Urinary bladder metastasis from breast cancer: A rare case report.

Breast cancer is a major contributor to cancer-related morbidity and mortality in women, which is primarily attributed to metastases. Common metastatic sites include the lungs, liver, and bone, whereas bladder metastasis is rare. We report a case of bladder metastasis from breast cancer in a 61-year-old woman, highlighting the challenges in diagnosis and treatment. The patient, previously diagnosed with invasive lobular carcinoma, presented with renal failure and underwent transurethral resection of bladder tumor. Pathological analysis confirmed metastasis from breast cancer. Bladder metastasis from breast cancer demands vigilance and prompt intervention because of its potential prognostic impact.

[Bladder Cancer Detected Incidentally by Cystoscopy before Radical Prostatectomy].

Radical prostatectomy is the treatment of choice for localized prostate cancer. In our institution, preoperative cystoscopy is performed routinely to clarify the prostate anatomy, including the median lobe and position of ureteral orifices. We conducted a retrospective analysis of 721 patients, from January 2008 to December 2022, our aim being to assess the clinical course of bladder cancer discovered incidentally through cystoscopy prior to radical prostatectomy. We found that bladder cancer was detected in eight of these patients (1.1%), seven of whom had low-grade, non-invasive, papillary urothelial carcinomas ; the remaining patient had a high-grade lesion. Notably, the pathological stage was Ta in all cases. The median duration of follow-up of patients with bladder cancer was initially set at 21 months (12-24 months). During the follow-up period, bladder cancer recurrence was identified in three patients. Patients who remained recurrence-free beyond the follow-up period underwent radical therapy. Importantly, no evidence of prostate cancer progression was detected throughout the follow-up period. Thus, incidental bladder cancer detected prior to radical prostatectomy is predominantly non-invasive, ensuring safe treatment of both the bladder and prostate cancers. Our findings suggest that cystoscopy could be omitted.

Bilateral adrenal metastases from renal cell carcinoma after robot-assisted partial nephrectomy.

Renal cell carcinoma often metastasizes to the adrenals; however, bilateral adrenal metastases are rare. We here report a patient with bilateral adrenal metastases from renal cell carcinoma after robot-assisted partial nephrectomy and review relevant published reports. A 64-year-old man underwent robot-assisted partial nephrectomy for a left renal tumor. During follow-up, he was diagnosed with bilateral adrenal metastases. He underwent left adrenalectomy followed by right partial adrenalectomy to preserve adrenal function. The renal tumor later metastasized to other parts of the body. He continues to receive systemic treatment and remains in partial remission. Patients with pT1aN0M0 renal cell carcinoma generally have a favorable prognosis. However, occasional such patients develop multiple metastases. To the best of our knowledge, this is the first reported case of bilateral adrenal metastases after partial nephrectomy. Clinicians should keep this rare scenario in mind.

[A Case of Aldosterone-Producing Adrenocortical Carcinoma].

A 59-year-old man presented with high blood pressure, hypokalemia and muscle weakness. His aldosterone/renin ratio was high and plasma renin activity was low. Computed tomography (CT) showed a heterogeneous left adrenal mass. Primary aldosteronism was diagnosed and laparoscopic left adrenalectomy was performed. The pathological diagnosis was adrenocortical carcinoma with positive surgical margins. He underwent radiotherapy and mitotane as adjuvant therapies. Subsequently, CT revealed multiple metastases, in the liver and retroperitoneum. After six courses of EDP (a combination of etoposide, doxorubicin and cisplatin), CT showed widespread metastases in the retroperitoneum and he chose to receive the best supportive care. Aldosterone-producing adrenocortical carcinoma is exceedingly rare. To the best of our knowledge, only67 cases have been reported. Complete resection is needed to improve prognosis and this was not achieved in our case. We therefore recommend careful selection of the operative procedure.

Myopericytoma in the corpus cavernosum of the penis: A case report of a rare disease.

