[A Case of Malacoplakia of the Prostate which was Difficult to Distinguish from Prostate Cancer].

A 70-year-old-man was referred with urination pain and pyuria. Prostate specific antigen was 10.6 ng/ml, and urine culture was Escherichia coli. The abdominal ultrasonography showed irregular low echo at the right lobe of prostate. Prostate magnetic resonance imaging (MRI) showed an extracapsular infiltrated prostate tumor in the right lobe. Levofloxacin was administered and prostate biopsy was performed. The pathological examination revealed that the prostate tissue was filled with inflammatory cells and had lost its glandular duct structure. The patient was diagnosed with malacoplakia of the prostate. Four months after prostate biopsy, prostate MRI imaging showed disappearance of the extracapsular infiltration in right peripheral zone.

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.

Squamous cell and urothelial carcinomas in an ileal neobladder.

Introduction: In cases of ileal neobladder following radical cystectomy for the treatment of bladder cancer, tumor development in the isolated gut segment is extremely rare. Herein, we report a case of squamous cell and urothelial carcinomas in the ileal neobladder 23 years after radical cystectomy. Case presentation: A 71-year-old man was referred to our hospital for further examination of a solitary tumor in an ileal neobladder. At the age of 48 years, he underwent radical cystectomy with ileal neobladder reconstruction. Transurethral resection of the bladder tumor was performed, and histopathological findings showed squamous cell carcinoma with high-grade urothelial carcinoma. Conclusion: To our knowledge, this is the first report of squamous cell and urothelial carcinomas in an ileal neobladder. While secondary tumor development in an ileal neobladder is rare, it is a cause for concern as a late postoperative adverse event. Therefore, long-term follow-ups are recommended.

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.

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.

[A Case of Prostatic Cancer that Had Bilateral Ureteral Metastases at Initial Diagnosis].

Ureteral metastases from prostate cancer are uncommon. We report a case of prostate cancer with bilateral ureteral metastases. A 76-year-old man visited our hospital because of serum prostate specific antigen (PSA) level of 40.7 ng/ml. Contrast-enhanced computed tomography revealed bilateral ureteral tumors causing bilateral hydronephrosis. Magnetic resonance imaging and prostate biopsy showed prostate cancer involving the bladder neck with bone metastases. Voided urine cytology suggested urothelial carcinoma. Retrograde pyelography demonstrated left ureteral filling defect and right lower ureteral stenosis. Left ureteral tumor and concomitant prostate cancer were suspected ; thus, combined androgen blockade therapy was initiated, and left nephroureterectomy was subsequently performed. Pathological and immunohistochemical examination of the left ureteral tumor revealed PSA-positive adenocarcinoma. The contralateral ureteral lesion was presumed to be metastasis from the same origin ; hence, prostate cancer with bilateral ureteral metastases was diagnosed. Although the mechanism is unknown, ureteral metastasis should be considered in the differential diagnosis of prostate cancer patients with ureteral tumor.

[Complete Transurethral Resection of Large Non-Muscle-Invasive Bladder Cancer Preoperatively Suspected to Be Muscle-Invasive Disease : A Case Report and Literature Review].

A 69-year-old man presented with gross hematuria. Cystoscopy revealed a large papillary tumor occupying the bladder. Magnetic resonance imaging showed a large bladder tumor more than 8cm in maximum diameter,suspected to be muscle-invasive disease. We performed the 1st transurethral resection of bladder tumor (TURBT) for the main purpose of pathological confirmation. Histopathological findings of the resected specimens showed urothelial carcinoma,low grade pTa. We performed subsequent treatments with TURBT twice,resulting in complete resection. The histopathological findings showed the same results as those of the 1st TURBT conclusively,which was consistent with non-muscle-invasive bladder cancer. He received intravesical instillation of pirarubicin eight times in total and has remained free from recurrence for more than 26 months after the final TURBT.

Spontaneous remission of rectal ulcer associated with SpaceOAR® hydrogel insertion in radiotherapy for prostate cancer.

INTRODUCTION: The SpaceOAR® hydrogel system separates the prostate and rectum to reduce rectal irradiation during prostate radiotherapy. However, it could induce rectal toxicity. CASE PRESENTATION: A 75-year-old man with localized prostate cancer underwent external beam radiotherapy with the use of SpaceOAR® System. However, postimplant magnetic resonance imaging showed hydrogel infiltration to the rectum. Three months after implantation, he complained of bowel symptoms, including bloody stool. Colonofiberscopy and computed tomography revealed a rectal ulcer associated with SpaceOAR® hydrogel insertion. He was treated with fasting, fluid replacement, and blood transfusion. One year after implantation, complete healing was confirmed during outpatient follow-up. CONCLUSION: To our knowledge, this is the first report of a rectal ulcer associated with SpaceOAR® hydrogel insertion assessed by magnetic resonance imaging beforehand. Postimplant magnetic resonance imaging evaluation might be a useful follow-up tool in such cases.

