Pre-first-line chemotherapy risk stratification for overall survival in advanced urothelial carcinoma in sequential therapy era.

PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.

Intrinsic and extrinsic factors causing hyperplasia of the prostate.

Prostatic hyperplasia is very common in elderly men and is a typical disease that reduces quality of life. Histologically, hyperplasia of the prostate gland causes obstruction at the bladder outlet, resulting in symptoms such as a weak urine stream. Various factors have been considered to cause histological enlargement of the prostate, but the underlying cause is still unknown. The factors that cause prostate hyperplasia can be broadly classified into intrinsic and extrinsic ones. Extrinsic factors include things that we directly come into contact with such as bacteria and food. On the other hand, intrinsic factors are those that cause changes in functions originally provided in the body due to some cause, including extrinsic factors, such as chronic inflammation and an imbalance of sex hormones. A large number of reports have been made to date regarding the etiology of prostatic hyperplasia, although they have not yet clarified the fundamental cause(s). The various factors currently known should be outlined for future research. Should it be possible to prevent this highly prevalent prostatic hyperplasia which is mainly cause of dcreasing quality of life, there is no doubt that it would be a huge contribution to humanity.

Comparison of Oncological Outcomes of Pembrolizumab as Second-line Therapy and Maintenance Avelumab Therapy in Advanced Urothelial Carcinoma After Platinum-based Chemotherapy.

BACKGROUND/AIM: Sequential therapy using chemotherapy and subsequent immune checkpoint inhibitor (ICI) treatment prolongs the survival of patients with advanced urothelial carcinoma (UC). However, no comparison data for oncological outcome between pembrolizumab and avelumab has been reported. Thus, we compared oncological outcomes between pembrolizumab as second-line therapy and maintenance avelumab therapy in patients with advanced UC. PATIENTS AND METHODS: We retrospectively evaluated patients with advanced UC treated with pembrolizumab or avelumab between January 2018 and February 2023. We compared oncological outcomes after adjusting for patient characteristics. Immune-related adverse events (AEs) in each group were evaluated using the Common Terminology Criteria for Adverse Events. RESULTS: There were 186 and 44 patients in the pembrolizumab- and avelumab-treated cohorts, respectively. After propensity score matching, 43 patients from each group were selected and analyzed. Median progression-free survival from the initiation of pembrolizumab and avelumab treatments was 126 and 139 days, respectively (log-rank test, p=0.625). Median overall survival in the pembrolizumab and avelumab cohorts were 658 days and not reached, respectively (log-rank test, p=0.249). Thirty-eight (20.4%) and 14 (31.8%) all-grade immune-related AEs were observed in 186 pembrolizumab- and 44 avelumab-treated patients, respectively (chi-squared test, p=0.112). Regarding endocrine-related AEs, 12 (6.5%) and none (0%) were observed in pembrolizumab- and avelumab-treated patients, respectively (Fisher's exact probability test, p=0.129). CONCLUSION: Pembrolizumab and maintenance avelumab therapy provide equivalent oncological outcomes in patients with advanced UC. Although no significant difference was observed, there might be a potential risk of higher endocrine-related AEs due to pembrolizumab compared to avelumab maintenance therapy.

Prevention of local symptoms in muscle invasive bladder cancer patients: clinical significance of local radiation therapy.

PURPOSE: To evaluate the significance of local radiation therapy (LRT) for prevention of local symptoms (LSs) caused by muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively reviewed the clinical records of 133 patients from 13 hospitals. MIBC patients with or without metastases who were treated with LRT alone from January 2015 through December 2020 were enrolled. Exclusion criteria were urinary diversion (UD) prior to LRT, non-MIBC, or lack of clinical information. LSs were defined as hematuria requiring invasive treatment or transfusion, UD after LRT, bladder tamponade, and opioid use for bladder pain. RESULTS: One hundred fourteen patients were finally enrolled in the study. During the median follow-up period of 13.5 months, 30 patients (26.3%) had LSs. Risk factors of LSs in multivariate analysis were a prior history of non-MIBC (NMIBC) (hazard ratio [HR] 2.99; 95% confidence interval [CI], 1.36 to 6.56; P < 0.01), radiation dose of less than 50 Gray (Gy) (HR 3.99; 95% CI, 1.80 to 8.82; P < 0.01), and tumor stage 3 or more (HR 2.43; 95% CI, 1.14 to 5.21; P = 0.02). Risk factors of overall survival (OS) in multivariate analysis were being female (HR 3.32; 95% CI, 1.68 to 6.58; P < 0.01), an age-adjusted Charlson Comorbidity index of 6 or more (HR 2.19; 95% CI, 1.18 to 4.10; P = 0.01), distant metastases (HR 3.20; 95% CI, 1.39 to 6.58; P < 0.01), and tumor size of 40 mm or more (HR 2.38; 95% CI, 1.34 to 4.52; P < 0.01). Toxicity (all grades) occurred in 40.4% of the patients, 4.8% with grade 3 or more and 95.2% with lower grades. CONCLUSIONS: We determined the risk factors for LSs in MIBC patients treated with LRT alone. An escalated-dose of 50 Gy or more may contribute to prevention of LSs caused by MIBC. Thus, dose-escalated LRT for MIBC patients who can expect favorable survival may be a good option to avoid future annoying LSs.

