Double Primary Cancer of the Prostate and Urothelial Cancer: A Single Institution Experience.

Prostate cancer (PCa) ranks as the second most common cancer in Japanese males, while bladder cancer (BC) holds the tenth spot. Among double urological cancers, the incidence of synchronous or metachronous BC and PCa is the highest. Reports on upper urinary tract (UUT) urothelial cancer (UC) in PCa patients are limited. Here, we present three cases of metachronous PCa and BC, with subsequent diagnosis of ureteral and renal pelvic cancer during the course of the disease. In the follow-up of patients with urological cancers, it is important to be aware not only of the progression of the initial cancer but also the potential development of a second cancer.

Real-world outcomes of patients with renal cell carcinoma, surgically treated at regional hospitals, based on a prospective long-term survey of the pre-robotic era.

PURPOSE: Renal cancer surgery is frequently performed in small regional hospitals in Japan. This study evaluated the outcomes of renal cancer surgery, comparing results from the pre-robotic surgery era with those obtained with robotic surgery. METHODS: This prospective cohort study was conducted on patients who underwent renal cancer surgery between 2008 and 2013 at 14 hospitals, comprising 13 regional hospitals and a university hospital, registered in the Tohoku Urological Evidence-Based Medicine Study Group. The patients' backgrounds; perioperative data; annual postoperative renal function; and prognostic surveys, performed over a median follow-up period of 10 years were obtained. RESULTS: In 930 surgical cases at the 14 registered hospitals, the 10-year recurrence-free survival rates of cT1a, cT1b, cT2, and cT3 were 0.9326, 0.8501, 0.5786, and 0.5101, respectively. Meanwhile, the 10-year overall survival rates were 0.9612, 0.8662, 0.7505, and 0.7209, respectively. Long-term observation in patients with cT1 showed that vessel involvement and high tumor grade were prognostic factors for recurrence. As a noteworthy fact, radical nephrectomy was performed in 53.3% of patients with cT1a at the regional hospitals. However, even in patients with preoperative chronic kidney disease stage 3, radical nephrectomy was not a prognostic factor of renal function. This indicates that compensatory mechanisms had been working for a long time in many patients who underwent radical nephrectomies without hypertension and preoperative proteinuria, which were predictors of end-stage renal disease. CONCLUSION: Based on a prospective long-term survey of the pre-robotic era, our results suggested no difference of the survival outcomes between the university hospital and regional hospitals. Our study provides baseline data to evaluate the outcomes of renal cancer robotic surgery, performed at regional hospitals.

Clinical response in metastatic castration-resistant prostate cancer (mCRPC) cases treated with supra-physiological doses of testosterone: Bipolar androgen therapy.

Androgen deprivation therapy is a standard of care for metastatic prostate cancer. A paradoxical approach utilizing high doses of testosterone in castration-resistant prostate cancer patients demonstrated clinical responses. Here, we report on four heavily pretreated Japanese patients (including one patient on hemodialysis) successfully treated with supra-physiological doses of testosterone.

Surgery to Avoid Stoma Construction in Invasive Prostate Cancer Extensively Infiltrating the Rectum.

A 61-year-old man tested positive for occult urinary and fecal occult blood and was diagnosed with invasive prostate cancer extensively infiltrating the rectum. After scrutiny, he was diagnosed with cT4N1M0 prostate cancer, and androgen deprivation therapy (ADT) was initiated with a gonadotropin-releasing hormone antagonist. A prostatic rectal resection was performed 6 months after ADT began. The bladder and urethra were anastomosed, the anus was preserved intact, and the sigmoid colon was anastomosed to the anus. A temporary ileostomy was constructed to allow eating and to prevent fistula formation. The ileostomy was closed 5 months post-operation as the patient wanted to live without a stoma. Although the patient died of other disease factors, he remained untreated for 1 year and 7 months post-operation, and his symptoms and disease control were well supported. We report that we were able to perform stoma-free surgical treatment for prostate cancer extensively infiltrating rectum.

[A Case of Upper Urinary Tract Stone in an Infant].

A 238-day-old female infant (122 days of age corrected for prematurity, weight 4,847 g) presented with macrohematuria. She was born at 23 weeks and3 days of pregnancy. Her birth weight was 492 g. Ultrasound revealeda 3×2 mm left ureteral stone and left hydronephrosis of grade I-II in the Society of Fetal Urology (SFU) Classification. She suffered from frequent vomiting and weight loss, and was treated with analgesics and rehydration. Eventually, left hydronephrosis was relieved, and she passed the stone at 271 days of age. The stone was 4×3×2 mm in size, and consisted of 98% calcium oxalate and2% calcium phosphate. No recurrent stone has been found during follow-up.

