Retrotrigonal Layer Dissection from a Posterior Approach Enables Bladder Neck Preservation in Robot-Assisted Radical Prostatectomy.

BACKGROUND: We developed a novel surgical technique: dissection of the retrotrigonal layer from a posterior approach in robot-assisted radical prostatectomy (RARP). This approach enables earlier access to the posterior space during bladder neck dissection and helps preserve the bladder neck. We evaluated the safety and efficacy of this technique in terms of bladder neck preservation Methods: We retrospectively reviewed 238 consecutive patients who underwent RARP using this technique from August 2021 to September 2023. Key metrics included the success rate of accessing the posterior space prior to bladder neck opening during the dissection and the rate of bladder neck preservation. In addition, oncological and surgical safety, as well as continence recovery, were assessed. RESULTS: The median age and prostate-specific antigen level were 72 (65-75) years and 7.35 (5.40-11.5) ng/mL, respectively. In 153 (64%) patients, the posterior space was successfully accessed before bladder neck opening, with the success rate increasing from 56% in the series' first half to 72% in the second half (p = 0.015). The bladder neck was preserved in 120 (53%) patients, and this rate increased from 39% in the first half to 63% in the second half (p = 0.0004). Positive surgical margins at the junction between the prostate and bladder were observed in 10 cases (4%). Bladder neck preservation correlated with early continence recovery (hazard ratio 1.37 [95% confidence interval 1.03-1.83], p = 0.030). The grade 3 complication associated with this technique occurred in one case (0.5%). CONCLUSION: Retrotrigonal layer dissection from a posterior approach in RARP enhances the safety and ease of bladder neck dissection and aids in its preservation, potentially leading to improved continence recovery.

A novel anterior approach that involves Retzius space development between the umbilical ligaments is associated with a lower incidence of postoperative inguinal hernia in robotic radical prostatectomy.

Background: To facilitate robotic radical prostatectomy (RP), we developed a novel anterior approach that utilizes a peritoneal incision between the umbilical ligaments to develop the Retzius space without contacting the internal inguinal rings, followed by closure of this space prior to prostatectomy and vesicourethral anastomosis. This approach could decrease the incidence of postoperative inguinal hernia (IH), similar to a Retzius-sparing RP (RS-RP). We compared the incidence of IH following this novel approach with that following conventional anterior RP and RS-RP. Methods: We retrospectively reviewed 532 patients who underwent robotic RP from September 2017 to August 2022. We compared the incidence of IH following novel anterior RP (n = 153) to that following conventional anterior RP (n = 284) and RS-RP (n = 95). We also assessed the independent factors associated with postoperative IH using Cox hazard models. Results: The 12- and 24-month cumulative incidences of postoperative IH following novel anterior RP were 1.3% and 1.3%, significantly lower than those associated with conventional anterior RP (8.0% and 12.6%, p = 0.009) but not significantly different from those following RS-RP (1.1% and 2.1%, p = 0.782). In multivariate analysis, use of the novel anterior RP approach, RS-RP, and body mass index were independent factors negatively associated with the occurrence of postoperative IH. Conclusions: This novel anterior approach involves developing the Retzius space between the umbilical ligaments and closure of this space following prostatectomy and vesicourethral anastomosis. It can decrease the incidence of IH compared to the conventional anterior approach. Prospective comparative studies are necessary to confirm the benefits of this approach.

Real-world outcomes of avelumab plus axitinib as first-line therapy in patients with advanced renal cell carcinoma in Japan: A multicenter, retrospective, observational study (J-DART).

