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In recent years, the usefulness of androgen receptor axis-targeted agents (ARATs) such as abiraterone, enzalutamide, and apalutamide for the upfront treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been demonstrated. However, it remains unclear which patients would truly benefit from these treatments. Furthermore, intraductal carcinoma of the prostate (IDC-P) is a known poor prognostic factor in patients with prostate cancer. We investigated the association between the presence of IDC-P and response to therapy in patients with mHSPC.This retrospective analysis included 318 patients with mHSPC who received treatment at Nagoya University and its 12 affiliated institutions between 2014 and 2021. Their biopsy specimens were evaluated for the presence of IDC-P. The patients were classified according to their first-line treatment into the ARAT (n = 100, receiving a combination of androgen-deprivation therapy [ADT] and ARAT) or conventional therapy (n = 218, receiving ADT with or without standard antiandrogen agents) group. We compared the overall survival (OS) and second progression-free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC-P to evaluate whether presence of IDC-P predicts the response to each treatment. PFS2 was defined as the period from mHSPC diagnosis to disease progression on second-line treatment or death. Propensity score matching with one-to-one nearest-neighbor matching was used to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of the patients were well-balanced after propensity score matching.Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD-P positive. In the propensity score-matched cohort, the OS and PFS2 of IDC-P-positive patients were significantly longer in the ARAT group than in the conventional group (OS: hazard ratio [HR], 0.36; p = 0.047; PFS2: HR, 0.30; p 0.001). In contrast, no difference in OS and PFS2 was observed between the ARAT and conventional groups in IDC-P-negative patients (OS: HR, 1.09; p = 0.920; PFS2: HR, 0.40; p = 0.264).The findings highlight a high prevalence of IDC-P among patients with mHSPC and suggest that IDC-P positivity may be a reliable indicator that ARAT should be implemented as first-line treatment.

The efficacy of anti-programmed celldeath protein 1 treatment in patients with urothelial carcinoma (UC) with molecular subtypes of histological variants has not been investigated. This study aimed to examine the impact of histological variants classified according to molecular subtypes on clinical outcomes in patients with platinum-resistant metastatic UC treated with pembrolizumab.Data of 168 patients with metastatic UC who received intravenous pembrolizumab after platinum-based chemotherapy between December 2017 and November 2020 were retrospectively reviewed. Relationships between histological variant type (basal or luminal molecular subtypes) and survival outcome and response to immunotherapy were examined. Clinicopathological factors were analyzed using the Cox proportional hazards model.UC with histological variants was identified in 19 (11.3%) cases (basal subtype in 12; luminal subtype in 7). The median age of the patients was 72.5 years (range=40-89 years). The performance status was 0-1 in 151 (89.9%) patients. Liver metastasis was detected in 44 (26.2%) patients. The median progression-free survival was 3.5 months (range=0.5-34.3 months). Treatment with immune checkpoint inhibitors resulted in an overall mean survival (from the start of treatment) of 8.1 months (range=1.2-34.3 months). Patients with basal-type UC had significantly shorter progression-free survival and cancer-specific survival than those with pure UC (p=0.010 and p=0.035, respectively). A complete response was observed in eight patients (seven with pure UC, one with basal type).The basal histological variant might be a potential prognostic indicator in patients with platinum-resistant metastatic UC treated with pembrolizumab.

Objectives To investigate the prevalence of postoperative complications after transvaginal mesh prolapse surgery, and whether modified transvaginal mesh prolapse surgery (without transobturator arms or posterior mesh) has less prevalence of mesh exposure compared with conventional transvaginal mesh prolapse surgery. Methods Medical charts were retrospectively examined for 2648 patients who underwent transvaginal mesh prolapse surgery in a general hospital (2006-2017). Conventional transvaginal mesh prolapse surgery (Prolift-type, n = 2258) was used, with a shift from 2015 to modified transvaginal mesh prolapse surgery (Uphold-type, n = 330). Patients were instructed to have >2 years of follow up and to report if they had problems regarding the operation. Results The prevalence of mesh exposure was 34 out of 2648 (1.28%); 18 vagina (0.68%), 10 bladder (0.38%), two ureter (0.08%) and four rectum (0.15%). The modified transvaginal mesh prolapse surgery group had only one case with vaginal exposure. Vaginal exposure was managed transvaginally or followed by observation. Rectal exposure was managed transvaginally without colostomy. Bladder exposure was managed by transurethral resection with saline. Open ureterocystostomy was carried out to treat ureteral exposure. In the conventional transvaginal mesh prolapse surgery group, three cases of ureteral stenosis and one case with vaginal evisceration of the small intestine were managed transvaginally. The prevalence of postoperative chronic pain was 13 out of 2648 (0.49%; with one patient in the modified transvaginal mesh prolapse surgery group). The patients underwent pharmacotherapy, and one patient underwent additional surgical treatment. Conclusions The reoperation rate as a result of complications after transvaginal mesh prolapse surgery seems to be low. The reoperation rate as a result of prolapse recurrence is also low. A shift from conventional transvaginal mesh prolapse surgery to modified transvaginal mesh prolapse surgery might contribute to a further decrease in the risk of complications.

Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UCUUT) is common. One of the mechanisms driving this is the implantation of cancer cells from the UCUUT at the RNUs. Therefore, their detection after RNU can assist in predicting IVR. This study aimed to examine the utility of UroVysion® as a tool for predicting bladder recurrence after RNU for UCUUT. We prospectively enrolled 65 patients who received RNU for high-grade UCUUT between October 2013 and April 2017. Of the 65 patients, 54 (83.1%) who had both bladder urine samples available immediately after RNU (0 postoperative days: POD) and 5 days after RNU (5POD) were selected. We performed UroVysion® and cytology. Twenty-two patients showed IVR with 32 foci. UroVysion® results at 0POD (26 patients, 48.1%) and/or 5POD (31 patients, 57.4%) were positive in 42 (77.8%) patients. The sensitivity, specificity, positive predictive value, and negative predictive value of UroVysion® for included cases were measured for both 0POD and 5POD samples; they were determined to be 95.5% (21/22), 34.4% (11/32), 50.0% (21/42), and 91.7% (11/12), respectively. For cytology, these values were 75.0% (15/20), 52.9% (18/34), 48.4% (15/31), and 78.3% (18/23), respectively. Forty-two (64.6%) patients who were UroVysion®-positive demonstrated IVR. The IVR rate between the group positive for either 0POD or 5POD and that negative for both significantly differed for both UroVysion® (p = 0.019) and cytology (p = 0.046). Multiple urine tests using UroVysion® after RNU could be a useful predictor for IVR.

Objectives: To elucidate if synthetic contrast enhanced computed tomography (CECT) images created from plain CT images using deep neural networks (DNN) could be used for screening, clinical diagnosis, and postoperative follow up of small diameter renal tumors by comparing the concordance rate between real and synthetic CECT images and the diagnoses according to 10 urologists. Methods: This retrospective, multicenter study included 155 patients (artificial intelligence training cohort [n=99], validation cohort [n=56]) who underwent surgery for small-diameter (≤40 mm) renal tumors, with the pathological diagnosis of renal cell carcinoma, during 2010 to 2020. Preoperatively, dynamic plain CT and CECT images were obtained. We created a learned DNN using pix2pix. We examined the quality of the synthetic CECT images created using this DNN and compared them with real CECT images using the zero mean normalized cross correlation parameter. We assessed concordance rates between real and synthetic images and diagnoses according to 10 urologists by creating a receiver operating characteristic curve and calculating the area under the curve (AUC). Results: The synthetic CECT images were highly concordant with the real CECT images, regardless of the existence or morphology of the renal tumor. Regarding the concordance rate, a greater AUC was obtained with synthetic CECT (AUC=0.892) than with only CT (AUC=0.720; p

Objective To evaluate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in patients with castration-resistant prostate cancer (CRPC) with intraductal carcinoma of the prostate (IDC-P) using a propensity score-matched analysis. Patients and methods We retrospectively identified 309 patients with CRPC from February 2007 to February 2016 at Nagoya University and its affiliated hospitals. All patients received initial androgen-deprivation therapy (ADT). After progression to CRPC, they received docetaxel or ARAT (abiraterone or enzalutamide) as first-line life-prolonging therapy. Docetaxel (70-75 mg/m2 ) every 3 weeks vs enzalutamide (160 mg) once daily orally or abiraterone (1 g) once daily plus prednisone (5 mg) twice daily orally was administered. The primary outcome of interest was overall survival (OS) from the time of CRPC diagnosis. A propensity score analysis with a 1:1 ratio using an optimal matching algorithm was used to adjust for confounding factors. Results Overall, 234 patients were analysed. Propensity score-matching identified 85 patients in each group. There were no significant differences in patient characteristics between the groups. The median OS in the docetaxel group was 38.2 vs 58.3 months in the ARAT group (P = 0.03). For patients with IDC-P, OS was significantly longer in the ARAT group than the docetaxel group (P = 0.01), and there was no significant difference in each group, as in patients without IDC-P (P = 0.67). A multivariate analysis showed that the presence of IDC-P, duration of primary ADT, visceral metastasis, and administration of ARAT as the first-line treatment for CRPC were independent prognostic factors for OS. Conclusion Administration of ARAT as the first-line treatment for CRPC may prolong OS more than that of docetaxel, especially in patients with IDC-P.

