To mesh or not mesh "apical prolapse," that is the question!

Surgical approaches for pelvic organ prolapse have evolved over the last 30 years and is a popular topic for debate, particularly when discussing apical prolapse. Transvaginal native tissue repairs remain the mainstay of POP surgeries, however, transabdominal approaches continue to evolve. Use of interposition material, such as synthetic polypropylene mesh, is the standard when performing an abdominal sacrocolpopexy, however, use of autologous fascia can be considered. This debate article provides an overview of this subject and highlights the value of different approaches to apical prolapse. The authors were asked to support their approach in various scenarios including:extremes of age, prior hysterectomy and intact uterus, desire to avoid mesh, sexual activity, and presence of comorbidities. In discussing common patient scenarios, ultimate decision making on specific POP surgeries is determined by patient preference and goals.

Sensation of incomplete bladder emptying in women: Lack of correlation to an elevated post-void residual.

INTRODUCTION/BACKGROUND: Sensation of incomplete bladder emptying (SIBE) has been shown to be correlated with an elevated post-void residual (PVR) in men, however, the significance of this symptom and whether it correlates with an elevated PVR in women is less clear. In this study, we assessed if SIBE in women is correlated with an elevated PVR and determined the relationship of SIBE to other lower urinary tract symptoms. METHODS/MATERIALS: Women ages ≥18 with lower urinary tract symptoms were eligible. SIBE was defined by a response "sometimes", "most of the time", or "all of the time" to the question "How often do you feel that your bladder has not emptied properly after you have urinated?" on the International Consultation on Incontinence Questionnaire. Frequency and bother of other lower urinary tract symptoms were also assessed to compare their relationship to SIBE. Elevated PVR was defined as ≥100 ml via ultrasound. RESULTS: We prospectively evaluated 95 women, 59% of whom reported SIBE. Compared to women without SIBE, women with SIBE reported more urinary hesitancy (51% vs. 18%, p = 0.002), intermittency (56% vs. 16%, p < 0.001), weak stream (36% vs. 5%, p < 0.001), dysuria (29% vs. 5%, p = 0.004), and straining (25% vs 5%, p = 0.013). However, there was no difference in elevated PVRs between women with and without SIBE [5/56, 9% vs. 4/39, 10%, (p = 0.99)]. All women, regardless of SIBE, reported higher bother from storage and incontinence symptoms versus voiding symptoms with no difference in overall bother scores. CONCLUSION: SIBE is a common complaint in women with lower urinary tract symptoms. While women with SIBE reported more voiding symptoms, they were more bothered by storage symptoms. Importantly, most of these women emptied their bladder well and were not more likely to have an elevated PVR than women without SIBE.

Impact of preoperative urodynamics on women undergoing pelvic organ prolapse surgery.

INTRODUCTION AND HYPOTHESIS: Preoperative urodynamic studies (UDS) are frequently performed before pelvic organ prolapse (POP) surgery to assess urethral and bladder function. The primary goal of this study is to examine how preoperative UDS are utilized and what value these studies have in patient treatment and/or counseling. METHODS: We retrospectively reviewed patients who underwent prolapse surgery and had preoperative UDS between June 2010 and February 2015. Indications for UDS were classified into four categories: (1) occult stress urinary incontinence only, (2) overactive bladder symptoms, (3) mixed or insensible urinary incontinence, and (4) voiding symptoms and/or elevated post-void residual. We identified changes in management or counseling that were directly attributable to UDS results prior to surgery. RESULTS: Three hundred ninety-two patients underwent urodynamic testing for indications 2-4 above, and 316 met the inclusion criteria. Fifty-seven percent (180/316) had OAB symptoms (34.4% wet, 65.6% dry), 40.2% (127/316) had mixed incontinence, and 17.1% (54/316) had voiding symptoms and/or elevated PVR. A total of 3.5% (11/316) patients had alteration in their management or counseling based on the results of the UDS; 29.4% (50/170) of the women evaluated for occult SUI alone or with other symptoms demonstrated it and 41 underwent sling placement. CONCLUSIONS: UDS did not have a significant impact on preoperative management or counseling in POP surgery if demonstration of occult SUI was not the indication for preoperative study in women committed to POP surgery. Major alterations in treatment were rare and occurred mostly in women with stress incontinence that also had concomitant voiding symptoms and/or elevated PVR.

