Risk stratification for bladder recurrence of upper urinary tract urothelial carcinoma after radical nephroureterectomy.

OBJECTIVES: To identify risk factors and develop a model for predicting recurrence of upper urinary tract urothelial carcinoma (UTUC) in the bladder in patients without a history of bladder cancer after radical nephroureterectomy (RNU). PATIENTS AND METHODS: We retrospectively reviewed 754 patients with UTUC without prior or concurrent bladder cancer or distant metastasis at 13 institutions in Japan. Univariate and multivariate Fine and Gray competing risks proportional hazards models were used to examine the cumulative incidence of bladder recurrence of UTUC. A risk stratification model and a nomogram were constructed. Two prediction models were compared using the concordance index (c-index) focusing on predictive accuracy and decision-curve analysis, which indicate whether a model is appropriate for decision-making and determining subsequent patient prognosis. RESULTS: The cumulative incidence rates of bladder UTUC recurrence at 1 and 5 years were 15 and 29%, respectively; the median time to bladder UTUC recurrence was 10 months. Multivariate analysis showed that papillary tumour architecture, absence of lymphovascular invasion and higher pathological T stage were both predictive factors for bladder cancer recurrence. The predictive accuracy of the risk stratification model and the nomogram for bladder cancer recurrence were not different (c-index: 0.60 and 0.62). According to the decision-curve analysis, the risk stratification was an acceptable model because the net benefit of the risk stratification was equivalent to that of the nomogram. The overall cumulative incidence rates of bladder cancer 5 years after RNU were 10, 26 and 44% in the low-, intermediate- and high-risk groups, respectively. CONCLUSIONS: We identified risk factors and developed a risk stratification model for UTUC recurrence in the bladder after RNU. This model could be used to provide both an individualised strategy to prevent recurrence and a risk-stratified surveillance protocol.

[Efficacy of Sunitinib Rechallenge in Metastatic Renal Cell Carcinoma : A Case Report].

A 67-year-old woman underwent radical nephrectomy (clear cell carcinoma, G2＞3, pT2b) for left renal cancer with pulmonary metastasis. After interferon-α treatment for 7 months, right iliac bone metastasis occurred. Pulmonary and right ileac bone metastases became larger after 4 months of first sunitinib administration. Replacement by everolimus treatment was not effective. After 6 months of sunitinib rechallenge therapy, pulmonary metastasis disappeared and right ileac bone metastasis became smaller. However, 1 month later, right costal and left femoral metastases occurred. She was kept on sunitinib treatment, and there were no changes in these metastases for 1 year. However, it was difficult to continue sunitinib treatment because of side effects, resulting in growth of metastases. Costal and femoral metastases showed a partial response to axtinib treatment given thereafter. Tyrosine kinase inhibitor rechallenge therapy had potential benefits and was tolerated in selected metastatic renal cell carcinoma patients.

Equivalent survival and improved preservation of renal function after distal ureterectomy compared with nephroureterectomy in patients with urothelial carcinoma of the distal ureter: a propensity score-matched multicenter study.

OBJECTIVES: To investigate the oncological and functional outcome of distal ureterectomy compared with nephroureterectomy in the management of distal ureteral urothelial carcinoma. METHODS: Using a database including upper urinary tract urothelial carcinoma patients (n = 1329), 282 patients were identified with urothelial carcinoma localized in the distal ureter on clinical evaluation. To adjust for potential baseline differences between groups, 43 patients undergoing distal ureterectomy were matched with 86 patients undergoing nephroureterectomy using propensity scoring. Cox regression models tested the effect of surgery type on recurrence-free survival and cancer-specific survival. Estimated glomerular filtration rate was measured before and after surgery. RESULTS: The median follow-up period was 50 months. There were no significant differences in 5-year recurrence-free survival and cancer-specific survival rates between the distal ureterectomy and nephroureterectomy groups (P = 0.22 and P = 0.70, respectively). Multivariate analysis showed that surgery type was not associated with recurrence-free survival and cancer-specific survival (P = 0.90 and P = 0.28, respectively). In the subanalysis, recurrence-free survival and cancer-specific survival in the distal ureterectomy group were equivalent to those of the nephroureterectomy group in both pTa-1 and pT2-4 patients. Renal function was better preserved in the distal ureterectomy group than in the nephroureterectomy group (rate of change in estimated glomerular filtration rate 2% vs -20%; P < 0.001). CONCLUSIONS: The oncological outcome of distal ureterectomy is comparable with that of nephroureterectomy in distal ureteral urothelial carcinoma patients, and distal ureterectomy provides better preservation of renal function. Distal ureterectomy would be feasible for carefully selected patients with distal ureteral urothelial carcinoma.

