[A Case of Long-Term Survival Following Multidisciplinary Therapy for Small Intestinal Metastasis of Bladder Cancer].

The patient was a 70-year-old man who underwent transurethral resection of a bladder tumor. The pathological diagnosis was urothelial carcinoma (UC) with sarcomatoid variant, ≧pT2. After neoadjuvant chemotherapy using gemcitabine and cisplatin (GC), radical cystectomy was performed. The histopathological diagnosis was no tumor remnant (ypT0ypN0). Seven months later, the patient underwent an emergency partial ileectomy for ileal occlusion, after sudden complaints of vomiting and abdominal pain and fullness. Postoperatively, two cycles of adjuvant GC chemotherapy were administered. Approximately 10 months after ileal metastasis, a mesenteric tumor appeared. After seven cycles of methotrexate/epirubicin/nedaplatin and 32 cycles of pembrolizumab therapy, the mesentery was resected. The pathological diagnosis was UC with sarcomatoid variant. No recurrence was noted for 2 years after resection of the mesentery.

[Malignant Peritoneal Mesothelioma Diagnosed as an Inguinal Mass : A Case Report].

Malignant peritoneal mesothelioma is generally characterized by chief complaints such as abdominal mass and abdominal pain. We report a case of malignant peritoneal mesothelioma diagnosed as an inguinal mass. A 69-year-old man was referred to our hospital complaining of abdominal distension and swelling in the right inguinal region. Abdominal/pelvic contrast-enhanced computed tomography revealed a 22 cm tumor from the right inguinal canal to the peritoneal cavity and a large amount of ascites. Because imaging analyses revealed no metastasis, we planned tumor resection. We resected the tumor with the peritoneum and right testis and sampled some nodules in the mesentery. Histopathological examination of the tumor led to the diagnosis of epithelial malignant mesothelioma. Adhering to chemotherapy guidelines for pleural malignant mesothelioma, six courses of pemetrexed and cisplatin combination chemotherapy were performed. He is alive with no evidence of new local tumor or nodules in the mesentery 1 year postoperatively.

[A CASE REPORT OF FUNGUS BALL FOUND DURING TRANSURETHRAL URETEROLITHOTOMY].

Herein we report the confirmation of fungus balls (circular collections of C.tropicalis) during a transurethral ureterolithotomy, which is as far as we know the first reported instance. A-61-year old man was referred to the urology department with bilateral ureteral calculi. Initially a transurethral ureterolithotomy was attempted but residual stones existed. During the second operation, we found numerous white fluffy material in the renal pelvis. Because of them, we were unable to have a clear field of vision to complete operation. During the third operation, we found the fungus balls again and cultured them. Cultures yielded C.tropicalis.

[NON-SPECIFIC GRANULOMATOUS PROSTATITIS: A CASE REPORT].

We report non-specific granulomatous prostatitis in a 58-year-old man who visited a Urology clinic with fever and dysuria. Digital rectal examination revealed prostatic tenderness, and laboratory examination of the urinary sediment revealed pyuria. Thus, he was diagnosed with acute bacterial prostatitis and treated with antibiotics. He remained symptomatic despite treatment; therefore, he was referred to our hospital. A second digital rectal examination (performed at our hospital) revealed stony hard nodules in the prostate and an irregularity of its surface. Moreover, magnetic resonance imaging (MRI) suggested a prostate cancer. We performed a transperineal needle biopsy, which revealed only non-specific inflammatory cells without any evidence of neoplasm in the specimen. Therefore, a definitive diagnosis could not be established. Nevertheless, he continued to show a high index of suspicion for prostatic malignancy based on his clinical findings. Therefore, we performed a transurethral resection of the prostate and a transrectal biopsy to obtain more specimens. Microscopic findings revealed granulomatous prostatitis without any evidence of prostate carcinoma. Notably, an MRI demonstrated remarkable shrinkage of the prostate 3 months after the diagnosis. Non-specific granulomatous prostatitis is a rare inflammatory disease. Because it is difficult to differentiate this disease from prostatic neoplasms based on clinical findings or imaging modalities such as MRI, a few reports have described performing a radical prostatectomy in patients. This disease usually demonstrates a good prognosis as was noted in our patient. We conclude that establishing a preoperative histopathological diagnosis is important to avoid invasive procedures.

