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Aim: Intravesical recurrence (IVR) after nephroureterectomy for upper tract urothelial carcinoma (UTUC) is relatively frequent, occurring in about 30-50% of patients. The aim of this study was to investigate the differences of the prognosis and IVR between open and laparoscopic surgery and to elucidate the risk factor of IVR., Patients and Methods: We retrospectively analyzed data from 403 patients with UTUC treated with laparoscopic or open nephroureterectomy at six affiliated hospitals between 1990 and 2015. The clinicopathological factors of each group were examined using Kaplan-Meier plots, and univariate and multivariate analyses., Results: There was no difference in recurrence and cancer-specific mortality between open and laparoscopic surgery in univariate and multivariate analyses. There was no significant difference in IVR rate between the laparoscopic and open groups (p = .22). Among the patients with IVR, 84% of patients relapsed within 2 years. Univariate analysis of IVR showed a significant increase in patients with low-grade (p = .03, HR = 1.64) or low-stage urothelial carcinoma (pT1 or lower, p = .006, HR = 1.77) with no lymph node involvement (p = .002, HR = 10.3) or lymphovascular invasion (p = .009, HR = 1.79). Surgical modality was not an independent factor. In multivariate analysis, there was no independent predictive factor for IVR., Conclusions: There was no difference in recurrence, cancer-specific mortality, and IVR between open and laparoscopic surgery. On the other hand, our results suggested that the low malignant potential tumor may be a risk factor for IVR. This finding provides insight into IVR, which may help with the development of personalized prevention and treatment strategies., (© 2022 John Wiley & Sons Australia, Ltd.)

OBJECTIVE. IgG4-related disease is characterized by extensive infiltration of IgG4-positive plasma cells and fibrosis in various organs. The objective of this study is to investigate CT findings of IgG4-related lesions involving the upper urinary tract and compare them with those of urothelial carcinomas. MATERIALS AND METHODS. This study reviewed pretreatment CT images of 13 consecutive patients with IgG4-related disease with upper urinary tract lesions and 80 consecutive patients with urothelial carcinomas. The findings assessed were laterality, location, growth pattern, margins, internal structure, presence of calcification and lipid component, enhancement pattern, and extraurinary findings. RESULTS. Bilaterality ( p < 0.0001), an extramural growth pattern ( p < 0.0001), a greater number of affected segments ( p = 0.04), and a gradual dynamic enhancement pattern ( p < 0.001) were significantly more frequent in patients with IgG4-related disease. With regard to extraurinary findings, paraaortic fat stranding ( p = 0.03), presacral fat stranding ( p < 0.001), fat stranding of the pelvic walls ( p < 0.001), and aortic involvement ( p < 0.001) were seen more frequently in patients with IgG4-related disease; on the other hand, there was no statistically significant difference in terms of frequency of pancreatic involvement. Hydronephrosis and renal involvement were seen more frequently in patients with urothelial carcinoma, although the difference was not statistically significant. CONCLUSION. CT findings suggestive of IgG4-related upper urinary tract lesions in comparison with urothelial carcinoma are bilateral and have a longer urinary tract involvement and exhibit an extramural growth pattern, ill-defined margins, a gradual enhancement pattern, aortic involvement, and fat stranding in the paraaortic, presacral, or pelvic wall areas.

Objectives: Polymerase I and transcript release factor (PTRF) has been implicated in cancer biology but its role in upper tract urothelial carcinoma (UTUC) is unknown. From a pilot transcriptome, we identified PTRF was significantly upregulated in high stage UTUC. Bladder cancer transcriptome from The Cancer Genome Atlas (TCGA) supported our finding and high PTRF level also predicted poor survival. We, therefore, investigated the correlation of PTRF with patients' clinicopathologic characteristics and outcomes in a multiracial UTUC cohort., Materials and Methods: By immunohistochemical staining, PTRF expression was determined using H-score. PTRF expression of 575 UTUCs from 8 institutions, including 118 Asians and 457 Caucasians, was compared with various clinicopathologic parameters. Human urothelial cancer cell lines were used to evaluate the level of PTRF protein and mRNA expression, and PTRF transcript level was assessed in fresh samples from 12 cases of the cohort. The impact of PTRF expression on disease progression, cancer-specific death and overall mortality was also examined., Results: High PTRF expression was significantly associated with multifocality (P = 0.023), high pathologic tumor stage (P < 0.00001), nonurothelial differentiation (P = 0.035), lymphovascular invasion (P = 0.003) and lymph node metastasis (P = 0.031). PTRF mRNA expression was also markedly increased in advanced stage UTUC (P = 0.0003). High PTRF expressing patients had consistently worse outcomes than patients with low PTRF expression regardless of demographic variation (all P < 0.005). In multivariate analysis, high PTRF expression was an independent predictor for progression-free survival (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.07-2.69, P = 0.025), cancer-specific survival (HR 2.09, 95% CI 1.28-3.42, P = 0.003), and overall survival (HR 2.04, 95% CI 1.33-3.14, P = 0.001)., Conclusions: Results indicate that PTRF is a predictive biomarker for progression and survival and an independent prognosticator of UTUC. Elevated PTRF could probably propel clinically aggressive disease and serve as a potential therapeutic target for UTUC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

BACKGROUND The treatment of inflammatory bowel disease aims to induce and maintain disease remission, avoid complications, and restore quality of life. The treatments include the use of immunosuppressants and biological therapy. Despite the effectiveness of these treatments in controlling disease activity and in limiting complications, there remains an increased risk of developing malignancies. CASE REPORT A 70-year-old male patient with ulcerative colitis who had pancolitis was initially treated with mesalazine. In 2010, the medication was changed to azathioprine due to clinical disease activity. The patient demonstrated clinical and endoscopic response to the medication, but presented recurrent facial lesions identified as non-melanoma skin cancer in 2014, 2015, and 2016. Azathioprine was discontinued and anti-TNF therapy was started, but no satisfactory clinical or endoscopic response was observed. The patient developed hematuria and a ureter tumor was found with subsequent ureteronephrectomy. Moreover, the patient underwent total colectomy with ileostomy as a treatment for refractory ulcerative colitis. CONCLUSIONS Immunosuppressive therapy can facilitate the development of malignant neoplasms, accelerate tumor growth, and favor the onset of metastases. The types of tumors most associated with its use are lymphoproliferative tumors and non-melanoma skin cancer. The benefits of adequate control of inflammatory bowel disease are clear and the use of immunosuppressants should not be limited by these potential adverse outcomes; however, the risk-benefit profile of immunosuppression should always be assessed on a case-by-case basis.

