[Idiopathic Thrombocytopenia Purpura After Pembrolizumab Treatment Against Locally Recurrent Bladder Cancer : A Case Report].

A man in his 70s visited our hospital for gross hematuria. He was diagnosed with invasive urothelial carcinoma (cT3N2M0) and underwent total cystectomy and ileum conduit construction after three courses of neoadjuvant chemotherapy. Eight months after the operation, the disease reoccurred in the pelvic lesion. He received pembrolizumab therapy but developed idiopathic thrombocytopenic purpura (ITP) immediately before the ninth course of administration; and, treatment was discontinued. Recovery of symptoms and normalization of blood test data were achieved 3.5months after starting steroid treatment. Reduction of recurrent disease has been maintained for 2 years.

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.

Impact of family history on clinicopathological variables and disease progression in Japanese prostate cancer patients undergoing robotic-assisted radical prostatectomy.

OBJECTIVE: We evaluated whether a first-degree family history (FH) of prostate cancer (PCa) in Japanese patients undergoing robotic-assisted radical prostatectomy (RP) is correlated with clinicopathological variables and disease progression. METHODS: We reviewed consecutive 392 localized PCa patients undergoing robotic-assisted RP at our institution between 2015 and 2020. Information on FH was obtained via a self-administered questionnaire. A positive FH was defined as having a first-degree FH: a father and/or one or more brothers with PCa prior to diagnosis. All patients had clinically localized PCa treated by robotic-assisted RP. We evaluated the relationship between clinical characteristics, pathological findings, and biochemical progression-free survival (bPFS) according to first-degree FH status. RESULTS: Median follow-up was 20.8 months. FH was identified in 42 (10.7%) patients. Patients in the FH group (median, 64.8 years) were diagnosed at a significantly younger age than patients in the non-FH (NFH) group (patients without FH) (median, 67.7 years) (p = 0.003). The 5-year bPFS in the FH and NFH groups was 72.0% and 78.1%, respectively (p = 0.90). A subgroup analysis revealed a significant difference in prostate-specific antigen (PSA) density between the FH group (median, 0.51 ng/ml/cm3 ) and the NFH group (median, 0.29 ng/ml/cm3 ) in patients younger than 60 years (p = 0.033). CONCLUSIONS: In this RP population, FH of PCa was not associated with worse clinical characteristics, pathological findings, or disease progression. Patients with a FH underwent surgery at a significantly younger age, and among patients <60 years, patients with a FH had significantly higher PSA density compared with patients without a FH.

[Initial Experience of Photodynamic Diagnosis-Assisted Transurethral Resection of Bladder Tumor (PDD-TURBT)].

Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is expected to be useful in preventing oversight of non-muscle-invasive bladder cancer (NMIBC) and in reducing the intravesical recurrence rate after transurethral resection of bladder tumor (TURBT). We report our initial experience with28 cases of PDD-assisted TURBT (122 samples) performed at our hospital from February 2018 to April 2019. The median age of the patients was 74.5 years, and 18 of the 28 were primary cases. Each patient underwent TURBT with oral administration of 5-ALA 20 mg/kg 3 hours before endoscopic examination. The sensitivity was 89.8% when both white light and blue light were used, which was superior to the sensitivity of 67.8% when using only white light (p＜0.01, McNemar's test). Among the first several cases, we experienced high false positivity, which suggested that some experience may be required to discriminate tumors from inflammatory lesions. In fact, the specificity and the positive likelihood ratio improved with experience. No grade 2 or higher adverse events were observed among our cases. The median follow-up period was 738 days, and 9 of 28 patients (32. 1%) had recurrence within the follow-up period. In conclusion, our initial experience with PDD-assisted TURBT demonstrated its excellent diagnostic sensitivity and safety, as previously reported.

[Presurgical Treatment with Axitinib and Pembrolizumab Reduced Operation Risk by Downsizing the Vena Cava Tumor Thrombus in Clear Cell Renal Cell Carcinoma : A Case Report].

A woman in her seventies complained of chest pain during exertion and visited a local hospital. Computed tomographic scan showed right renal cell carcinoma with inferior vena cava (IVC) tumor thrombus extending above the diaphragm, and the patient was referred to our hospital. She was diagnosed with right renal cell carcinoma cT3cN0M0, with level IV IVC thrombus by Mayo classification. Axitinib and pembrolizumab were administered against intractable advanced renal cell carcinoma. The dose of axitinib was reduced due to grade 3 liver dysfunction. Right nephrectomy together with IVC thrombectomy was performed because the primary lesion had shrunk, and the level of IVC thrombus had become level III. The pathological results were clear cell carcinoma, pT3c, G3, Fuhrman grade3, INFA, v1, and ly0. Axitinib and pembrolizumab might be a presurgical option against an intractable renal cell carcinoma with an IVC thrombus.