Introduction: Myopericytomas usually occur in the extremities of older individuals; however, they also rarely occur in the penis. We report a case of myopericytoma in the corpus cavernosum of the penis and review the relevant literature. Case presentation: A 76-year-old man presented with a slow-growing painless nodule on the left side of the penis. On physical examination, a non-tender, 7-mm mass was palpable. This tumor showed inhomogeneous low signal intensity on T2-weighted magnetic resonance imaging. The mass was excised and a myopericytoma diagnosed by pathological examination of the operative specimen. Conclusion: We here report a rare case of myopericytoma in the corpus cavernosum of the penis. To the best of our knowledge, this is the second reported case of a myopericytoma in the penis and the first in the corpus cavernosum of the penis. Clinicians should keep this rare possibility in mind when investigating a mass in the penis.

Extracellular vesicles secreted from bone metastatic renal cell carcinoma promote angiogenesis and endothelial gap formation in bone marrow in a time-dependent manner in a preclinical mouse model.

Introduction: Bone is a major metastatic site of renal cell carcinoma (RCC). Recently, it is well recognized that bone metastatic tumor cells remodel bone marrow vasculature. However, the precise mechanism underlying cell-cell communication between bone metastatic RCC and the cells in bone marrow remains unknown. Extracellular vesicles (EVs) reportedly play crucial roles in intercellular communication between metastatic tumor cells and bone marrow. Therefore, we conducted the current study to clarify the histological alteration in vascular endothelium in bone marrow induced by EVs secreted from bone metastatic RCC cells as well as association between angiogenesis in bone marrow and bone metastasis formation. Materials and methods: We established a bone metastatic RCC cell line (786-O BM) by in vivo selection and observed phenotypic changes in tissues when EVs were intravenously injected into immunodeficient mice. Proteomic analysis was performed to identify the protein cargo of EVs that could contribute to histological changes in bone. Tissue exudative EVs (Te-EVs) from cancer tissues of patients with bone metastatic RCC (BM-EV) and those with locally advanced disease (LA-EV) were compared for in vitro function and protein cargo. Results: Treatment of mice with EVs from 786-O BM promoted angiogenesis in the bone marrow in a time-dependent manner and increased the gaps of capillary endothelium. 786-O BM EVs also promoted tube formation in vitro. Proteomic analysis of EVs identified aminopeptidase N (APN) as a candidate protein that enhances angiogenesis. APN knockdown in 786-O BM resulted in reduced angiogenesis in vitro and in vivo. When parental 786-O cells were intracardially injected 12 weeks after treatment with786-O BM EVs, more bone metastasis developed compared to those treated with EVs from parental 786-O cells. In patient samples, BM-EVs contained higher APN compared to LA-EV. In addition, BM-EVs promoted tube formation in vitro compared to LA-EVs. Conclusion: EVs from bone metastatic RCC promote angiogenesis and gap formation in capillary endothelium in bone marrow in a time-dependent manner.

[A Case of Multiple Penile Schwannoma].

A 48-year-old man presented with a painless nodule on the right ventral aspect of the penile shaft root. The patient visited the hospital and complained that the mass was growing. On physical examinations, a 5 cm mass without tenderness was palpated. An isoechoic mass about 4 cm in size was observed on ultrasonography. Inhomogeneous high signal intensity was observed on T2-weighted magnetic resonance imaging. A needle biopsy revealed schwannoma. During surgery for excision of the tumor, another small tumor was detected both tumors were resected. Both tumors were diagnosed as schwannoma by pathological examination. Out of 40 cases of penile schwannoma reported, eight were of multiple tumors. In our case, it was difficult to detect the other small tumor by preoperative diagnosis. Therefore, we recommend careful observation during surgery.

[A Case of Bladder Plasmacytoma Diagnosed during Treatment of Multiple Myeloma].