Total Autologous Fascia Lata Anterior and Apical Pelvic Organ Prolapse Repair: A New Technique and Initial Experience.

OBJECTIVE: To address renewed interest in nonmesh transvaginal Pelvic Organ Prolapse (POP) repair since the FDA reclassification of transvaginal mesh, our goal was to develop a transvaginal sacrospinous fixation for anterior and apical POP using only autologous fascia lata. We report our experience in 33 patients. METHODS: Autologous Anterior and Apical Pelvic Organ Prolapse (AAA-POP) repair utilizes a 4 × 14 cm piece of fascia lata harvested through a 3-4-inch upper thigh incision. The graft is reconfigured to provide apical fixation to the sacrospinous ligaments and distal fixation to the obturator fascia. Patients were followed by history, SEAPI scores, POP-Q scores, and Visual Analogue Pain Score. Treatment success was defined as absence of symptomatic anterior or apical POP. RESULTS: Thirty-three patients (mean age 63, mean follow-up 12 months) underwent AAA-POP. Treatment was successful in 31 patients (94%), and 2 failures were due to uterine prolapse. Mean harvest site Visual Analog Pain score was 0.27. Five and 7 patients developed nonbothersome thigh bulges and wound paresthesias, respectively. All 4 harvest-site seromas resolved, with 2 requiring simple aspiration. Eleven patients developed urinary retention, 10 (91%) of them after concurrent pubovaginal sling. All resolved after sling loosening (6 patients) or sling lysis (4 patients). CONCLUSION: AAA-POP is an efficacious treatment for patients desiring nonmesh POP repair. Postoperative harvest site issues are minor and typically resolve with expectant management. Patients should be counseled about the potential risk of failure with a uterine-sparing approach and the risk of urinary retention with concurrent pubovaginal sling.

Vaginal Dehiscence and Evisceration After Robotic-assisted Radical Cystectomy: A Case Series and Review of the Literature.

OBJECTIVE: To describe a rare complication in 5 women who had vaginal prolapse, dehiscence, and/or evisceration after having undergone robotic-assisted radical cystectomy with creation of ileal conduit urinary diversion. Radical cystectomy is the standard of care in the extirpative treatment for muscle invasive urothelial carcinoma. Anterior exenteration in the female patient requires removal of the anterior vaginal wall, urethra, uterus, and adnexa which results in significant changes to the pelvic floor. METHODS: Retrospective identification of all women having undergone robotic-assisted radical cystectomy for urothelial carcinoma who ultimately represented with vaginal prolapse, dehiscence, and/or evisceration between January 2012 and April 2019. We identified patient characteristics detailing their presentation. A review of the available literature highlighted the lack of available information in this uncommon cohort. RESULTS: Five women with vaginal dehiscence and/or evisceration who had previously undergone robotic-assisted radical cystectomy, anterior vaginectomy with urethrectomy, pelvic lymph node dissection, and creation of ileal conduit by 4 surgeons were identified. Mean interval time to initial presentation of prolapse or dehiscence was 44.4 weeks (range 11-120). In the 2 patients that eviscerated prior to repair, this occurred at 5 and 25 weeks after initial outpatient consultation. All reconstructive efforts were approached transvaginally. Two patients underwent 2 or more repairs. Management options included expectant management, pessary, and immediate vs delayed transvaginal surgical repair. CONCLUSION: Our case series describes the unique and potentially devastating complication of vaginal dehiscence and bowel evisceration in women with history of robotic-assisted radical cystectomy.

Improved Detection of Pelvic Organ Prolapse: Comparative Utility of Defecography Phase Sequence to Nondefecography Valsalva Maneuvers in Dynamic Pelvic Floor Magnetic Resonance Imaging.

