Impact of Histological Variants on Clinical Responses to Pembrolizumab in Patients With Metastatic Urothelial Cancer.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: The basal histological variant might be a potential prognostic indicator in patients with platinum-resistant metastatic UC treated with pembrolizumab.

Hyperammonemic encephalopathy associated with post-radiotherapy vesicointestinal fistula following cervical cancer.

The majority of hyperammonemic encephalopathy is due to liver cirrhosis. However, urinary tract infection caused by urease-producing bacteria increases ammonia in urine and can lead to hyperammonemic encephalopathy, especially in cases with obstructive uropathy and vesicointestinal fistula. This is the first case report of hyperammonemic encephalopathy in a cervical cancer patient associated with postradiotherapy vesicointestinal fistula. A 52-year-old woman developed diarrhea due to vesicosigmoidal fistula 14 years after radical hysterectomy and radiotherapy to treat cervical cancer. She refused urinary and/or fecal diversion. Twelve months after the diagnosis of fistula, she was admitted due to somnolence. Blood examination showed hyperammonemia without liver dysfunction. Urine culture showed Proteus rettgeri and Klebsiella pneumoniae. She recovered after intravenous antibiotics. Eight months after recovery, she was readmitted due to somnolence reoccurring with failed intravenous, but successful oral antibiotic treatment. She finally agreed to undergo percutaneous nephrostomy and hyperammonemia never recurred during 7 years of follow-up.

Drug-induced cystitis caused by herbal medicine (Bofutsushosan).

Bofutsushosan (BTS), one of many traditional Japanese medicines (Kampo medicines) is attracting attention for obesity and metabolic syndrome. We report allergic cystitis caused by 8-year BTS usage in a 70-year-old female. The patient presented with micturition pain with sterile pyuria over a 3-month period. Cystoscopy showed diffuse urothelial erythema and edema. Urine cytology specimens showed increased eosinophilic cells. By discontinuing BTS, the cystitis symptoms disappeared after 4 days, and urinalysis normalized. Resuming BTS without physician approval resulted in cystitis symptoms and after cessation the symptoms rapidly subsided. This is the first English case report linking allergic cystitis to herbal medicine.

Grade group 2 (10% ≥ GP4) patients have very similar malignant potential with grade group 1 patients, given the risk of intraductal carcinoma of the prostate.

BACKGROUND: It has been argued that grade group 2 (GG2) with a low Gleason pattern 4 (GP4) proportion should be an indication for active surveillance (AS) of prostate cancer (PCa). However, the cut-off GP4 proportion for AS remains unclear. Here, we evaluated the effect of GP4 proportion and IDC-P on cancer recurrence following radical prostatectomy (RP) in GG1 and GG2 patients, and identified candidates for AS. METHODS: We retrospectively evaluated 646 patients with PCa who underwent RP between 2005 and 2014, and whose specimens were of GG1 or GG2 status. RESULTS: The GGs were as follows: GG1, 25.2% (n = 163); GG2 (5% ≥ GP4), 11.4% (n = 74); GG2 (5% < GP4 ≤ 10%), 25.9% (n = 167); and GG2 (20% ≤ GP4), 37.5% (n = 242). IDC-P was detected in 26 patients (4%), i.e., in 2/167 GG2 (5% < GP4 ≤ 10%; 1%) cases and 24/242 GG2 (20% ≤ GP4; 10%) cases. GG2 patients with IDC-P exhibited a significantly poorer prognosis than did those without IDC-P (P < 0.0001), as did GG2 (20% ≤ GP4) patients without IDC-P (P < 0.05). The GG2 (5% ≥ GP4) and (5% < GP4 ≤ 10%) groups exhibited prognoses similar to those of the GG1 patients. In multivariate analysis, GG2 (20% ≤ GP4) without IDC-P, the presence of IDC-P, and the prostate-specific antigen level at diagnosis significantly predicted prognosis (P < 0.05, < 0.0001, and < 0.0001, respectively). CONCLUSION: Our findings suggest that GG2 (GP4 ≤ 10%) patients could be indicated for AS, similar to GG1 patients, given the risk of IDC-P tumors.

pT3 subclassification of renal pelvic cancer considering the tumor location improves the patients' prognostic accuracy.