A 78-year-old man was treated with Bortezomib, Lenalidomide, and Dexamethasone, for multiple myeloma. Two years after the start of treatment, the patient came to our department with a complaint of gross hematuria. Cystoscopy revealed a tumor on the left wall of the bladder. Urine cytology was negative. Magnetic resonance imaging (MRI) of the lower abdomen showed a slightly high signal on the T2-weighted image, indicating an intravesical mass lesion invading outside the bladder. Contrast-enhanced computed tomography (CT) also showed an intravesical mass and enlarged left external iliac lymph node swelling. Transurethral resection of bladder tumor was performed. The resection specimen showed tumor cells. The pathological examination revealed CD138 (+) and light-chain restriction. The patient was diagnosed with plasmacytoma. The patient was treated with radiation therapy for plasmacytoma of the bladder and surrounding lymph nodes, and then with daratumumab and dexamethasone for multiple myeloma for one year; however, the patient died because of worsening of multiple myeloma.

[A Case of Primary Renal Angiosarcoma with a Rapidly Worsening Course].

A 69-year-old man presented with left flank pain and underwent a computed tomographic scan, which revealed a large left renal mass of 16×9×5 cm. A left nephrectomy was performed. Pathological analysis revealed that the tumor was consistent with angiosarcoma of the left kidney with a negative surgical margin. He received combination therapy with radiation therapy and four courses of chemotherapy with doxorubicin and ifosfamide. However, he died 10 months after surgery because of pleural dissemination and peritoneal dissemination. Primary renal angiosarcoma is an extremely rare and highly aggressive tumor with a dismal survival rate, and a satisfactory surgical margin is necessary for its successful treatment. If primary renal angiosarcoma is suspected, biopsy may be considered before surgery. Primary renal angiosarcoma treatment with combination therapy of surgery, radiotherapy, and chemotherapy by a specialist multidisciplinary team with experience and expertise in sarcoma is preferable. Development of therapy for angiosarcoma is awaited.

Robot-assisted partial nephrectomy via retroperitoneal approach in a patient with horseshoe kidney.

INTRODUCTION: Horseshoe kidney is a renal fusion anomaly often associated with ectopia, malformation, and vascular changes. Robot-assisted partial nephrectomy is selected for patients with T1a renal cell carcinoma; however, there are few reports of renal cell carcinoma in horseshoe kidney. We present a case of robot-assisted partial nephrectomy via a retroperitoneal approach in a patient with horseshoe kidney with a brief literature review. CASE PRESENTATION: An 84-year-old woman presented with a 2-cm mass in horseshoe kidney. She underwent robot-assisted laparoscopic partial nephrectomy via a retroperitoneal approach. CONCLUSION: The use of robot-assisted laparoscopic partial nephrectomy in patients with horseshoe kidney is very rare, and only four cases have been reported. Because of the unique anatomical structure, surgeons need to consider surgical strategy more carefully, considering tumor location, vascular anatomy, and past history of abdominal surgery.

[A Case of Ureteral Metastasis from Prostate Cancer].

Ureteral metastasis from prostate cancer is rare. The present case report describes an 83-year-old patient with distant metastasis of prostate cancer to the right ureter that caused hydronephrosis. Upon initial examination at our hospital, he presented with a high prostate-specific antigen (PSA) level of 10.0 ng/ml. He was diagnosed with prostate adenocarcinoma, with Gleason score of 10 (5＋5) and clinical staging of cT2aN0M0. Intensity-modulated radiation therapy (IMRT) was performed after 1 year and 7 months of androgen depriation therapy. At 1 year and 4 months after IMRT, PSA increased to 3.068 ng/ml. Computed tomography scan revealed right hydronephrosis and thickening of the right ureter. We could not identify obvious malignant cells on ureteroscopic biopsy, and right nephroureterectomy was performed. Pathological examination revealed ureteral metastasis of prostate cancer. Six months after nephroureterectomy, PSA increased to 3.037 ng/ml. He was diagnosed with castration-resistant prostate cancer and has been treated with enzalutamide.

Detection of von Hippel-Lindau gene mutation in circulating cell-free DNA for clear cell renal cell carcinoma.