Rationale: Primary carcinosarcoma of the upper urinary tract is rare. Ureteral duplication is one of the most common urinary tract malformations. Additionally, the association between ureteral duplication and malignancy is unknown. To the best of our knowledge, no cases of malignant tumors diagnosed as carcinosarcoma with ureteral duplication have been reported. We herein report the case of a patient with carcinosarcoma of the ureteropelvic junction associated with incomplete ureteral duplication., Patient Concerns: A 60-year-old Japanese woman presented with painless gross hematuria. She had a history of total hysterectomy and chemotherapy for endometrioid carcinoma 5 years before. She had no history of occupational chemical exposure., Diagnoses: Radiographic imaging revealed right incomplete ureteral duplication, hydronephrosis, and a polypoid tumor in the ureteropelvic junction of the lower moiety of the right kidney. Urine cytology showed a small amount of degenerated atypical epithelial and nonepithelial cells. The transureteral biopsy specimen showed dysplastic urothelial cells and atypical myoid spindle cells. These findings were indefinite for malignancy., Interventions: The patient underwent right nephroureterectomy. Pathological examination of the resected tumor showed a biphasic neoplasm composed of carcinomatous and sarcomatous components. The sarcomatous component was immunohistochemically positive for vimentin, desmin, h-caldesmon, and α-SMA and negative for pancytokeratin (AE1/AE3), low molecular weight cytokeratin (CAM 5.2), EMA, E-cadherin, GATA3, uroplakin 2, and p63. Based on these findings, we diagnosed the tumor as carcinosarcoma., Outcomes: The postoperative course was uneventful. No additional therapy was administered. The patient has remained alive without recurrence for 21 months since surgery., Lessons: Carcinosarcoma can arise from ureteral duplication. Although the majority of carcinosarcomas of the upper urinary tract are diagnosed at an advanced stage and have a poor prognosis, some can have a less aggressive course. Further studies are needed to determine the association between ureteral duplication and malignancy.

Purpose of Review: Our aim is to review recent investigations into the recurrence of urothelial carcinoma in the upper urinary tract following bladder cancer therapy focusing on surveillance and management., Recent Findings: After radical cystectomy, rates of recurrence in the upper tract are between 0.75 and 6.4%. The poor prognosis of upper tract urothelial carcinoma (UTUC) is in part attributable to delayed diagnosis. Guidelines recommend a gradual de-escalation of surveillance in disease-free patients with the potential for discontinuation beyond 5 years. Previous guideline audits have shown that recurrences are still missed, suggesting a need for longer follow-up. Studies propose risk stratifying patients by age, comorbidities, and tumor stage to warrant closer surveillance and identify adjuvant therapy candidates. Larger studies are needed to advise treatment of UTUC after a urothelial bladder cancer (UBC) diagnosis, as these patients face poorer outcomes following radical nephroureterectomy. Clinical trials have demonstrated the efficacy of neoadjuvant and adjuvant systemic therapy after radical nephroureterectomy for primary UTUC; however, the literature is lacking robust data on patients who develop urothelial carcinoma in the upper tract following an initial UBC diagnosis., Summary: Many asymptomatic recurrences of urothelial carcinoma in the upper tract are undetected by current surveillance guideline recommendations. Higher level evidence is needed to confirm the efficacy of prolonged and risk-adapted surveillance of patients with UBC and the extirpative management of recurrence in the upper tract after UBC treatment.

Urothelial carcinoma in the upper tract is rare and often discussed separately. Many established risk factors were identified for the disease, including genetic and external risk factors. Radiographic survey, endoscopic examination and urine cytology remained the most important diagnostic modalities. In localized upper tract urothelial carcinomas, radical nephroureterectomy with bladder cuff excision are the gold standard for large, high-grade and suspected invasive tumors of the renal pelvis and proximal ureter, whereas kidney-sparing surgeries should be considered in patients with low-risk disease. Advances in technology have given endoscopic surgery an important role, not only in diagnosis, but also in treatment. Although platinum-based combination chemotherapy is efficacious in advanced or metastatic disease, current established chemotherapy regimens are toxic and lack a sustained response. Immune checkpoint inhibitors have led to a new era of treatment for advanced or metastatic urothelial carcinomas. The remarkable results achieved thus far show that immunotherapy will likely be the future treatment paradigm. The combination of immune checkpoint inhibitors and other agents is another inspiring avenue to explore that could benefit even more patients. With respect to the high incidence rate and different clinical appearance of upper tract urothelial carcinomas in Taiwan, a possible correlation exists between exposure to certain external risk factors, such as arsenic in drinking water and aristolochic acid in Chinese herbal medicine. As more gene sequencing differences between upper tract urothelial carcinomas and various disease causes are detailed, this has warranted the era of individualized screening and treatment for the disease., (© 2018 The Japanese Urological Association.)

Introduction: Primary small cell carcinoma (SCC) after renal transplantation is very rare. Here, we reported 1 case of primary SCC after renal transplantation and analyzed its clinical and pathological characteristics., Case Presentation: A 55-year-old female underwent renal transplantation in our hospital 2 years ago and had been using tacrolimus for immunosuppressive therapy. Because of abdominal distention, the patient was admitted to our hospital. Computed tomography (CT) showed a malignant tumor of left kidney. Patient underwent surgical treatment and radical nephrectomy and lymph node dissection were selected. Postoperative pathological diagnosis was primary renal parenchyma and ureteral SCC. The patient has been treated with combination chemotherapy of lowpol (100 mg per day) and etoposide (10 mg per day). His vital signs are stable now, and he is receiving further treatment in our hospital., Conclusion: Because of immunosuppressive drugs use, the incidence of malignancies has increased significantly after renal transplantation. This case highlights the difficulty of diagnosis of primary SCC and the necessity of checking for neuroendocrine tumor after organ transplantation.

Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UCs of the upper urinary tract and the urinary bladder were identified in the Danish hereditary nonpolyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole-genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from patients with Lynch syndrome were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data were analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as urothelial-like tumors with only 20% being genomically unstable, basal/SCC-like, or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger datasets revealed that Lynch syndrome-associated UC shares molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset., (© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Competing Interests: Conflict of interest: None declared.

Background: We present a case of asynchronously occurring adenocarcinomas 29 and 36 years after ureterosigmoidostomy for bladder cancer, respectively, at both anastomosis sites., Case Presentation: A colonoscopy that was performed on a 69-year-old man because of bloody stool and an elevated carcinoembryonic antigen (CEA) level revealed a polypoid lesion at the right ureterosigmoid anastomosis site 29 years after the patient's ureterosigmoidostomy. Endoscopic resection was performed, and the lesion was diagnosed as adenocarcinoma. Seven years later (36 years after ureterosigmoidostomy), an elevated lesion was detected at the left ureterosigmoid anastomosis site by colonoscopy performed after detection of high CEA levels. Biopsy revealed an adenocarcinoma that was immunohistologically positive for CDX2; sigmoidectomy and ureterectomy were subsequently performed. The pathological diagnosis of the second tumor was adenocarcinoma arising in the ureterosigmoid anastomosis site and invading the left ureter., Conclusions: Diligent long-term follow-up of patients who underwent ureterosigmoidostomy is essential.