Whether pT3 urothelial carcinoma of the renal pelvis (UCRP) and urothelial carcinoma of the ureter (UCU) have the same prognosis is controversial, this study compared the prognosis of pT3 UCRP with that of pT3 UCU. We retrospectively evaluated 954 patients who underwent nephroureterectomy at our institutions between January 1983 and December 2017. All surgical specimens were reviewed by a single genitourinary pathologist. Cases of pT3 UCRP were subclassified as pT3a (urothelial carcinomas extending only to the renal medulla) and pT3b (urothelial carcinomas extending into the renal cortex and/or peripelvic adipose tissue). Fine and Gray's model was used to predict recurrence-free survival (RFS) and cancer-specific survival (CSS). A total of 493 (51.7%) had UCRP and 461 (48.3%) had UCU. Within this group, 202 patients had pT3 UCRP and 146 had pT3 UCU. The pT3 subclassification of UCRP resulted in 79 cases of pT3a and 120 of pT3b. The difference in 5-year CSS among the pT3a UCRP, pT2 UCRP, and pT2 UCU subgroups was not statistically significant (pT3a UCRP vs pT2 UCRP, HR = 0.69, p = 0.56; pT3a UCRP vs pT2 UCU, HR = 0.66, p = 0.31) However, RFS and CSS were significantly higher in the pT3a UCRP group than in the pT3b group (pT3a vs pT3b, HR = 2.59, p = 0.0038 and pT3a vs pT3b, HR = 3.10, p = 0.001). The results suggest that our proposed pT3 subclassification better predicts the prognosis of UCRP patients than does the pT3 of the current AJCC/UICC classification.

[PELVIC ORGAN PROLAPSE AND INGUINAL HERNIA AGGRAVATED BY OVARIAN FIBROTHECOMA WITH ASCITES].

We present a case of pelvic organ prolapse and inguinal hernia worsened by a benign ovarian tumor with ascites. A 61-year-old woman was referred to us complaining of feeling of something protruding from her vagina. She was diagnosed with Stage III cystocele. Behavioral therapy was administered as she had only slight subjective symptoms. She visited us eight months later due to a rapid aggravation of cystocele and voiding difficulty. She subsequently developed acute abdominal pain caused by incarcerated inguinal hernia. Abdominal ultrasound, MRI and CT showed a 10.6×9.0 cm pelvic mass with ascites. As an ovarian cancer with peritoneal dissemination was suspected, she immediately underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and colposuspension. Pathological diagnosis was fibrothecoma, a benign ovarian tumor. Postoperative course was uneventful, and ascites quickly disappeared in a manner similar to Meigs syndrome. Although no procedure was done to manage inguinal hernia, it was unproblematic for 18 months, after that it worsened, necessitating hernial repair. She had no recurrence of prolapse or ascites.Increased intra-abdominal pressure due to abdominal mass or ascites can worsen prolapse and hernial diseases such as inguinal, umbilical, and abdominal hernia. In this case, ovarian fibrothecoma with ascites seemed to be responsible for worsening of the prolapse and inguinal hernia. To conclude, it is important to consider background diseases when examining patients with prolapse and coexisting hernial diseases.

Mesh exposure after transvaginal mesh prolapse surgery: Out of permissible range?

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.

UroVysion® predicts intravesical recurrence after radical nephroureterectomy for urothelial carcinoma of the upper urinary tract: a prospective study.

BACKGROUND: 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. METHODS: We prospectively enrolled 65 patients who received RNU for high-grade UCUUT between October 2013 and April 2017. RESULTS: 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). CONCLUSION: Multiple urine tests using UroVysion® after RNU could be a useful predictor for IVR.

"Central Road" cystoscopic finding: The road to worsened incontinence following laparoscopic sacrocolpopexy.

INTRODUCTION: This paper presents the "Central Road" cystoscopic finding accompanied by magnified mixed urinary incontinence following laparoscopic sacrocolopopexy. CASE PRESENTATION: A 70-year-old female experienced severe mixed urinary incontinence upon completing laparoscopic sacrocolopopexy. The cystoscopy showed a cord-like appearance in the center of the bladder trigon and posterior wall. Videourodynamics confirmed stress urinary incontinence, and chain cystourethrography indicated that the proximal urethra was open and the posterior vesicourethral angle was atypically widened. After implanting a midurethral sling, mixed urinary incontinence was cured subjectively and objectively without medication. CONCLUSION: The "Central Road" cystoscopic finding can be a signpost pointing to laparoscopic sacrocolopopexy mesh overtensioning, which can cause dekinking of the bladder neck, exacerbate stress urinary incontinence, and possibly lead to stress-induced instability. A midurethral sling successfully relieved mixed urinary incontinence in this case, but it might be necessary to loosen the laparoscopic sacrocolopopexy mesh in some other cases.

The clinical benefit of sequential therapy with androgen receptor axis-targeted agents alone in patients with castration-resistant prostate cancer: A propensity score-matched comparison study.