OBJECTIVES: In the phase 3 JAVELIN Renal 101 trial in patients with advanced renal cell carcinoma (aRCC), objective response rate (ORR) and progression-free survival (PFS) were significantly improved in patients treated with first-line avelumab plus axitinib vs sunitinib. Here we evaluate real-world outcomes with first-line avelumab plus axitinib in Japanese patients with aRCC. METHODS: In this multicenter, noninterventional, retrospective study, clinical data from patients with aRCC treated with first-line avelumab plus axitinib between December 2019 and December 2020 in Japan were reviewed. Endpoints included ORR and PFS per investigator assessment, and time to treatment discontinuation (TTD). RESULTS: Data from 48 patients (median age, 69 years) from 12 sites were analyzed. Median follow-up was 10.4 months (range, 2.6-16.5), and median duration of treatment was 7.4 months (range, 0.5-16.5). International Metastatic RCC Database Consortium risk category was favorable, intermediate, or poor in 16.7%, 54.2%, and 29.2% of patients, respectively. The ORR was 48.8% (95% CI, 33.3%-64.5%), including complete response in 3/43 patients (7.0%). Thirteen patients (27.1%) had disease progression or died, and median PFS was 15.3 months (95% CI, 9.7 months - not estimable). At data cutoff, 24 patients (50.0%) were still receiving avelumab plus axitinib, and median TTD was 15.2 months (95% CI, 7.4 months - not estimable). Three patients (6.3%) received high-dose corticosteroid treatment for immune-related adverse events, and 8 (16.7%) received treatment for infusion-related reactions. CONCLUSIONS: We report the first real-world evidence of the effectiveness and tolerability of first-line avelumab plus axitinib in Japanese patients with aRCC. Results were comparable with the JAVELIN Renal 101 trial.

[A Case of Left Renal Cell Carcinoma with Renal Arteriovenous Fistula and Multiple Vascular Malformation Undergoing Nephrectomy].

A 69-year-old woman was referred to our hospital for the treatment of a left renal tumor found by computed tomography (CT) during examination for microscopic hematuria. Contrast-enhanced CT showed a 5 cm tumor in the inferior pole of the left kidney. Left renal cell carcinoma (RCC) (cT1bN0M0) was suspected. In addition, the left renal and gonadal veins were dilated and enhanced in an arterial phase; renal arteriovenous fistula (RAVF) was suspected. Moreover, there were multiple focal arterial dilatations, suggesting the presence of multiple vascular malformation. Hereditary aortic disease, including vascular Ehlers-Danlos syndrome (vEDS), was a concern. In general, surgery is not recommended for patients with vEDS, due to vascular fragility. As such, a panel analysis of genes for hereditary aortic diseases, including vEDS, was performed; no pathogenic variants in candidate genes including COL3A1 were identified. After detailed discussions with the patient, she underwent a left nephrectomy, following transcatheter arterial embolization (TAE) of the left renal artery. We prepared a balloon catheter for aortic occlusion as a preventative measure for massive bleeding; this was not the case, as only a small amount of intraoperative bleeding occurred. Thus, the nephrectomy was performed successfully without using the balloon catheter. The patient recovered uneventfully and was discharged on day 8. Pathological examination showed clear-cell RCC (pT1a) and a RAVF near the tumor. Herein we report this case of left RCC with RAVF and multiple arterial malformation, which was successfully managed by evaluating preoperative risks with a genetic test, followed by TAE of the renal artery and open nephrectomy.

Association between immune-related adverse events and survival in patients with renal cell carcinoma treated with nivolumab plus ipilimumab: immortal time bias-corrected analysis.