The therapeutic landscape of metastatic clear cell renal cell carcinoma (ccRCC) has rapidly expanded, and there is an urgent need to develop noninvasive biomarkers that can select an optimal therapy or evaluate the response in real time. To evaluate the clinical utility of circulating tumor DNA (ctDNA) analysis in ccRCC, we established a highly sensitive assay to detect mutations in von Hippel-Lindau gene (VHL) using a combination of digital PCR and multiplex PCR-based targeted sequencing. The unique assay could detect VHL mutations with a variant allele frequency (VAF) <1.0%. Further, we profiled the mutation status of VHL in 76 cell-free DNA (cfDNA) and 50 tumor tissues from 56 patients with ccRCC using the assay. Thirteen VHL mutations were identified in cfDNA from 12 (21.4%) patients with a median VAF of 0.78% (range, 0.13%-4.20%). Of the 28 patients with VHL mutations in matched tumor tissues, eight (28.6%) also had VHL mutation in cfDNA with a median VAF of 0.47% (range, 0.13%-2.88%). In serial ctDNA analysis from one patient, we confirmed that the VAF of VHL mutation changed consistent with tumor size by radiographic imaging during systemic treatment. In conclusion, VHL mutation in cfDNA was detected only in a small number of patients even using the highly sensitive assay; nevertheless, we showed the potential of ctDNA analysis as a novel biomarker in ccRCC.

[Risk Factors for Recurrence in Patients with Pathological Lymph Node-Positive Prostate Cancer after Extended Lymph Node Dissection in Laparoscopic and Robotic-Assisted Radical Prostatectomy].

From April 2007 to April 2018, we performed lymph node dissection in 305 cases of laparoscopic radical prostatectomy and 202 cases of robot-assisted radical prostatectomy at our hospital, and there were 68 cases with positive lymph node metastasis (pN1). Of these 68 cases, we examined retrospectively 62 cases in which extended lymph node dissection (ELND) was performed. The median number of removed lymph nodes was 25 (interquartile range [IQR] ; 18-34) and the median number of metastatic lymph nodes was 1 (IQR ; 1-3). Postoperative prostate-specific antigen (PSA) recurrence was observed in 40 of the 62 patients. The median time to PSA recurrence was 24 months. After univariate analysis, PSA at initial diagnosis (iPSA) of 10 ng/ml or more, pathological Gleason score (pGS) of 8 or more, total number of lymph node metastases of 2 or more, and positive surgical margin (RM＋) were found to be riskfactors of PSA recurrence. In multivariate analysis, iPSA of 10 ng/ml or more, pGS of 8 or more and RM＋ were independent riskfactors of PSA recurrence (p＜0.05). In the cases without riskfactors such as iPSA≥10, pGS≥8, and RM＋, immediate postoperative adjuvant therapy may be avoided even with pN1.

Rapid recurrence of squamous cell carcinoma at a lymphocele after nephroureterectomy: A rare case report.

INTRODUCTION: Lymphoceles are sometimes formed after pelvic lymph node dissection. However, recurrence at lymphoceles has not been reported previously. Here, we report a case of rapid prognosis of the recurrence at a lymphocele after nephroureterectomy. CASE PRESENTATION: A 78-year-old man underwent retroperitoneoscopic radical nephroureterectomy with pelvic lymphadenectomy for left ureteral urothelial carcinoma. The histopathological diagnosis was high-grade invasive urothelial carcinoma with squamous differentiation. Follow-up computed tomography at 3 months postoperatively showed a lymphocele with a small solid component, in the left pelvic region. At 7 months postoperatively, he presented with severe fatigue, and computed tomography showed a solid tumor had replaced the lymphocele. Computed tomography-guided biopsy was performed and histopathological diagnosis was squamous cell carcinoma. CONCLUSION: This report provides support for possible recurrence at the lymphocele after nephroureterectomy. If lymphocele occurs after surgery for malignant disease, it is recommended to follow up with the possibility of recurrence in the lymphatic cysts in mind.