[Long survival in a patient with advanced ureteral carcinoma treated with TIN regimen (paclitaxel, ifosfamide, nedaplatin) and radiotherapy : a case report].

A 69-year-old man diagnosed with right ureteral carcinoma pT3N0M1 (PUL) underwent nephroureterectomy. He was treated with MVAC chemotherapy (methotrexate, vinblastin, adriamycin, cisplatin), but local recurrence and right pelvic lymph node metastasis occurred. Radiotherapy to both metastatic lesions was well tolerated, but the pulmonary metastases increased. After treatment with TIN chemotherapy (paclitaxel, ifosfamide and nedaplatin), pulmonary metastases almost disappeared. He was treated with radiotherapy to remaining pulmonary metastasis. Now 7 years after operation, pulmonary metastasis appears to have diminished.

[Complete remission by sorafenib for local reccurence of renal cell carcinoma with a tempraly elevation of C-reactive protein: a case report].

A 66-year-old man appeared with a local recurrence of RCC 9 months after nephrectomy (clear cell carcinoma > sarcomatoid carcinoma, G2 > 3, pT3a). A tempraly elevation of serum C-reactive protein (CRP) appeared on administration of sorafenib and decrease of vascularity of the tumor was found on CT. After 13 months of sorafenib administration the recurrent tumor disappeared completely and serum CRP was normalized concomitantly. He currently remains in complete remission for 37 months.

[Multiple myeloma diagnosed during hormonal therapy for prostate cancer: report of two cases].

Case 1: A 73-year-old man presented with a serum prostate specific antigen (PSA) level of 30.2 ng/ml, and was diagnosed with prostate cancer (cT3aN0M1, stageD2), for which hormonal therapy (maximal androgen blockade : MAB) was commenced. Nine months later he developed back pain, and osteolytic bone lesions progressed despite a stable, low PSA level (0.087 ng/ml). He was diagnosed with multiple myeloma on the basis of positive M protein on immunoelectrophoresis. MP combination therapy (melphalan and prednisolone) was commenced, but the patient died of multiple myeloma 33 months later. Case 2: A 70-year-old man was diagnosed with prostate cancer (PSA 19 ng/ml) at another hospital 5 years ago, and underwent hormonal therapy (luteinizing hormone-releasing hormone (LHRH) agonist only). He was referred to our hospital and underwent bicalutamide+MAB combination therapy due to a raised PSA level (58 ng/ml) and multiple bone metastases. His PSA level dropped to around 20 ng/ml, but 2 years later he developed back pain, and bone metastases with osteolytic change were seen in the skull, ribs, and limbs. Needle aspiration biopsy of a fist-sized soft tissue mass in the chest wall showed multiple myeloma. Although chemotherapy with melphalan was commenced, the patient died of multiple myeloma 8 months after its diagnosis. Both these cases exhibited rapidly progressing bone lesions, regardless of an absence of any large fluctuations in serum PSA levels, during hormonal therapy for prostate cancer. Further investigations yielded the diagnosis of multiple myeloma. If progression of bone lesions does not match the status of prostate cancer as surmised from the serum PSA level, we should consider the possibility of multiple myeloma, and biopsy of one of the bone lesions.