[Pneumothorax during Pazopanib Therapy in a Patient with Soft Tissue Sarcoma].

Pazopanib is an anti-angiogenic multi-targeted tyrosine kinase inhibitor used for treating soft tissue sarcomas and renal cell carcinoma. Although the occurrence of pneumothorax during pazopanib treatment has been recognized as an adverse event, there have been no reports of pneumothorax in patients treated with pazopanib. Here, we present the case of a 71- year-old male patient who developed pneumothorax during adjuvant pazopanib therapy after surgery for metastasized renal cell carcinoma. Left hilar and mediastinal lymph node swelling was detected in the postoperative surveillance after surgery, and radiological findings showed lymph node metastasis from renal cell carcinoma. Consequently, left upper lobectomy and mediastinal lymph node dissection were performed, and subsequent pathological examination confirmed the aforementioned diagnosis. Pazopanib was administered as an adjuvant therapy. However, the patient developed left pneumothorax on day 101. Although chest tube drainage was performed, massive air leak continued. A surgery was performed to repair the persistent air leak. This case demonstrates that pneumothorax should be recognized as an adverse event of pazopanib.

A case of pheochromocytoma crisis with persistent hypotension successfully managed with vasopressin.

We report the first case of pheochromocytoma crisis with hypotension that was successfully treated with vasopressin. A 64-year-old patient was diagnosed as pheochromocytoma crisis. Although irregularities in circulating plasma volume were corrected by fluid management, hypotension due to vasodilation persisted. Since it was considered to be desirable to use a vasoconstrictor whose action was not mediated via adrenergic receptors, we administrated vasopressin as a non-adrenergic vasopressor. Consequently, sufficient vasoconstriction and pressor effect were achieved without any complications. Finally, the adrenalectomy was performed safely. Vasopressin might be effective and safe treatment for pheochromocytoma crisis with hypotension caused by vasodilation.

[A Case of Testicular Tumor with Multiple Metastasis Leading to Complete Response after Treatment Interruption].

A 39-year-old man experiencing cranial nerve symptoms was referred to our neurosurgery department after a brain tumor was detected on computed tomography (CT) scans at a local hospital. Due to convulsive symptoms, the patient was admitted to our hospital for detailed examination. The patient was diagnosed with right testicular tumor, multiple brain metastases, multiple lung metastases and right kidney metastases, and was transferred to our urology department. Since the testicular tumor was staged as IIIC and identified as poor prognosis by the International Germ Cell Consensus classification (IGCCC), Bleomycin Etoposide Cisplatin (BEP) chemotherapy was initiated prior to surgery. A right high orchiectomy was performed after two courses of BEP chemotherapy. Histopathology revealed mixed germ cell tumors (seminoma and/or embryonal carcinoma+teratoma) along with the following results : ly (-) ; Intratubular Malignant Germ Cells (ITMGC) (+, viable) ; tunica albuginea invasion (-) ; spermatic cord invasion (-) ; tumor size (73× 50×45 mm). Two additional courses of BEP chemotherapy and two courses of Paclitaxel Ifomaide Cisplatin(TIP) chemotherapy were performed successively. The CT revealed metastatic lesions shrinking steadily but the metastatic foci still remained. Since tumor markers were not negative, continuous chemotherapy was considered. However, strong side effects were expected, and treatment was discontinued. Since then,the tumors continued to shrink, and the tumor markers became negative. Currently, the patient maintains complete response and is being followed-up.

Familial testicular germ cell tumors in two brothers.

INTRODUCTION: Two percent of testicular germ cell tumors occur in family clusters. Here, we report metachronous testicular germ cell tumors in two brothers. CASE PRESENTATION: An elder brother was diagnosed at the age of 30 years old and the pathological diagnosis was mixed testicular germ cell tumor. A tumor in the younger brother was suspected during testicular self-examination. It was confirmed by ultrasound examination at the age of 30 years old, 3 years and 6 months after the diagnosis of the testicular tumor in elder brother. The pathological diagnosis was pure seminoma. Both brothers had stage 1 testicular germ cell tumors and no recurrence was observed during the follow-up period of 4 years and 4 months and 10 months, respectively. CONCLUSION: Various histological types of tumor can occur in members of one family. Besides genetic predisposition, shared diet, environmental exposure and other factors can contribute to the familial testicular cancer. Testicular self-examination is recommended for family members of a person with testicular germ cell tumor.