Purpose: Although cigarette smoking is a well established risk factor for urothelial cancer, its role in urothelial cancer prognosis is still undetermined. In this meta-analysis we quantify the role of lifetime smoking history in bladder cancer recurrence, progression and survival by pooling available data on nonmuscle invasive bladder cancer, muscle invasive bladder cancer and upper tract urothelial carcinoma., Materials and Methods: A total of 24 studies, comprising data from 13,114 patients with bladder cancer and 2,259 patients with upper tract urothelial carcinoma, were included in this meta-analysis. Publication bias was addressed through Egger's test, and the heterogeneity among studies was assessed by the I(2) test statistic and subgroup analyses., Results: Current smokers at diagnosis are at increased risk for local recurrence in nonmuscle invasive bladder cancer (HR 1.27, 95% CI 1.09-1.46) and smokers with muscle invasive bladder cancer have an increased risk of dying of bladder cancer (HR 1.23, 95% CI 1.02-1.44). In the upper tract urothelial carcinoma population smokers have an increased risk of recurrence in the operative bed (HR 1.57, 95% CI 1.19-1.95) and of death from upper tract urothelial carcinoma (HR 1.53, 95% CI 1.13-1.92). We did not identify significant heterogeneity among included studies., Conclusions: The body of evidence is limited due to the absence of prospective studies. However, the results from this meta-analysis unambiguously support the hypothesis that lifetime cigarette smokers are at increased risk for a more malignant type of urothelial carcinoma associated with a worse prognosis., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

The success of human kidney allotransplantation was realized over six decades ago. First described 50 years ago, renal autotransplantation has been utilized sparingly as a salvage procedure for patients at risk of losing renal function, either from a benign or malignant condition. While classically associated with colorectal malignancies, Lynch syndrome also carries a small yet significant risk for the development of ureteral carcinoma. For these patients who develop chronic kidney disease, allotransplantation may not be an option due to the lifelong risk of several malignancies. We report the first known case of renal autotransplantation in a patient with metachronous ureteral cancer due to Lynch syndrome., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Purpose: Upper urinary tract (pyelocalyceal cavities and ureter) urothelial carcinoma is a relatively rare neoplastic disease. Although diagnosis and treatment of this tumor variant have improved significantly, accurate risk stratification remains a challenge. To identify the putative oncogene involved in urothelial carcinoma progression we performed bioinformatics guided experimental investigation targeting chromosome 19q13., Materials and Methods: We investigated the effects of EMP3 on cancer cell growth, migration and adhesion in transfection and siRNA experiments in vitro. Crosstalk of integrins or ErbB2 with EMP3 was examined by reverse transcriptase-polymerase chain reaction and immunoblot. The potential involvement of epigenetic alterations of EMP3 in vitro and in vivo was analyzed by methylation specific polymerase chain reaction. To validate clinical relevance we measured EMP3 expression at the mRNA and protein levels in a cohort of 77 patients with upper urinary tract urothelial carcinoma and compared prognostic significance in relation to that of ErbB2 expression., Results: We noted functional crosstalk between ErbB2 and EMP3 in vitro. EMP3 over expression promoted cancer cell proliferation and migration but suppressed cell adhesion in vitro. EMP3 activated the ErbB2-PI3K-AKT pathway to increase cell growth in vitro. In the clinical cohort Kaplan-Meier survival estimates showed that ErbB2 and EMP3 co-expression was the most important indicator of progression-free and metastasis-free survival in patients with upper urinary tract urothelial carcinoma (log rank test p = 0.018 and 0.04, respectively)., Conclusions: EMP3 is an important prognostic indicator for selecting patients with upper urinary tract urothelial carcinoma for more intensive therapy. EMP3 is an innovative co-targeting candidate for designing ErbB2 based cancer therapy., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the site-specific pattern of disease recurrence and/or metastasis and the associated patient outcomes after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC)., Methods: A total of 733 patients with UTUC from a retrospective multi-institutional cohort were included, with a median follow-up of 34 months. Associated patient outcomes were analyzed by multivariate analysis. To evaluate the influence of primary tumor location, we divided it into four areas: renal pelvis, and upper, middle, and lower ureter., Results: A total of 218 patients experienced disease recurrence, with the majority of relapses occurring within the first 3 years. Cumulative incidence rates of first disease recurrence at 1 and 3 years were 18.9 and 29.8 %, respectively. Of these patients, 38.5 % developed distant recurrence; 17.4 % experienced both local and distant recurrences; and 44.0 % developed isolated local recurrence. The predominant sites of distant metastasis were lung, liver, and bone. Multivariate analysis revealed that the prevalence of local recurrence and lung metastasis was significantly associated, with primary tumor location being independent of other clinicopathological variables. Lower/middle ureter tumors had a higher rate of local recurrence in the pelvic cavity, and renal pelvic tumors had a higher prevalence of distant relapse in the lungs. Similar results were obtained when rerunning the data set by excluding patients who received adjuvant chemotherapy (n = 131)., Conclusions: This multi-institutional study provided a detailed picture of metastatic behavior after RNU, and primary tumor locations were associated with unique patterns of metastatic spread in UTUC patients.

Objective: Carcinoma of the renal pelvis and ureter are unusual tumours and our limited knowledge comes mainly from case reports and small series from large academic hospitals, as a rule without histopathological review. This study reports aetiological and demographical factors as well as clinicopathological findings of all patients in a large geographical region., Material and Methods: All patients in western Sweden with a renal pelvic or ureteral tumour diagnosed between 1971 and 1998 (n = 930) were included. Untreated cases were not excluded. Demographic data and results of preoperative examinations were retrieved from the original clinical records. The histopathological slides were reviewed and tumour stage, grade, configuration, presence of carcinoma in situ and angiolymphatic invasion were determined., Results: The majority of patients (80%) had invasive or high-grade tumours. Carcinoma in situ was present among 30% of patients with non-invasive high-grade tumours. Angiolymphatic invasion (62%) and solid (non-papillary) growth pattern (84%) were very common among patients with stage T2-T4 tumours. Twenty-three women out of 138 (16.7%) with ureteral carcinoma had a history of abdominal radiotherapy for gynaecological cancer 22 years (median) earlier. Forty-one patients out of 930 (4.4%) had a history of abuse of phenacetin-containing analgesics., Conclusions: This study demonstrates a very high incidence of high-grade upper tract tumours with carcinoma in situ, angiolymphatic invasion and solid (non-papillary) growth pattern, which underscores the malignant character of the disease. The possible association between pelvic radiotherapy and ureteral carcinoma warrants further study.

