Pembrolizumab Therapy Leading to Complete Remission for Recurrence of Pulmonary Metastases after their Resection and Radical Cystectomy following Gemcitabine and Cisplatin Therapy.

A 64-year-old man was diagnosed with invasive bladder and right lower ureteral urothelial cancer with right pelvic lymph node and lung metastases. He received four courses of gemcitabine and cisplatin therapy. He underwent lung metastasectomy and radical cystoprostatectomy, with not only primary lesions but also metastatic lesions showing a complete response. New multiple lung metastases were revealed five months after adjuvant chemotherapy. On starting pembrolizumab therapy, the metastatic lesions are notably reduced in size. He is currently receiving pembrolizumab therapy, and no recurrence has been observed for over one year.

A case of cabozantinib therapy leading to complete remission for massive intra-intestinal bleeding and worsening metastatic sites following nivolumab and ipilimumab therapy.

A woman in her 50s had recurrent renal cell carcinoma six years after nephrectomy. The patient was treated with nivolumab plus ipilimumab therapy starting in May 2022. She was rushed to hospital due to melena and severe anemia in September 2022. CT showed massive leakage of contrast medium into the gastrointestinal tract and mild enlargement of the metastatic tumors. Nivolumab was discontinued and she was started on cabozantinib as second-line therapy. After cabozantinib therapy, the anemia subsided. The metastatic tumors have shrunk significantly, with no further recurrence being observed as of September 2023.

Complete remission following pembrolizumab therapy for a patient with nephroureterectomy positive-margin carcinoma in situ and bladder cancer unresponsive to Bacille Calmette-Guérin therapy.

An 82-year-old man was diagnosed with synchronous non-muscle-invasive bladder cancer and left lower ureteral carcinoma. He underwent transurethral resection of the bladder tumor, followed by total left nephroureterectomy after preoperative chemotherapy with four courses of gemcitabine and carboplatin. Histopathological findings showed positive-margin carcinoma in situ. In addition, since recurrence of non-muscle-invasive bladder cancer was observed in the bladder, Bacille Calmette-Guérin intravesical infusion therapy was performed, but the cancer persisted due to treatment resistance. After that, pembrolizumab therapy was performed, and complete remission was achieved.

Prostate-specific antigen doubling time following radium-223 treatment as a predictor of the clinical course in patients with metastatic castration-resistant prostate cancer.

Objectives: To identify useful biomarkers by reviewing laboratory data for a predictor of the clinical course following treatment with radium-223 dichloride (Ra-223) in patients with metastatic castration-resistant prostate cancer. Methods: Eighteen metastatic castration-resistant prostate cancer patients who were administered Ra-223 at our hospital were retrospectively enrolled in this study. Prostate-specific antigen doubling times before and after the administration of Ra-223 were evaluated as prognostic factors for metastatic castration-resistant prostate cancer patients treated with Ra-223 using the Kaplan-Meier method and Log-rank test. Results: Four patients failed to complete the planned six-time Ra-223 treatments with the exacerbation of their condition. In the 14 patients who completed the planned Ra-223 treatment, before the Ra-223 treatment, no significant differences were observed in overall survival between patients with prostate-specific antigen doubling time of 6 months or less and those with prostate-specific antigen doubling time of more than 6 months or stable (p = 0.642). Following the completion of the Ra-223 treatment, overall survival was significantly shorter in patients with prostate-specific antigen doubling time of 6 months or less than in those with prostate-specific antigen doubling time of more than 6 months or stable (p = 0.007). Conclusion: Prostate-specific antigen doubling time after the Ra-223 treatment is a useful predictor of the clinical course following treatment in metastatic castration-resistant prostate cancer patients.

Primary lung cancer treatable with radical resection after complete remission with pembrolizumab therapy following gemcitabine and carboplatin chemotherapy for multiple metastases of bladder cancer.