Primary amelanotic malignant melanoma of the male urethra with inguinal lymph node metastasis successfully controlled by nivolumab: A case report.

We report a rare case of primary amelanotic malignant melanoma of the male urethra. A 65-year-old man with a urethral mass was referred to our hospital. A pathological diagnosis of a biopsy specimen revealed malignant melanoma. Thereafter, the patient underwent partial penectomy. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received DAV-Feron in an adjuvant setting; however, PET-CT revealed multiple metastasis. After receiving more than 10 cycles of nivolumab, the accumulation of FDG was no longer observed on PET-CT. The patient is currently free from recurrence at 20 months after nivolumab treatment.

[GIANT BLADDER CALCULI TREATED WITH SINGLE-STAGE SIMULTANEOUS PERCUTANEOUS SUPRAPUBIC AND TRANSURETHRAL CYSTOLITHOTRIPSY: A CASE REPORT].

An 82-year-old man presented with lower abdominal pain and general malaise. Noncontrast computed tomography revealed a remarkably enlarged prostate and a full bladder with a giant stone 80 mm in diameter causing bilateral hydroureteronephrosis. Laboratory data demonstrated systemic inflammation and renal dysfunction with hyperkalemia. Acute postrenal dysfunction caused by urinary retention was diagnosed. A urethral catheter was inserted and emergent dialysis was initiated. After renal function recovered, we performed lithotripsy for the urinary bladder calculi. To achieve stone free status with a single-stage procedure, we performed simultaneous percutaneous suprapubic and transurethral cystolithotripsy. The procedure was successfully performed without significant complications.The patient was discharged 9 days after surgery, although clean intermittent catheterization was required.Giant bladder calculi are often treated with cystolithotomy because transurethral cystolithotripsy requires time to remove all fragments. In this case, we achieved stone free status in acceptable operative time by performing simultaneous percutaneous suprapubic and transurethral cystolithotripsy. In conclusion, the endourological management is an effective treatment choice, even in a case with a giant bladder calculus.

The utility and limitations of contrast-enhanced ultrasound for the diagnosis and treatment of prostate cancer.

In association with the widespread use of prostate specific antigen (PSA) screening, the numbers of men identified with early-stage prostate cancer (PCa) are increasing in the developed countries, including Japan. However, the accurate localization of PCa lesions in diagnostic imaging is still difficult because PCa has a tendency to be multifocal in the prostate gland. Contrast-enhanced ultrasound (CEUS) improves the detection of PCa by visualizing cancerous lesions in order to target a needle biopsy. CEUS has the potential to enable not only accurate diagnoses but also novel treatments such as focal therapy. The combination of CEUS and other modalities is expected to improve the diagnosis of PCa and its treatment.

Validation of a patient-specific simulator for laparoscopic renal surgery.

OBJECTIVES: To describe and to validate a novel patient-specific virtual-reality based simulator for laparoscopic surgery. METHODS: Three surgeons carried out 13 preoperative simulations at Yokohama City University Hospital, Yokohama, Kanagawa, Japan, from 2011 to 2012. The procedures included seven nephrectomies, four partial nephrectomies and two pyeloplasties. We evaluated whether the anatomies reproduced by the simulator matched those encountered during the actual operations. Furthermore, the surgeons were asked to use visual analog scales (from 1 to 5; higher scores are better) to evaluate the anatomical integrity and utility of the simulations, and their intraoperative confidence during the subsequent surgical procedures. RESULTS: The simulator reproduced the patients' anatomies almost perfectly. Only a few minor mistakes were identified. Regarding the surgeons' evaluations of the system, the mean scores for the anatomical integrity and utility of the simulations, and the surgeons' intraoperative confidence were 3.4, 4.2 and 4.1, respectively. In all 13 cases, the surgeons were able to carry out preoperative training with ease, and they stated that the simulator was useful for producing preoperative images. CONCLUSIONS: A patient-specific simulator for laparoscopic renal surgery has been successfully developed. This system correctly reproduces anatomical structures, and it seems to be a useful preoperative training tool.