[A Case of Primary Ewing Sarcoma of the Kidney Treated with Multidisciplinary Approach].

A woman in her 40s visited our hospital for further examination and treatment of a left renal tumor. Imaging studies showed that the patient had a large left renal tumor, 10.5 cm in diameter, which contained foci of necrosis. Open left radical nephrectomy was performed. In pathological examination, hematoxylin-eosin staining showed uniform small round cells with alveolar growth. Immunohistochemistry findings showed that CD99 and NKX2. 2 were positive, and synaptophysin was focally positive. Fluorescence in situ hybridization confirmed (11 ; 22) (q24 ; q12) chromosomal translocation which led to diagnosis of primary Ewing sarcoma of the kidney. Two months after the surgery, new tumors were found inside and outside of the left psoas muscles and in the left paracolic gutter. Six courses of chemotherapy were administered with VDC (vincristine/doxorubicin/cyclophosphamide) and IE (ifosfamide/etoposide). After completing the combined chemotherapy, the recurrent tumors disappeared completely on imaging. To prevent further recurrence, external radiation was administered to the left retroperitoneal region. About 16 months after the surgery, numerous new tumors appeared in the left retroperitoneal, left pleura, and erector spinae muscles. Chemotherapy was resumed following radiotherapy, and then trabectedin was administered. However, she eventually died of progressive disease at 26 months after the surgery.

[A Case of Metastatic Mucinous Adenocarcinoma Derived from the Right Ovary to the Ileal Ureter].

A 76-year-old woman presented with temporary right back pain and renal dysfunction. She had undergone ileal ureter interposition for right ureteral resection due to retroperitoneal liposarcoma about forty years ago. Abdominal computed tomographic (CT) scan showed right hydronephrosis and a stenosis in the middle of the ileal ureter. The symptoms were relieved, and the patient was followed. Six months later, however, a contrast enhanced lesion was newly observed at the stenosis of the ileal ureter, and nineteen months later, right ovarian tumor and peritoneal dissemination were subsequently observed. Aiming at diagnosis and cytoreduction, right nephroureterectomy and bilateral oophorectomy were performed. Histopathological findings of the resected tumors showed common characteristics of infiltrating and proliferating adenocarcinoma. Immunohistochemistry findings showed that Cytokeratin 7 and Cytokeratin 20 stained positive. On the other hand, Mucin 2 and Special AT-rich sequence-binding protein 2 were not found. The histopathological diagnosis was metastatic mucinous adenocarcinoma of the ovary with ileal ureter and a wide peritoneal dissemination. The patient rejected adjuvant chemotherapy and a new lesion was found in the pelvic fourmonths afterthe surgery.

[A Case of Malignant Lymphoma with an Elevated Serum IgG4].

A man in his 60s was referred to our hospital for further examination of left hydronephrosis and renal dysfunction. An enhanced abdominal computed tomographic scan showed that the patient had chronic abdominal aortic dissection and a non-enhancing retroperitoneal soft tissue occupying the front of the abdominal aorta as well as the bilateral common iliac arteries. The left ureter was compressed by the soft tissue at the fourth lumbar level. No tumor markers were significantly elevated and idiopathic retroperitoneal fibrosis was suspected to be the cause. Before starting treatment, however, right hydronephrosis was newly observed. We placed bilateral ureteral stents and reviewed our diagnosis. Elevated serum IgG4 and accumulation of 18F-fluorodeoxyglucose in the soft tissue were the points at issue. To determine the diagnosis, we performed open wedge biopsy. Histopathological findings showed mainly fibrous connective tissue with lymphocytic infiltration, which was positive for CD10, CD20, and bcl-2. These findings indicated follicular lymphoma. Induction chemotherapy was performed with 6 cycles of rituximab/cyclophosphamide/vincristine/prednisolone. The soft tissue tumor shrank markedly and the patient has been free from bilateral ureteral stents.

[A Case of Advanced Right Renal Pelvic Cancer with Left Supraclavicular Lymph Node Metastasis that Attained Long-Term Survival by Multidisciplinary Treatments].

A man in his 70s was referred to our hospital for further examination of a positive occult blood finding. Imaging studies showed that the patient had right renal pelvic cancer with interaortocaval, multiple paracaval and left supraclavicular lymph node metastases (cT3N2Ml). Induction chemotherapy was performed with 5 cycles of MEC (methotrexate/epirubicin/cisplatin) followed by 2 cycles of GT (gemcitabine/paclitaxel). After the combined chemotherapies, the residual lesions were the primary tumor in the right renal pelvis and the left supraclavicular lymph node. Right total nephroureterectomy combined with lymph node dissection of paraaortic, paracaval, and interaortocaval area and left cervical area were performed. Histopathologically the postoperative T stage of the primary tumor was determined as ypT3. As for lymph nodes dissected, an interaortocaval lymph node alone, but not the other nodes, contained viable cancer cells. Adjuvant chemotherapy was performed with 7 courses of GT therapy. The patient had intravesical recurrence once and received transurethral resection of bladder tumor followed by intravesical instillations of Bacillus Calmette-Guerin (BCG). Finally, the patient has been free from recurrence for 10 years after the final treatment.