Introduction: We report a patient with the complete remission of multiple metastases and primary bladder lesions of bladder cancer who developed primary lung cancer requiring radical resection. Case presentation: A 68-year-old man diagnosed with invasive bladder cancer, right hydroureteronephrosis, and multiple metastases were administered six courses of gemcitabine and carboplatin chemotherapy and thereafter has been receiving pembrolizumab therapy. Bladder cancer and multiple metastases decreased in size, whereas a ground-glass opacity lesion in the lung gradually increased in size. Fluorodeoxyglucose-positron emission tomography revealed the accumulation of fluorodeoxyglucose in the ground-glass opacity lesion only. The patient was diagnosed with primary lung cancer and underwent a thoracoscopic lobectomy. Histopathological findings showed ALK-negative, EGFR L858R mutation-positive invasive adenocarcinoma with a programmed death-ligand 1 tumor proportion score of less than 1%. Conclusion: This is the first case report of patients with the complete remission of multiple metastases of bladder cancer who developed primary lung cancer requiring radical resection.

Laparoscopic Nephroureterectomy with Heminephrectomy for Urothelial Carcinoma of the Upper Renal Pelvis on the Left Side of the Horseshoe Kidney.

A 70-year-old male was diagnosed with urothelial carcinoma of the upper renal pelvis on the left side of the horseshoe kidney. Preoperative thin-slice contrast-enhanced CT with three-dimensional reconstruction of the images revealed that two arteries arising from the aorta supplied the left moiety of the horseshoe kidney. He underwent laparoscopic transperitoneal nephroureterectomy with heminephrectomy on the left side of the horseshoe kidney visualized by indocyanine green fluorescence system. The histopathological findings of the renal pelvic tumor revealed invasive urothelial carcinoma with squamous differentiation, high grade, and pT3.

Successful Response of Pembrolizumab Rechallenge after Radiotherapy for a Patient with Bladder Cancer of Nonresponse of Pembrolizumab First Challenge.

We report a patient with advanced bladder cancer in which the primary lesion and metastatic site disappeared following the pembrolizumab therapy rechallenge after radiotherapy for bladder cancer lesion of nonresponse of pembrolizumab first challenge. A 76-year-old man with advanced bladder cancer received three courses of the chemotherapy with gemcitabine and cisplatin combination; however, the chemotherapy was stopped because of adverse events. The patient started pembrolizumab therapy; however, the effect was not observed. Radiation therapy was given to the primary lesion and pelvic lymph node metastases for the purpose of local control of the lesions. Because the primary lesion was regrowth and para-aortic lymph node metastasis appeared, pembrolizumab therapy was resumed. Thereafter, the primary lesion and metastatic site disappeared.

Multidisciplinary Therapy in Men with Newly Diagnosed Oligometastatic Prostate Cancer.

PURPOSE: To assess the use of aggressive local therapy with systemic therapy for patients with oligometastatic prostate cancer. PATIENTS AND METHODS: Patients with oligometastatic prostate cancer received systemic therapy centered on androgen deprivation therapy (ADT). After six months or more of ADT, the patients received radiation therapy or surgery for the prostate, and radiation therapy for all metastatic sites. ADT was continued for 2-3 years after local therapy. RESULTS: Twelve patients who were judged to be able to undergo radiotherapy or surgical treatment of the prostate and radiation therapy for all metastatic sites and one case of pubic bone recurrence after radical prostatectomy were included. Bone metastases (n = 11) and para-aortic lymph node metastases (n = 2) were found. The number of bone metastases was one (n = 7), two (n = 3), and three (n = 1). Radiation therapy (70-74 Gy) was performed on the prostate in 11 of 12 patients. A prostatectomy was performed on one patient who was judged to be unable to receive a sufficient dose to the metastatic site when radical radiation was applied to the prostate. Radiation therapy (45-60 Gy) was performed on all metastatic sites. Prostate-specific antigen (PSA) levels increased again during treatment in three patients. There was a significant difference in PSA levels before local therapies between the three patients who developed castration-resistant prostate cancer (CRPC) during the course of treatment and the eight patients who did not progress to CRPC (p = 0.012). There was also a significant difference in PSA levels after local therapies between the three patients who developed CRPC during the course of treatment and the eight patients who did not progress to CRPC (p = 0.012). Four patients completed treatment. In one patient in whom the testosterone level recovered to the normal level the PSA level remained the level below the measurement sensitivity. CONCLUSION: Aggressive local therapy in combination with systemic therapy centered on ADT is a promising treatment option for oligometastatic prostate cancer.