BACKGROUND: The optimal sequential therapy for castration-resistant prostate cancer (CRPC) remains unknown. In recent years, some doubts have emerged regarding the clinical benefit of sequential therapy with androgen receptor axis-targeted agents (ART) such as abiraterone (ABI) or enzalutamide (ENZ) for patients with CRPC. We compared the effect of ART-to-ART (AA) sequential therapy after castration resistance with that of docetaxel (DTX)-combined sequential therapy (ART to DTX or DTX to ART) in patients with CRPC. METHODS: We retrospectively identified and analyzed the data of 315 patients with CRPC treated in our seven affiliated institutions between 2009 and 2019. All patients received either DTX or ART (ABI or ENZ) as the first- or second-line therapy after castration resistance. We compared the overall survival (OS) and the second progression-free survival (PFS2), calculated from the initiation of first-line therapy after castration resistance, between the AA sequence group and the DTX-combined sequence group. PFS2 was defined as the period from the start of first-line treatment after castration resistance to progression on second-line treatment. To minimize selection bias from possible confounders, we performed propensity score matching using one-to-one nearest neighbor matching without replacement. RESULTS: Overall, 106 and 209 patients were administered the AA sequential therapy and DTX-combined sequential therapy, respectively. The clinicopathological variables of patients were well balanced after propensity score matching, and there were no significant differences between the two groups. In the propensity score-matched cohort, OS was not significantly different between the two groups (median, 37.9 vs. 45.4 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.68-1.79; p = .701), while PFS2 was significantly shorter in the AA group than in the DTX-combined group (median, 12.9 vs. 21.6 months; HR, 1.70; 95% CI, 1.16-2.48; p = .007). CONCLUSIONS: Certain patients with CRPC can benefit from ART-to-ART sequential therapy in a daily clinical setting.

Presence of constipation predicts the therapeutic efficacy of pembrolizumab in metastatic urothelial cancer patients.

OBJECTIVES: To study bowel function in urothelial cancer patients treated with pembrolizumab and to assess its association with treatment efficacy. METHODS: This retrospective study was analyzed for patients with metastatic urothelial cancer who received immune checkpoint inhibitor treatment between December 2017 and June 2019 at Nagoya University and affiliated hospitals in Japan. The association between bowel dysfunction (defined as constipation or need for laxatives) and treatment efficacy was investigated. RESULTS: We retrospectively enrolled 73 patients with metastatic urothelial cancer who received immune checkpoint inhibitor treatment. All patients received pembrolizumab at 200 mg per bodyweight administered intravenously every 3 weeks. Performance status was 0-1 in 58 patients (79.5%), and liver metastasis was detected in 22 patients (30.1%). The median age was 72 years (range 40-89 years). A total of 45 patients had constipation. The median progression-free survival and overall survival from the start of immune checkpoint inhibitor treatment was 4.0 months (95% confidence interval 1.0-17.3) and 6.6 months (95% confidence interval 1.0-18.0), respectively. Patients with constipation had a significantly higher risk of disease progression (P = 0.005). There was no significant association between constipation and overall survival (P = 0.131). However, complete response was observed among two patients treated with immune checkpoint inhibitor, both of whom did not present constipation. CONCLUSION: The presence of constipation might be a prognostic factor for urothelial cancer patients undergoing immune checkpoint inhibitor treatment.

Effect of core needle biopsy number on intraductal carcinoma of the prostate (IDC-P) diagnosis in patients with metastatic hormone-sensitive prostate cancer.

BACKGROUND: The number of core needle biopsies in metastatic prostate cancer cases are sometimes reduced to avoid various complications. We analyzed whether core needle biopsy number influence IDC-P detection rate in patients with metastatic castration-sensitive prostate cancer (mHSPC). METHODS: We retrospectively evaluated data from 150 patients diagnosed with mHSPC. Subjects were allocated to three groups according to the number of core biopsies performed: ≤ 5, 6-9, and ≥ 10. The study endpoints were the cancer-specific survival (CSS) and overall survival (OS) rates. RESULTS: For patients who underwent ≥ 10 core biopsies, a significant difference on CSS was detected between with or without IDC-P (P = 0.016). On the other hand, the difference decreased as the number of core biopsies became smaller (6-9; P = 0.322 and ≤ 5; P = 0.815). A similar trend was identified for the OS outcome. A significant difference on OS was also found between with or without IDC-P in patients who underwent ≥ 10 and 6-9 core needle biopsies (P = 0.0002 and 0.017, respectively), but not in those who underwent ≤ 5 core biopsies (P = 0.341). IDC-P served as a stronger prognostic marker for CSS and OS than did the other factors included in the multivariate analysis for patients had ≥ 10 core biopsies (P = 0.016, and P = 0.0014, respectively). CONCLUSIONS: Given the IDC-P detection and its value as a prognostic marker, we propose the performance of ≥ 10 core biopsy procedures in patients diagnosed with mHSPC to minimize the sampling error of the IDC-P.