Primitive neuroectodermal tumor/Ewing's sarcoma of the urinary bladder: a case report and its molecular diagnosis.

We report a rare case of primitive neuroectodermal tumor/Ewing's sarcoma (PNET/ES) arising from the urinary bladder. A 65-year-old man presented with hematuria and dysuria. Computed tomography revealed an enlarged invasive tumor at the base of the bladder. No additional abnormal findings were disclosed by other diagnostic imaging methods. The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99). EWS-FLI1 fusion transcripts were detected by reverse transcriptase polymerase chain reaction and direct sequencing, confirming the diagnosis of PNET/ES. The patient developed swollen pelvic lymph nodes as well as multiple lung metastases at 8 months postoperatively. No effective results could be obtained even with systemic chemotherapy consisting of vincristine, ifosfamide, doxorubicin and etoposide (VIDE) based on the EUROpean Ewing tumour Working Initiative of National Groups 1999 (EURO-E.W.I.N.G. 99) multinational trial. The patient died of acute superior mesenteric artery thrombosis at 22 months postoperatively. PNET/ES could have been included in past cases of small cell carcinoma because of the difficulty in its differential diagnosis. Exact diagnosis is crucial for deciding the treatment strategy for rare bladder tumors consisting of small round cells.

Prognostic Accuracy of the qSOFA Score for In-Hospital Mortality in Elderly Patients with Obstructive Acute Pyelonephritis: A Multi-Institutional Study.

Prognostic accuracy of the quick sequential organ failure assessment (qSOFA) score for mortality may be limited in elderly patients. Using our multi-institutional database, we classified obstructive acute pyelonephritis (OAPN) patients into young and elderly groups, and evaluated predictive performance of the qSOFA score for in-hospital mortality. qSOFA score ≥ 2 was an independent predictor for in-hospital mortality, as was higher age, and Charlson comorbidity index (CCI) ≥ 2. In young patients, the area under the curve (AUC) of the qSOFA score for in-hospital mortality was 0.85, whereas it was 0.61 in elderly patients. The sensitivity and specificity of qSOFA score ≥ 2 for in-hospital mortality was 80% and 80% in young patients, and 50% and 68% in elderly patients, respectively. For elderly patients, we developed the CCI-incorporated qSOFA score, which showed higher prognostic accuracy compared with the qSOFA score (AUC, 0.66 vs. 0.61, p < 0.001). Therefore, the prognostic accuracy of the qSOFA score for in-hospital mortality was high in young OAPN patients, but modest in elderly patients. Although it can work as a screening tool to determine therapeutic management in young patients, for elderly patients, the presence of comorbidities should be considered at the initial assessment.

[A case of hypospadias with a dicentric Y chromosome].

An infant was referred to our department with complaint of abnormality of the external genitalia. Hypospadias and right inguinal hernia were detected and left testis was palpable, but right testis was not palpable. Chromosomal examination revealed 45, X/46, X, idic (Y) (q11.2). On ultrasonographic examination, uterus and ovary were not recognized. At one year of age, we performed operation of right inguinal hernia and right cryptorchism. During operation right spermatic cord and epididymis were detected, but right testis was not detected. At two years of age, urethroplasty was performed. After the operation closure of hypospadias fistulas was performed. Now the patient does not have fistulas and has good clinical progress.

Ureteral Involvement Is Associated with Poor Prognosis in Upper Urinary Tract Urothelial Carcinoma Patients Treated by Nephroureterectomy: A Multicenter Database Study.