Ten-year outcomes of I¹²5 low-dose-rate brachytherapy for clinically localized prostate cancer: a single-institution experience in Japan.

PURPOSE: To report 10-year outcomes of patients treated with I(125) low-dose-rate brachytherapy (BT) for clinically localized prostate cancer. METHODS: A group of 1,060 patients with clinically localized prostate cancer treated with I(125) BT between March 2004 and December 2013 at the Yokohama City University Hospital were identified. The records of 743 patients with a minimum of 2 years of follow-up were reviewed. Cohorts were categorized according to National Comprehensive Cancer Network risk classification, and biochemical outcomes plus overall survival were examined. Biochemical failure was defined as nadir prostate-specific antigen (PSA) level + 2 ng/mL. Univariate and multivariate Cox proportional hazards were used to determine predictors of biochemical failure. RESULTS: A total of 743 patients met the criteria with a median follow-up of 54.6 months (range 24-114 months). The median age was 70 years (range 48-83). The 5- and 7-year overall survival rates were 98.8 and 97.6 %, and the 5- and 7-year biochemical failure-free survival rates were 92.6 and 91.0 %, respectively. With regard to distant metastases and survival, the 5- and 7-year metastatic-free survival rates were 98.2 and 95.9 %, respectively. A multivariate analysis revealed that initial PSA (p = 0.005; HR 1.097, 95 % CI 1.028-1.170), age (p = 0.001; HR 0.931, 95 % CI 0.893-0.971), and T stage (T1c vs. T2a) (p = 0.002; HR2.417, 95 % CI 1.319-4.267) were independent predictors of biochemical failure. CONCLUSIONS: I(125) low-dose-rate BT resulted in excellent survival and morbidity outcomes for localized prostate cancer at a single institution. Further studies are needed to obtain long-term outcomes.

The early response of renal cell carcinoma to tyrosine kinase inhibitors evaluated by FDG PET/CT was not influenced by metastatic organ.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for advanced renal cell carcinoma (RCC), but it has been unclear whether the antitumor effect of TKIs depends on the organ where the RCC metastasis is located. We previously reported that the FDG accumulation assessed by FDG PET/CT, was a powerful index for evaluating the biological response to TKI. In this study we investigated the differences in FDG accumulation and the response to TKI as assessed by FDG PET/CT among various organs where RCC were located. METHODS: A total of 48 patients with advanced RCC treated with a TKI (25 with sunitinib and 23 with sorafenib) were evaluated by FDG PET/CT before and at 1 month after a TKI treatment initiation. The maximum standardized uptake value (SUVmax) of all RCC lesions were measured and analyzed. RESULTS: We evaluated 190 RCC lesions. The pretreatment SUVmax values (mean ± SD) were as follows: in the 49 lung metastases, 4.1 ± 3.3; in the 40 bone metastases, 5.4 ± 1.6; in the 37 lymph node metastases, 6.7 ± 2.7; in the 29 abdominal parenchymal organ metastases, 6.6 ± 2.7; in the 26 muscle or soft tissue metastases, 4.4 ± 2.6; and in the nine primary lesions, 8.9 ± 3.9. Significant differences in the SUVmax were revealed between metastases and primary lesions (p = 0.006) and between lung metastases and non-lung metastases (p < 0.001). The SUVmax change ratios at 1 month after TKI treatment started were -14.2 ± 48.4% in the lung metastases, -10.4 ± 23.3% in the bone metastases, -9.3 ± 47.4% in the lymph node metastases, -24.5 ± 41.7% in the abdominal parenchymal organ metastases, -10.6 ± 47.4% in the muscle or soft tissue metastases, and -24.2 ± 18.3% in the primary lesions. There was no significant difference among the organs (p = 0.531). CONCLUSIONS: The decrease ratio of FDG accumulation of RCC lesions evaluated by PET/CT at 1 month after TKI treatment initiation was not influenced by the organs where the RCC metastasis was located. This result suggests that TKIs can be used to treat patients with advanced RCC regardless of the metastatic site.