Isolated Adrenocorticotropic Hormone Deficiency Associated with Severe Hyperkalemia During Pembrolizumab Therapy in a Patient with Ureteral Cancer and an Ileal Conduit: A Case Report and Literature Review.

BACKGROUND Immune checkpoint inhibitors (ICIs) are anticancer medications that enhance the antitumor immune response. The clinical benefit afforded by ICIs, however, can be accompanied by immune-related adverse events (IRAEs). One of the common endocrine IRAEs is hypophysitis, which often causes hypopituitarism with secondary adrenal insufficiency (AI). Secondary AI, including isolated adrenocorticotropic hormone (ACTH) deficiency (IAD), is often associated with hyponatremia. Here, we report an unusual case of ICI-related IAD associated with severe hyperkalemia. CASE REPORT A 78-year-old woman who had an ileal conduit, chronic kidney disease, type 2 diabetes mellitus, and hypertension and was taking an angiotensin II receptor blocker began treatment for advanced ureteral cancer with the anti-programmed cell death protein 1 inhibitor pembrolizumab. The therapy effectively controlled the cancer, but 4 1/2 months after starting it, the patient developed anorexia, general weakness, and muscle pain and was diagnosed with IAD associated with severe hyperkalemia and hyperchloremic metabolic acidosis. She recovered after prompt administration of corticosteroids and treatment with sodium bicarbonate, glucose/insulin, and cation exchange resins. CONCLUSIONS Hyperkalemia is a common symptom of primary AI but is less common in patients with central AI because a lack of ACTH does not cause aldosterone deficiency and mineralocorticoid action is preserved. The present case demonstrates the need for physicians to be aware of severe hyperkalemia as a life-threatening complication of secondary AI induced by ICIs, particularly in patients with predisposing factors, such as kidney dysfunction, diabetes mellitus, an ileal conduit, and renin-angiotensin-aldosterone system inhibitor use.

Clear Cell Adenocarcinoma of the Ureter Similar to Clear Cell Renal Cell Carcinoma Histology.

A 70-year-old woman was referred to our hospital with gross hematuria and diagnosed with right invasive ureteral cancer and bladder urothelial carcinoma in situ. Intravesical BCG therapy and neoadjuvant chemotherapy with carboplatin and gemcitabine were performed at the same time. Subsequently, laparoscopic right nephroureterectomy was performed. Urothelial carcinoma in situ persisted; however, most of the tumor was clear cell carcinoma. The clear cell carcinoma lesion had clear cytoplasm with round nuclei and visible nucleoli in an insular arrangement as is the case with clear cell renal cell carcinoma. No transitional lesion between clear cell adenocarcinoma and urothelial carcinoma was presented. The clear cell carcinoma lesion was GATA3 negative and HNF4α positive; however, the urothelial cancer lesion was GATA3 positive and HNF4α negative. Clear cell carcinoma was diagnosed as clear cell adenocarcinoma similar to clear cell renal cell carcinoma histology.

Significance of PSA Screening in Niigata, Japan: Survey of Actual Status of New Cases of Prostate Cancer.