Intraoperative hypothermia is a significant prognostic predictor of radical cystectomy especially for stage II muscle-invasive bladder cancer.

The objective of this study was to evaluate intraoperative hypothermia as a predictor of complication and prognosis in patients with muscle-invasive bladder cancer treated with radical cystectomy.The data of 124 patients treated with radical cystectomy for muscle-invasive bladder cancer in our department, from 2003 to 2016, were retrospectively collected. The patients were divided into 2 groups according to the lowest intraoperative deep body temperature, that is, the hypothermia group (<96.8°F) and the normothermia group (≥96.8°F). Preoperative and intraoperative variables were compared among the 2 groups, and factors associated with complications, recurrences, and survivals were analyzed.Sixty-eight (54.8%) of the 124 patients presented intraoperative hypothermia. There was no significant difference in the patient's characteristics between the 2 groups. Postoperative complications (Clavien-Dindo ≤III) of any types occurred in 15 patients (22.1%) in the hypothermia group, as compared with 8 patients (14.3%) in the normothermia group (P = .27). The hypothermia group had a higher pathologic stage (P = .029) and a higher recurrence rate within 12 months (P = .013), as compared with the normothermia group. Intraoperative hypothermia was an independent prognostic factor for overall survival in all patients (hazard ratio [HR] 2.47; 95% confidence interval [CI], 1.01-2.85; P = .047). When stratified by disease stage, stage II intraoperative hypothermia was an independent prognostic factor for disease-free survival (HR 3.35; 95% CI, 1.27-8.83; P = .015) and overall survival (HR 4.24; 95% CI, 1.38-12.9; P = .011).This study suggests that intraoperative hypothermia could be a significant predictor for recurrence and survival in muscle-invasive bladder cancer treated with radical cystectomy.

[PHEOCHROMOCYTOMA CRISIS WITH MIBG SCINTIGRAPHY NEGATIVE: A CASE REPORT].

We report a case of pheochromocytoma crisis with negative MIBG scintigraphy. A 48-year-old man was admitted for hypertension crisis. Computed tomographic scan revealed a 60 mm right adrenal mass. The MIBG scintigraphy was negative, but we diagnosed pheochromocytoma crisis because of high blood catecholamine levels. We successfully managed the patient's hemodynamics through medical treatment and the patient was able to recover from the crisis. After appropriate preparation, the tumor was removed via laparotomy. SDHB mutation, related to the negative MIBG scintigraphy, was also denied pathologically by immunostaining procedures. Histopathologically, it showed a wide range of necrotic images. So the cause of the crisis was thought to be the release of a large amount of catecholamine from necrotic tumor cells. It was thought that scintigraphy became negative due to the decreased MIBG uptake of tumor cells with extensive necrosis.

Bladder cancer metastasis producing beta-human chorionic gonadotropin, squamous cell carcinoma antigen, granulocyte-colony stimulating factor, and parathyroid hormone-related protein.

INTRODUCTION: In urothelial cancer, several paraneoplastic syndromes can be triggered by the aberrant expression of hormones, growth factors or lymphokines by tumor cells. CASE PRESENTATION: A 71-year-old female patient underwent radical cystectomy for muscle-invasive urothelial cancer. Shortly after the operation, the patient presented with a leukemoid reaction and hypercalcemia. Computed tomography scans revealed a rapidly progressing tumor on the left pelvic side, and serum levels of granulocyte-colony stimulating factor, parathyroid hormone-related protein, and beta human chorionic gonadotropin were elevated. The patient also tested positive for serum squamous cell carcinoma antigen. Hypercalcemia was successfully treated with denosumab. However, the patient's leukocyte counts steadily increased, her condition deteriorated and she passed away. CONCLUSION: To the best of our knowledge, this is the first report of urothelial cancer that tested positive for four tumor markers. The findings support the idea that poorly differentiated bladder carcinomas can ectopically secrete multiple proteins causing pleiotropic paraneoplastic syndromes.

Usefulness of multi-parametric MRI for diagnosis of invasive urothelial cancer: Case reports of bladder and ureteral cancer.