Tumor signatures of PTHLH overexpression, high serum calcium, and poor prognosis were observed exclusively in clear cell but not non clear cell renal carcinomas.

High serum calcium (Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone (PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma (RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization (WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset (n = 683) and/or as of recurrence (n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival (OS) and disease-free survival (DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs.

Evaluation and validation of the core lower urinary tract symptom score as an outcome assessment tool for the treatment of benign prostatic hyperplasia: effects of the α1-adrenoreceptor antagonist silodosin.

We investigated the Core Lower Urinary Tract Symptom Score as an outcome assessment tool for the treatment of lower urinary tract symptoms using silodosin. In addition, the ability of the Core Lower Urinary Tract Symptom Score to detect overactive bladder in male patients with lower urinary tract symptoms was examined. The present study included 241 males with benign prostatic hyperplasia treated at 31 medical facilities between June 2009 and December 2010. All patients were given silodosin, and the effects of silodosin intake were measured using four questionnaires: the Core Lower Urinary Tract Symptom Score, International Prostate Symptom Score, Overactive Bladder Symptom Score and Quality-of-Life index. The efficacy of silodosin for treating lower urinary tract symptoms was validated according to the total scores of all four questionnaires weighted equally (P < 0.05). Spearman's ρ among the Core Lower Urinary Tract Symptom Score, International Prostate Symptom Score and Overactive Bladder Symptom Score showed a mild-high correlation. However, the correlation between the baseline values of the Core Lower Urinary Tract Symptom Score and Quality-of-Life index was low in the groups with benign prostatic hyperplasia (ρ = 0.314) and benign prostatic hyperplasia/overactive bladder (ρ = 0.244). Our findings showed the Core Lower Urinary Tract Symptom Score, both its total score and each subscore, is able to show the efficacy of silodosin, similar to other questionnaires. The Core Lower Urinary Tract Symptom Score is also useful for identifying overactive bladder symptoms in patients with benign prostatic hyperplasia. As the Core Lower Urinary Tract Symptom Score does not correlate well with the Quality-of-Life index, these two questionnaires might be better used in combination to assess treatment outcomes.

[A case of metastatic renal cell carcinoma associated with Birt-Hogg-Dubé syndrome treated with molecular-targeting agents].

A 56-year-old man was referred to our clinic because of left lumbar pain and a left solitary renal tumor (9. 8 cm in diameter) and bilateral pulmonary metastases detected by computed tomographic scan. Pathologic diagnosis following open radical nephrectomy was papillary renal cell carcinoma, G2, pT2aN0M1. Subsequently, the patient was sequentially treated with interleukin-2 (3 months (mo), progressive disease (PD)), interferon-alpha (3 mo, PD), and oral S-1 as a clinical trial (28 mo, PD). Because of skin fibrofolliculomas, pulmonary cysts, and spontaneous pneumothorax history, Birt-Hogg-Dubé (BHD) syndrome was suspected during the treatment course, despite his having no family history of the disease. Subsequent genetic testing revealed a FLCN germline mutation (c. 1285dupC). He was started on molecular-targeting therapies sequentially, i.e., sorafenib (1 mo, PD), sunitinib (4 mo, PD), and everolimus (7 mo, PD). The patient died of progressive disease at 78 mo from the initial nephrectomy and 30 mo from the start of targeted agents. Loss of FLCN function has been shown to result in the upregulation of the PI3K/mTORC1 pathway in both in vitro experiments and in vivo FLCN knockout mice models. Despite its use as the sixth-line systematic treatment, the mTOR inhibitor everolimus exhibited a relatively long-term effect as compared with the previously used tyrosine kinase inhibitors and in contrast to the results in the RECORD-1 clinical trial. This finding may provide insight into the molecular mechanism of BHDassociated renal tumors.

