Vashistha V, Shabsigh A, Zynger DL
Utility and diagnostic accuracy of ureteroscopic biopsy in upper tract urothelial carcinoma.
Arch Pathol Lab Med. 2013; 137(3):400-7 [PubMed]

CONTEXT: Ureteroscopic biopsy is the gold standard for the histopathologic diagnosis of urothelial carcinoma of the upper urinary tract.
OBJECTIVE: To assess the accuracy of endoscopically obtained biopsy samples in diagnosing, grading, and staging urothelial carcinoma and correlate diagnostic findings to biopsy sample size.
DESIGN: We retrospectively reviewed endoscopic biopsies of the ureter, renal pelvis, and ureteropelvic junction from 2008 to 2011. Biopsy diagnoses that were discordant with follow-up pathology and/or ureteroscopic impression were re-reviewed and samples were immunohistochemically analyzed.
RESULTS: Endoscopic biopsies (n = 118) yielded a sensitivity of 85.4% for the ureter (n = 79), 77.8% for the renal pelvis (n = 37), and 100% for the ureteropelvic junction (n = 2). A specificity of 100% for all locations and a diagnostic accuracy of 98.3% were identified. The median sample size was 0.3 cm for true positives, 0.3 cm for true negatives, and 0.2 cm for false negatives with no statistical significance. We found that 87.1% of tumors diagnosed on biopsy had concordant grade and 60.0% had concordant pT stage with follow-up surgical resections (n = 43) and biopsies (n = 24). Biopsy samples with concordant tumor grades (mean = 0.6 cm) compared with follow-up resection were larger than biopsy samples with discordant grades (mean = 0.3 cm) (P = .04).
CONCLUSIONS: Though highly specific, endoscopic biopsy does provide a significant false-negative rate owing to both sampling and diagnostic errors when assessing the upper urinary tract for urothelial carcinoma. Tumor grading is accurate, particularly with larger tissue samples, but tumor staging is unreliable.

Vogelzang NJ
Antiangiogenic agents, chemotherapy, and the treatment of metastatic transitional cell carcinoma.
J Clin Oncol. 2013; 31(6):670-5 [PubMed]

A 69-year-old man with a 100 pack-year history of smoking developed gross hematuria. His medical history included hypertension, a silent myocardial infarction, and a cerebrovascular accident complicated by seizures. Cystoscopy and biopsy showed a 4-cm mass at the right ureteral orifice positive for a high-grade papillary transitional cell carcinoma (TCC) with muscularis propria invasion (Fig 1). The computed tomography (CT)/positron emission tomography (PET) scan of the chest, abdomen, and pelvis showed hydronephrosis and hydroureter with marked cortical thinning and multiple bilateral PET-avid pulmonary nodules, with the largest in the left upper lung measuring 3.0 × 2.5 cm (Figs 2A, 3A), biopsy of which showed invasive high-grade urothelial carcinoma. The patient consented to join a clinical trial for metastatic TCC (USON [US Oncology Network study] 06040) involving treatment with gemcitabine, cisplatin, and sunitinib (GCS) 37.5 mg per day. Four days later, he experienced a 10-day hospitalization for acute pancreatitis and neutropenia. Sunitinib was discontinued, and he completed four additional cycles of GC. CT/PET showed that the right ureteral mass and all lung nodules had regressed or disappeared (Figs 2B, 3B). The largest remaining lung nodule at 1.4 cm showed no metabolic activity. He underwent a radical cystoprostatectomy and right nephroureterectomy, disclosing residual high-grade urothelial carcinoma infiltrating the full thickness of the ureteral wall. There was carcinoma in situ of the bladder, and 42 nodes were negative for cancer. The surgery was followed by a small, uncomplicated myocardial infarction. A scheduled left thoracotomy to remove the remaining nodule was cancelled. No additional chemotherapy was administered, and the patient remains free of recurrence 2 years from initiation of chemotherapy. The 1.4-cm nodule has calcified and remains stable and metabolically inactive. He has no sequelae of chemotherapy or surgery, with a creatinine level of 1.35 mg/dL.

Simonato A, Varca V, Gregori A, et al.
Elective segmental ureterectomy for transitional cell carcinoma of the ureter: long-term follow-up in a series of 73 patients.
BJU Int. 2012; 110(11 Pt B):E744-9 [PubMed]

UNLABELLED: What's known on the subject? and What does the study add? Upper Urinary Tract (UUT) Transitional Cell Carcinoma (TCC) is an uncommon disease and represents approximately 5% of all urothelial carcinomas. We report our series on 73 patients treated with Kidney Sparing Surgery for UUT TCC. Good results have been achieved in terms of oncological outcome comparing this conservative approach to the radical nephrourectomy.
OBJECTIVES: • To report the long-term oncological outcome in patients with transitional cell carcinoma of the ureter electively treated with kidney-sparing surgery. • To compare our data with the few series reported in the literature.
PATIENTS AND METHODS: • We considered 73 patients with transitional cell carcinoma of the distal ureter treated in five Italian Departments of Urology. • The following surgeries were carried out: 38 reimplantations on psoas hitch bladder (52%), 21 end-to-end anastomoses (28.8%), 11 direct ureterocystoneostomies (15.1%) and three reimplantations on Boari flap bladder (4.1%). • The median follow-up was 87 months.
RESULTS: • Tumours were pTa in 42.5% of patients, pT1 in 31.5%, pT2 in 17.8% and pT3 in 8.2%. • Recurrence of bladder urothelial carcinoma was found in 10 patients (13.7%) after a median time of 28 months. • The bladder recurrence-free survival at 5 years was 82.2%. • The overall survival at 5 years was 85.3% and the cancer-specific survival rate at 5 years was 94.1%.
CONCLUSION: • Our data show that segmental ureterectomy procedures do not result in worse cancer control compared with data in the literature regarding nephroureterectomy.