PURPOSE: This study aims to investigate the utility of prostate-specific antigen (PSA) screening by conducting an all-case survey of newly diagnosed prostate cancer patients at Niigata Prefecture, Japan. PATIENTS AND METHODS: Depending on whether patients were subjected to screening, information was prospectively collected on all prostate cancer patients newly diagnosed between October 1, 2019, and September 30, 2020, at all institutions in Niigata Prefecture where urologists performing prostate biopsy routinely work and differences in clinical parameters were investigated. RESULTS: PSA was measured in 478 out of 1332 patients (35.8%) as part of a community health screening. The rate of metastatic carcinoma (M1) in all patients was 14.9%. When patients were divided into three categories of population-based screening (community health screening and workplace health screening), opportunistic screening (PSA measurements at complete medical check-ups or on patient request), and testing triggered by clinical symptoms or findings, the proportion of metastatic cancer was 4.5%, 3.7%, and 30.6%, respectively, demonstrating that the number of distant metastases was significantly lesser in all patients who underwent screening. CONCLUSION: The one-year all-case survey of newly diagnosed prostate cancer patients demonstrated that PSA screening significantly contributed to the early diagnosis of current prostate cancer in Japan.

Primary malignant melanoma of the female urethra: A case report.

Primary malignant melanoma of a female urethra is extremely rare. A 71-year-old female was referred to our hospital with bleeding from the urethral meatus. Magnetic resonance imaging revealed a mass of 25 mm in diameter at the external urethral meatus. She underwent anterior pelvic exenteration and ileal conduit diversion. Histopathological findings were urethral malignant melanoma, pT3apN0M0 (stage IIA). Nine months after surgery, computed tomography revealed a local recurrence in the pelvis, the patient was treated with immunotherapy using combined nivolumab and ipilimumab; however, she did not respond to treatment and died 22 months following diagnosis.

Urothelial carcinoma with sarcomatoid/osteosarcoma variant of the bladder: A case report.

A 67-year-old man was diagnosed with non-muscle invasive bladder cancer and underwent transurethral resection of the lesions in August 2017. The pathological findings revealed high-grade urothelial carcinoma. The tumor relapsed as urothelial carcinoma with sarcomatoid/osteosarcoma variant with vascular invasion, and transurethral resection was performed in December 2017. He underwent laparoscopic radical cystoprostatectomy and orthotopic neobladder reconstruction using ileum in March 2018. The patient developed lung metastasis in July 2018. He underwent four courses of chemotherapy with doxorubicin and thoracoscopic left lower lobectomy of the lung in October 2018.

Granulocytic/myeloid sarcoma with trisomy 21 presented as an epididymal tumor: A case report and review of the literature.

Myeloid sarcoma is an extramedullary tumor composed of immature myeloid cells and occurs in various extramedullary sites. We report a 48-year-old man diagnosed with myeloid sarcoma in the epididymis. He was admitted to our hospital due to a painless right intrascrotal mass. Magnetic resonance imaging showed a 30 mm tumor in the right epididymis, and we subsequently performed right high orchiectomy. The pathological diagnosis was myeloid sarcoma. Bone marrow aspiration and biopsy revealed no hematological disease, and cytogenetic analysis in the bone marrow showed normal karyotype. He was diagnosed with isolated myeloid sarcoma in the epididymis. Six months after the operation, myeloid sarcoma recurred in the para aorta and left sub-diaphragm. Bone marrow examination revealed myelodysplastic syndrome, and cytogenetic analysis showed 46, XY. We performed surgical resection of the recurrent mass, and cytogenetic analysis showed 47, XY, +21. He was diagnosed with recurrent MS with adult-onset trisomy 21. Although the effect of trisomy 21 on prognosis is unknown, the patient is currently undergoing systemic chemotherapy with maintained remission.

Emergence of undifferentiated urothelial carcinoma after pembrolizumab treatment for patient with invasive urothelial bladder cancer: A case report.

An 83-year-old man received pembrolizumab treatment after anticancer chemotherapy with gemcitabine and cisplatin for advanced bladder cancer. Pathological findings revealed invasive urothelial carcinoma with squamous differentiation before treatment. After seven courses of pembrolizumab treatment, the tumor disappeared. After 15 courses of the treatment, the tumor regrew. Pathological findings revealed invasive undifferentiated urothelial carcinoma consisting of relatively small tumor cells of the same size as lymphocytes, negative for neuroendocrine markers. Programmed death-ligand 1 expressions in tumor tissue changed from positive before treatment to negative after pembrolizumab treatment.