[A case of myocardiac metastasis of clear cell renal carcinoma successfully treated with sunitinib].

A 65-year-old male was referred to our clinic from orthopedics because his right gastrocnemius muscle tumor was diagnosed as a metastatic renal cell carcinoma (RCC) with clear cell/spindle cell morphology. He had right nephrectomy for RCC 18 years previously. At 17 months following the first visit to our clinic, brain, lung and right gluteus medius muscle metastases were identified on positron emission tomography computed tomography (PET-CT). The echocardiogram for the evaluation of his heart function incidentally revealed a 3 cm nodular lesion in the right ventricular wall suggesting myocardiac metastasis. He started to take sunitinib at a standard dose of 50 mg/day. A subsequent echocardiogram during the 2nd cycle of sunitinib showed complete disappearance of the myocardiac metastasis. After the 2nd cycle, PET-CT revealed a partial response (PR) for the other metastases. He received 8 cycles of sunitinib. The best response was PR, and progression-free survival was 6 months. After that, he took everolimus for 7 months. Although the myocardiac metastasis continued to show a complete response during the treatment course, he died of progressive lung metastases at 21 months following the administration of sunitinib. Diagnosis of myocardiac metastasis of RCC during the treatment course as well as its successful treatment with molecular targeting agents has rarely been reported.

Early ultrasonographic evaluation of tumor thrombus level during sunitinib therapy for renal cell carcinoma.

A 72-year-old man presenting with a 14-cm left renal mass, an inferior vena cava (IVC) tumor thrombus, and pulmonary metastases underwent renal mass biopsy that revealed clear cell renal cell carcinoma. Because of metastases and the extent of the tumor thrombus, sunitinib was administered, which resulted in a marked reduction in the tumor thrombus (from level III to level II after 11 weeks of treatment). Ultrasonography, preceding computed tomography, showed a slight shrinkage of the tumor thrombus level in the first 2 weeks. Therefore, ultrasound may be advantageous to monitor the IVC tumor thrombus level during the early phase of targeted therapy.

Usefulness of perflubutane microbubble-enhanced ultrasound in imaging and detection of prostate cancer: phase II multicenter clinical trial.

PURPOSE: To explore the possibility of targeted biopsy (TBx) using transrectal ultrasound (US) with perflubutane microbubbles, we studied the findings of different cancerous tissue imaging modalities and evaluated needle biopsy in prostate cancer (PCa) using contrast-enhanced US (CEUS) in a multicenter clinical trial. METHODS: Seventy-one patients undergoing prostate biopsy received intravenous injection of perflubutane microbubbles (Sonazoid(®)). We evaluated and compared images obtained by CEUS. The safety observation period was 2 days after contrast administration. RESULTS: Among the 30 patients with cancer, one or more sites with findings suggestive of cancer in CEUS were detected in 23 patients (32.4%) by TBx. Although 22 patients had positive cores of cancer by systematic biopsy (SBx), 8 patients had positive cores of cancer in TBx alone (11.3%). There was a significant difference in cancer detection rate by TBx between two cohorts with PSA < 10 ng/mL (22.9%) and PSA ≥ 10 ng/mL (52.2%) (P < 0.02). Close observation of various CEUS findings with Sonazoid(®) enabled targeting of cancerous areas, and consequently, a significant difference (P < 0.05) in the detection rate of cancer was recognized in the transition zone (TZ): SBx; 21/120 (17.5%) and TBx; 17/55 (30.9%). The incidence of adverse events was 6.7% and that of adverse reactions was 4%. CONCLUSIONS: CEUS with Sonazoid(®) improved the detection rate of PCa by visualizing cancerous lesions. More detailed examination of CEUS images provided efficient characterization especially in the TZ area. TBx according to this procedure is expected to enable a lower number of biopsies and more accurate diagnosis of PCa.

Laparoscopic nephroureterectomy for adult patient with primary obstructive megaureter.