A rare case of pyoderma gangrenosum occurring at the site of laparoscopic port following laparoscopic radical nephrectomy.

Introduction: Pyoderma gangrenosum is a rare dermatological disease associated with underlying inflammatory conditions. Case presentation: A 59-year-old man was diagnosed with right renal cancer cT1aN0M0 and laparoscopic right radical nephrectomy was performed. Five days after surgery, he had a high-grade fever, surgical site flare, and severe pain. At first, we diagnosed surgical site infection and wound dehiscence. Despite treatment for infection, his general condition and dermatological symptoms did not improve. Thereafter, a dermatologist advised us to perform a skin biopsy and blood culture examinations. Finally, the man was diagnosed with pyoderma gangrenosum according to the pathology of the skin biopsy and negative blood culture. After both intravenous administration of predonisolone and a topical corticosteroid, the high-grade fever and dermatological symptoms improved greatly. Conclusion: Although pyoderma gangrenosum is a rare disease, we should bear in mind the disease since the treatment strategy is completely different from that for surgical site infection.

Efficacy of vibegron in patients with overactive bladder: Multicenter prospective study of real-world clinical practice in Japan, SCCOP study 19-01.

OBJECTIVE: To evaluate the efficacy and safety of vibegron in patients with overactive bladder (OAB) in real-world clinical practice in Japan. METHODS: This multicenter, prospective, non-controlled study consecutively enrolled patients with OAB determined by an OAB symptom score (OABSS) of three points or more and a question 3 (urgency) score of two points or more. A total of 212 patients from 43 institutions were recruited from January 2019 through March 2020. Vibegron, 50 mg, was administrated daily for 8 weeks as first-line monotherapy (first-line group, FL), monotherapy switching from antimuscarinics (post-antimuscarinic group, PA) or mirabegron (post-mirabegron group, PM) and combination therapy with antimuscarinics (add-on group). The OABSS was collected at baseline and every 2 weeks. Adverse events were recorded at every visit. RESULTS: Of the 212 patients registered, 188 (male 76, female 112) were eligible for analysis (124 in the FL group, 27 in PA, 29 in PM, and eight in the add-on group). The add-on group was excluded from further analysis due to its small number. The OABSS (mean ± SD) showed significant improvement in all groups (FL; 8.8 ± 2.5, 3.8 ± 2.8, PM; 9.4 ± 2.2, 4.5 ± 4.0, PM; 8.9 ± 2.5, 4.7 ± 3.3 at 0 and 8 weeks, respectively). The overall incidence of adverse events was 25%. No grade 3 or higher adverse events were observed. CONCLUSIONS: In the real-world clinical setting, vibegron is effective and well-tolerated by OAB patients, including those switching therapy from antimuscarinics and mirabegron.

Pre-pembrolizumab neutrophil-to-lymphocyte ratio (NLR) predicts the efficacy of second-line pembrolizumab treatment in urothelial cancer regardless of the pre-chemo NLR.

Neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with prognosis of urothelial cancer (UC) patients receiving systemic chemotherapy or immunotherapy. However, it has not been elucidated how preceding first-line chemotherapy affects NLR and subsequent second-line pembrolizumab treatment. This multicenter study analyzed 458 patients with metastatic UC who received first-line chemotherapy and second-line pembrolizumab with regard to pre-chemotherapy and pre-pembrolizumab NLR in association with the efficacy of chemotherapy and pembrolizumab treatment. NLR was increased in 47% while decreased in 53% of patients before and after first-line chemotherapy. High pre-chemotherapy NLR (≥ 3) was significantly associated with unfavorable overall (OS, P = 0.0001) and progression-free (P < 0.0001) survivals after first-line chemotherapy. However, pre-chemotherapy NLR showed only modest influence on radiological response and survival after second-line pembrolizumab treatment, whereas pre-pembrolizumab NLR showed higher association. NLR decrease was associated with partial response or greater objective response by first-line chemotherapy, while NLR increase was associated with higher patient age. In conclusion, immediate pre-chemotherapy and pre-pembrolizumab NLR was significantly associated with efficacy of the following treatment, respectively. However, even patients with high pre-chemotherapy NLR achieved favorable OS if they had their NLR reduced by chemotherapy, whereas those with high pre-chemotherapy NLR yielded unfavorable OS if they had their NLR remained high after chemotherapy, suggesting that chemotherapy may have differential effect on the efficacy of subsequent pembrolizumab treatment in UC patients.

Efficacy and safety of pembrolizumab for older patients with chemoresistant urothelial carcinoma assessed using propensity score matching.

BACKGROUND: We used real-world and large-scale data to assess the clinical efficacy and safety of pembrolizumab in older patients with advanced urothelial carcinoma (UC). METHODS: A total of 608 patients who received pembrolizumab for the treatment of chemoresistant UC were retrospectively analyzed. All patients were histologically diagnosed with pure UC. Using propensity score matching (PSM) (ECOG performance status, site of metastasis, hemoglobin level and neutrophil-to-lymphocyte ratio, 1:1 matching), the overall survival (OS) and adverse events (AEs) of patients <75 and ≥75 years old were compared. RESULTS: The median follow-up (IQR) period was 16.1 (9.9-20.5) months. After PSM, there were 215 patients each in the aged <75 years and aged ≥75-year-old groups. The median OS of all patients was estimated to be 10.4 months (95% confidence interval [CI] = 8.8-12.1). After PSM, the median OS was 7.8 months (95% CI = 5.2-10.4) in the <75-year-old group and 10.4 months (95% CI = 7.3-13.5) in the ≥75-year-old group (P = 0.186). Any-grade AEs were more frequently reported in the ≥75-year-old group in comparison to the age <75-year-old group (55.3% vs. 41.9%, P = 0.007), whereas there was no significant difference between the two groups in the incidence of grade ≥3 AEs (10.2% vs. 12.6%, P = 0.544). The objective response rate, defined as complete remission or a partial response, was 22.8% in the <75-year-old group and 25.1% in the ≥75-year-old group (P = 0.651). CONCLUSIONS: The present study demonstrates that age does not affect the efficacy and safety of pembrolizumab treatment for advanced chemoresistant UC. Pembrolizumab treatment should not be avoided based on chronological age; however, close monitoring for the development of treatment-related AE should be considered for older patients.

[A Case of Diagnosed Lynch Syndrome in a Patient with Ureteral Cancer].

Lynch syndrome (LS) is an autosomal dominant genetic disorder in which tumors are known to develop at an early age. Upper tract urothelial carcinoma is one of the tumors related to Lynch syndrome. A 49-year-old woman visited a urologic clinic due to left abdominal pain. She had a history of ovarian cancer. Her mother had a history of colorectal cancer and renal pelvic cancer, and her grandmother had had colorectal cancer. After detailed examination, she received laparoscopic left nephroureterectomy and she was pathologically diagnosed with left ureteral cancer. LS was suspected based on her past history, family history, and age. A microsatellite instability (MSI) test gave a positive result, and genetic analysis confirmed a mutation in the MSH2 gene, leading to the diagnosis of Lynch syndrome. Although LS has a high frequency of carcinogenesis, it is thought that an improved prognosis can be achieved by early discovery and treatment of cancer in LS patients. From our case report, we recommend screening of LS in patients with a past/family history, who have had an upper tract urothelial carcinoma. Once LS is diagnosed, the patient should be followed by a planned surveillance of cancer development.

[A Case of Detrusor Hyperactivity with Impaired Contractility (DHIC) after Transverse Myelitis].