[Neoajuvant Chemotherapy with Gemcitabine and Cisplatin Plus S-1 for Primary Female Urethral Adenocarcinoma].

A 67-year-old female presented for evaluation of a left inguinal mass. Contrast-enhanced computed tomography revealed a tumor surrounding the urethra. Magnetic resonance imaging showed that the tumor had invaded the bladder neck on the anterior aspect of the urethra. The serum carbohydrate antigen 19-9 level was elevated. The clinical diagnosis was a primary adenocarcinoma of the female urethra (cT4N2M0). The initial treatment consisted of gemcitabine plus cisplatin (GC) and oral fluoropyrimidine (S-1). A total cysto-urethrectomy with anterior vaginal wall resection, pelvic and inguinal lymphadenectomy, and urinary diversion with ileal conduit formation were performed. The final diagnosis was urethral adenocarcinoma (ypT4ypN2, stage IV). Twelve months post-operatively, there was no evidence of recurrence or distant metastases.

[A Case of Extragonadal Germ Cell Tumor Treated by Induction Therapy with A Reduced Bep Regimen].

A 21-year-old man with chief complaints of left hypochondriac and chest pain was shown to have multiple masses in the lung, a pleural effusion in the right cavum thoracis, a mediastinal mass, and lymphadenopathy detected by computed tomographic scan. He was diagnosed with an extragonadal germ cell tumor based on pathologic findings from lung biopsies and elevation of the serum total human chorionic gonadotropin. He underwent a reduced chemotherapy regimen consisting of bleomycin, cisplatin, and etoposide (reduced BEP) to lower the risk of acute respiratory distress syndrome (ARDS), a manifestation of choriocarcinoma syndrome, which occurs at induction chemotherapy with the full-dose BEP regimen. Choriocarcinoma syndrome did not develop during chemotherapy, and he has been disease-free since salvage chemotherapy and subsequent retroperitoneal lymph node dissection.

Transvaginal surgery using self-cut mesh for pelvic organ prolapse: 3-year clinical outcomes.

OBJECTIVES: To evaluate subjective and objective outcomes, complication, recurrence, and reoperation rates after transvaginal mesh surgery for the management of pelvic organ prolapse. METHODS: This was a retrospective analysis of transvaginal mesh surgery carried out using self-cut mesh measuring subjective outcomes using validated questionnaires, and objective outcomes using Pelvic Organ Prolapse Quantification. Patients diagnosed with stage ≥2 pelvic organ prolapse were counseled about all possible surgical options. After thorough explanation about the benefits and risks during transvaginal mesh surgery, patients who gave signed consent were scheduled for surgery and evaluated at 1 and 3 years postoperatively. RESULTS: We included 101 patients who completed a minimum of 3-year follow up. One year and 3-year follow up showed significant improvement both on subjective and objective outcomes. Recurrences were observed in three patients (3%), with one (1%) patient undergoing reoperation. One case (1%) of intraoperative complication (bladder injury) and four cases (4%) of postoperative complications (two mesh exposure, one hematoma and one significant increase in post-voiding residual) were recorded. Overall patients' satisfaction was positive. CONCLUSIONS: Transvaginal mesh surgery using self-cut mesh is associated with significant improvement in both subjective and objective outcomes, offering low recurrence and complication rates, and high patient satisfaction rates. It can be a safe, effective and cost-efficient option not only for recurrence cases, but also as primary management of pelvic organ prolapse using a standardized technique and proper patient selection.

Enzalutamide versus abiraterone as a first-line endocrine therapy for castration-resistant prostate cancer (ENABLE study for PCa): a study protocol for a multicenter randomized phase III trial.

BACKGROUND: Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC. METHODS/DESIGN: The present study is a phase III, investigator-initiated, multicenter, head-to-head, randomized controlled trial investigating enzalutamide vs. abiraterone as a first-line treatment for CRPC patients. Patients will be randomly assigned to an enzalutamide or an abiraterone treatment group. The primary endpoint is the time to prostate-specific antigen progression. The target sample size is set at 100 patients per group (total, 200 patients). The study duration is 5 years, and the duration for recruitment is 2 years and 6 months. DISCUSSION: Thus far, there have been no prospective head-to-head studies comparing enzalutamide and abiraterone. This ENABLE study will clarify which agent should be prioritized for CRPC patients and enable clinicians to decide the appropriate treatment before chemotherapy. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center identifier UMIN000015529 . Registrated 11/1/2014.