Razor-type dermatomes enable quick and thin vaginal dissection with less bleeding in colpocleisis.

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.

Response of intraductal carcinoma of the prostate to androgen deprivation therapy predicts prostate cancer prognosis in radical prostatectomy patients.

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) has a poor prognosis and is thought to be completely resistant to current therapies, including androgen deprivation therapy (ADT). However, to date, there are no data showing direct evidence of such resistance. METHODS: We retrospectively evaluated 145 patients with high-risk prostate cancer who underwent radical prostatectomy (RP) with neoadjuvant ADT between 1991 and 2005. All patient data were collected from slides prepared from needle biopsy (NB) samples of prostate tissue and RP specimens. Data were analyzed in terms of serum level of prostate specific antigen (PSA), Gleason score of NB samples, clinical T stage, the positive cancer core rate, maximum cancer extension rate, presence of Gleason pattern 5, and presence of IDC-P in both NB samples and RP specimens. RESULTS: The median initial PSA was 33.2 ng/mL (range, 2.4-296 ng/mL), and the median follow-up period was 109 months (range, 11-257 months). The preoperative median ADT period was 4 months (range, 1-20 months). IDC-P was present in 53 patients (37%) in NB samples and 65 (45%) in RP. The patients were divided into three groups based on the presence or absence of IDC-P in NB/RP samples (IDC-P-negative at biopsy: 92 cases, IDC-P-positive at biopsy with IDC-P disappearance: 15 cases, and IDC-P-positive at biopsy with IDC-P persistence: 38 cases). Overall, 28% of IDC-P-positive cases in NB samples showed the disappearance of IDC-P at RP. IDC-P persistence cases showed the poorest prognosis, while IDC-P disappearance cases had a similar prognosis to that of IDC-P-negative at biopsy cases in terms of disease-free survival, cancer-specific survival, and overall survival (P = .0018, P = .0087, and P = .0034, respectively). CONCLUSIONS: Some cases with IDC-P responded to ADT and demonstrated favorable clinical outcomes similar to those of cases without IDC-P. These findings indicate that cases with IDC-P are heterogeneous.

Propensity score-matched comparison of docetaxel and androgen receptor axis-targeted agents in patients with castration-resistant intraductal carcinoma of the prostate.

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.

Influence of the Body Mass Index and its Effect on Tumor Characteristics and Survival among a Population with Access to Surgical Management of Upper Tract Urothelial Carcinoma.

OBJECTIVE: To examine the association between the body mass index (BMI) and the risk of survival, and to evaluate whether tumor characteristics differ by BMI in patients with upper tract urothelial carcinoma (UTUC) managed by surgery. METHODS: A clinical series on 876 patients with localized UTUC following nephroureterectomy with a bladder cuff, with data from Osaka Medical College registry (discovery cohort) and the Nagoya group (validation cohort) was examined. In addition to analyzing the overall survival and cancer-specific survival (CSS), the survival impact adjusted by pathological variables was also assessed by the BMI group. RESULTS: The percentage of high risk features including positive lymphovascular invasion was doubled in the discovery cohort compared to the validation cohort. The group of BMI ≥ 25 kg/m2 was associated with improved CSS in the discovery cohort (p = 0.004), and this tendency was verified in the validation cohort (p = 0.006). Nonproportional hazards existed for the group of BMI ≥ 25 kg/m2 and the BMI 18.5-25 kg/m2 relative to the group of BMI < 18.5 kg/m2, with a change in the CSS hazard. In multivariable Cox models, the BMI group had a superior predictive value compared with other pre-clinical factors both in the discovery cohort (HR = 3.85, p = 0.01; 95%CI: 0.09-0.73) and the validation cohort (HR = 1.56, p = 0.01; 95%CI: 0.45-0.91). When adjusted by lymphovascular invasion, the concordance of the model proposed by the discovery cohort (0.52) challenged in the validation cohort was 0.59. CONCLUSIONS: We found a clinically relevant signature for high risk patients with BMI grouping. Further research is necessary on whether tailoring recommendations for weight and nutrition management to tumor characteristics will improve outcomes.

The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance.