We report a case of urothelial carcinoma (UC) in a 69-year-old man that occurred after renal transplantation. He had started receiving hemodialysis therapy in 2004 due to diabetic nephropathy and underwent living related renal transplantation from his brother in 2005. He was referred to our hospital in May 2009 with asymptomatic microscopic hematuria. Cystoscopy findings revealed multiple bladder tumors, and transurethral resection of bladder tumor (TUR-BT) followed by intravesical instillation of pirarubicin was performed. Histopathological findings revealed UC (G1>G2, pTa). Cytology findings after the operation did not become negative; urine specimen from the native right ureter was positive, and abdominal computed tomography (CT) demonstrated a right pelvic tumor. In January 2010, a laparoscopic right nephroureterectomy was performed and pathological examination findings revealed UC in the right pelvis (G3>G2, INFβ, pT3). In March 2010, recurrence of the bladder tumor was demonstrated as carcinoma in situ (CIS) of the bladder and left native ureter. In June 2010, a radical cystectomy with left nephroureterectomy and ileal conduit diversion were performed. One week after that operation, laboratory results revealed abnormal hepatic function and CT showed multiple liver metastases. The patient died in August 2010, 2 months after surgery.

Unlabelled: Study Type--Prognosis (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinoma (UUT-UC) is a rare disease, usually treated by nephroureterectomy, occurring in a population with a median age of 70 years and with frequent tobacco use and other comorbidities. We know that the American Society of Anesthesiologists (ASA) score has prognostic value in urological oncology but this has not been assessed in UUT-UC. Using a multi-institutional French database, we have shown that the 5-year cancer-specific survival differed significantly between ASA 1, ASA 2 and ASA 3 patients (83.8%, 76.9% and 70.6%, respectively; P = 0.01). ASA status had a significant impact on cancer-specific survival in univariate and multivariate analyses, with a threefold higher risk of mortality at 5 years for ASA 3 compared with ASA 1 patients (P = 0.04)., Objective: • To evaluate the impact of American Society of Anesthesiologists (ASA) scores on the survival of patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UUT-UC)., Patients and Methods: • A retrospective multi-institutional cohort study of the French collaborative national database of UUT-UC treated by RNU in 20 centres from 1995 to 2010. • The influence of age, gender and ASA score on survival was assessed using a univariable and multivariable Cox regression analysis with pathological features used as covariables., Results: • Overall, 554 patients were included. The median follow-up was 26 months (10-48 months), and the median age was 69.5 years (61-76 years). In total, 114 (20.6%) patients were classified as ASA 1, 326 (58.8%) as ASA 2 and 114 (20.6%) as ASA 3. • The 5-year recurrence-free survival (P = 0.21) and metastasis-free survival (P = 0.22) were not significantly different between ASA 1 (52.8% and 76%), ASA 2 (51.9% and 75.3%) and ASA 3 patients (44.1% and 68.2%, respectively). • The 5-year cancer-specific survival differed significantly between ASA 1, ASA 2 and ASA 3 patients (83.8%, 76.9% and 70.6%, respectively; P = 0.01). • ASA status had a significant impact on cancer-specific survival in univariate and multivariate analyses, with a threefold higher risk of mortality at 5 years for ASA 3 compared with ASA 1 patients (P = 0.04)., Conclusions: • ASA classification correlates significantly with cancer-specific survival after RNU for UUT-UC. • It is a further pre-operative clinical variable that can be incorporated into future risk prediction tools for UUT-UC to improve their accuracy., (© 2012 BJU INTERNATIONAL.)

Increased risk for urological tumors has been observed in mutation carriers with Lynch syndrome (LS). In this study, we evaluated the clinical features of uroepithelial (bladder and ureter) and kidney cancers in 974 Finnish mutation carriers. Altogether 30 patients had a total of 34 urological tumors: 12 ureter, 12 bladder, and 10 kidney cancers. Urological tumor was the only tumor in 9 (30 %) patients, and metachronous other tumor occurred in 21 (70 %). The occurrence of uroepithelial cancers was significantly higher in MSH2 mutation carriers (6 %; 95 % CI, 2.7-11.0) than in MLH1 carriers (2 %; 95 % CI, 1.1-3.2) and MSH6 mutation carriers (0 %) (p = 0.014). The mean ages of patients at the time of diagnosis were: bladder cancer, 57 years; ureter cancer, 58 years; and kidney cancer, 64 years. Overall 5-year survival rates were 70 % (95 % CI, 0.32-0.89) in bladder cancer, 81 % (95 % CI, 0.45-0.95) in ureter cancer, and 75 % (95 % CI, 0.31-0.93) in kidney cancer. Cancer-specific 5-year survival rates were 70 % (95 % CI, 0.32-0.89) in bladder cancer, 91 % (95 % CI, 0.51-0.98) in ureter cancer, and 100 % in kidney cancer. In conclusion, early age of onset was observed in patients with uroepithelial tumors, but not in patients with kidney cancer. The frequency of uroepithelial tumors was significantly higher in MSH2 mutation carriers than in MLH1 carriers. Further studies with larger numbers of patients, however, are needed to evaluate the potential benefit of surveillance of urological tumors in LS.

Despite a ban on the use of plants of the Aristolochia genus in herbal medicine, as they contain known carcinogens, urothelial carcinoma attributable to the use of this plant seems to be more common than previously thought.

Objectives: To examine the incidence of and the risk factors for upper urinary tract recurrence in patients undergoing a radical cystectomy for bladder cancer, and to examine the clinical course of patients harboring upper urinary tract recurrence., Methods: This retrospective study included 362 patients who underwent radical cystectomy for bladder cancer. Patients with a history of upper urinary tract recurrence and concomitant upper urinary tract recurrence at cystectomy were excluded., Results: After a median follow up of 48 months (range 0-214) after radical cystectomy, 11 patients (3.0%) developed upper urinary tract recurrence. The median time to upper urinary tract recurrence was 48.4 months (range 11.6-78.6). The overall probability of upper urinary tract recurrence was 3.3% at 5 years. The median overall survival period after upper urinary tract recurrence was 23.5 months (range 4.3-53.9), with a better overall survival for patients who received a radical operation than for those who did not (38.6 months vs 11.9 months, respectively; P=0.03). At multivariable analysis, the presence of carcinoma in situ (P < 0.01) and invasion of the urethra (P = 0.02) were independent risk factors for upper urinary tract recurrence. The 5-year upper urinary tract recurrence was significantly higher for patients positive for either of these risk factors than for those without risk factors (12.0% vs 0.9%, respectively; P < 0.001)., Conclusions: This study shows that the presence of carcinoma in situ and cancer invading the urethra are risk factors for upper urinary tract recurrence. Close follow up is needed for early detection of upper urinary tract recurrence in patients at higher risk., (© 2011 The Japanese Urological Association.)