BACKGROUND: The prognostic significance of tumor location for patients with upper urinary tract urothelial carcinoma (UUT-UC) has been disputed. Several papers have reported that ureteral cancer is associated with worse prognosis. OBJECTIVE: To investigate the prognostic significance of the presence of ureteral tumors in UUT-UC patients who underwent radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS: In this multicenter retrospective study, 1068 eligible patients (median follow-up: 40 mo [interquartile range: 17-77 mo]) were divided into three groups based on tumor location: renal pelvic, ureteral, and both-regional (having both renal pelvic and ureteral tumors). The ureteral and both-regional groups were subsequently integrated into the ureteral involvement group to evaluate its prognostic impact. INTERVENTION: All patients underwent RNU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The prognostic impact of tumor location on survival was analyzed. RESULTS AND LIMITATIONS: The renal pelvic, ureteral, and both-regional groups consisted of 507 (47.5%), 430 (40.3%), and 131 (12.3%) patients, respectively. The ureteral and both-regional groups had a higher rate of lymphovascular invasion and lymph node metastasis compared with the renal pelvic group. The renal pelvic and both-regional tumors presented more frequently with locally advanced stages (pT3/T4) compared with the ureteral tumors. The 5-yr cancer-specific survival (CSS) and progression-free survival (PFS) rates of patients in the ureteral (70.5% and 66.7%, respectively) and both-regional groups (64.8% and 57.8%, respectively) were significantly worse than those in the renal pelvic group (81.9% and 78.1%, respectively). In a multivariate analysis, the presence of ureteral involvement was a significant prognostic factor for CSS (hazard ratio [HR]: 1.50; p=0.006) and PFS (HR: 1.35; p=0.023). This study is inherently limited by the biases associated with its retrospective and multicenter design. CONCLUSIONS: The presence of ureteral involvement had a significant impact on the survival of surgically treated UUT-UC patients associated with a poor prognosis. PATIENT SUMMARY: We demonstrated that the ureteral involvement was associated with poor survival compared with patients with renal pelvic tumor only in upper urinary tract urothelial patients treated by nephroureterectomy.

[Vesicorectal fistula caused by pelvic metastasis of penile cancer: a case report].

A 65-year-old man was referred to our hospital complaining of glans induration. Tumor biopsy revealed squamous cell carcinoma. Although he was given radiation therapy and subcutaneous injection therapy of bleomycin, viable cancer cells remained. Then he was given combination chemotherapy of bleomycin and cisplatin, and paint therapy of bleomycin ointment. Local recurrence with a cauliflower-like tumor occurred five years after the chemotherapy. Then we performed total penectomy and reconstructive surgery of penis. Five years later, discharge of urine from anal appeared. Computerized tomography of pelvis demonstrated a mass 3 cm in diameter in the anterior portion of anal and cystogram demonstrated a vesicorectal fistula. We tried to perform fistulectomy, but foiled because of large fistula. Then we inserted a urethral catheter, which resulted in obstruction of fistula by its balloon, and we made a cystostomy for securing urinary tract. Pathological examination of tissue around the fistula revealed squamous cell carcinoma. His quality of life was improved, but his general condition became worse gradually and he died of cancer.

[Giant sarcomatoid carcinoma with spontaneous vesical rupture: a case report].

A 60-year-old woman has been on steroids under the diagnosis of polymyositis for 25 years. She was referred to our hospital complaining of asymptomatic macroscopic hematuria and lower abdominal pain. Physical examination revealed abdominal tenderness and rigidity. We suspected peritonitis because of free air image on the abdominal roentogenogram. The computed tomographic (CT) scan demonstrated an 8 cm solid mass in the bladder and defect of anterior wall of urinary bladder. Then we performed total cystectomy with cutaneous ureterostomy and partial resection of ileum as an emergency operation. Macroscopically, intra-peritoneal bladder rupture and severe adhesion of necrotic bladder dome wall to ileum were recognized and the tumor 8 cm in diameter existed in posterior wall of urinary bladder. Microscopic examination showed sarcomatoid carcinoma with spindle cell component and no invasion to ileum was recognized. Multiple lung, liver and bone metastasis appeared 6 months after the operation. She died of cancer 11 months after the operation.