PURPOSE: To evaluate the utility of a defecography phase (DP) sequence in dynamic pelvic floor MRI (DPMRI), in comparison to DPMRI utilizing only non-defecography Valsalva maneuvers (VM). MATERIALS AND METHODS: Inclusion criteria identified 237 female patients with symptoms and/or physical exam findings of pelvic floor prolapse. All DPMRI exams were obtained following insertion of ultrasound gel into the rectum and vagina. Steady-state free-precession sequences in sagittal plane were acquired in the resting state, followed by dynamic cine acquisitions during VM and DP. In all phases, two experienced radiologists performed blinded review using the H-line, M-line, Organ prolapse (HMO) system. The presence of a rectocele, enterocele and inferior descent of the anorectal junction, bladder base, and vaginal vault were recorded in all patients using the pubococcygeal line as a fixed landmark. RESULTS: DPMRI with DP detected significantly more number of patients than VM (p<0.0001) with vaginal prolapse (231/237, 97.5% vs. 177/237, 74.7%), anorectal prolapse (227/237, 95.8% vs. 197/237, 83.1%), cystocele (197/237, 83.1% vs. 108/237, 45.6%), and rectocele (154/237, 65% vs. 93/237, 39.2%). The median cycstocele (3.2cm vs. 1cm), vaginal prolapse (3cm vs. 1.5cm), anorectal prolapse (5.4cm vs. 4.2cm), H-line (8cm vs. 7.2cm) and M-line (5.3cm vs. 3.9cm) were significantly higher with DP than VM (p<0.0001). CONCLUSIONS: Addition of DP to DPMRI demonstrates a greater degree of pelvic floor instability as compared to imaging performed during VM alone. Pelvic floor structures may show mild descent or appear normal during VM, with marked prolapse on subsequent DP images.

Dynamic Pelvic Magnetic Resonance Imaging Evaluation of Pelvic Organ Prolapse Compared to Physical Examination Findings.

OBJECTIVE: To compare dynamic magnetic resonance imaging (dMRI) defecography phase findings with physical examination (PE) grading in the evaluation of pelvic organ prolapse (POP). METHODS: We retrospectively reviewed 274 consecutive patients who underwent dMRI with defecography. Baden-Walker grading of POP, absolute dMRI values, and grading by dMRI were collected for anterior, apical, and posterior compartments. Anatomically significant POP on PE was defined as Baden-Walker Grade ≥3 and on dMRI by dMRI Grade ≥2. A Spearman's Rank correlation was performed between absolute dMRI values and respective POP grades. RESULTS: A total of 178 female patients were included. Anatomically insignificant and significant cystoceles had a 26.4% (19/72) and 84.6% (66/78) agreement respectively. Anatomically insignificant and significant apical prolapse had a 2.0% (2/100) and 62.9% (17/27) agreement respectively. Anatomically insignificant and significant posterior prolapse had a 49.5% (51/103) and 78.7% (59/75) agreement respectively. PE detected only 30% (9/30) of total dMRI detected enteroceles and misdiagnosed 10% (3/30) of these patients with a rectocele. CONCLUSION: The dMRI defecography phase correlated well for anatomically significant prolapse in anterior and posterior compartments. dMRI was superior to PE for enterocele detection and was better able to distinguish an enterocele from a rectocele. Thus, dMRI may have the greatest diagnostic value in cases where the presence of an enterocele is unclear in apical and/or posterior compartments.

A rare diaphragmatic ureteral herniation case report: endoscopic and open reconstructive management.