Objective: To assess the incidence, characteristics and outcome of upper urinary tract tumors (UUTTs) that developed in patients who underwent radical cystectomy for urothelial carcinoma., Methods: We performed an analysis of original and review articles that were related to post-cystectomy UUTTs. The articles were published from 1984 through 2011 and were identified by searching the Pub Med database., Results: The incidence of post-cystectomy UUTT ranges from 2-6% and is stable over time. The primary risk factors include a tumor in the distal ureter in the cystectomy specimen and signs of multifocal disease (e.g., multiplicity, a history of non-muscle-invasive bladder tumor, diffuse carcinoma in situ and the presence of a tumor in the prostatic urethra). The median time between cystectomy and UUTT exceeded three years in 70% of the reviewed cases. Even with regular radiological follow-up visits, over 50% of cases were diagnosed after clinical onset, and over 70% were in an advanced stage. Currently, a multidetector computed tomography urography is the standard technique for studying the upper urinary tract. In patients with urinary diversion, the maximum yield of cytology can be obtained when this technique is used to confirm a clinical or radiological suspicion of UUTT. Nephroureterectomy is the treatment of choice for these tumors. The high prevalence of high-grade and stage UUTT results in endourological treatment being restricted to only selected cases. Despite surgery, fewer than 30% of post-cystectomy UUTT patients experience prolonged survival., Conclusions: Post-cystectomy UUTT is rare and usually has a late onset. A distal ureteral tumor and the presence of multifocal disease are its primary risk factors. Most cases of post-cystectomy UUTT are diagnosed clinically and in advanced stages.

Kaposi sarcoma after an organ transplant is rare and infrequently involves internal organs. There are 2 reported cases in the English literature of Kaposi sarcoma originating from the transplant ureter after kidney transplant. We report a case of Kaposi sarcoma that occurred in the native ureter of the liver transplant recipient. Initially, the patient refused any further investigation and management and 2 years subsequent, had to undergo a left radical nephroureterectomy owing to the loss of renal function and distending pain. He recovered very well and no recurrence was detected at 47 months' follow-up. To our knowledge, it is the first report in English. We review the literature on this topic and explore the therapeutic principles and histologic features of this sarcoma.

During screening of 20 selected patients with hereditary non-polyposis colorectal cancer (HNPCC) (Lynch syndrome) carried out in the Department of Urology of Odense University Hospital from 2001 to 2010, two patients without urologic symptoms with cancer in the ureter were found. The purpose of the present case report is to underline the importance of referring those patients with HNPCC that have increased risk of urologic cancer to screening of the urinary tract. Furthermore, this paper seeks to point out the necessity of further investigation in the risk of urologic cancer in the different mutations causing HNPCC, as well as the effects of the different screening methods in order to find the optimal screening population and the optimal screening method.

Objective: To analyze and summarize the risk factors of malignant tumor after renal transplantation., Methods: We retrospectively analyzed 435 renal recipients who underwent renal transplantation in our institute from May 1991 to March 2011, and found 14 patients developed malignant tumor, of which 12 were from our institute, and the other 2 were referred from other institute. We analyzed the risk factors of those tumors for their incidence, classification, time of final diagnosis, immunity suppression therapy and prognosis., Results: The incidence of malignant tumors after renal transplantation in our hospital was 2.8%.Of the 14 cases, 11 were urothelial tumor (6 cases developed both in pelvis and ureter, 2 cases of primary ureter cancer and 3 cases of primary bladder cancer), and the other 3 were thyroid carcinoma, colon carcinoma and lymphoma. We carried out radical corrections in 13 patients,of whom 10 were in good status, 2 underwent the secondary operation in 1 year due to relapse (one patient died in half a year due to tumor size expansion), and 1 died from repeated relapse in 3 years. Chemotherapy was used for the patient with lymphoma., Conclusion: Immunity suppression and surgery are associated with the high incidence of maglinant tumor (78% were urinary tract tumors) after renal transplantation. The risk of tumor is strongly associated with the recipient's survival. The key point of management is early diagnosis and treatment. Further attention should be emphasized to painless gross hematuria, unconfirmed back pain, hydronephrosis, hydroureter and infections.

Purpose: Patients with Lynch syndrome are much more likely to have generally rare upper urinary tract urothelial carcinoma but not bladder urothelial carcinoma. While the risk has been quantified, to our knowledge there is no description of how this population of patients with Lynch syndrome and upper urinary tract cancer differs from the general population with upper urinary tract cancer., Materials and Methods: We obtained retrospective data on a cohort of patients with Lynch syndrome from the Hereditary Cancer Center in Omaha, Nebraska and compared the data to those on a control general population from western Sweden. These data were supplemented by a new survey about exposure to known risk factors., Results: Of the patients with Lynch syndrome 91% had mutations in MSH2 rather than in MSH1 and 79% showed upper tract urothelial carcinoma a mean of 15.85 years after prior Lynch syndrome-type cancer. Median age at diagnosis was 62 years vs 70 in the general population (p <0.0001). Only half of our patients had a significant smoking history and the male-to-female ratio was 0.95. Of patients with Lynch syndrome 51% had urothelial carcinoma in the ureter while it occurred in the renal pelvis in 65% of the general population (p = 0.0013). Similar numbers of high grade tumors were found in the Lynch syndrome and general populations (88% and 74%, respectively, p = 0.1108)., Conclusions: Upper urinary tract tumors develop at a younger age and are more likely to be in the ureter with an almost equal gender ratio in patients with Lynch syndrome. It has high grade potential similar to that in the general population., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Understanding of the role of radiation as a cause of kidney cancer remains limited. The most common types of kidney cancer are renal cell carcinoma and renal pelvis carcinoma. It has been posited that these entities differ in their degree of radiogenicity. Recent analyses of cancer incidence and mortality in the Life Span Study (LSS) of Japanese atomic bomb survivors have examined associations between ionizing radiation and renal cell carcinoma, but these analyses have not reported results for cancer of the renal pelvis and ureters. This paper reports the results of analyses of kidney cancer incidence during the period 1958-1998 among 105,427 atomic bomb survivors. Poisson regression methods were used to derive estimates of associations between radiation dose (in sievert, Sv) and cancer of the renal parenchyma (n = 167), and cancer of the renal pelvis and ureter (n = 80). Heterogeneity by cancer site was tested by joint modeling of cancer risks. Radiation dose was positively associated with cancers of the renal pelvis and ureter [excess relative rate (ERR)/Sv = 1.65; 90% confidence interval (CI): 0.37, 3.78]. The magnitude of this association was larger than the estimated association between radiation dose and cancer of the renal parenchyma (ERR/Sv = 0.27; 90% CI = -0.19, 0.98). While the association between radiation and cancer of the renal parenchyma was of greater magnitude at ages <55 years (ERR/Sv = 2.82; 90% CI = 0.45, 8.89) than at older attained ages (ERR/Sv = -0.11; 90% CI = nd, 0.53), the association between radiation and cancers of the renal pelvis and ureter varied minimally across these categories of attained age. A test of heterogeneity of type-specific risks provides modest support for the conclusion that risks vary by kidney cancer site (LRT = 2.34, 1 d.f., P = 0.13). Since some studies of radiation-exposed populations examine these sites in aggregate, results were also derived for the combined category of cancer of the renal parenchyma, renal pelvis and ureters. Overall, there was a positive association between radiation and the combined category of cancer of the renal parenchyma, renal pelvis and ureters (ERR/Sv = 0.60, 90% CI: 0.09, 1.30). Updated follow-up of the LSS cohort provides substantial additional information on the association between radiation and cancer of the renal pelvis and ureter, a site not examined in recent reports on analyses of these data. The results are suggestive of differences between the different regions of the kidney in sensitivity to the carcinogenic effects of ionizing radiation.