A 44-year-old man was carried to the hospital in an ambulance because of dyspnea, paralysis and dysuria after signs of the flu. Acute encephalomyelitis was diagnosed by examination of magnetic resonance imaging. Antimicrobial treatment and respirator management was carried out with indwelling of urethral catheter for urinary retention. After improvement of encephalitis, the urethral catheter was removed. However, he still needed medical care because of persistent lower urinary tract symptoms. He complained of urge incontinence and urination frequency. Decrease of functional bladder capacity was noticed in a frequency volume chart. After consulting with our neurologist, acute transverse myelitis was diagnosed from imaging and neurological findings. Pressure flow study (PFS)demonstrated detrusor overactive during the filling phase and insufficient contractility during the voiding phase. We reached the diagnosis of detrusor hyperactivity with impaired contractility (DHIC). We did not introduce clean intermittent catheterization but used the mirabegron instead. Although storage symptoms did not improve on the mirabegron monotherapy, the symptoms improved by solifenacin added. There is a possibility that combination therapy with mirabegron and solifenacin is effective for DHIC.

Which Happens Earlier, Lower Urinary Tract Symptoms or Erectile Dysfunction?

INTRODUCTION: Although an association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) has been suggested, it was not clarified whether LUTS developed before ED or vice versa. AIM: To clarify whether LUTS develop before ED or vice versa and which symptoms predicted the onset of the other condition in a longitudinal community-based study. METHODS: We conducted a longitudinal community-based study on LUTS and ED in aged Japanese men. A follow-up study was conducted to determine their longitudinal changes of LUTS and ED after 15 years. Erectile function was evaluated using a validated questionnaire. LUTS were evaluated based on the International Prostate Symptom Score, quality of life index, and prostate volume. MAIN OUTCOME MEASURE: We evaluated the baseline symptoms among the participants who had LUTS and ED in the follow-up survey and what prior symptoms could predict the onset of the other condition using the data from a long-term longitudinal survey. RESULTS: A total of 108 men were enrolled in this study. Of the 47 men having both LUTS and ED in the follow-up study, men having only LUTS (n = 16) were more frequent than those having only ED (n = 6) in the initial study. Likewise, of the 38 men having both nocturia and ED at the time of the follow-up study, those having only nocturia (n = 12) were more frequent than those having only ED (n = 5) in the initial study. In multivariable analysis, age 60 years or older (odds ratio: 7.10, 95% CI: 2.09-24.13) and nocturia (odds ratio: 15.83, 95% CI: 3.05-82.15) were independent predictors for the onset of ED. CONCLUSION: There were more men with prior onset of LUTS, especially nocturia, than men with prior onset of ED among those with both ED and LUTS in this long-term longitudinal study. Nocturia may be a predictor of subsequent ED. Matsuda Y, Kobayashi K, Fukuta F, et al. Which Happens Earlier, Lower Urinary Tract Symptoms or Erectile Dysfunction?. J Sex Med 2021;9:100275.

Successful mycophenolate mofetil treatment of a patient with severe steroid-refractory hepatitis evoked by nivolumab plus ipilimumab treatment for relapsed bladder cancer.

Mycophenolate mofetil resulted in rapid improvement of steroid-refractory immune-related adverse event hepatitis, induced by nivolumab plus ipilimumab.

Does cognitive behavioral therapy using a self-check sheet improve night-time frequency in patients with nocturia? Results of a multicenter randomized controlled trial.

OBJECTIVE: To determine whether cognitive behavioral therapy using a self-check sheet is effective in improving night-time frequency of patients with nocturia. METHODS: We carried out a multicenter, open-labeled, randomized controlled trial in eight institutions. Patients having two or more episodes of nocturia were randomly assigned to either cognitive behavioral therapy with completion of frequency volume charts regularly (cognitive behavioral therapy group) or frequency volume charts regularly alone (frequency volume charts group). The cognitive behavioral therapy checklist was composed of eight items: wake up time/bedtime, mealtime, napping, alcohol/caffeine intake, water intake, salt intake, exercise and taking a bath. A physician explained cognitive behavioral therapy within 5 min using a brief manual. The patients in the cognitive behavioral therapy group filled out the self-check sheet every day. The primary end-point was the difference in night-time frequency based on the International Prostate Symptom Score Q7 at 4 weeks. RESULTS: Of the 100 first-visit patients randomly allocated, 37 in the cognitive behavioral therapy group and 41 in the frequency volume charts group completed the protocol. No difference was observed in the mean ± standard deviation of night-time frequency at 4 weeks between the cognitive behavioral therapy group (2.6 ± 1.0) and the frequency volume charts group (3.1 ± 1.2; P = 0.056). However, when six patients with achievement of cognitive behavioral therapy of <50% were excluded from the analysis, night-time frequency at 4 weeks was significantly lower in the cognitive behavioral therapy group (2.5 ± 1.0) than in the frequency volume charts group (3.1 ± 1.2; P = 0.027). CONCLUSIONS: The efficacy of cognitive behavioral therapy using a self-check sheet for nocturia remains to be shown. However, strictly practicing cognitive behavioral therapy might be beneficial to these patients.