BACKGROUND: Immune-related adverse events (irAEs) in patients treated with immune check inhibitors are associated with favourable response rate and survivals in multiple cancers, including renal cell carcinoma (RCC). The aim of this study was to investigate how irAEs were associated with improved survivals in advanced RCC patients treated with nivolumab plus ipilimumab. MATERIALS AND METHODS: This retrospective study included patients who received nivolumab plus ipilimumab at six centres, institutions, or hospitals between September 2018 and February 2022. We assessed associations of the development and the number of irAEs with overall survival (OS) and progression-free survival (PFS). To eliminate immortal time bias, landmark analysis and a Cox model with time-dependent variables were used. RESULTS: This study included 129 patients with a median follow-up of 12.3 months. The 2-year OS and PFS rates were 55% and 42%, respectively. Ninety six patients experienced irAEs. The development of irAEs was positively associated with OS and PFS rates (hazard ratio [HR] 0.328, 95% confidence interval [CI] 0.165-0.648, p = 0.001; HR 0.334, 95% CI 0.151-0.737, p = 0.007). Patients who experienced multiple irAEs had longer OS (HR 0.507, 95% CI 0.235-1.097, p = 0.085 or HR 0.245, 95% CI 0.110-0.544, p < 0.001) and PFS (HR 0.572, 95% CI 0.316-1.036, p = 0.085 or HR 0.267, 95% CI 0.113-0.628, p = 0.002) compared with those who experienced single or zero irAE. CONCLUSIONS: Developing irAEs, particularly multiple irAEs, is associated with favourable survivals in advanced RCC patients treated with nivolumab plus ipilimumab.

Medium-Term Risk of Recurrent Pelvic Organ Prolapse within 2-Year Follow-Up after Laparoscopic Sacrocolpopexy.

Objective: The present study was performed to determine the risk of recurrent pelvic organ prolapse (POP) within 2 years after laparoscopic sacrocolpopexy (LSC) in patients with uterovaginal prolapse. Materials and Methods: A retrospective comparative study was performed in a population of 204 patients over a 2-year follow-up period following LSC with concomitant supracervical hysterectomy or uterine preservation at a single urological clinic between 2015 and 2019. The primary outcome was surgical failure following LSC in cases of POP, focusing on failures occurring before the 2ndyear of follow-up. Logistic regression analysis was used to determine the odds ratios (ORs) for surgical failure. Results: The primary outcome, surgical failure in cases of POP, occurred 2 years after the initial surgery in 19 of the 204 patients (9.3%) (95% confidence interval [CI], 5.7% - 14.2%). Surgical failure was most common in the anterior compartment (n = 10, 4.9%), and further surgery was performed in seven of the patients with surgical failure (3.4%). The poor primary outcome was predicted by lysis of adhesions (OR, 7.5, 95% CI, 1.6-33.8, P = 0.008) and preoperative POP stage IV (OR, 3.5; 95% CI, 1.1-10.8, P = 0.03) on multivariable logistic regression analysis. Conclusion: The overall rate of surgical failure following LSC in our cohort was 9.3% over the 2-year follow-up period after surgery, and preoperative prolapse stage IV was associated with a higher risk of recurrence.

Retzius-sparing robotic prostatectomy is associated with higher positive surgical margin rate in anterior tumors, but not in posterior tumors, compared to conventional anterior robotic prostatectomy.

Objectives: The analysis of the oncological outcomes and postoperative continence recovery between conventional robotic-assisted radical prostatectomy (cRARP) and Retzius-sparing RARP (rsRARP), and the effect of the tumor location on them. Materials and methods: A total of 317 patients who underwent cRARP (n = 228) or rsRARP (n = 89) from August 2017 to July 2020 were assessed. Patients were categorized into groups based on the tumor location by pathology. Positive surgical margin (PSM) rates and biochemical recurrence (BCR)-free survivals and continence recovery were compared between the two procedures. Results: Patient age, prostate-specific antigen (PSA) levels, clinical stages, and Gleason score were not significantly different between the two groups. There was no significant difference in PSM rates (25.8% vs. 33.7%, p = 0.13) or BCR-free survivals (p = 0.28) between cRARP and rsRARP in patients. When tumor was located in the anterior lesion in the prostatectomy pathology, rsRARP was associated with significantly higher PSM rates than cRARP (53.3% in rsRARP vs. 27.0% in cRARP, p = 0.0086), while BCR-free survival did not vary significantly (hazard ratio: 2.15, p = 0.11). When tumors were identified in the posterior in prostatectomy pathology, PSM rates (28.8% in rsRARP vs. 24.7% in cRARP, p = 0.59) or BCR-free survivals (hazard ratio: 0.78, p = 0.51) did not differ significantly between the two groups. rsRARP yielded superior continence recovery in all time points compared to cRARP, which was not affected by the pathological tumor location. Conclusion: In posterior tumors, rsRARP results in similar oncological outcomes as cRARP with superior continence recovery, while in anterior tumors, rsRARP may associate with higher PSM rate, combined with improved continence recovery.