Introduction and hypothesis Although colpocleisis is a low-invasive surgical option to treat pelvic organ prolapse, it sometimes involves a long operative time with substantial bleeding. To streamline the vaginal dissection process in colpoclesis, we introduced the usage of dermatomes. Methods All patients were sexually inactive women with post-hysterectomy prolapse. Data of the dermatome group were retrospectively compared with those of the historical control group based on operative features, perioperative complications and pathology of dissected tissue. In the dermatome group, 34 women underwent total colpocleisis with vaginal dissection using dermatomes; 4 were done mainly with electric dermatomes, and 30 were done with razor-type dermatomes. In the control group, 20 women underwent total colpocleisis with vaginal dissection using Metzenbaum scissors. Results Using dermatomes in vaginal dissection was helpful to shorten total operative time (including perineoplasty) by one third from 76 to 51 min, to shorten the time of colpocleisis by half, from 62 to 32 min, and to reduce intraoperative bleeding by 76%, from 62 to 15 ml. In addition, none in the dermatome group and 2/20 patients in the control group had unintended peritoneal opening. Dissection with scissors removed not only the epithelium and submucosal layer but also the muscle layer. This was minimized with razor-type dermatomes and never occurred with electric dermatomes. Whereas electric dermatomes are difficult to get accustomed to and are expensive, razor-type dermatomes enable thinner dissection compared with scissors, are easy to handle and are inexpensive. Conclusions Razor-type dermatomes enable quick and thin vaginal dissection with less bleeding. Therefore, they can be recommended as a practical tool for colpocleisis, a prolapse operation mainly for frail elderly patients.

We experienced two cases of urethral prolapse misdiagnosed as pelvic organ prolapse. One patient, an 87-year-old woman, was referred to us from a gynecological clinic with a supposed uterine prolapse. The other patient, an 84-year-old woman, was referred to us from the Department of Urology in a general hospital with a supposed recurrence of cystocele following a transvaginal mesh repair. We diagnosed both of them as having a urethral prolapse through pelvic examination and cystoscopy. Both patients were treated uneventfully with the four-quadrant excisional technique. Urethral prolapse is a relatively rare disease and as such, urologists and gynecologists may have little exposure to the symptoms in a clinical setting, resulting to misdiagnosis or delayed diagnosis. We discussed the differential diagnosis of urethral prolapse.

(Case) A 56-year-old woman who complained of urinary frequency and macrohematuria. Abdominal US, enhanced CT and MRI revealed a left renal tumor. A left radical nephrectomy was performed in May 1997, and the pathological diagnosis was renal fibrosarcoma. Follow-up computed CT was performed routinely. A metastatic lesion in the right lung revealed 19 months after the nephrectomy.She underwent partial pneumonectomy in January 1999, and the pathological diagnosis was also fibrosarcoma. She was followed up until 2009 without recurrence.In 2015, she was admitted in the Department of Orthopedics due to femoral neck fracture in 2015, thus we could find out she was alive, tumor-free 18 years after the nephrectomy. We added the immunohistochemistical study to her specimen of kidney and lung, and the diagnosis was changed to undifferentiated/unclassified sarcoma. (Conclusion) Metastatic renal sarcoma has a poor prognosis in general. We experienced a long-term survival case of undifferentiated/unclassified renal sarcoma with lung metastasis, and report it with some literature review.

Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UCUUT) is common. One of the mechanisms driving this is the implantation of cancer cells from the UCUUT at the RNUs. Therefore, their detection after RNU can assist in predicting IVR. This study aimed to examine the utility of UroVysionWe prospectively enrolled 65 patients who received RNU for high-grade UCUUT between October 2013 and April 2017.Of the 65 patients, 54 (83.1%) who had both bladder urine samples available immediately after RNU (0 postoperative days: POD) and 5 days after RNU (5POD) were selected. We performed UroVysionMultiple urine tests using UroVysion