Intraoperative intraocular pressure changes during robot-assisted radical prostatectomy: associations with perioperative and clinicopathological factors.

BACKGROUND: Steep Trendelenburg position (ST) during robot-assisted radical prostatectomy (RARP) poses a risk of increase in intraocular pressure (IOP) in men receiving robot-assisted radical prostatectomy (RARP). The aim of the study was to identify clinicopathological factors associated with increased IOP during RARP. METHODS: We prospectively studied 59 consecutive prostate cancer patients without glaucoma. IOP was measured at 6 predefined time points before, during and after the operation (T1 to T6). RESULTS: Compared with T1, IOP decreased after beginning of anesthesia(T2) (by - 6.5 mmHg, p < 0.05), and increased 1 h after induction of pneumoperitoneum in the steep Trendelenburg position (ST) (T3) (+ 7.3 mmHg, p < 0.05). IOP continued to increase until the end of ST (T4) (+ 10.2 mmHg, p < 0.05), and declined when the patient was returned to supine position under general anesthesia (T5) (T1: 20.0 and T5: 20.1 mmHg, p above 0.05). The console time affected the elevation of IOP in ST; IOP elevation during ST was more prominent in men with a console time of ≥4 h (n = 39) than in those with a console time of < 4 h (n = 19) (19.8 ± 6.3 and 15.4 ± 5.8 mmHg, respectively, p < 0.05). Of the 59 patients, 29 had a high baseline IOP (20.0 mmHg or higher), and their IOP elevated during ST was also reduced at T5 (T1: 22.6 and T5: 21.7 mmHg, p above 0.05). There were no postoperative ocular complications. CONCLUSIONS: Console time of < 4 h is important to prevent extreme elevation of IOP during RARP. Without long console time, RARP may be safely performed in those with relatively high baseline IOP.

Achieving PSA < 0.2 ng/ml before Radiation Therapy Is a Strong Predictor of Treatment Success in Patients with High-Risk Locally Advanced Prostate Cancer.

BACKGROUND: To predict long-term treatment outcome of radiation therapy (RT) plus androgen deprivation therapy (ADT) for high-risk locally advanced prostate cancer. METHODS: In total, 204 patients with the National Comprehensive Cancer Network (NCCN) high risk locally advanced prostate cancer (PSA > 20 ng/ml, Gleason score ≧ 8, clinical T stage ≧ 3a) were treated with definitive RT with ADT. Median follow up period was 113 months (IQR: 95-128). Median neoadjuvant ADT and total ADT duration were 7 months (IQR: 6-10) and 27 months (IQR: 14-38), respectively. RESULTS: PSA recurrence-free survival (PSA-RFS), cancer specific survival (CSS), and overall survival (OS) rates at 5 years were 84.1%, 98.5%, and 93.6%, respectively, and 67.9%, 91.2%, and 78.1%, respectively, at 10 years. Pre-RT PSA less than 0.2 ng/ml was associated with superior outcomes of PSA-RFS (HR = 0.42, 95% CI: 0.25-0.70, p = 0.001), CSS (HR = 0.27, 95% CI: 0.09-0.82, p = 0.013), and OS (HR = 0.48, 95% CI: 0.26-0.91, p = 0.021). On multivariate analysis, age (≥70 y.o.) and pre-RT PSA (≥0.2 ng/ml) were factors predictive of poorer OS (p = 0.032) , but iPSA, T stage, Gleason score, number of NCCN high-risk criteria, a combination with anti-androgen therapy and neoadjuvant ADT duration were not predictive of treatment outcome. CONCLUSION: In patient with high-risk prostate cancer, RT plus ADT achieved good oncologic outcomes. PSA < 0.2 ng/ml before radiation therapy is a strong independent predictor for long overall survival.

Simultaneous Laparoscopic Surgery for Bladder Diverticulum and Urachal Remnant: A Case Report.