Laparoscopic excision of an acquired ureteral diverticulum: A case report.

Ureteral diverticula, especially acquired diverticula, are rare. Surgery is indicated when a diverticulum is accompanied by complications such as stones, pyelonephritis, stenosis, and signs of malignancy. A 59-year-old woman visited our urology department with asymptomatic macrohematuria. Enhanced CT scan revealed a right ureteral diverticulum with a 16-mm diameter that contained two tiny stones inside. After 8 months, the size of these stones increased; therefore, the patient underwent laparoscopic resection of the ureteral diverticulum and end-to-end anastomosis of the ureter. Subsequent histopathology of the excised specimen revealed an acquired diverticulum. Follow-up intravenous pyelography showed adequate urine passage with only minor dilatation of the pelvis at 3 months after the operation. The laparoscopic approach is believed to be feasible for ureteral diverticula cases that require ureteral end-to-end anastomosis.

[Post-Operative Urethral Stricture after Holmium Laser Enucleation of the Prostate].

Holmium laser enucleation of the prostate (HoLEP) is a safe and effective surgical procedure for patients suffering from comparatively larger benign prostatic hyperplasia. However, the rate of postoperative urethral stricture (POUS) is relatively high, which can render further invasive intervention. Here we assessed the POUS rate, riskfactors and outcomes in 206 patients with benign prostatic hyperplasia who underwent HoLEP at our hospital between January 2006 and December 2015. POUS was observed in 24 patients (11.7%). The rate of intraoperative urethral stricture was significantly higher in the patients with POUS (8 out of 24 patients, 33.3%) than in those without POUS (12 out of 186 patients, 6.6%). The odds ratio was 7.08, 95% and combination index (CI) was 2.53-19.9, p<0.001). The relative riskfor POUS based on intraoperative urethral stricture was 4.65 (95% CI : 2.28-9.48). The most common POUS site was external urethral orifice (12 out of 24 cases). The POUS onset was significantly earlier in patients with external urethral orifice than the other sites (p=0.0389). The site of postoperative stricture concurred with that of intraoperative stricture at a high rate (7 out of 8 patients). Significant differences were observed between patients with and without POUS within one month in international prostate symptom score, quality of life score and in Qmax after the operation, while they were improved by simple interventions such as bougie. In conclusion, we should consider the possibility of POUS when the patient had an intraoperative stricture in HoLEP.

[Initial Clinical Experience of Nivolumab for Metastatic Renal Cell Carcinoma].

Nivolumab was approved as a new agent for advanced renal cell carcinoma (RCC) in Japan on September 2016. Nivolumab is an immune checkpoint inhibitor that activates the cytotoxic immune response and has exerted antitumor effects in a mechanism different from other available molecular targeted agents. Therefore, its response pattern, efficacy and adverse events are different from those of the molecular targeted agents for RCC. Here, we report our initial clinical experience with nivolumab. From December 2016 to September 2017, we applied nivolumab to 7 patients with metastatic RCC. The most common metastatic site was the lungs, followed by lymph nodes, bones and brain. According to the immune-related response criteria, the efficacy was stable disease in 2 patients and progressive disease in 5 patients. In 5 cases with multiple metastases, responses differed with the site of metastasis. The response was best in lung metastasis and worst in brain metastasis. Six cases had minor adverse events. In two cases, we discontinued administration of nivolumab temporarily. The patients recovered completely and we considered nivolumab effective and safe for treatment of metastatic RCC.

Case with bromine exposure leading to respiratory insufficiency.

A 21-year-old male had a chemical burn on the right forearm when he inadvertently spilled bromine during an experiment. Since he inhaled vaporized bromine and had dyspnea and pharyngalgia, he arrived at our hospital in an ambulance as an emergency patient. On arrival, he kept a clear consciousness with a pulse rate of 98, body temperature of 36.8 degrees C, blood pressure of 132/80 mmHg, respiratory rate of 25, and oxygen saturation of 100%. (10 L/min of oxygen were administered.) He had marked dry coughs. His clothes had a foreign odor with mucosal irritation. Arterial blood gas analysis and blood biochemistry were normal. Based on these findings, he was diagnosed with chemical airway damage and bulbar conjunctiva from the exposure to bromine and a chemical burn on the right forearm. His respiratory condition became worse after admission, resulting in pulmonary edema. He was endotracheally intubated and controlled with an artificial ventilator on Day 3 after his injury. He was continuously treated with steroids and sivelestat sodium hydrate, which gradually improved his respiration. He was released from the artificial ventilator and extubated on Day 7. Although dyspnea associated with body movement and hoarseness persisted after extubation, the symptoms decreased and he was discharged on Day 41. This rare case is worth attention because serious respiratory insufficiency requiring artificial ventilation due to pulmonary edema from bromine exposure has not been reported in Japan.