Clinical outcomes of nivolumab plus ipilimumab in patients with metastatic non-clear cell renal cell carcinoma: Real-world data from a Japanese multicenter retrospective study.

OBJECTIVES: Although nivolumab plus ipilimumab has become a standard treatment regimen for metastatic clear cell renal cell carcinoma (ccRCC), its efficacy in non-clear cell carcinoma (nccRCC) has not been fully examined. In the current study, we evaluated the clinical outcomes of nivolumab plus ipilimumab in nccRCC compared with ccRCC. METHODS: We retrospectively analyzed 22 patients with metastatic and/or locally advanced unresectable nccRCC who received nivolumab plus ipilimumab as a first-line therapy and compared them with 107 patients with ccRCC. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity were compared between the nccRCC and ccRCC groups. RESULTS: The histology of nccRCC included eight papillary, six unclassified, three chromophobe, two collecting duct carcinoma, and three other subtypes. Best objective response in nccRCC patients included three complete responses and five partial responses, resulting in an ORR of 36%, while that in ccRCC patients was 50% (p = 0.22). With a median follow-up of 11.9 months, OS was significantly shorter in patients with nccRCC than in those with ccRCC (median 20.8 months vs. not reached, p = 0.04), while there was no significant difference in PFS (median 6.3 vs. 10.8 months, p = 0.21). Treatment-related adverse events occurred in 14 (64%) nccRCC patients and 81 (76%) ccRCC patients. CONCLUSIONS: Combination treatment with nivolumab and ipilimumab demonstrated modest clinical efficacy in patients with nccRCC compared with patients with ccRCC, suggesting it could be a therapeutic option for metastatic nccRCC patients.

Prostate-specific antigen level, biopsy grade group, and tumor-capsular contact length on magnetic resonance imaging are independently associated with an extraprostatic extension.

OBJECTIVE: To define the clinicopathological and radiological factors independently associated with the existence of an extraprostatic extension in radical prostatectomy specimens. METHODS: A total of 202 patients who underwent robotic prostatectomy following biparametric magnetic resonance imaging were assessed. We evaluated the clinicopathological and magnetic resonance imaging variables. We performed receiver-operating characteristic curve analyses to identify factors associated with extraprostatic extension. We engaged in multivariate analysis to identify factors independently associated with such extension. RESULTS: Extraprostatic extensions were apparent in the final prostatectomy specimens of 62 patients (31%). The areas under the curves of the prostate-specific antigen level, the biopsy grade group, and the tumor-capsular contact length on magnetic resonance imaging were 0.76, 0.71, and 0.70, respectively, in receiver-operating characteristic analysis when used to predict extraprostatic extension; thus, higher than the areas under the curves of the other variables (0.61-0.68). The prostate-specific antigen level (odds ratio 1.090, p = 0.004), the biopsy grade group (odds ratios 2.678 and 6.358, p = 0.017 and p < 0.001 for grade group 3-4 and 5), and the tumor-capsular contact length (odds ratio 1.079, p = 0.001) were independently associated with extraprostatic extension. When the three factors were combined, the area under the receiver-operator characteristic curve increased to 0.79. CONCLUSIONS: The prostate-specific antigen level, the biopsy grade group, and the tumor-capsular contact length on magnetic resonance imaging were independently associated with extracapsular extension.

Combination of biparametric magnetic resonance imaging with prostate-specific antigen density to stratify the risk of significant prostate cancer: Initial biopsy and long-term follow-up results.