BACKGROUND: Ureteral herniations are a rare occurrence, generally found incidentally on cross sectional imaging or during surgical intervention for unrelated processes. Several locations of ureteral herniations can occur including the inguinal, femoral, sciatic, obturator, and thoracic regions. While few reports of ureteral hernias are reported in the literature overall, the vast majority of those reported are inguinoscrotal herniations found during evaluation and treatment of inguinal hernias. Pelvic outlet ureteral herniations intrinsically are more common secondary to their dependent locations. Intrathoracic ureteral herniations through diaphragmatic defects are an exceptionally rare subset of ureteral herniations and have only been described sparingly. Fewer than ten case reports of diaphramatic ureteral herniations have been reported and none have described both cystoscopic management and open reconstruction. CASE PRESENTATION: We report the case of a 81 year old female with flank pain who was found to have idiopathic diaphragmatic hernia with incarcerated proximal ureter. She had no prior injury or surgery that explained her clinical presentation. She was initially observed and then managed conservatively with ureteral stent exchanges. Ultimately she underwent open surgical repair of her diaphragmatic hernia, reduction, resection and anastomosis of redundant proximal incarcerated ureteral segment, and nephropexy for a hypermobile right renal unit. This case report illustrates the pre- and post-operative imaging studies of a very rare intrathoracic ureteral herniation as well as surgical approach to repair. CONCLUSION: A herniated ureter is a potential source of serious renal and ureteral complications. The thoracic herniation of ureter is the rarest of the ureteral herniations. When discovered, they should be managed to preserve renal function and prevent strangulation of the affected segment of ureter. This case report documents the treatment of a thoracic ureteral herniation with observation, conservative endoscopic management, and finally open surgical reconstruction.

Review Article: Preoperative Evaluation and Optimization of the Geriatric Urological Patient.

INTRODUCTION: Geriatric urological patients are at higher risk for postoperative morbidity and mortality compared to their younger counterparts because of an increased prevalence of comorbidities and functional impairments. A comprehensive preoperative evaluation is necessary to identify and address these issues, as well as to optimize perioperative physiological and functional status. METHODS: The presence of frailty in geriatric patients is an especially important indicator of increased perioperative surgical risk but frailty screening is poorly addressed in the majority of guidelines on preoperative screening. Geriatric patients are categorized as frail, pre-frail or nonfrail. Preoperative evaluation of these patients should include nutritional status, a psychosocial assessment, and assessment of aftercare and social support. RESULTS: Routine preoperative laboratory and radiographic evaluations are not recommended based solely on age. Rather, an individualized, pragmatic approach founded on the preoperative assessment, evidence-based guidelines, and the nature and extent of the surgery is advised. CONCLUSIONS: Following these recommendations will provide the urologist a thorough and practical approach to the preoperative evaluation of geriatric urological patients, with the ultimate goal of reducing perioperative morbidity and mortality.

Rare Leiomyoma of the Tunica Dartos: A Case Report with Clinical Relevance for Malignant Transformation and HLRCC.

Background. Genital leiomyomas fall under the broader category of cutaneous leiomyomas, which are rare smooth muscle neoplasms accounting for 5% of all leiomyomas. Genital leiomyomas arising from the dartos muscle are exceedingly rare with fewer than 30 cases reported in the literature. They are typically benign and adequately treated with simple surgical excision; however, previously reported cases of malignant transformation and a possible link to the hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome warrant closer follow-up. Case Presentation. We report a case of a 47-year-old male refugee from Rwanda found to have a mobile, pea-sized, mildly painful scrotal lesion near the left penoscrotal junction and 1.5 cm indeterminate vascular mass in the right kidney. Surgical excision of the scrotal nodule was performed and the diagnosis of a dartoic leiomyoma was rendered. The presence of moderate nuclear atypia, rare mitotic activity, and close surgical margins prompted a wide reexcision. We report the surgical approach, pathologic findings, and clinical follow-up related to this scrotal lesion. Conclusion. Scrotal leiomyomas demonstrate a high rate of recurrence and pose a risk for malignant transformation. They may also indicate an underlying autosomal dominant syndrome associated with increased risk for development of an aggressive form of renal cell carcinoma. When discovered, management should include surgical excision, screening for syndromic features, and routine follow-up.

Seminal Vesicle Leiomyoma Mimicking Extra-prostatic Extension of Prostatic Adenocarcinoma.

