation.     

Platelet-rich Plasma Promotes Restoration of the Anterior Vaginal Wall for the Treatment of Pelvic Floor Dysfunction in Rats

Study ObjectiveTo determine the efficacy of using platelet-rich plasma (PRP) for vaginal wall repair in rats with vaginal wall impairment induced by vaginal distension (VD).DesignA single-blind, randomized study.SettingA certified animal research facility.AnimalsTwenty-four female Sprague Dawley rats.InterventionsFemale Sprague Dawley rats were divided into sham (n = 8), VD (n = 8), and VD + PRP (n = 8) groups. Vaginal tissues from the VD group were dissected at 28-day post injury. VD + PRP rats received vaginal PRP injections on the 1st, 7th, 14th, and 21st day after VD and sacrificed on the 28th day.Measurements and Main ResultsUrodynamic tests were performed in all rats. Immunohistochemistry was used to evaluate matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9). Masson's staining was used to evaluate collagen fibers and calculate collagen volume fraction. Collagen fiber damage was confirmed in the VD group, evidenced by thinner and sparse distribution of collagen fibers, with significantly higher MMP-2 and MMP-9 expression than the sham group (p <.05). The collagen fiber damage in the vaginal wall likely led to pelvic floor dysfunction (PFD), evidenced by significantly decreased bladder leak-point pressure (p <.01) and abdominal leak-point pressure (p <.01) in the VD group compared with the sham group. After completion of the PRP treatment, a significantly higher collagen volume fraction (p <.01) and significantly increased bladder leak-point pressure (p <.05) and abdominal leak-point pressure (p <.01) were achieved in the VD + PRP compared with the VD group, thus indicating repair of the vaginal wall and improvement of PFD.ConclusionPRP injections facilitate the regeneration of vaginal wall tissue, particularly collagen fiber, after VD, leading to functional improvement of PFD. Findings support the feasibility of using PRP as a novel treatment for PFD.     

Hydroxyl Fasudil,an Inhibitor of Rho Signaling,Improves Erectile Function in Diabetic Rats: A Role for Neuronal ROCK

IntroductionThe pathogenesis of diabetic erectile dysfunction (ED) includes neuropathy, but the molecular basis for neurogenic ED is incompletely understood. The RhoA/ROCK pathway has been implicated in diabetic neuropathy and in ED, but its role in diabetic neurogenic ED is not known.AimsThe aim of this study was to determine whether hydroxyl fasudil, a ROCK inhibitor, affects diabetic neuropathy‐related ED.MethodsType 1 diabetes mellitus was induced in male rats by streptozotocin (75 mg/kg, intraperitoneally). After 8 weeks, diabetic rats were administered hydroxyl fasudil, a selective ROCK inhibitor (10 mg/kg/day, intraperitoneally) or vehicle, for 4 weeks. Age‐matched control, nondiabetic, rats were treated intraperitoneally for 4 weeks with saline. At week 12, after a 2 day washout, neuro‐stimulated erectile function was evaluated. Major pelvic ganglia (MPG) were collected for Western blot analysis of RhoA, ROCK‐1, ROCK‐2, phospho (P)‐AKT (Ser⁴⁷³), and P‐phosphatase and tensin homolog (P‐PTEN) (Ser³⁸⁰/Thr^382/383).Main Outcome MeasuresEffect of ROCK inhibitor hydroxyl fasudil on erectile function and ROCK/P‐AKT/P‐PTEN pathway in the MPG of diabetic rats.ResultsErectile response was significantly (P < 0.05) reduced in diabetic rats compared with nondiabetic rats and was preserved (P < 0.05) in diabetic rats treated with hydroxyl fasudil. In diabetic rats, RhoA and ROCK‐2 protein expressions in MPG were increased (P < 0.05) and remained increased in hydroxyl fasudil‐treated rats. P‐AKT (Ser⁴⁷³) expression was decreased (P < 0.05), whereas P‐PTEN (Ser³⁸⁰/Thr^382/383) expression was increased (P < 0.05) in MPG of diabetic rats compared with nondiabetic rats, and both were reversed (P < 0.05) in diabetic rats treated with hydroxyl fasudil.ConclusionImproved erectile function and restored P‐AKT and P‐PTEN in the MPG with hydroxyl fasudil treatment suggest the role of Rho signaling via PTEN/AKT pathway in neurogenic diabetic ED. Sezen SF, Lagoda G, Musicki B, and Burnett AL. Hydroxyl fasudil, an inhibitor of Rho signaling, improves erectile function in diabetic rats: A role for neuronal ROCK. J Sex Med 2014;11:2164‐2171.     