BACKGROUND: Although the presence of intraductal carcinoma of the prostate (IDC-P) influences biochemical failure in radical prostatectomy patients, no data are available regarding the impact of its integration into the classification grade group system. Thus, the aim of this study was to enhance the utility of the grade group system by integrating the presence of IDC-P. METHODS: This study was a retrospective evaluation of 1019 patients with prostate cancer who underwent radical prostatectomy between 2005 and 2013 without neoadjuvant or adjuvant therapy. The data on age, prostate-specific antigen (PSA) level at diagnosis, pathological T stage (pT), presence of Gleason pattern 5 (GP5), presence of IDC-P, and surgical margin status were analyzed to predict PSA recurrence after prostatectomy. RESULTS: The median patient age was 67 (range, 45-80) years and the median initial PSA level was 6.8 (range, 0.4-82) ng/mL. The median follow-up period was 82 (range, 0.7-148) months. IDC-P was detected in 157 patients (15.4%). Among these patients, the increase in the positive rate of IDC-P correlated with tumor upgrading. The grade groups (GGs) were as follows: GG1 without IDC-P, 16.0% (n = 163); GG2 without IDC-P, 46.1% (n = 470); GG3 without IDC-P, 15.7% (n = 160); GG4 without IDC-P, 2.6% (n = 27); GG5 without IDC-P, 4.1% (n = 42); any GG with IDC-P, 15.4% [n = 157; GG 2 (n = 29); GG3 (n = 60); GG4 (n = 13); GG5 (n = 55)]. Any grade Group with IDC-P showed significantly worse prognosis than any other group without IDC-P (P < 0.0001). In a multivariate analysis, integration of the IDC-P into the Grade Groups, the PSA level at diagnosis, and the surgical margin status were significant prognostic predictors (P < 0.0001, < 0.0001 and < 0.0001, respectively). CONCLUSIONS: Integrating the presence of IDC-P into the grade group system will result in more accurate predictions of patient outcome.

Chronological change of renal pathological findings in the proliferative glomerulonephritis with monoclonal IgG deposits considered to have recurred early after kidney transplantation.

Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a rare disease that recently became recognized. Its pathological findings are characterized by the deposition of a single heavy chain subclass and a single light chain isotype. PGNMID has been proven to recur in renal allografts. Herein, the authors describe the case of a 46-year-old man who presented with nephrotic syndrome and progressive kidney injury following kidney transplantation. One month after transplantation, his clinical condition stabilized; however, the protocol biopsy showed depositions of IgG and complement on the glomeruli by immunofluorescence staining. Electron microscopy (EM) revealed granular electron-dense deposits (EDD) in the mesangium. Thereafter, renal biopsy was repeated because his proteinuria level increased. Proliferative glomerulonephritis, mainly in the mesangium, with IgG and complement deposits and mesangial and subendothelial EDD were observed; however, the pathological diagnosis was difficult. Renal dysfunction then became apparent, and renal biopsy was performed again 4 years and 10 months after kidney transplantation. Glomerular deposits on a single IgG subclass and a single light chain isotype (IgG3 kappa) with membranoproliferative features were observed. Abundant subendothelial EDD were detected on EM. Finally, the patient was diagnosed with PGNMID. Since it seemed that PGNMID had already developed at 1 month after transplantation, we considered recurrent PGNMID case in the allograft. The treatment for PGNMID has not been established yet, and even in this case, the graft function was eventually lost. For improving renal prognosis, early diagnosis and further investigation on the treatment are necessary.

Diagnostic Utility of UroVysion Combined With Conventional Urinary Cytology for Urothelial Carcinoma of the Upper Urinary Tract.

OBJECTIVES: We prospectively evaluated the utility of UroVysion in urothelial carcinomas of the upper urinary tract (UCUUTs). METHODS: Ninety patients who received nephroureterectomy for UCUUT were enrolled. We performed urinary cytology and UroVysion before nephroureterectomy. We also performed the assays on 23 volunteers without a history of urothelial carcinoma. RESULTS: Seventy-five high-grade urothelial carcinomas (HGUCs), 10 low-grade urothelial carcinomas, and five other conditions were enrolled. Sensitivity, specificity, positive predictive value, and negative predictive value for HGUC detection by urinary cytology were 28.0%, 100.0%, 100.0%, and 31.6%, respectively; for detection by fluorescence in situ hybridization, these values were 60.0%, 84.0%, 93.8%, and 41.2%, respectively. UroVysion detected the only deletion of 9p21 in eight of 23 samples negative for HGUC by urinary cytology and in three of 23 volunteers. CONCLUSIONS: Combining urinary cytology and UroVysion can improve the diagnostic accuracy of UCUUT. Caution is advised in diagnosing UCUUT based only on deletion of 9p21.

[TWO CASES OF URETHRAL PROLAPSE MISDIAGNOSED AS PELVIC ORGAN PROLAPSE].

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.