Leiomyomas are common smooth muscle neoplasms; however, leiomyomas of the seminal vesicles are extremely rare. We report a case of seminal vesicle leiomyoma in a 55-year-old African American male who underwent robot assisted laparoscopic prostatectomy (RALP) for Gleason 8 (4 + 4) adenocarcinoma. An incidental nodule arising from the left seminal vesicle was discovered during surgery, complicating the surgical dissection and suggesting extra-prostatic extension. The histologic findings in this case raised the possibility that this seminal vesicle leiomyoma may have arisen from a remnant of the mid-portion of the Müllerian duct; however, a thorough immunohistochemical (IHC) workup disproved this theory.

Cellular prostatic acid phosphatase (cPAcP) serves as a useful biomarker of histone deacetylase (HDAC) inhibitors in prostate cancer cell growth suppression.

BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed solid tumor and the second leading cancer death in the United States, and also one of the major cancer-related deaths in Chinese. Androgen deprivation therapy (ADT) is the first line treatment for metastatic PCa. PCa ultimately relapses with subsequent ADT treatment failure and becomes castrate-resistant (CR). It is important to develop effective therapies with a surrogate marker towards CR PCa. METHOD: Histone deacetylase (HDAC) inhibitors were examined to determine their effects in androgen receptor (AR)/cellular prostatic acid phosphatase (cPAcP)-positive PCa cells, including LNCaP C-33, C-81, C4-2 and C4-2B and MDA PCa2b androgen-sensitive and androgen-independent cells, and AR/cPAcP-negative PCa cells, including PC-3 and DU 145 cells. Cell growth was determined by cell number counting. Western blot analyses were carried out to determine AR, cPAcP and PSA protein levels. RESULTS: cPAcP protein level was increased by HDAC inhibitor treatment. Valproic acid, a HDAC inhibitor, suppressed the growth of AR/cPAcP-positive PCa cells by over 50% in steroid-reduced conditions, higher than on AR/cPAcP-negative PCa cells. Further, HDAC inhibitor pretreatments increased androgen responsiveness as demonstrated by PSA protein level quantitation. CONCLUSION: Our results clearly demonstrate that HDAC inhibitors can induce cPAcP protein level, increase androgen responsiveness, and exhibit higher inhibitory activities on AR/cPAcP-positive PCa cells than on AR/cPAcP-negative PCa cells. Upon HDAC inhibitor pretreatment, PSA level was greatly elevated by androgens. This data indicates the potential clinical importance of cPAcP serving as a useful biomarker in the identification of PCa patient sub-population suitable for HDAC inhibitor treatment.

Reactive oxygen species induced by p66Shc longevity protein mediate nongenomic androgen action via tyrosine phosphorylation signaling to enhance tumorigenicity of prostate cancer cells.

Steroid hormones exhibit diverse biological activities. Despite intensive studies on steroid function at the genomic level, their nongenomic actions remain an enigma. In this study, we investigated the role of reactive oxygen species (ROS) in androgen-stimulated prostate cancer (PCa) cell proliferation. In androgen-treated PCa cells, increased cell growth and ROS production correlated with elevated p66Shc protein, an authentic oxidase. This growth stimulation was blocked by antioxidants. Further, elevated expression of p66Shc protein by cDNA transfection encoding wild-type protein, but not a redox-deficient (W134F) mutant, was associated with increased PCa cell proliferation. Conversely, knockdown of p66Shc expression by shRNA resulted in diminished cell growth. Increased p66Shc expression in PCa cells enhanced their tumorigenicity in xenograft animals. Importantly, p66Shc protein level is higher in clinical prostate adenocarcinomas than in adjacent noncancerous cells. Expression of redox-deficient p66Shc mutant protein abolished androgen-stimulated cell growth. In androgen-treated, H(2)O(2)-treated, and p66Shc cDNA-transfected PCa cells, cellular prostatic acid phosphatase, an authentic tyrosine phosphatase, was inactivated by reversible oxidation; subsequently, ErbB-2 was activated by phosphorylation at tyrosine-1221/1222. These results together support the notion that androgens induce ROS production through the elevation of p66Shc protein, which inactivates tyrosine phosphatase activity for the activation of interacting tyrosine kinase, leading to increased cell proliferation and enhanced tumorigenicity. Our results thus suggest that p66Shc protein functions at the critical junction point between androgens and tyrosine phosphorylation signaling in human PCa cells.