Acceptance and Commitment Therapy to Increase Adherence to Penile Injection Therapy-Based Rehabilitation After Radical Prostatectomy: Pilot Randomized Controlled Trial

IntroductionDespite the importance of using penile injections as part of a penile rehabilitation program, men have difficulty complying with these programs.AimTo test a novel psychological intervention based on Acceptance and Commitment Therapy for erectile dysfunction (ACT-ED) to help men utilize penile injections.MethodsThis pilot randomized controlled trial (RCT) recruited men who were beginning a standard care (SC) structured penile rehabilitation program following radical prostatectomy. The SC program instructed patients to use penile injections 2 to 3 times per week. Participants were randomized to SC+ACT-ED or SC+enhanced monitoring (EM). Over 4 months, patients in the SC+ACT-ED group received SC plus 4 ACT sessions and 3 ACT phone calls; those in the EM group received SC plus 7 phone calls from an experienced sexual medicine nurse practitioner. Participants were assessed at study entry and at 4 and 8 months. For this pilot study, the goal was to determine initial efficacy (ie, effect sizes, where d = 0.2 is small, d = 0.5 is medium, and d = 0.8 is large).Main Outcome MeasurePrimary outcomes were feasibility and use of penile injections. Secondary outcomes were ED treatment satisfaction (ie, Erectile Dysfunction Inventory of Treatment Satisfaction, or EDITS), sexual Self-Esteem and Relationship (SEAR) quality, sexual bother (SB), and prostate cancer treatment regret.ResultsThe 53 participants were randomized (ACT, n = 26; EM, n = 27). The study acceptance rate was 61%. At 4 months, the ACT-ED group utilized more penile injections per week (1.7) compared to the EM group (0.9) (d = 1.25; P = .001) and was more adherent to penile rehabilitation compared to the EM group (ACT, 44%; EM, 10%; relative risk [RR], 4.4; P = .02). These gains were maintained at 8 months for injections per week (ACT, 1.2; EM, 0.7; d = 1.08; P = .03) and approached significance for adherence (ACT, 18%; EM, 0%; P = .10). At 4 months, ACT-ED, compared to EM, reported moderate effects for greater satisfaction with ED treatment (d = 0.41; P = .22), greater sexual self-esteem (d = 0.54; P = .07) and sexual confidence (d = 0.48; P = .07), lower sexual bother (d = 0.43; P = .17), and lower prostate cancer treatment regret (d = 0.74; P = .02). At 8 months, moderate effects in favor of ACT-ED were maintained for greater sexual self-esteem (d = 0.40; P = .19) and less treatment regret (d = 0.47; P = .16).Clinical ImplicationsACT concepts may help men utilize penile injections and cope with the effects of ED.Strengths and LimitationsStrengths include use of an innovative intervention utilizing ACT concepts and pilot RCT. Limitations include the pilot nature of the study (eg, small samples size, lack of statistical power).ConclusionACT-ED is feasible and significantly increases the use of penile injections. ACT-ED also shows promise (moderate effects) for increasing satisfaction with penile injections and sexual self-esteem while decreasing sexual bother and prostate cancer treatment regret.Nelson CJ, Saracino RM, Napolitano S, et al. Acceptance and Commitment Therapy to Increase Adherence to Penile Injection Therapy-Based Rehabilitation After Radical Prostatectomy: Pilot Randomized Controlled Trial. J Sex Med 2019; 19:1398–1408.     

Factors that affect early recurrence after prolapse repair by a nonanchored vaginal mesh procedure

ObjectiveProsima (Ethicon, Somerville, NJ, USA) is a novel procedure for treating pelvic organ prolapse (POP) that uses nonanchored vaginal mesh. However, nonfixation of the mesh may limit effectiveness. The aim of this study was to evaluate the safety, efficacy, and limitations of this procedure.Materials and methodsFrom January 2011 through to December 2011, 52 patients with symptomatic POP ≥ Stage 2 undergoing the Prosima procedure at a tertiary hospital were enrolled consecutively in this prospective study. A Data and Safety Monitoring Plan (DSMP) was developed to assess the results.ResultsFifty of the 52 patients (96%) attended the 3–6-month postoperative assessment. Symptom and quality-of-life scores were found to have improved significantly after surgery (p < 0.05). Forty-two patients (84%) underwent successful treatment for POP (Stage 0-1). The other eight patients (16%) were found to have recurrent Stage 2 anterior vaginal wall prolapse, although most of them (5/8) were asymptomatic. The highest morbidity, namely vaginal mesh exposure, occurred in four patients (8%) and was managed as a minor issue. Statistical analysis showed that anatomic recurrence was significantly (p < 0.05) associated with a “preoperative Ba ≥ +4 cm” (odds ratio = 20.57), “conservation of the prolapsed uterus” (odds ratio = 10.56) and “use of a concomitant midurethral sling” (odds ratio = 0.076).ConclusionProsima seems to have limitations when used to manage severe anterior vaginal wall prolapse and concomitant surgery may further affect its effectiveness. The information obtained from this study's DSMP will contribute to developing a strategy to improve the use of nonanchored vaginal mesh for POP repair.     