To evaluate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in patients with castration-resistant prostate cancer (CRPC) with intraductal carcinoma of the prostate (IDC-P) using a propensity score-matched analysis.We retrospectively identified 309 patients with CRPC from February 2007 to February 2016 at Nagoya University and its affiliated hospitals. All patients received initial androgen-deprivation therapy (ADT). After progression to CRPC, they received docetaxel or ARAT (abiraterone or enzalutamide) as first-line life-prolonging therapy. Docetaxel (70-75 mg/mOverall, 234 patients were analysed. Propensity score-matching identified 85 patients in each group. There were no significant differences in patient characteristics between the groups. The median OS in the docetaxel group was 38.2 vs 58.3 months in the ARAT group (P = 0.03). For patients with IDC-P, OS was significantly longer in the ARAT group than the docetaxel group (P = 0.01), and there was no significant difference in each group, as in patients without IDC-P (P = 0.67). A multivariate analysis showed that the presence of IDC-P, duration of primary ADT, visceral metastasis, and administration of ARAT as the first-line treatment for CRPC were independent prognostic factors for OS.Administration of ARAT as the first-line treatment for CRPC may prolong OS more than that of docetaxel, especially in patients with IDC-P.

(Objective) A FDA alert in 2011 warned about postoperative chronic pain following transvaginal mesh (TVM) for pelvic organ prolapse (POP). We studied cases with chronic pain after TVM, natural tissue repair (NTR) and laparoscopic salcocopopexy (LSC). (Methods) We retrospectively reviewed medical charts of patients who underwent POP operations in our hospital or were referred to us after POP operations in other hospitals between 2006 and 2016. Postoperative chronic pain was defined as persistent pain for more than three months following the first three months from the time of POP operations.Patients' characteristics and treatments were analyzed. (Results) In patients who underwent POP operations in our hospital, the rates of chronic postoperative pain after TVM, NTR and LSC were 12/2,457 (0.49%), 1/402 (0.26%) and 0/29 (0%), respectively. Another 8 patients were referred to us after POP operations in other hospitals. Thus, a total of 21 patients (15: TVM, 6: NTR) had either medications, surgical treatment or were referred to other doctors due to postoperative chronic pain. All of them were parous women aged 53 to 81 years old. Preoperative chronic pelvic pain was found in seven patients (33%), and another four patients (19%) had orthopedic diseases with chronic pain. The main locations of pain were; vagina 11, vulva 2, urinary bladder 2, urethra 1, coccyx 1, buttocks 1, anus 1, perineum 1 and groin 1. Nineteen patients had pharmacological treatment using tricyclic antidepressants, Ca2+ channel α2δ ligand and/or serotonin-noradrenalin reuptake inhibitor (SNRI); 9 (47%) of the patients showed a notable improvement. Three patients following TVM had surgical treatment; one with bladder mesh exposure was resolved with TURis, one with vaginal mesh exposure was resolved with mesh trimming, but one with tenderness on the mesh arm did not improve after a partial mesh removal. Four patients were referred to pain clinics. (Conclusions) Postoperative chronic pain can occur following both TVM and NTR therefore, attentive listening and proper medication are important as initial therapies. It is mandatory to examine the presence of mesh exposure in patients after using mesh. We should be careful about preoperative chronic pain, pelvic or elsewhere, as a risk factor for postoperative chronic pain.

(Objective) A rise of intra-abdominal pressure may exacerbate pelvic organ prolapse (POP) as well as abdominal hernias. This paper aims to assess the possible risk factors of an abdominal mass and ascites as comorbidities of POP. (Methods) We retrospectively reviewed the medical charts of 2,748 POP patients between 2010 and 2016 and extracted eight cases (0.3%) with abdominal mass and ascites as risk factors. (Results) All eight patients were multiparous women aged between 52 and 88 years old. Three patients (cases 1-3) were referred to us for surgery related to POP from gynecologists with previously undetected ovarian tumors. In case 1, we noticed abdominal distension during a transvaginal mesh (TVM) operation. Postoperative CT and MRI scans confirmed the presence of an ovarian tumor 24 cm in diameter (mucinous cystic tumor, borderline malignant). In case 2, transvaginal ultrasound could not detect the ovaries, but a transabdominal ultrasound, which was done to investigate urinary retention, revealed an ovarian tumor 18 cm in diameter (mucinous cystic adenoma). In case 3, a detailed patient history outlined the patient's sense of abdominal fullness and a transvaginal ultrasound found ovarian cancer 10 cm in diameter with ascites (serous adenocarcinoma). Case 4 suffered from autosomal dominant polycystic kidney disease (ADPKD) with large liver cysts. The patient underwent a TVM operation to treat the presenting POP with unusual bleeding (460 g). Case 5 had abdominal distension and cystocele due to huge abdominal mass (recurrence of malignant lymphoma); she desired conservative follow-up to tumor and POP due to old age (88 years old). Two patients suffered from end-stage cancer (case 6: colorectal cancer, case 7: breast cancer) with liver metastasis. In cases 6 and 7, the patients' POP worsened with the increase of ascites, which was managed conservatively. Case 8 presented with liver cirrhosis related ascites and a total uterine prolapse, simultaneously. Colpocleisis was cancelled due to the onset of hepatic coma. (Conclusions) Abdominal mass and ascites are risk factors of POP by increasing abdominal pressure and lesions such as ovarian tumors may present as POP. Even when POP patients are referred from gynecologists, a vaginal examination, carefully recorded patient history, and abdominal palpation should be included as part of a standard treatment regimen to reliably exclude underlying diseases.