Ubiquitin-specific peptidase 20 targets TRAF6 and human T cell leukemia virus type 1 tax to negatively regulate NF-kappaB signaling.

NF-κB plays a key role in innate and acquired immunity. Its activity is regulated through intricate signaling networks. Persistent or excessive activation of NF-κB induces diseases, such as autoimmune disorders and malignant neoplasms. Infection by human T cell leukemia virus type 1 (HTLV-1) causes a fatal hematopoietic malignancy termed adult T cell leukemia (ATL). The HTLV-1 viral oncoprotein Tax functions pivotally in leukemogenesis through its potent activation of NF-κB. Recent findings suggest that protein ubiquitination is crucial for proper regulation of NF-κB signaling and for Tax activity. Here, we report that ubiquitin-specific peptidase USP20 deubiquitinates TRAF6 and Tax and suppresses interleukin 1ß (IL-1ß)- and Tax-induced NF-κB activation. Our results point to USP20 as a key negative regulator of Tax-induced NF-κB signaling.

Induction therapy does not increase surgical morbidity after esophagectomy for cancer.

BACKGROUND: A complete pathological response after induction therapy for esophageal cancer offers survival benefits, but induction therapy may increase the risk of postoperative complications and mortality. METHODS: We performed a retrospective review of consecutive patients who underwent esophagectomy for esophageal cancer to identify preoperative predictors of complications and assess the possible influence of induction therapy on surgical outcomes. RESULTS: Between 1988 and 2003, 170 esophagectomies were performed on our service; 95 (55.9%) underwent surgery alone and 75 (44.1%) received preoperative chemotherapy, 35 of whom also had preoperative radiation therapy. Based on multivariable regression analyses, independent covariates for complication categories included performance status (pulmonary, cardiovascular, total complications, and death), age (cardiovascular and other complications), and FEV(1)% (pulmonary complications). Whether patients received induction therapy was unrelated to the incidence of postoperative complications. CONCLUSIONS: We found no evidence that induction therapy adversely influences the incidence of postoperative morbidity or mortality after esophagectomy for cancer.

Expression of ADAMs (a disintegrin and metalloproteases) and TIMP-3 (tissue inhibitor of metalloproteinase-3) in human prostatic adenocarcinomas.

A disintegrin and metalloproteases (ADAMs) are proteins that contain both a disintegrin and metalloprotease domain and have potential implications for the metastasis of human cancer cells via cell adhesion and protease activities. In this study, we analyzed the expression levels of ADAM-9, ADAM-10 and ADAM-17 (TNF-alpha converting enzyme, TACE), and TIMP-3 (tissue inhibitor of metalloproteinase-3) in human prostatic tumor cell lines as well as in clinical patient materials (BPH and tumor tissue samples). Human prostatic tumor cell lines (MDA PCa 2b, LNCaP-C33, -C51, -C81, -Pro5, -Ln3, -C4-2, PC3, and DU145) showed varied levels of expression for ADAM-9, -10 and -17 mRNA. A strong expression of ADAM-17/TACE was further revealed by Western blot analysis in prostatic tumor cell lines. In the case of clinical material, all the tumor samples (8/8) revealed the expression of ADAM-9, -10, and -17 compared to the specimens of benign prostatic hyperplasia (BPH) where 80% of (8/10) samples showed the expression of ADAM-9, 86% (6/7) of ADAM-10, and 30% (3/10) of ADAM-17/TACE. Interestingly, expression of a potent inhibitor of ADAM-17 (TIMP-3) was not detected in any prostatic tumor cell lines (0/9), while TIMP-3 expression was detected in 82% (9/11) of BPH samples. Androgen-sensitive LNCaP-C33 cells exhibited differences in ADAMs regulation by 5alpha-dihydrotestosterone (DHT), while such differences were not detectable in androgen-independent LNCaP-C81 cells. These results suggest that an inverse expression pattern of ADAM-17/TACE and TIMP-3, and the regulation of ADAMs with DHT might play an important role in the pathogenesis of prostate cancer.