OBJECTIVES: To assess whether the combination of biparametric magnetic resonance imaging with prostate-specific antigen density can properly stratify the risk of significant prostate cancer in patients undergoing prostate biopsies and how this approach affects the detection of prostate cancer during follow-up in patients who do not undergo prostate biopsy. METHODS: In total, 411 biopsy-naïve patients who had elevated prostate-specific antigen levels and then underwent biparametric magnetic resonance imaging for suspicious prostate cancer were analyzed: 203 patients underwent prostate biopsies, whereas 208 patients did not. Significant prostate cancer detection rates stratified by the combination of Prostate Imaging Reporting and Data System score and prostate-specific antigen density were assessed in patients who underwent prostate biopsies. The cumulative incidence of prostate cancer detection during the follow-up was assessed in patients who omitted biopsy. RESULTS: The negative predictive value for significant prostate cancer was 89% for Prostate Imaging Reporting and Data System scores 1-3, which increased to 97% when prostate-specific antigen density <0.15 ng/ml/cm3 was combined. Among patients who did not undergo biopsy, patients with Prostate Imaging Reporting and Data System scores 1-3 plus prostate-specific antigen density <0.15 ng/ml/cm3 included significantly less cases in which significant prostate cancer was detected during the follow-up, compared with the others (3.2% versus 17% at 36 months). CONCLUSIONS: Restriction of prostate biopsies to patients with Prostate Imaging Reporting and Data System scores 4-5 or prostate-specific antigen density ≥0.15 ng/ml/cm3 proved to be the good biopsy strategy, effectively balancing risks and benefits.

Hypereosinophilia is a predictive biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma.

BACKGROUND: This study aimed to evaluate whether hypereosinophilia is a clinical biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma treated with nivolumab plus ipilimumab. METHODS: This was a retrospective cohort study conducted at Jichi Medical University Saitama Medical Center between January 2018 and December 2020. In total, 12 patients with renal cell carcinoma who presented with immune checkpoint inhibitor-induced hypopituitarism were enrolled in this study. The clinical parameters and symptoms at baseline, last visit, and onset of hypopituitarism were analyzed. RESULTS: The median period from the initial treatment with immune checkpoint inhibitors to the onset of hypopituitarism was 82.5 (range: 56-196) days. Most patients developed hypopituitarism within 6 months. One patient presented with hypophysitis and 11 patients presented with isolated adrenocorticotropic hormone deficiency. The major symptoms noted at onset were fatigue (66.7%) and loss of appetite (41.7%). None of the patients had symptoms during the last visit. However, four developed hypereosinophilia. Eosinophil fraction (%) and eosinophil count (/µL) increased during the last visit and at the onset of hypopituitarism, respectively. The serum sodium and plasma glucose levels were similar. CONCLUSIONS: The eosinophil count increased before the onset of hypopituitarism. Thus, hypereosinophilia can be an early predictor of hypopituitarism.

Severity of Cystocele and Risk Factors of Postoperative Stress Urinary Incontinence after Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse.

Objectives: Knowledge on the severity of cystocele and incidence of postoperative stress urinary incontinence (SUI) after prolapse repair is lacking. This study investigated the incidence and risk factors of postoperative SUI following laparoscopic sacrocolpopexy (LSC). Materials and Methods: We retrospectively reviewed the charts of 83 women without occult SUI who underwent LSC for pelvic organ prolapse and developed SUI over 3 months postoperatively. We used Fisher's exact test, the Mann-Whitney U-test, and logistic regression for statistical data analyses. Results: After 3 months, the incidences of postoperative SUI were 50% and 24% in those who did and did not report preoperative SUI, respectively. Eventually, postoperative SUI was reported by 39% and 9% of the women with and without preoperative SUI, respectively. Increased Ba (point of maximal anterior vaginal wall prolapse) measurement (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.0-2.06; P = 0.04) and preoperative SUI (OR, 3.95; 95% CI, 1.14-13.7; P = 0.03) were the risk factors for postoperative SUI. Conclusion: Our findings suggest that counseling regarding the risk of postoperative SUI should be conducted for women with preoperative advanced cystocele or bothersome SUI.