[Urinary schistosomiasis: report of a case].

A 20-year-old unmarried Ghanaian man complaining of macroscopic hematuria and cystitis symptom was admitted to our institute. Abdominal ultrasound revealed a hyper echoic lesion in the entire bladder wall. Computed tomography showed a calcification of the whole bladder wall and of the left lower ureter. Flexible cystoscopy revealed many nodular masses, so-called 'bilharzial tubercles', at the trigone and posterior wall of the urinary bladder, and there was partial bleeding. Pathological examination revealed granuloma with many calcified eggs of schistosome haematobium. He was diagnosed with Bilharzial schistosomiasis and was treated with 1,500 mg of praziquantel for two days. However the therapeutic effect was insufficient. Therefore, he was treated with 2,400 mg of praziquantel for two days, and the symptoms disappeared.

Enzalutamide versus Abiraterone Plus Prednisolone for Nonmetastatic Castration-Resistant Prostate Cancer: A Sub-Analysis from the ENABLE Study for PCa.

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.

PSA doubling time 4.65 months as an optimal cut-off of Japanese nonmetastatic castration-resistant prostate cancer.

A multicenter study of nonmetastatic castration-resistant prostate cancer (nmCRPC) was conducted to identify the optimal cut-off value of prostate-specific antigen (PSA) doubling time (PSADT) that correlated with the prognosis in Japanese nmCRPC. Of the 515 patients diagnosed and treated for nmCRPC at 25 participating Japanese Urological Oncology Group centers, 450 patients with complete clinical information were included. The prognostic values of clinical factors were evaluated with respect to prostate specific antigen progression-free (PFS), cancer-specific survival (CSS), and overall survival (OS). The optimal cutoff value of PSADT was identified using survival tree analysis by Python. The Median PSA and PSADT at diagnosis of nmCRPC were 3.3 ng/ml, and 5.2 months, respectively. Patients treated with novel hormonal therapy (NHT) showed significantly longer PFS (HR: hazard ratio 0.38, p < 0.0001) and PFS2 (HR 0.45, p < 0.0001) than those treated with vintage nonsteroidal antiandrogen agent (Vintage). The survival tree identified 4.65 months as the most prognostic PSADT cutoff point. Among the clinical and pathological factors PSADT of < 4.65 months remained an independent prognostic factor for OS (HR 2.96, p = 0.0003) and CSS (HR 3.66, p < 0.0001). Current data represented optimal cut-off of PSADT 4.65 months for a Japanese nmCRPC.

[A case of primary malignant lymphoma of the prostate with characteristic MRI findings].

Here, we report a case of malignant lymphoma (ML) of the prostate. A 77-year-old man was referred to our hospital with the chief complaint of left lumbago. Computed tomography imaging showed a large mass below the bladder, as well as left hydronephrosis resulting from infiltration of the mass. Magnetic resonance imaging (MRI) revealed enlargement and high-intensity of the whole prostate with diffusionweighted image. An enlarged, stony, hard prostate was palpable on digital rectal examination, but the prostate-specific antigen (PSA) level was 4.65 ng/ml. Since the patient developed urinary retention and macrohematuria, transurethral hemostasis and biopsy were performed. Histological findings and immunohistochemical studies revealed diffuse large B-cell non-Hodgkin's lymphoma (DLBCL). MRI is thought to play a critical role in localization diagnosis of Non-Hodgkin's lymphoma (NHL) since NHL demonstrates characteristic signs. Although the frequency of primary ML of the prostate is low, by paying careful attention to the characteristic signs on MRI and examination findings, we should consider a differential diagnosis of ML of the prostate, which is not a typical manifestation of prostatic cancer.

[Clinical study of 62 patients with symptoms of male climacterium].