The role of aristolochic acid in the etiology of Balkan endemic nephropathy (BEN) and associated upper urothelial carcinoma (UUC) was recently confirmed. The aim of this study was to determine the marker(s) specific for BEN-associated UUC. A total of 82 patients with UUC (38 from the BEN region and 44 control tumors) were included in the study. The Ki-67 index in BEN tumors correlated with the grade and multifocality (p < 0.05), but in regression analysis, only the grade of BEN tumor. The p53 index was significantly higher in BEN than in control tumors (p < 0.05), as well as the alteration of p53 (p < 0.05). BEN low-stage tumors, tumors without limphovascular invasion (LVI), and tumors of the renal pelvis had a higher p53 index than the control tumors (p < 0.05, 0.01, 0.05, respectively). The Ki-67 index was higher in control tumors with high-stage and solid growth than in BEN UUC (p < 0.050, 0.005). The Ki-67 correlated with the grade, growth, stage, LVI, and multifocality of UUC on the best way, but not with the group. In regression analysis, only multifocality of UUC had predictive influence on Ki-67 activity (p < 0.001). P53 correlated with the grade, growth, and group (p < 0.05). This investigation identifies the p53 pathway as the specific cell cycle marker involved in BEN-associated UUC.

Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case-control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio [OR]=2.9; 95% confidence interval [CI]=1.9-4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2-H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found.

Primary cancers of the ureter and renal pelvis are rare tumours, > 90% of which are transitional cell carcinomas. Only approximately 5% of urothelial tumours arise in the upper urinary tract (UUT). Many environmental factors contribute to the development of these cancers. Some are similar to bladder cancer-associated factors (tobacco, occupational exposure), while others are more specific to carcinogenesis of the UUT (phenacetine, Balkan endemic nephropathy [BEN], Chinese herb nephropathy or association with Blackfoot disease [BFD]). This review discusses the environmental factors involved in UUT carcinoma. Tobacco and occupational exposure remain the principal exogenous risk factors for developing these tumours. Conversely, carcinogenesis of UUT tumours resulting from phenacetine consumption has almost disappeared. Although the incidence of BEN is also on the decline, roles for aristolochic acid and the consumption of Chinese herbs in the physiopathology and induction of this nephropathy, respectively, have proposed. In Taiwan, the association of this tumour type with BFD and arsenic exposure remains unclear to date. As some genetic polymorphisms are associated with an increased risk of cancer or faster disease progression, there is variability in interindividual susceptibility to the development of UUT carcinoma when exposed to the aforementioned risk factors Cytosolic sulfotransferases (SULTs) catalyse the detoxification of many environmental chemicals but also in the bioactivation of dietary and other mutagens. Polymorphism of the SULT gene, is thought to confer susceptibility to upper tract tumours.

Endometriosis is found in the urinary tract in 1-2% of women suffering from this disease. The most common site is urinary bladder (81%). In the ureter it is found in only 15% of cases and it mainly involves the pelvic part. The authors present a case of 49-year old woman who was diagnosed with an endometriotic tumour in the stump of the ureter, 13 years after left nephrectomy performed for hydronephrosis and lack of the kidney's function confirmed in renal scintigraphy. After laser ablation and hormonal therapy the tumour burden was diminished and symptoms resolved.

Aim: Adenocarcinomas of the upper urinary tract are very rare malignancies often related to primary genitourinary and extraurinary tumours. Primary adenocarcinomas are even rarer. There are no clinical guidelines for the management of primary ureteral adenocarcinoma. Our objective is to propose a management algoritm of this sort of tumours., Methods: We report a case of adenocarcinoma affecting a ureteral stump in a patient who previously underwent a nephrectomy. A review of literature is performed., Results: After the ureterectomy the pathologist diagnosed a ureteral adenocarcinoma. We performed an extension study in order to discard an extraurinary origin., Conclusions: Adenocarcinoma of the ureteral stump is a very rare malignancy. About the clinic and pathologic characterization, there is no an established reference due to the short number of previous reports. Clinical presentation may include previous nephrectomy, flank pain, dysuria, urgency and/or gross hematuria. It seem necessary the complete resection of the urinary tract when a nephrectomy is performed. Adjuvant chemotherapy can be employed with uncertain results.

Background/purpose: This study investigated the incidence of upper urinary tract urothelial carcinoma (UUT-UC) in eastern Taiwan and its association with chronic kidney disease (CKD)., Methods: A total of 110 patients with histologically proven UUT-UC over a recent 20-year period were retrospectively analyzed to determine the clinical profile, overall survival and correlation with CKD., Results: The mean age at diagnosis was 68.7 +/- 9.8 years (range, 43-93 years), and the male to female ratio was 1 to 1.16 (51:59). The ratio of urothelial carcinoma (UC) of the renal pelvis to UC of the ureter to UC of the bladder was 1.2:1:6.7. UC of the renal pelvis accounted for 10.8% of all urinary tract UC, and for 41% of all renal cancer detected during the study period. The 2-, 5- and 10-year cancer-specific survival rates of patients with UUT-UC were 75%, 53.0% and 29%, respectively. Patients with high grade and high stage UUT-UC had significantly worse prognosis than those with low grade (p = 0.0047) and low stage (p = 0.0021). Of the 110 patients, 64 (58%) had impaired renal function (glomerular filtration rate < 60 mL/min/1.73 m2; defined as CKD), including 14 (13%) with end-stage renal disease (ESRD) before diagnosis. Patients with CKD or ESRD had significantly worse prognosis than those with normal renal function (p = 0.0399). High grade UC was found in 35 of 58 patients with CKD or ESRD (60%), which was significantly higher than in patients with normal renal function (12/26, 26%; p = 0.019)., Conclusion: A high proportion of UUT-UC was observed among all UCs and a significantly higher percentage of high grade UUT-UC (60%) were found in patients with CKD or ESRD in eastern Taiwan. These findings suggest that CKD and ESRD might play a role in the development of UC especially in the upper urinary tract.