[Clinical Course and Treatment of Acute Urinary Retention after Robot- Assisted Laparoscopic Radical Prostatectomy : A Single Institution Experience of 11 Cases].

Robot-assisted laparoscopic radical prostatectomy (RARP) is becoming the standard treatment procedure for localized prostate cancer. The main complications associated with RARP include urinary incontinence and sexual dysfunction. In addition, acute urinary retention (AUR) after urethral catheter removal is sometimes seen. Early catheter removal is a risk factor for AUR, and administration of alphablockers before catheter removal reduces the occurrence of AUR. However, the ideal management of AUR after RARP is not known. Here we report the clinical course and treatment after AUR. We performed 279 RARPs at our institution, and AUR developed in 11 cases. In all cases, urination status was improved after placement of a urinary catheter or intermittent catheterization. Later, urethral stricture was seen in 2 out of 11 cases. Ourstudy suggests that when AUR is observed afterRARP, catheterur ination should be initially performed. If urinary retention recurs, a urinary catheter should be placed with administration of alpha-blockers. The catheter is removed after about 3 days, and administration of analgesics is effective for reducing the pain on urination. If urination status is not improved, evaluation of the urethral stricture should be considered.

Black adrenal adenoma causing subclinical Cushing's syndrome complicated with pheochromocytoma.

INTRODUCTION: The development of adrenocortical adenoma and pheochromocytoma within the same adrenal gland is very rare. Furthermore, no reports have described coincident black adrenal adenoma and pheochromocytoma. We herein report a rare case of coincident black adrenal adenoma and pheochromocytoma in the same adrenal gland. CASE PRESENTATION: A 71-year-old Japanese woman was hospitalized because a right adrenal tumor had been incidentally found by computed tomography. She was diagnosed with subclinical Cushing's syndrome and underwent laparoscopic right adrenalectomy. The tumor contained two adrenal nodules. The cut surface of the larger nodule was brownish-black on macroscopic examination. Pathological studies revealed coincident black adrenal adenoma and pheochromocytoma. CONCLUSION: To the best of our knowledge, this is the first report of coincident black adrenal adenoma causing subclinical Cushing's syndrome and pheochromocytoma in the same adrenal gland. The mechanism of this rare scenario is unclear, and further study is necessary.

Functional and genomic characterization of patient-derived xenograft model to study the adaptation to mTORC1 inhibitor in clear cell renal cell carcinoma.

Resistance to the mechanistic target of rapamycin (mTOR) inhibitors, which are a standard treatment for advanced clear cell renal cell carcinoma (ccRCC), eventually develops in most cases. In this study, we established a patient-derived xenograft (PDX) model which acquired resistance to the mTOR inhibitor temsirolimus, and explored the underlying mechanisms of resistance acquisition. Temsirolimus was administered to PDX model mice, and one cohort of PDX models acquired resistance after repeated passages. PDX tumors were genetically analyzed by whole-exome sequencing and detected several genetic alterations specific to resistant tumors. Among them, mutations in ANKRD12 and DNMT1 were already identified in the early passage of a resistant PDX model, and we focused on a DNMT1 mutation as a potential candidate for developing the resistant phenotype. While DNMT1 expression in temsirolimus-resistant tumors was comparable with the control tumors, DNMT enzyme activity was decreased in resistant tumors compared with controls. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated heterozygous knockdown of DNMT1 in the temsirolimus-sensitive ccRCC (786-O) cell line was shown to result in a temsirolimus-resistant phenotype in vitro and in vivo. Integrated gene profiles using methylation and microarray analyses of PDX tumors suggested a global shift for the hypomethylation status including promotor regions, and showed the upregulation of several molecules that regulate the mTOR pathway in temsirolimus-resistant tumors. Present study showed the feasibility of PDX model to explore the mechanisms of mTOR resistance acquisition and suggested that genetic alterations, including that of DNMT1, which alter the methylation status in cancer cells, are one of the potential mechanisms of developing resistance to temsirolimus.