We prospectively reviewed the records of 62 patients who had sought evaluation at our hospital with a chief complaint of male climacteric symptoms. Late-onset hypogonadism (LOH)-related symptoms were evaluated during the initial visit based on the Aging Males' Symptoms (AMS) score, International Index of Erectile Function (IIEF) -5 score, and Center for Epidemiologic Studies Depression Scale (CES-D). Laboratory and endocrinologic testing, including the free testosterone (FT) level, was performed with blood samples collected before 10 : 00 am. The AMS psychological and CES-D scores in patients with a FT ＞8.5 pg/ml were significantly higher than those in patients with a FT ≦8.5 pg/ml. The study included 32 patients who were diagnosed with LOH (FT ≦8.5 pg/ml) and treated with androgen replacement therapy (ART). The total, somatic, psychological, and sexual scores of the AMS were significantly decreased after the third intramuscular administration of testosterone enanthate; there were no serious complications. Because a significant proportion of depressed patients may be amongst the patients with aging male's symptoms, it is important to consider depression in the exclusion diagnosis during a clinical examination for LOH.

[Effective dimethyl sulfoxide (DMSO) occlusive dressing technique for amyloidosis of the urinary bladder].

A 48-year-old married woman complaining of macroscopic hematuria and cystitis symptom was admitted to our institute. Flexible cystoscopy revealed many yellowish, nodular masses at the paries posterior of the urinary bladder, and cold-punch biopsy proved it to be amyloidosis. Serum amyloid protein A (SAA) was high, and suggested systemic amyloidosis. Renal biopsy and colon fiberscopy did not reveal any abnormalities. We therefore diagnosed a primary localized amyloidosis of the urinary bladder. Transurethral resection and dimethyl sulfoxide (DMSO) infusion therapy are used to treat amyloidosis of the urinary bladder. However there is no definite cure for amyloidosis of the urinary bladder. Therefore we selected DMSO occlusive dressing technique therapy. After 5 years of therapy, there was no evidence of a recurrence of amyloidosis.

[First 25 cases of photo-selective vaporization of the prostate (PVP) with 120-watt high performance system for benign prostatic hyperplasia].

PURPOSE: We examined the safety and efficacy of photo-selective vaporization of the prostate (PVP) using a 120-W high-performance system (HPS) for benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: We prospectively reviewed the records of 25 patients who had undergone PVP using a 120-W HPS in our institution. Patients were evaluated pre-operatively, and at 2 weeks and 1, 3, and 6 months postoperatively. RESULT: The mean age was 73.6 years, and the mean estimated preoperative prostate volume was 51.5 ml. Laser vaporization was performed successfully in all 25 patients. The operating time was 104 +/- 29 minutes. The mean decrease in hemoglobin was 0.6 g/dl on post-operative day 1. The International Prostate Symptom Score (IPSS), QOL score, maximum flow rate, and residual urine volume were significantly improved 2 weeks after the procedure. There were no serious complications during the peri-operative period, and no patients were transfused. CONCLUSION: PVP using a 120-W HPS was shown to be an effective, safe procedure for patients with BPH and lower urinary tract symptoms.

Mixed epithelial and stromal tumor of the kidney with long-term imaging follow-up.

Mixed epithelial and stromal tumor (MEST) of the kidney is a rare benign tumor with malignant potential, and is characterized by epithelial and stromal proliferation with a variety of cellularity and growth pattern. MEST of the kidney is often depicted as a well-defined, solid mass with a cystic component. However, due to the rarity of the disease, there are no reports of its progression in serial imaging examinations. This report presents the case of a 68-year-old woman with MEST who was followed for 13 years by computed tomography (CT). To the best of our knowledge, this is the first report of image findings of MEST of the kidney over a follow-up period longer than 10 years.

Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study.

Pembrolizumab, an anti-programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum-refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9 months. The 2-year relapse-free survival (RFS), treatment-free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re-administered to 12 patients. Pembrolizumab re-challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score-matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months (p = 0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.

Succinate dehydrogenase B-deficient renal cell carcinoma with a germline variant in a Japanese patient: a case report.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare renal cancer. A 75-year-old Japanese female presented with gross hematuria. Computed tomography revealed two tumors in the left kidney, which were resected. Immunohistochemistry indicated negative staining for the B subunit of SDH (SDHB) in the resected specimen, leading to a final diagnosis of SDHB-deficient RCC. Genetic testing for SDHB showed a RCC germline variant in exon 6 (NM_003000.3:c.642 G > C) that was previously reported but associated with a novel phenotype (i.e., RCC). Twenty-six years prior, her daughter, who was 25 years old at the time, had undergone radical nephrectomy for a pathologic diagnosis of renal oncocytoma of the right kidney; SDHB immunostaining of her daughter's tumor was also negative retrospectively. We confirmed that her daughter carried the germline variant in SDHB exon 6, similar to the patient. The patient had no evidence of disease progression at 15 months after surgery.