Expression of the p63 and Notch signaling systems in rat testes during postnatal development: comparison with their expression levels in the epididymis and vas deferens.

The role of tubular structures that contribute to the passage of spermatozoa is not solely passive; these structures actively contribute to their own functions, although these tubules and ducts are contiguous and collaborate in the development of the male gamete along their lengths. The testis has the specific function to generate spermatozoa and spermatozoa undergo numerous changes as they pass through the epididymis. A member of the p53 family of genes, p63, is highly expressed in the basal layers of epithelial tissues and plays a key role in maintaining their cell populations, whereas Notch 1 and its ligand Jagged 2 have an important role in the differentiation of germ cells and Jagged 2 is up-regulated by TAp63, one of the p63 isoforms, which transactivates p53 target genes and induces apoptosis. Although the presence of p63 in most epithelia is established, the role of p63 and its possible relationship with the Notch system in the seminiferous epithelium have not been examined. Therefore, we investigated the expression of p63, Jagged 2, and Notch 1 in the testis during postnatal development in comparison with their expression levels in the vaso-epididymal epithelium. In the testis, the expression of TAp63 mRNA increased at day 14 after birth and the expressions of Jagged 2 and Notch 1 mRNA increased at day 16 after birth, suggesting that TAp63-mediated Jagged 2 induction activates the Notch signaling system. On the other hand, the strong signal of DeltaNp63 mRNA was already recognized in the vas deferens at day 0 after birth and advanced chronologically along the duct to the caput epididymis and p63 protein was expressed in basal cells in their epithelium, whereas the mRNAs of Jagged 2 and Notch 1 were maintained at a low level. Consequently, examination of our data raises the probability that TAp63 has an important role for maintenance of germ cell numbers, triggering or balancing the development, differentiation, and apoptosis of germ cells in the testis, which is completely different from the role of DeltaNp63 in other epithelial tissues.

[Successful trans-stomal operation for multiple urinary stones occurring in the Indiana continent urinary diversion: a case report].

A total cystectomy with the Indiana continent diversion was performed on a 73-year-old man under the diagnosis of invasive bladder cancer in 1992. In 1994 there appeared a few urinary stones in his Indiana continent urinary diversion. Extracorporeal shock wave lithotripsy (ESWL) was successfully performed. In 1999 a few urinary stones recurred and ESWL was performed. Stones could not be discharged because of stricture of the efferent limb, although stones were crushed down into small pieces by repeated ESWL. The number and sizes of stones gradually increased. Dilatation of the stoma followed by a trans-stomal operation was performed and all of the stones except for one were extracted.

[Extracorporeal shockwave lithotripsy in the treatment of distal ureteral stones larger than 10 mm in diameter].

Optimal treatment for distal ureteral stones remains controversial. During a period of 10 years, from December 1992 to December 2002, 103 distal ureteral stones larger than 10 mm in diameter were treated at our institution with extracorporeal shock wave lithotripsy (ESWL) using the Siemens Lithostar. Only 2 patients had a ureteral stent in place at the time of treatment. The overall stone-free rate was 98% with 1-12 session and 3-month stone-free rate was 95.1%. These data reveal that a high success rate was achieved in multisession ESWL. Therefore, ESWL is considered to be acceptable as first-line therapy for fragmentation of distal ureteral stones larger than 10 mm in diameter.

[Three cases of congenital penile curvature].

Congenital penile curvature is a rare disease. We experienced three cases of congenital penile curvature. Penile curvature was recognized in all cases from adolescence. Induration and cordee were not palpable in the penis of all cases. We performed modified Nesbit method in all cases. Penile curvature, however, recurred in 1 case.

[A case of hypogonadotrophic hypogonadism causing lumbar stress fracture].