239 Background: The sequence of use of life-prolonging therapy (docetaxel, abiraterone, enzalutamide, and cabazitaxel) is unclear in patients with castration-resistant prostate cancer (CRPC). Methods: We retrospectively identified a total of 316 patients diagnosed with CRPC from September 2003 to April 2019 at Nagoya University and its affiliated hospitals. All patients were treated with >2 life-prolonging therapies. We divided these patients into four groups based on the sequence of drug administration. The group of patients who were treated using the sequence of abiraterone to enzalutamide or enzalutamide to abiraterone was termed as AA. The group treated using the sequence of abiraterone or enzalutamide to docetaxel was termed as AD. The group treated using the sequence of docetaxel to abiraterone or enzalutamide was termed as DA. Lastly, the group treated using the sequence of docetaxel to cabazitaxel was termed as DC. We investigated the overall survival (OS) from the time of diagnosis of CRPC. In addition, we estimated combined progression-free survival (combined PFS) defined as the sum of the PFS of each agent. Results: The number of patients in AA, AD, DA, and DC was 106, 69, 130, and 11, respectively. Regarding AA, AD, DA, and DC, the median ages were 72, 70, 68, and 64 years, respectively. The proportion of patients who had de novo distant metastasis was 66%, 65%, 58%, and 73% in AA, AD, DA, and DC, respectively. Further, the median OS was 68.7, 54.5, 68.6, and 22.0 months for AA, AD, DA, and DC, respectively. Notably, no significant differences related to OS were observed between AA and AD ( p = 0.06), AA and DA ( p = 0.24), as well as AD and DA ( p = 0.46). The median combined PFS was 8.6, 10.1, 13.9, and 5.6 months for AA, AD, DA, and DC, respectively. In terms of combined PFS, a significant difference was observed between AA and DA ( p < 0.001) as well as AD and DA ( p = 0.003). OS and combined PFS were significantly poor in DC compared with those in the other groups. Conclusions: No significant differences related to OS were observed regarding the sequence of use of docetaxel, abiraterone, and enzalutamide. Notably, combined PFS was comparatively better in DA than in any other group.

209 Background: Enzalutamide (ENZ) was approved to prolong survival for castration-resistant prostate cancer (CRPC) patients before and after chemotherapy. No factor was identified to predict the effectiveness of ENZ so far. .Intraductal carcinoma of the prostate (IDC-P) was newly recognized on 2017 EAU guideline and considering as a poor prognostic factor、although there has been no reports to predict the therapeutic effects of ENZ according to the presence of IDC-P. In this study, we evaluated the efficacy of ENZ for CRPC patients with or without IDC-P. Methods: We retrospectively identified 199 CRPC patients treated with ENZ from 2014 to 2018 in author-affiliated hospitals. All needle biopsy slides were reviewed by a single genitourinary pathologist and IDC-P was defined according to the criteria of McNeal at initial biopsy. Endpoint is overall survival (OS) from the time of CRPC diagnosis and time to treatment failure of ENZ. PSA response is defined as over 50% PSA decline from baseline. Results: The median patient age was 71 (range, 49–90) years. The median initial PSA was 154 ng/ml (range, 3.9–24736 ng/ml). The patients who received docetaxel were 42/199 (21%). IDC-P was detected in 98 patients (49%) at initial prostate biopsy. PSA response was 70.5% in patients without IDC-P and 53.9% in patients with IDC-P. The median OS from the time of CRPC was 37.9 and 71.5 months with and without IDC-P, respectively (P=0.013). There was no significant difference on OS in CRPC patients with IDC-P between before and after docetaxel (P=0.941). Same result was observed in CRPC patients without IDC-P (P=0.86). In time to treatment failure by ENZ, patients with IDC-P showed worse prognosis than patients without IDC-P after docetaxel (P=0.068). On the other hand, the difference disappeared before docetaxel regardless the presence of IDC-P (P=0.94). Conclusions: IDC-P is a poor prognostic factor for CRPC patients treated with ENZ. ENZ may be most effective for CRPC patients with IDC-P before chemotherapy.