Port-site incisional hernia from an 8-mm robotic trocar following robot-assisted radical cystectomy: Report of a rare case.

INTRODUCTION: Port-site incisional hernia is a rare but well-known complication following a laparoscopic procedure and it may cause severe adverse outcomes, such as intestinal necrosis. Here, we report a rare case of hernia that occurred from an 8-mm trocar after robot-assisted radical cystectomy. CASE PRESENTATION: An 80-year-old woman was diagnosed with cT2bN1M0 bladder cancer. She underwent robot-assisted radical cystectomy. Nine days after surgery, she complained of severe abdominal pain. Computed tomography showed herniation of small intestine. Emergency explorative laparotomy revealed herniation of small intestine from an 8-mm trocar site. A section of the small bowel was necrotic and was resected. CONCLUSION: It is debatable whether we should routinely close the fascia of an 8-mm trocar site. The patient was an elderly woman with multiple major abdominal surgery histories and hernia risk factors. For these patients, fascial closure of the 8-mm trocar site may be indicated.

Prognosis of patients with muscle invasive bladder cancer who are intolerable to receive any anti-cancer treatment.

BACKGROUND: The aim of this retrospective study was to evaluate the prognosis of patients who had been diagnosed with muscle invasive bladder cancer (MIBC) and did not receive anti-cancer treatment because of their physical characteristics. METHODS: Between January 2012 and October 2019, 96 patients were diagnosed with MIBC (cT2-4N0M0) in our institution. Of those, 64 patients had undergone radical cystectomy (RC), 6 had received palliative radiation therapy, and 26 had not received any anti-cancer treatment. We further evaluated the 26 patients who had received no anti-cancer treatment. RESULTS: The no anti-cancer treatment group were significantly older (91 vs. 75 years, p<0.001), comprised fewer men (42% vs. 72%, p=0.015), and had poorer performance status (PS) (mean 2.69 vs. 0.32, p<0.001) than the RC group. The follow periods were 9.5 months and 28.5 months, respectively. Median overall survival (OS) was 12 months in the no anti-cancer treatment group, whereas the median OS was not reached during the study period in the RC group. In univariate analysis, OS was significantly associated with estimated GFR (eGFR) less than 30 mL/min/1.73m2 (median OS, 10 vs 16 months, p = 0.044). Multivariate analysis demonstrated that eGFR was significantly associated with OS (hazards ratio 0.267 [95% CI 0.0858-0.8357]; p = 0.0023). CONCLUSIONS: We evaluated the prognosis of patients with untreated MIBC. Their median OS was 12 months and eGFR was a significant prognostic factor. These findings may help in counseling patients about prognosis if no anti-cancer treatment is given.

[Radical Nephroureterectomy in Octogenarians].

We compared the perioperative and oncological outcomes of radical nephroureterectomy for renal pelvic and ureteral cancer between octogenarians and younger patients. We examined 146 patients attending our hospital from January 2012 to December 2019. The octogenarian group included 48 patients and the control group (younger patients) 98 patients. The median body mass index (BMI) (21.2 vs 23.4 kg/m^2, p<0.001), American Society of Anesthesiologists (ASA) score (p=0.044), preoperative albumin concentration (p=0.04) and operation time (287 vs 314 min, p=0.029) differed significantly between the two groups. However, there were no significant differences in perioperative complications between the two groups. According to multivariable analysis of overall survival, pT3 or higher pathology was a significant indicator of poor prognosis in all patients. In the octogenarian group alone, perioperative transfusion was the only other factor significantly associated with prognosis, whereas anti-CD55 monoclonal antibody (RM1) was a significant factor in the control group. There were significant differences between the octogenarian and control groups with respect to overall survival in those with pT2 or below stage disease (60.2% vs 87.5%, p=0.049), but not to cancer-specific survival (≤pT2 : 73.5% vs 94.2%, p=0.202 ≥pT3 : 72.2% vs 63.8%, p=0. 87). Our findings indicate that nephroureterectomy is a safe and efficient procedure for selected octogenarian patients.