Fatal fulminant hepatitis induced by combined ipilimumab and nivolumab therapy despite favorable histologic response and confirmed by autopsy in a patient with clear cell renal cell carcinoma.

Effective management of immune-related adverse events in patients receiving immunotherapy for cancer is problematic. In this report, we present the case of a 58-year-old man with advanced clear cell renal cell carcinoma who responded well to a combination of ipilimumab and nivolumab. However, after two courses of treatment, he developed fulminant hepatitis and died. An autopsy confirmed that the primary lesion in the left kidney was more than 99% necrotic with only six small residual tumor lesions. These lesions were infiltrated by large numbers of CD8-positive/TIA-1-positive lymphocytes. However, a metastatic lesion in the right kidney harbored few lymphocytes. Furthermore, the tumor cells in the metastatic lesion and one of the residual lesions showed decreased expression of HLA class I molecules, which are a prerequisite for cytotoxic T-lymphocyte-mediated immunotherapy in tumor cells. In this patient, more than 80% of hepatocytes were destroyed and the parenchyma was infiltrated with CD8-positive/TIA-1-positive lymphocytes. The patient had polyuria, which was attributed to neurohypophysitis caused by the infiltration of CD8-positive/TIA-1-positive lymphocytes. We believe that this is an instructive case for immuno-oncologists.

[A Case of Fibroepithelial Polyp that was Difficult to Distinguish from Renal Pelvic Carcinoma].

A 56-year-old woman presented with left flank pain. Computed tomography revealed hydronephrosis and a 35 mm mass in the left renal pelvis. Ureteroscopy revealed a white elevated lesion in the left renal pelvis. Tissue biopsy was performed and the histological findings showed no evidence of malignancy. Urine cytology was class III. Based on these results, we could not completely rule out malignancy. Left retroperitoneoscopic nephroureterectomy was performed and a pedunculated white mass was found in the renal pelvis. The pathological diagnosis was a fibroepithelial polyp of the renal pelvis. Fibroepithelial polyps in the urinary tract are relatively rare, and those in the renal pelvis even more so. When the preoperative diagnosis shows no malignant findings, fibroepithelial polyps should be considered as a differential diagnosis.

Dynamic changes of bone metastasis predict bone-predominant status to benefit from radium-223 dichloride for patients with castration-resistant prostate cancer.

BACKGROUND: To best employ radium-223 dichloride (Ra-223) for patients with castration-resistant prostate cancer (CRPC) and bone metastasis, we investigated the bone-predominant status in patients treated with Ra-223. METHODS: We retrospectively evaluated 127 CRPC patients who underwent treatment with Ra-223. The patients were divided into three groups based on the types of dynamic changes of bone metastasis between diagnosis and just before Ra-223: (a) only known lesions; (b) de novo lesions; (c) new progressive lesions. We developed the risk assessment using predictive factors based on progression-free survival (PFS). RESULTS: During the median follow-up period of 10.4 months, the median PFS in the only known lesions group was 11.3 months compared to 8.1 months in the de novo lesions group and 5.1 months in the new progressive lesions group (P < .001). In multivariate analysis, the type of the new progressive lesions in bone metastasis (HR 1.45, 95% CI 1.13-1.66, P = .003), performance status of >1 (HR 1.74, 95% CI 1.04-2.89, P = .034), PSA value of >100 ng/mL (HR 1.59, 95% CI 1.02-2.50, P = .043), and PSA doubling time (PSADT) of <3 months (HR 1.53, 95% CI 1.11-2.03, P = .007) were independent unfavorable predictive factors for PFS. The risk assessment for PFS was highlighted when the type of dynamic changes of bone metastasis was combined with PSADT just before Ra-223 treatment. This was associated with non-bone metastasis progression, especially visceral metastasis, and overall survival. CONCLUSIONS: Risk assessment in combination with dynamic changes of bone metastasis and PSADT determines the bone-predominant metastasis type to benefit from Ra-223.