Combining the Tumor Contact Length and Apparent Diffusion Coefficient Better Predicts Extraprostatic Extension of Prostate Cancer with Capsular Abutment: A 3 Tesla MR Imaging Study.

PURPOSE: To assess the diagnostic performance of the tumor contact length (TCL) and apparent diffusion coefficient (ADC) for predicting extraprostatic extension (EPE) of prostate cancer with capsular abutment (CA). METHODS: Ninety-three patients with biopsy-proven prostate cancer underwent 3-Tesla MRI, including diffusion-weighted imaging (b value = 0, 2000 s/mm2) and radical prostatectomy. Two experienced radiologists, blinded to the clinicopathological data, retrospectively assessed the presence of CA on T2-weighted imaging (T2WI). TCL on T2WI and ADC values were measured on detecting CA in prostate cancer. We used the receiver operating characteristic curves to assess the diagnostic performance of TCL and ADC values for predicting EPE. RESULTS: CA was present in 58 prostate cancers among 93 patients. The cut-off value for TCL was 6.9 mm, which yielded an area under the curve (AUC) of 0.75. This corresponded to a sensitivity, specificity, and accuracy of 84.2%, 61.5%, and 69.0%, respectively. The cut-off value for ADC was 0.63 × 10-3 mm2/s, which yielded an AUC of 0.76. This, in turn, corresponded to a sensitivity, specificity, and accuracy of 84.2%, 59.0%, and 67.2%, respectively. The combined cut-off value of TCL and ADC yielded an AUC of 0.82. The specificity (84.6%) and accuracy (81.0%) of the combined value were superior to their individual values (P < 0.05). CONCLUSION: A combination of TCL and ADC values provided high specificity and accuracy for detecting EPE of prostatic cancer with CA.

Less invasive and equivalent short-term outcomes with simultaneous en bloc robot-assisted radical cystectomy and laparoscopic nephroureterectomy: Comparison with conventional open radical cystectomy and nephroureterectomy.

INTRODUCTION: To clarify the safety and efficacy of en bloc simultaneous robot-assisted radical cystectomy (RARC) and laparoscopic nephroureterectomy (LNU) for synchronous muscle-invasive bladder carcinoma and upper tract urothelial carcinoma (UTUC) or UTUC of a solitary kidney, we evaluated the perioperative and short-term outcomes of this surgical procedure compared with those of simultaneous open radical cystectomy and nephroureterectomy. METHODS: We prospectively enrolled consecutive patients receiving en bloc simultaneous RARC and LNU between December 2018 and March 2020 at two institutes. Patients' characteristics, surgical, perioperative, and pathological outcomes and recurrence rate within 6 months were compared with a historical control receiving simultaneous open radical cystectomy and nephroureterectomy. RESULTS: Ten patients receiving simultaneous RARC and LNU and 17 receiving simultaneous open radical cystectomy and nephroureterectomy were included in the study. Simultaneous RARC and LNU significantly reduced bleeding volume and blood transfusion (P < .0001, P < .0001, respectively) and significantly prolonged operating time (P = .035). RARC and LNU significantly shortened hospitalization after operation (P = .003) and showed reduced tendency of postoperative complications within 30 days but not significantly (P = .25). Pathological characteristics and recurrence within 6 months were not significantly different between the two groups. CONCLUSION: Our results suggested that en bloc simultaneous RARC and LNU were safer surgical procedures with equivalent short-term oncological outcomes compared to conventional open procedures. It can be a standard minimally invasive surgical method in countries where robot-assisted radical nephroureterectomy is inaccessible.

Laparoscopic sacrocolpopexy for pelvic organ prolapse in the elderly: safety and outcomes.