The presence or absence of metastasis has critical implications for therapeutic decision-making in urothelial cancer (UC). Conventional magnetic resonance imaging (MRI) utilizing anatomic T1- and T2-weighted images has modest efficacy in detecting lymph node and distant metastases in UC. However, incorporation of functional techniques including diffusion weighted imaging and dynamic contrast-enhanced imaging, may improve the accuracy of lesion detection and staging. Multiparametric (mp)MRI is widely used in the imaging of prostate and breast cancers, though its usefulness in UC has yet to be fully elucidated. The present study reports on mpMRI in the context of two cases of bladder and ureteral cancer, and imaging results with pathological diagnosis.

[High Orchidectomy and Histopathology to Differentiate Granulomatous Orchitis from Testicular Malignancy : Case Report and Literature Review].

A 59-year-old man presented with pain and swelling of the right scrotum. Magnetic resonance imaging revealed a mass withsignal intensity similar to background on an apparent diffusion coefficient (ADC)-map of the upper region of the right testis. Inflammation was considered, but a testicular tumor could not be ruled out. Right high orchidectomy and histopathological assessment revealed granulomatous orchitis. The cause, clinical course and treatment of rare granulomatous orchitis remain unknown. Granulomatous orchitis and testicular tumor are difficult to discriminate, and high orchidectomy is usually applied along with histopathological assessment to achieve a definitive diagnosis. On the other hand, some patients who were only medically treated for granulomatous orchitis have recovered. We recently found that diffusionweighted imaging and ADC values derived from magnetic resonance images can differentiate testicular tumor from orchitis. We suggest an algorithm for the diagnosis and treatment of granulomatous orchitis considering the present patient and previous reports.

[Two Cases of Urachal Carcinoma Treated by TS-1/CDDP as Adjuvant Chemotherapy].

Case 1 : A 48-year-old man presenting with gross hematuria was suspected to have a tumor located in the bladder dome. He was referred to our department for further examination and treatment. Cystoscopy showed a dome-shaped mass in the supravesical region. Computed tomography and magnetic resonance imaging indicated the possibility of urachal carcinoma and peritoneal dissemination. Therefore, partial cystectomy with urachal resection was performed. The intraoperative findings were disseminated peritoneal nodules and mucus entering the peritoneal cavity from the tumor. On pathological examination, the tumor was classified as a mucinous-type adenocarcinoma, and 6 courses of TS-1/cisplatin (CDDP) therapy were administered to the patient as adjuvant chemotherapy. To date (10 months since the surgery), there has been no disease progression. Case 2 : A 76-year-old woman was referred to our department with a finding of a tumor in the bladder dome during her detailed examination for lung tumors. Cystoscopy showed nodular tumors, indicating lung metastases of the urachal carcinoma. Therefore, partial cystectomy with urachal resection was performed. On pathological examination, the tumor was classified as an enteric-type adenocarcinoma, and 2 courses of TS-1/CDDP therapy were administered to the patient as adjuvant chemotherapy. However, due to the development of marked bone marrow depression, the drugs had to be discontinued. Nonetheless, the lung metastases markedly diminished in size. To date (9 months since the discontinuation of chemotherapy), there has been no disease progression.

Updated recommendation on molecular-targeted therapy for metastatic renal cell cancer.

Molecular-targeted therapy was recommended for the systemic therapy of renal cell cancer (RCC) in the RCC guidelines, but these guidelines do not address the order of administration of the multiple presently available agents. There are several aspects that remain unknown regarding the optimal administration order and combination of molecular-targeted drugs. Until the optimal treatment sequence is determined by clinical trials, treatment individualization is required for each patient based on patient and disease characteristics. We herein investigate 12 cases of RCC patients who received axitinib. Axitinib was used as the first-line drug in 4 cases, second-line in 5 cases, third-line in 1 case and as a fourth-line drug in 2 cases. Partial response (PR) was observed in 4 cases (30%) and stable disease in 4 cases (30%) during axitinib treatment, with an overall response rate of 60%. The duration of PR ranged from 6 to 19 months. Based on our cases, axitinib exhibited reasonable therapeutic efficacy as first- as well as second-line treatment. However, more cases are required to draw firm conclusions.

Treatment sequence in castration-resistant prostate cancer: A retrospective study in the new anti-androgen era.