Two cases of osteoblastic bone metastasis from muscle-invasive bladder cancer with discrepancy in response to chemotherapy: problems and limitations of bone biopsy.

We report two cases of muscle-invasive bladder cancer (MIBC) with increasing multiple osteoblastic bone lesions but shrinking other lesions in response to chemotherapy. Case 1 had MIBC and received radical cystectomy followed by adjuvant gemcitabine plus cisplatin chemotherapy (GC). Three years after, follow computed tomography (CT) showed development of multiple lymph node metastasis, and then we performed GC as a first-line systemic chemotherapy. After two cycles of GC, CT showed de novo multiple osteoblastic lesions although metastatic lymph nodes were shrunk. Biopsy of the sternum revealed metastatic urothelial carcinoma. Case 2 had MIBC with multiple osteoblastic lesions on CT and bone scintigraphy, which was initially diagnosed as cT3bN0M1. After one cycle of GC, the number of osteoblastic lesions obviously increased although bladder tumor was regressed. Since the clinical course was unusual, biopsy of the clavicle was done. The histological diagnosis was benign osteoblastic bone disease, then the clinical diagnosis was revised to non-metastatic MIBC, and radical cystectomy was performed. Ten months after surgery, the patients complained worsening backache and CT showed increase in number of osteoblastic lesions. Eventually, ilium biopsy revealed bone metastasis of urothelial carcinoma. In case of atypical finding and unusual clinical course, biopsy of suspected metastatic lesion may be informative although adequate sampling should be secured.

[A Case of Panperitonitis Caused by Spontaneous Bladder Rupture].

A female septuagenarian had poorly controlled diabetes mellitus for more than 20 years. She had persistent pyuria, but did not seek further examination. In 2019, she was transported to our hospital by ambulance for sudden abdominal pain. Physical examination showed a sign of panperitonitis with sepsis. Computed tomography showed ascites and intraperitoneal free air. In addition, there was also a defect in the bladder wall, suggesting bladder rupture. Blood tests showed a marked increase in serum creatinine in addition to increased inflammatory reactants. Because perforation of gastrointestinal tract could not be excluded, an emergency laparotomy was performed. An intraperitoneal perforation of the posterior wall of the bladder was revealed, though there was no intestinal damage. The bladder wall was repaired and cystostomy was performed followed by irrigation and drainage of the abdominal cavity. After the operation, her abdominal symptom resolved and her general status improved. We speculated that voiding disturbance due to neurogenic bladder associated with diabetes mellitus and chronic infection caused the spontaneous bladder rupture. Most cases of spontaneous bladder rupture are associated with a history of pelvic surgery or irradiation, which suggests that this case is extremely rare. In patients with repeated urinary tract infection and underlying disease affecting bladder function, evaluation and appropriate management of bladder dysfunction should be performed ; otherwise, spontaneous bladder rupture may occur.

[Durable Response after Discontinuation Due to Immune-Related Adverse Events in a Patient with Metastatic Clear Cell Renal Cell Carcinoma : A Case Report].

A 70-year-old female with metastatic clear cell renal cell carcinoma was treated with nivolumab. After three dosages, she developed interstitial lung disease which required steroid therapy and nivolumab was discontinued. Thereafter, the target lesion continued to shrinkand the best response was partial response 15 weeks after discontinuation of nivolumab, the reduction rate of which eventually reached 49.1%. Other immune-related adverse events (irAEs), nephrotic syndrome and acute kidney injury developed 34 weeks after discontinuation of nivolumab, leading to irreversible kidney injury that required chronic hemodialysis. Although the target lesion continued to shrink, a new lesion developed 48 weeks after discontinuation of nivolumab. Subsequently, targeted therapies were added, but she died of cancer 13 months after resuming medical treatment. In this case, although various irAEs developed, the effectiveness of nivolumab was sustained even after it was discontinued.