A 57-year-old man was referred to our hospital for further evaluation on hypogonadotrophic hypogonadism causing a stress fracture of the 4th lumbar vertebrae. Azoospermia had been pointed out at the age 30, but hormonal evaluation had not been performed. Physical examination revealed an eunuchoidal body proportion, a stretched phallus length of 4 cm and bilateral scrotal testes of 6 ml. Hormonal evaluation demonstrated a testosterone level of 13 ng/dl (normal, 320 to 1,030 ng/dl), a luteinizing hormone of 0.2 mU/ml (normal, 1.8 to 9.2 mU/ml) and a follicular stimulating hormone of 1.0 mU/ml (normal, 1.6 to 10.7 mU/ml). Results of a stress test of gonadotrophin-releasing hormone was a low delay type. Computerized tomography showed no abnormality in the hypothalamic-pituitary region. The patient was treated with the substitution therapy of androgen. The therapy was discontinued 6 months later because of severe nipple pain. We should perform hormonal evaluation and other examinations for male infertility.

[A case of spermatic cord tuberculosis].

A 47-year-old man visited our hospital with a complaint of a right intrascrotal mass. The results of a laboratory examination were unremarkable. An ultrasonographic examination of the right scrotum demonstrated a low echoic legion, 2.5 x 1.3 x 0.7 cm in diameter. A right spermatic cord tumor was diagnosed. Right high orchiectomy was performed. Microscopic examination showed a granulomatous lesion with Langhans large cells. Tuberculin skin test was strongly positive. From these findings we diagnosed the patient with tuberculosis in the spermatic cord.

Bimodal pattern of the impact of body mass index on cancer-specific survival of upper urinary tract urothelial carcinoma patients.

AIM: To clarify how body mass index (BMI) affects the risk of death from upper urinary tract urothelial carcinoma (UUTUC) we investigated the impact of BMI on UUTUC using a Japanese multicenter database. PATIENTS AND METHODS: Between January 1995 and December 2010, 1,329 patients with upper urinary tract tumors were treated in 13 institutions in Japan. From this group, a cohort of 1,014 patients treated with radical nephroureterectomy was retrospectively reviewed. BMI was categorized into the following three groups: BMI <22.5, BMI 22.5 to <25 and BMI ≥ 25. The association between each group and cancer-specific survival (CSS) was analyzed using Cox proportional hazards regression models. RESULTS: The median BMI was 22.4 kg/m(2) (interquartile range, 20.5-24.8). Out of all patients, 213 (21%) died of UUTUC. Hazard ratios of the BMI ≥ 25 and the BMI <22.5 group were 1.76 and 1.66, respectively. CONCLUSION: Both higher and lower BMI affect the prognosis of UUTUC treated with radical nephroureterectomy.

New hammock hypothesis-based method for the treatment of stress urinary incontinence: the first 29 urethral supports with a small fascial patch.

AIM: We have developed a new method requiring no manipulations of the retropubic passages, and carried out a retrospective study to assess the effectiveness, safety and early results of this new procedure in the treatment of female stress urinary incontinence. METHODS: From January 2001 to September 2003, 29 patients underwent our new surgery for the treatment of SUI. A 3 x 2 cm vertical rectangle was harvested from the rectus fascia. A convex horizontal incision was made over the mid urethra and bladder neck. The retropubic space was entered to the urethropelvic ligament spreading toward the junctions between urethropelvic ligament and tendinous arc. One suture was made at the point lateral to the bladder neck. Another suture was made behind the pubic bone. These two sutures were sutured again and tied with the short side end of the harvested fascia. The same procedure was performed on the other side. RESULTS: Of 29 patients, 26 (89.7%) were cured of stress urinary incontinence and 3 were improved. None of the patients had difficulty in voiding after the operation. Maximum flow rates were almost the same before and after surgery. None of the patients had any adverse events. CONCLUSION: This procedure, which requires no manipulations of the retropubic passages, is safe and effective for the treatment of stress urinary incontinence.