A 44-year-old woman visited a hospital with microscopic hematuria in June 2009. Computed tomography showed a large bladder diverticulum at right lateral wall and urachal remnant. Cystoscopic examination showed a large diverticulum at the right lateral wall that closes to the dome. She was followed up closely without therapeutic intervention; however, the residual urine increased gradually and frequent bladder diverticulitis developed. She underwent laparoscopic bladder diverticulectomy and excision of the urachal remnant simultaneously without any complications in August 2017. Laparoscopic approach for a large bladder diverticulum and urachal remnant is useful with safe, effective, and minimally invasive.

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer.

INTRODUCTION: Adverse events with enzalutamide widely used for men with castration-resistant prostate cancer are of interest. CASE PRESENTATION: A 76-year-old man developed castration-resistant prostate cancer. He received 160 mg of enzalutamide daily. On the 13th day after treatment, severe thrombocytopenia was observed (platelet count: 1.9 × 104/µL). Normal coagulation and fibrinolytic systems suggested thrombocytopenia induced by enzalutamide. Enzalutamide was withdrawn immediately, and platelet count uneventfully recovered to 7.0 × 104/µL and 28.8 × 104/µL 9 and 30 days after discontinuation, respectively. He restarted enzalutamide therapy without thrombocytopenia recurrence. However, 81 days after restarting enzalutamide, he experienced a seizure. There were no significant findings from brain computed tomography, which suggested that the seizure was also an enzalutamide-associated adverse event. CONCLUSION: Thrombocytopenia may occur early following enzalutamide therapy, and blood analysis within 2 weeks after treatment may facilitate its management. Enzalutamide-induced thrombocytopenia, complicated by seizure, has not been reported.

A carbon 21 steroidal metabolite from progestin, 20ß-hydroxy-5α-dihydroprogesterone, stimulates the androgen receptor in prostate cancer cells.

BACKGROUND: Clarifying the mechanisms underlying prostate cancer (PC) progression and resistance to androgen deprivation therapy (ADT) is an urgent clinical issue. ADT influences steroidal metabolism in patients with PC and promotes the accumulation of carbon 21 steroids (C21s), such as progestin. Because the enzymes responsible for C21s metabolism are similar to those for androgen metabolism, PC cells may be able to metabolize C21s intracellularly. Therefore, there is a possibility that intracrine C21s are implicated in PC progression and resistance to ADT, and the influence of C21s on PC cells is yet to be elucidated. In the present study, we focused on 20ß-hydroxy-5α-dihydroprogesterone (20ß-OHDHP), a C21s metabolized from progestin, and showed that 20ß-OHDHP is synthesized in PC cells and is able to directly stimulate the androgen receptor (AR). METHODS: LNCaP, VCaP, and DU145 cells, which express a mutant AR (mAR), wild-type AR (wAR), and glucocorticoid receptor (GR), respectively, were incubated in the presence of several agents. After incubation, cell growth was determined by the MTS assay. PSA levels were determined by an enzyme immunoassay, and C21s and androgen levels were measured using liquid chromatography-mass spectrometry. Gene expression was analyzed by quantitative real-time polymerase chain reaction, and steroidal-receptor-related signaling was determined by a reporter assay. RESULTS: We affirmed that 20ß-OHDHP was synthesized from pregnenolone intracellularly in LNCaP and VCaP cells, and 20ß-OHDHP significantly promoted the growth of both cell lines without androgen conversion. 20ß-OHDHP directly stimulated both mAR and wAR. The presence of 20ß-OHDHP was sufficient for the proliferation and survival of LNCaP or VCaP cells, and 20ß-OHDHP promoted cell growth even in the presence of abiraterone. Using DU145 cells, we affirmed that 20ß-OHDHP did not stimulate GR, which has a potential to bypass AR signaling in PC cells promote PC cell growth. CONCLUSIONS: Under ADT, 20ß-OHDHP synthesized intracellularly from accumulated progestin in PC cells may accelerate cell growth via stimulation of both wAR and mAR. This pathway may represent an interesting candidate for targeted therapy.