A comparative study of laparoscopic sacrocolpopexy and total vaginal mesh procedure using lightweight polypropylene meshes for prolapse repair

ObjectiveUse of vaginal meshes for treatment of pelvic organ prolapse (POP) remains controversial. A trend toward abdominal approaches and the development of new meshes has been noted. We compared the 1-year results of two different approaches using new lightweight meshes.Materials and methodsSixty-nine (95.8%) of 72 women with POP Stage ≥ 2, who underwent laparoscopic sacrocolpopexy (LSC) (n = 39) or a total vaginal mesh (TVM) procedure (n = 30) using lightweight polypropylene meshes, were studied. Baseline and follow-up assessments included a pelvic examination and a composite condition-specific questionnaire. A detailed comparison of 1-year outcomes was made. Data were analyzed using appropriate statistical methods.ResultsCompared to the TVM group, the LSC group was characterized by a younger age (53.7 years vs. 64.1 years, p < 0.001) and a longer operating time (264 minutes vs. 177.6 minutes, p < 0.001). Objective anatomic success (POP Stage ≤ 1) rates were similar between groups after statistical adjustment, i.e., 84.6% (33/39) and 86.7% (26/30) after LSC and TVM (p = 0.94), respectively. However, the dominant recurrence sites were different with anterior (n = 6) most frequent after LSC and apical (n = 4) most frequent after TVM. Reoperations were needed for the four (13.3%) apical recurrences in the TVM group. No serious complications were noted. We found “cystocele as the dominant prolapse” (p = 0.016; odds ratio = 6.94) and “suspension of prolapsed (POP Stage ≥ 2) uterus” (p = 0.025; odds ratio = 7.00) significantly affected recurrence after LSC and TVM, respectively.ConclusionPOP repair by LSC or TVM using the new lightweight polypropylene meshes seems to be safe and has comparable outcomes, but limitations may vary.     

Impact of treatment modality on overall survival in women with advanced endometrial cancer: A National Cancer Database analysis

ObjectiveTo evaluate overall survival (OS) in women with advanced endometrial cancer (EC) following chemotherapy alone (CT), neoadjuvant chemotherapy and interval debulking surgery (NACT + IDS) or primary cytoreductive surgery and chemotherapy (PCS + CT).MethodsThe National Cancer Database (NCDB) was queried for patients with stage III/IV EC from 2004 to 2015. Univariable and multivariable Cox proportional hazards analyses assessed the impact of treatment modality upon OS.ResultsOf 48,179 women identified, 5531 received CT (11.5%), 2614 NACT + IDS (5.4%) and 40,034 PCS + CT (83.1%). Median OS was 11.1 months for CT, 25.1 months for NACT + IDS and 60.9 months for PCS + CT (p < 0.001). On multivariate analysis, NACT + IDS (HR 0.44 (0.40, 0.49); p < 0.001) and PCS + CT (HR 0.32 (0.30, 0.35); p < 0.001) were associated with improved OS vs. CT alone. Age, African American race, income, higher Charlson comorbidity index and grade were predictors of worse OS (p < 0.001). On subgroup analysis by stage (III/IV) and histology (Type I/II), PCS + CT improved OS for all patients, compared to NACT + IDS (p < 0.001) and CT (p < 0.001). NACT + IDS was associated with improved OS vs. CT in stage III type I (HR 0.50; 95% CI 0.38, 0.67; p < 0.001), stage IV type I (HR 0.43; 95% CI 0.35, 0.52; p < 0.001), and stage IV type II EC (HR 0.43; 95% CI 0.36, 0.51; p < 0.001), but not stage III type II EC (HR 0.76; 95% CI 0.56, 1.03; p = 0.08).ConclusionsIn women with advanced EC, PCS + CT is associated with improved OS compared to NACT + IDS or CT alone, regardless of stage or histology. Additionally, NACT + IDS is associated with superior OS in stage III type I and all stage IV EC compared to CT alone. Where feasible, surgery should be incorporated into treatment planning in women with advanced EC.