Due to its low postoperative complication rate, vaginal surgery is the preferred intervention for pelvic organ prolapse (POP) in elderly patients. We aimed to assess outcomes and perioperative complication rates associated with laparoscopic sacrocolpopexy (LSC) in elderly women. We retrospectively reviewed the medical records of 74 consecutive patients [52 (70.3%) aged <75 years; 22 (29.7%) aged ≥75 years] with POP who underwent LSC between August 2015 and December 2017. We evaluated preoperative risks using the Charlson Comorbidity Index (CCI) and complications, using the Clavien-Dindo grading (CDG). No between-group differences were observed in CCI. CDG indicated fewer perioperative complications in patients aged >75 years. Anatomical success rates at 15 months were 95.5% and 90.4% in patients aged ≥75 and <75 years, respectively. LSC has a high anatomical correction rate and few perioperative complications regardless of age. Thus, the appropriate surgical intervention method would depend on the patient's health and comorbidities.IMPACT STATEMENTWhat is already known on this subject? Laparoscopic sacrocolpopexy (LSC) is a superior method to vaginal surgery because of its anatomical and functional outcomes, particularly regarding sexual activity.What do the results of this study add? In this single-center study with a 15-month follow-up, we demonstrated that LSC has a high anatomical correction rate and few perioperative complications regardless of age at the time of surgery. Furthermore, there was no significant difference in the rate of complications between the ≥75 and <75 years groups. Thus, LSC may be considered for women aged >75 years. However, in these elderly patients, the surgical method should be determined according to their health status and medical comorbidities.What the implications are of these findings for clinical practice and/or further research? Age should not be the basis for exclusion from laparoscopic procedures. Moreover, LSC is a suitable and valid option for elderly women with POP. As the study population consisted of a homogenous group of Japanese women, it lacks generalisability. Studies evaluating these outcomes are required in other populations.

Real-World Incidence of Immune-Related Adverse Events Associated with Nivolumab Plus Ipilimumab in Patients with Advanced Renal Cell Carcinoma: A Retrospective Observational Study.

Real-world incidence of immune-related adverse events (irAEs) associated with nivolumab plus ipilimumab in patients with renal cell carcinoma (RCC) has been rarely demonstrated. The present study aims to report the safety outcomes of this combination therapy in the real-life population. We conducted a multi-institutional retrospective observational study that assessed the incidence and severity of irAEs associated with nivolumab plus ipilimumab in 41 Japanese patients with metastatic and/or locally advanced RCC. The irAEs were classified into endocrine and non-endocrine irAEs. The median age and follow-up period were 68 years and 13.0 months, respectively. Endocrine irAEs were observed in 66% of patients, including hypopituitarism in 44%, hyperthyroidism in 41%, and primary hypothyroidism in 22%, while non-endocrine irAEs were observed in 54%. All patients experiencing hypopituitarism presented with adrenocorticotropic hormone deficiency, causing secondary adrenal insufficiency, which required permanent corticosteroid replacement therapy. There was an association between the incidence of endocrine irAEs and high-grade non-endocrine irAEs other than skin-related irAEs (p = 0.027). When patients experienced two or more endocrine irAEs, they had a 35% chance of experiencing high-grade non-endocrine irAEs other than skin-related irAEs. Nivolumab plus ipilimumab may lead to a high prevalence of endocrine irAEs in "real-world" patients. Endocrine irAEs may be associated with non-endocrine irAEs other than skin-related irAEs.

Spontaneous recovery of immune checkpoint inhibitor-induced thyroiditis with high free T4 level: A case report.

We describe a case of severe hyperthyroidism with high free thyroxine and C-reactive protein levels, wherein thyroid function rapidly improved without treatment. In a similar case, conservative management with imaging follow-up can be considered.

[A Case of Metachronous Occurrence of Interstitial Pneumonitis and Hypophysitis Following Nivolumab Plus Ipilimumab for Metastatic Renal Cell Carcinoma].