We report two cases of left ureteral carcinoma that may have been related to prior radiotherapy and anticancer chemotherapy for stage II testicular seminoma. Both patients had undergone radiotherapy (60 Gy) and cisplatin-based chemotherapy, one 17 years before the present presentation and the other 24 years earlier. They underwent retroperitoneoscopy-assisted left nephroureterectomy under a diagnosis of left upper ureteral cancer, established by means of ureteroscopy and brush biopsy. The urologic and radiologic outcomes have been satisfactory after more than 2 years of follow-up. Recently, some investigators have reported that testicular cancer survivors are at significantly increased risk of solid tumors for at least 35 years after treatment. Young patients may have a high risk of cancer when they reach an advanced age.

Malignant transformation and particularly malignant mixed mullerian tumor arising in extragenital endometriosis is extremely rare and occurs in the majority of cases after estrogen replacement therapy. We present a case of a 75-year-old woman who developed a ureteral malignant mullerian carcinosarcoma in a context of florid endometriosis. The patient had a history of total hysterectomy with bilateral salpingo-oophorectomy 30 years earlier for extensive endometriosis. Since 5 years, the patient has been on phytoestrogen supplementation consisting of 72 mg/day of superconcentrated soy isoflavones. This is the first case of ureteral mullerian carcinosarcoma arising in endometriosis foci after extensive phytoestrogen supplementation. Our data suggest that phytoestrogens at least in concentrated form may play a role not only in maintenance of endometriosis but also in its malignant transformation. Given the extraordinary popularity and availability of these dietary supplements, several studies are indispensable regarding their safety particularly in women with extensive endometriosis.

Primary tumor originated from ureteral stump following nephrectomy for benign disease is extremely rare. A 79-year-old male was referred to our department for asymptomatic macroscopic hematuria. He had undergone left simple nephrectomy for renal tuberculosis 52 years ago. Cystoscopic examination revealed a ureteral tumor on the residual ureteral orifice. Under the diagnosis of left ureteral stump tumor, which was subsequently enhanced on computer tomographic scan and magnetic resonance imaging, he received partial cystectomy and excision of the left ureteral stump. The histological examination revealed grade 2 to 3 urothelial carcinoma with muscle invasion (pT2). He received no adjuvant chemotherapy. He is now alive and free from recurrence 2 months post-operatively. This is the 21st case reported in the Japanese literature.

Objective: The occurrence of primary carcinoma of the ureteral stump after nephrectomy is rare. In this study, we evaluated the clinical characteristics of ureteral stump tumors after nephrectomy for benign renal disease., Methods: During a 16-year period, 318 consecutive patients underwent simple nephrectomy for benign renal disease (216 cases) or for donation (102 cases). Eight of these 318 patients diagnosed as having an ureteral stump tumor were treated by ipsilateral ureterectomy with cuff excision of the bladder. Pathologic findings, tumor stages, and clinical characteristics were analyzed., Results: The eight ureteral stump tumors comprised; 6 transitional cell carcinomas (TCCs) and 2 squamous cell carcinomas (SCCs). The mean interval between nephrectomy and ureteral stump tumor diagnosis was 76.5 months. Six of the 8 patients had pyonephrosis and two renal tuberculosis as original renal diseases. Four of the 6 TCCs were stage T1 and 2 stage T2. There was no concomitant bladder tumor at stump tumor diagnosis. Hematuria was the major presenting symptom in 3 of the 8 patients and 4 patients were diagnosed by follow-up imaging study. Two of the 6 ureteral stump TCC patients developed bladder TCC during follow-up. The 5-year survival rate of patients with ureteral stump tumor was 37.5%. T1G1 TCC was associated with a better survival than T2 or G2 TCC. No ureteral stump tumor occurred in cases of donor nephrectomy., Conclusion: This study demonstrate, that long-term closed observation is needed to detect ureteral stump tumor, particularly in patients that have undergo nephrectomy for a long-standing inflammatory renal disease such as pyonephrosis or tuberculosis. Hematuria is a major presenting symptom of ureteral stump tumor. However, a follow-up imaging study is also important for ureteral stump tumor detection. The prognosis is poor in cases developing ureteral stump SCC, bladder tumor recurrence, or a high-grade ureteral tumor.

The treatment of a man with six metachronous primary cancers is described. The primary lesions were in the soft palate, both edges of the tongue, the hard palate, the esophagus, and the right ureter. Pathologically, all of the first five tumors in the head and neck and esophagus were proven to be squamous cell carcinoma with various grades of differentiation, and the last one was transitional cell carcinoma. The cancers were found in the early clinical stage, and were completely controlled one by one except for the ureteral tumor under treatment. His characteristic medical history and physical findings, i.e. bilateral cataracts, short stature, baldness, diabetes mellitus, high-pitched voice, and multiple malignancies, met the clinical criteria for possible Werner syndrome, a genetic premature aging disorder, though the possibility of phenocopy of this syndrome has not been ruled out. We have followed him carefully because he might be vulnerable to malignant tumor formation.

Background: Synchronous bilateral urothelial tumors of the upper urinary tract are very rare. The authors reported baseline and long-term follow-up data for all patients in western Sweden during a 28-year period., Methods: The authors performed a clinical and histopathologic study of all patients in western Sweden who were diagnosed with a malignant neoplasm in the renal pelvis or ureter between 1971 and 1998., Results: Of 936 patients, 15 (1.6%) had synchronous bilateral tumors. The incidence of such tumors decreased in each successive decade. Abuse of phenacetin-containing analgesics by patients also decreased during the study period, as did the incidence of renal papillary necrosis. The median age at diagnosis of bilateral tumors was 68 years, and 80% of the patients were male. Eleven patients had bilateral tumors of the renal pelvis, two had bilateral ureteral tumors, and two had tumors of the renal pelvis and contralateral ureter. Partial renal pelvic, ureteral, or kidney resection on at least one side was possible in eight patients, and four patients were left untreated on at least one side. Only three patients underwent bilateral nephroureterectomy. Twelve patients (80%) had bladder carcinoma diagnosed either before or after diagnosis of the upper tract tumors. The median survival period for the 11 patients who received surgery for their bilateral tumors was 84 months., Conclusions: The decreasing incidence of synchronous bilateral upper tract tumors may be related to the prohibition of phenacetin-containing analgesics in the 1960s. Partial resection with preservation of the renal parenchyma was possible in the majority of patients. Survival for patients with bilateral tumors did not differ from that of patients with unilateral tumors., (Copyright 2004 American Cancer Society.)