In recent years, abiraterone acetate (AA) and enzalutamide (EZL) have become available for the treatment of cancer. Prior clinical trials have demonstrated the benefits of these agents in males with castration-resistant prostate cancer (CRPC). The optimal sequencing of available therapies in the context of efficacy and known cross-resistance remains uncertain. Based on the mechanisms of action and accessible clinical data, AA and EZL may be indicated for the early stages of prostate cancer. Until clinical trials are conducted to determine the best treatment sequence, individualized therapy is required for each patient based on the clinicopathological characteristics. In the present study, 46 sequential patients (median age: 77, range 59-89; median serum PSA level: 56 ng/ml, range 1.5-3,211) with CRPC treated with EZL (160 mg/day) were retrospectively analyzed between June 2014 and July 2015 at the following institutions: Yamagata Prefectural Central Hospital (Yamagata, Japan); Yamagata Tokushukai Hospital (Yamagata, Japan); Ishinomaki Red Cross Hospital (Ishinomaki, Japan); Kan-etsu Hospital (Tsurugashima, Japan); Niigata Cancer Center Hospital (Niigata, Japan); Sakado Central Hospital (Sakado, Japan). A total of 18 patients were pre-treated with Docetaxel (DOC) and 28 patients were DOC-naïve. Once EZL therapy was initiated, increases in prostate specific antigen (PSA) levels were observed in 3/18 patients (17%) pre-treated with DOC and in 6/20 (30%) who were DOC-naïve. In total, 8/28 DOC-naïve patients were treated with AA without EZL. An increase in the PSA level was observed in only 1/8 (12%) cases following AA treatment in the DOC-naïve group. It was demonstrated that AA had a better efficacy in DOC-naïve patients. The efficacy of EZL was limited in AA-pre-treated patients following DOC administration.

Efficacy of early ureteral ligation on prevention of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma: a prospective single-arm multicenter clinical trial.

OBJECTIVE: The rate of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma is high. Seeding upper urinary tract urothelial carcinoma cells onto the damaged bladder wall is considered to be one of the causes of intravesical recurrence after radical nephroureterectomy. We evaluated the utility of early ureteral ligation in preventing the intravesical recurrence. METHODS: This prospective single-arm clinical trial included patients who underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma in the Tohoku Urological Evidence-Based Medicine Study Group between 2012 and 2013. Early ureteral ligation was defined as ligation of the ureter as quickly as possible after expanding the retroperitoneal space. A historical control was extracted from 454 patients who underwent radical nephroureterectomy in the same group, using propensity score-matched analysis. Intravesical recurrence-free survival rates were analyzed using Kaplan-Meier curves. Factors predicting intravesical recurrence were assessed using multivariate analyses. RESULTS: Seventy-four patients underwent early ureteral ligation. Seventeen (23%) patients had intravesical recurrence with a median follow-up period of 24 months. The 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 81% and 76%, and in the control group 75% and 63%, respectively (P = 0.160). In patients with renal pelvic cancer, the 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 89% and 86%, but in the control group 74% and 64%, respectively (P = 0.025). However, intravesical recurrence-free survival rates were similar in patients with ureteral cancer. Multivariate analyses of a subset of patients with renal pelvic cancer identified early ureteral ligation as an independent predictor of intravesical recurrence. CONCLUSIONS: Early ureteral ligation decreases the rate of intravesical recurrence after radical nephroureterectomy in patients with renal pelvic cancer. Thus, early ureteral ligation might help in prevention of intravesical recurrence for renal pelvic cancer.

[LONG-TERM OUTCOME IN PATIENTS WITH RETROPERITONEAL LIPOSARCOMA, A SINGLE INSTITUTION STUDY].

(Objectives) To evaluate the outcomes of patients who were surgically treated for retroperitoneal liposarcoma in our hospital from February 2002 to August 2015. (Methods) Fifteen patients were surgically treated for retroperitoneal liposarcoma in our hospital during the study period. All patients were diagnosed with liposarcoma on pathological examination. The mean follow-up period was 46.7 months (range, 1-126 months). (Results) There was no difference in the sex distribution of the patients (7 men and 8 women). The median age was 67 years (range, 33-78 years). The median tumor diameter was 24 cm (range, 7.5-45 cm) and the median tumor weight was 1,959 g (range, 545-15,400 g). One patient's operation was unsuccessful, with incomplete tumor resection. The surgical margin was positive in two patients. The 5- and 10-year survival rates were 67% and 50%, respectively. There was a significant difference in the survival rate between complete resection and incomplete resection, including surgical margin-positive patients (p=0.0019). Moreover, there was a significant difference in the recurrence-free rate between complete resection and surgical margin-positive patients (p=0.013). There was no significant difference according to whether removal of the tumor with adjacent viscera or removal of the tumor only had been performed (p=0.09 and 0.90, respectively). (Conclusions) Surgery is the mainstay of treatment for retroperitoneal liposarcoma, and complete resection is necessary.