A 29-year-old female with a complaint of abdominal distension was referred to our hospital. She had a history of being treated for pyelonephritis three times. By computed tomography and retrograde pyelography, she was diagnosed with adult left primary megaureter. Her left renal function was severely deteriorated. She hoped for surgical intervention before becoming pregnant. Laparoscopic nephroureterectomy for megaureters seems to be difficult due to the large size. By sucking urine from an inserted ureteral catheter and setting trocar positions, we successfully performed laparoscopic nephroureterectomy for megaureter.

Comparison of the loss of renal function after cold ischemia open partial nephrectomy, warm ischemia laparoscopic partial nephrectomy and laparoscopic partial nephrectomy using microwave coagulation.

PURPOSE: Nephron sparing surgery is an effective surgical option in patients with renal cell carcinoma. Laparoscopic partial nephrectomy involves clamping and unclamping techniques of the renal vasculature. This study compared the postoperative renal function of partial nephrectomy using an estimation of the glomerular filtration rate (eGFR) for a Japanese population in 3 procedures; open partial nephrectomy in cold ischemia (OPN), laparoscopic partial nephrectomy in warm ischemia (LPN), and microwave coagulation using laparoscopic partial nephrectomy without ischemia (MLPN). MATERIALS AND METHODS: A total of 57 patients underwent partial nephrectomy in Yokohama City University Hospital from July 2002 to July 2008. 18 of these patients underwent OPN, 17 patients received MLPN, and 22 patients had LPN. The renal function evaluation included eGFR, as recommended by The Japanese Society of Nephrology. RESULTS: There was no significant difference between the 3 groups in the reduction of eGFR. eGFR loss in the OPN group was significantly higher in patients that experienced over 20 minutes of ischemia time. eGFR loss in LPN group was significantly higher in patients that experienced over 30 minutes of ischemia time. CONCLUSION: This study showed that all 3 procedures for small renal tumor resection were safe and effective for preserving postoperative renal function.

Presurgical downstaging of vena caval tumor thrombus in advanced clear cell renal cell carcinoma using temsirolimus.

A 63-year-old man presenting with a 7.2-cm right renal mass, an inferior vena cava tumor thrombus, and pulmonary metastases underwent renal mass biopsy that revealed clear cell renal cell carcinoma. Temsirolimus (25 mg weekly) was given because of the extent of the disease and poor performance status, which resulted in a marked reduction in the tumor thrombus (from level III to level I) after 20 weeks of treatment. Subsequently, radical nephrectomy and tumor thrombectomy were carried out. Final pathological analysis confirmed the diagnosis of high-grade clear cell carcinoma (pT4N0M1). One year after initiation of temsirolimus therapy, the patient remained alive despite the presence of disease.

Laparoscopic nephroureterectomy in renal pelvic urothelial carcinoma with situs inversus totalis: preoperative training using a patient-specific simulator.

OBJECTIVE: To report the first case of preoperative training using a patient-specific laparoscopic simulator for a patient with situs inversus totalis (SIT). MATERIALS AND METHODS: A 61-year-old man presented with gross hematuria and was diagnosed with right renal pelvic cancer T1N0M0. A whole-body computed tomography (CT) scan also revealed his organs showed a mirror image, with left-to-right reversal, and SIT was diagnosed. A laparoscopic right nephroureterectomy through a retroperitoneal approach was scheduled. Before the operation, we practiced the operation using a patient-specific laparoscopic surgical simulator that we have developed. The patient's CT data were used to reproduce the retroperitoneal space in the simulator, and the surgeon trained and became familiar with his SIT anatomy. RESULTS: The insufflation time was 182 minutes, and the estimated blood loss was 50 mL. The surgeon was able to complete the right retroperitoneoscopic nephroureterectomy safely, without any problems. CONCLUSION: To our knowledge, we report the first case of preoperative training using a patient-specific simulator for a patient with SIT. Preoperative training was useful, and retroperitoneoscopic nephroureterectomy was successfully performed in a patient with renal pelvic urothelial carcinoma and SIT.