A 71-year-old man presented with neck pain. He was diagnosed with renal cell carcinoma of the left kidney with lung and bone metastases. After laparoscopic left nephrectomy, nivolumab plus ipilimumab was introduced as a first-line therapy for intermediate risk metastatic renal cell carcinoma based on the IMDC risk classification. After four cycles of nivolumab plus ipilimumab, he experienced dyspnea and was diagnosed with interstitial pneumonitis. Corticosteroid therapy was initiated, after which the symptoms of interstitial pneumonitis subsided. Corticosteroid therapy was tapered and discontinued after two months of treatment. The patient experienced fatigue at one week after the discontinuation of corticosteroid therapy and was diagnosed with isolated ACTH deficiency due to hypophysitis. He recovered after hydrocortisone treatment. This case involved two different immune-related adverse events (irAE), interstitial pneumonitis and hypophysitis, that occurred asynchronously following nivolumab plus ipilimumab therapy. It is important to observe the patient's condition carefully whether additional irAEs arise when corticosteroid therapy is tapered or discontinued.

Calcium Channel Blockers Are Associated with Nocturia in Men Aged 40 Years or Older.

BACKGROUND: The associations of nocturia with hypertension and anti-hypertensive agents (AHTs) remain to be validated. METHODS: This cross-sectional study examined whether blood pressure and/or frequently used classes of AHTs had consistent associations with nocturia. METHODS: A total of 418 male patients aged ≥ 40 years were retrospectively assessed in terms of the International Prostate Symptom Score (IPSS), prescription medications, and blood pressure. Nocturia was evaluated using item 7 of the IPSS, and two or more episodes of nocturia per night was considered to indicate clinically important nocturia. RESULTS: Patients taking calcium channel blockers (CCBs), but not other AHTs, experienced more episodes of nocturia than patients not taking AHTs (1.77 ± 1.07, 1.90 ± 1.19, and 1.48 ± 0.98 in CCBs alone, CCBs + other AHTs, and other AHTs alone, vs. 1.35 ± 1.08 in not taking AHTs; p = 0.014, p < 0.0001, and p = 0.91, respectively), whereas there was no significant difference in the number of nocturia episodes between patients with elevated and normal blood pressure. In multivariate analysis, CCB (odds ratio (OR) = 2.68, p < 0.0001) and age (OR = 1.06, p < 0.0001) were independently associated with clinically important nocturia. CONCLUSION: CCB was associated with nocturia, while AHTs other than CCBs and elevated blood pressure were not.

Association between time to lithotripsy and stone-free rate in patients with ureteral stones undergoing shock wave lithotripsy.

Early shock wave lithotripsy is associated with higher stone-free rate compared to delayed treatment of ureteral stones, but may constitute overtreatment because ureteral stones can pass spontaneously. We studied the association between time to treatment and stone-free rate in patients with ureteral stones to determine optimal shock wave lithotripsy timing. We retrospectively analyzed 537 patients undergoing shock wave lithotripsy for ureteral stones. Patients were divided into five groups according to time from onset of symptoms to lithotripsy-urgent (0-3 days), early (4-30 days), late (31-60 days), long-delayed lithotripsy (≥ 61 days), and asymptomatic. Stone-free rates were compared among groups. Mean age and stone size were 55.6 ± 13.1 years and 7.48 ± 3.29 mm, respectively. Mean number of shock wave lithotripsy sessions and stone-free rate were 1.37 and 91.6%, respectively, in the overall population. Stone-free rates were 95.2%, 96.8%, 91.3%, 86.3%, and 82.7% in urgent, early, late, long-delayed lithotripsy, and asymptomatic groups, respectively. Long-delayed lithotripsy and asymptomatic groups had significantly more lithotripsy sessions and lower stone-free rate, compared to urgent and early lithotripsy groups. In multivariate analysis, time to lithotripsy [long-delayed lithotripsy (odds ratio: 0.273, p = 0.004) and asymptomatic nature (odds ratio: 0.236, p = 0.002)] and age (odds ratio: 0.959, p = 0.003) independently affected stone-free rate. In conclusion, time to lithotripsy is a strong predictive factor for stone-free status following shock wave lithotripsy. Urgent shock wave lithotripsy did not improve stone-free rate if performed within 1 month. However, time to shock wave lithotripsy > 2 months reduced likelihood of stone-free status.