Background: Aristolochic acid-associated nephropathy (AAN) is a specific type of renal disease that predisposes patients to a high risk of urothelial carcinoma. The authors have analyzed DNA from a patient who had urothelial malignancy 6 years after presenting with AAN and later had a breast carcinoma that metastasized to the liver., Methods and Results: DNA was isolated from the primary breast tumor, the liver tumor, and the original urothelial malignancy and assayed for aristolochic acid (AA)-DNA adducts and mutations in the p53 gene. The adduct detected was the adenosine adduct of aristolochic acid I 7-(deoxyadenosin-N6-yl)aristolactam I (dA-AAI). In DNA from the breast and liver tumors the authors showed the same missense mutation in codon 245 (GGC-->GAC; Gly-->Asp) of exon 7 of p53. In contrast, DNA extracted from the urothelial tumor showed an AAG to TAG mutation in codon 139 (Lys-->Stop) of exon 5., Conclusion: A to T transversions, as observed here, are the typical mutations observed in the H-ras gene of tumors induced when rodents are treated with AA and correspond with DNA adduct formation at adenosine residues. These data indicate the probable molecular mechanism whereby AA causes urothelial malignancy.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by an excess of extracolonic malignancies including those of the urinary tract. We report a case of metachronous bilateral ureteral cancer associated with HNPCC. A 51-year-old man was referred to Nara National Hospital for further examination of left hydronephrosis on excretory urography performed on the periodical follow-up for colon cancer. Computed tomography showed a mass in the left lower ureter and urine cytology was demonstrated class V. The operation was performed under the diagnosis of left ureteral cancer. The histopathological diagnosis was transitional cell carcinoma, grade 2, pT1. After 4 months of the operation, he presented with gross hematuria. Retrograde pyelography demonstrated tumors in the right side (ureter and renal pelvis) and the histopathological diagnosis of the biopsy specimens revealed transitional cell carcinoma, grade 2. We performed 4 times of BCG instillation followed by laser ablation of the tumor. The reported case was compatible for Japanese clinical criteria, group B for HNPCC.

Background: Contralateral, metachronous upper urinary tract (UUT) tumors after primary transitional cell carcinoma (TCC) of the UUT are reported rarely, and to the authors' knowledge the risk factors have not been determined to date. In addition, few reports have described the characteristics of recurrent bladder tumors and contralateral UUT tumors and any relation between theses tumor types., Methods: Statistical analysis of data from 223 patients with documented primary UUT-TCC was undertaken. After excluding bilateral involvement and distant metastases, 12 variables were analyzed by multivariate analysis in 189 patients to determine the risk factors for recurrent urothelial tumors., Results: The incidence rates of recurrent bladder tumors and contralateral UUT tumors were 31.2% and 5.8%, respectively. Multiplicity was determined as a risk factor for recurrent bladder tumors. Renal insufficiency, uremia, and concurrent bladder tumors significantly predisposed patients to develop contralateral UUT tumors after primary UUT-TCC. The time intervals and stage distributions differed significantly between recurrent bladder tumors and contralateral UTT tumors. Patients who had recurrent bladder tumors had earlier stage tumors and had a shorter time to recur compared with patients who had contralateral, metachronous UUT tumors., Conclusions: For patients with primary UUT-TCC, regular follow-up by cystoscopy is necessary to detect recurrent bladder tumors. Intravenous urography or retrograde pyelography should be performed for patients who have a high risk of developing contralateral UUT tumors., (Copyright 2003 American Cancer Society.)

Transitional cell carcinoma (TCC) of ureter and renal pelvis is relatively uncommon. Smoking, occupational carcinogens, analgesic abuse, Balkan nephropathy are the risk factors. Cytogenetic studies revealed that the most frequent aberration is the partial or complete loss of chromosome 9. Approximately 20-50% of patients with upper urinary tract (UUT) TCC have bladder cancer at some point on their course, whereas the incidence of UUT TCC after primary bladder cancer is 0.7-4%. Excretory urography and retrograde pyelography are the conventional diagnostic tools; however, ureteropyeloscopy combined with cytology and biopsy is more accurate. Grade and stage of the disease have the most significant impact on survival. Nephroureterectomy with bladder cuff excision has been the mainstay of treatment. Local resection may be appropriate for distal ureteral lesions especially when the disease is low grade and stage. Advances in endourology have made it possible to treat many tumors conservatively. Ureteroscopic and to a certain extent percutaneous surgical approaches are widely used today especially in patients with low grade, low stage disease. Endoscopic close surveillance is mandatory for these patients. Adjuvant topical therapies appear to be safe but confirmation of any benefits awaits the results of further large studies. More recently, laparoscopic techniques have become a viable alternative to open surgery, but long term cancer control data are lacking. Aggressive surgical resection does not affect the outcome of patients with advanced disease. Adjuvant radiotherapy is ineffective, and systemic chemotherapy results in a low complete response rate for patients with metastases.

We reviewed the clinical, radiographic, and pathologic findings of ureteral transitional cell carcinoma (TCC) in a blackfoot disease (BFD) endemic area in southern Taiwan to increase understanding of tumor behavior in this area, which has a high incidence of urothelium carcinoma. From August 1995 to February 2002, 28 histologically proven ureteral TCCs from this area were eligible for study. There was an unusual female predominance (male:female ratio, 1:1.333). The urographic filling defects in the 28 ureteral TCCs were classified into four categories. An ovoid filling defect was significantly associated with non-invasive tumors (p = 0.003) and a trend toward low tumor grades (p = 0.073). The risk of ureteral TCC in this BFD endemic area of southern Taiwan remained high between August 1995 and February 2002. Urographic surveillance provides a simple, clear, inexpensive method to study the extent, location, and morphology of the ureteral mass. Detailed assessment of the image could be useful for preoperative planning and predicting prognosis. Large-scale, randomized, prospective clinical trials are needed to validate our results.

A 43-year-old man presented with left hydronephrosis, incidentally found by ultrasonography. He had undergone transurethral bladder tumor resection when he was 29 years old. Cystoscopy revealed a tumor protruding from the left ureteral orifice. Left partial ureterectomy was performed, and its histopathological diagnosis was ureteral inverted papilloma. He has remained free of disease for 18 months after the surgery.

We report a case of carcinosarcoma of the renal pelvis and ureter arising in an 89-year-old man who presented at our hospital with gross hematuria. Abdominal computed tomography, excretory pyelography, and retrograde pyelography demonstrated that left hydronephrosis was caused by an ureteral tumor. Left urine cytology indicated transitional cell carcinoma. The patient underwent chemotherapy and radiation therapy. However, gross hematuria recurred, and the patient underwent left nephroureterectomy. The surgical specimen showed carcinosarcoma in the renal pelvis and ureter histologically. He has been free of cancer for 1.5 years.