Kitamura H, Igarashi M, Tanaka T, et al.
A role for preoperative systemic chemotherapy in node-positive upper tract urothelial carcinoma treated with radical nephroureterectomy.
Jpn J Clin Oncol. 2012; 42(12):1192-6 [PubMed]

OBJECTIVE: There are few reports investigating the potential benefits of preoperative systemic chemotherapy for patients with node-positive upper tract urothelial carcinoma. The purpose of this study was to examine the impact of preoperative systemic chemotherapy on the clinical outcomes of patients with node-positive upper tract urothelial carcinoma treated by radical nephroureterectomy.
METHODS: Data were collected on 195 consecutive patients with upper tract urothelial carcinoma treated by radical nephroureterectomy between 1995 and 2010 at a single institute. Of these, 29 patients with node-positive disease but no visceral metastasis were retrospectively evaluated. In patients who underwent preoperative systemic chemotherapy, tumor response, post-therapy pathological downstaging to either residual disease at radical nephroureterectomy or no residual lymph node metastasis (pN0) and toxicity were the endpoints of interest. Overall survival was compared between two groups: those with and without preoperative chemotherapy.
RESULTS: All patients underwent regional lymphadenectomy. Overall, 15 patients (52%) underwent preoperative systemic chemotherapy. Pathological downstaging was achieved in 47%, including pN0, but there was no pathological complete response. Eighty-six percent of the patients with pathological downstaging had no evidence of recurrence. The median overall survivals were 38 and 9 months for patients with and without preoperative systemic chemotherapy, respectively (hazard ratio: 0.26, P = 0.015, log-rank test). There was no significant difference in operative morbidity between the two groups, and no operations were delayed because of preoperative chemotherapy.
CONCLUSIONS: The survival of patients who undergo preoperative systemic chemotherapy following radical nephroureterectomy seems to be superior to that of those undergoing radical nephroureterectomy alone. However, to confirm this, prospective randomized studies are needed.

Jankovic Velickovic L, Ristic Petrovic A, Stojnev S, et al.
Angiogenesis in upper tract urothelial carcinoma associated with Balkan endemic nephropathy.
Int J Clin Exp Pathol. 2012; 5(7):674-83 [PubMed] Free Access to Full Article

Upper tract urothelial carcinoma (UTUC) associated with Balkan endemic nephropathy (BEN) is characterized by a number of aberrations in cell-cycle regulation and apoptosis. The aim of this study was to detect angiogenesis-related marker(s) specific for BEN UTUC, and to examine the influence of HIF 1α upon angiogenesis and apoptosis in UTUC. Present investigation included 110 patients with UTUC, 50 from BEN region and 60 control tumors. Altered expression of VEGFR1 was more often present in control UTUC than in BEN tumors (p<0.005). It was associated with high grade, low and high stage, solid growth, and metaplastic change of control UTUC. Microvessel density assessed by CD31 (MVD CD31) was significantly higher in UTUC with lymphovascular invasion (p<0.05), and in BEN tumors with papillary growth (p<0.05). Discriminant analysis indicated that BEN and control tumors do not differ significantly in expression of angiogenesis related markers. The most important discriminant variable that determined control UTUC was expression of VEGFR1 (p=0.002). HIF 1α in UTUC significantly correlated with the low stage, papillary growth and expression of Bcl-2, Caspase-3 index, and MVD CD34 (p<0.001; 0.0005; 0.01; 0.005; 0.01, respectively). HIF-1α may be helpful marker in evaluation of UTUC, especially when combined with angiogenesis and apoptosis.

Tyler A
Urothelial cancers: ureter, renal pelvis, and bladder.
Semin Oncol Nurs. 2012; 28(3):154-62 [PubMed]

OBJECTIVES: To review the diagnosis, treatment, and nursing management of patients with urothelial cancers.
DATA SOURCES: PubMed, Ovid MEDLINE, Text books, and clinical experience.
CONCLUSION: Progress is being made in the surgical and systemic management of urothelial cancers, and the oncology nurse is in a position to make an impact on patient education and overall quality of life.
IMPLICATIONS FOR NURSING PRACTICE: Nursing care begins at pre-diagnostic testing and continues through treatment for metastatic disease. Nurses must be knowledgeable about diagnostic tests, treatment options, and the quality-of-life implications of associated surgeries and/or treatments to support and guide patients. Education should be comprehensive, addressing not only treatment side effects but also long-term implications on patients' lives and lifestyles.

Rai BP, Shelley M, Coles B, et al.
Surgical management for upper urinary tract transitional cell carcinoma (UUT-TCC): a systematic review.
BJU Int. 2012; 110(10):1426-35 [PubMed]

Surgical management of upper urinary tract transitional cell carcinoma (UUT-TCC) has significantly changed over the past two decades. Data for several new surgical techniques, including nephron-sparing surgery (NSS), is emerging. The study systematically reviewed the literature comparing (randomised and observational studies) surgical and oncological outcomes for various surgical techniques MEDLINE, EMBASE, Cochrane Library, CINAHL, British Nursing Index, AMED, LILACS, Web of Science, Scopus, Biosis, TRIP, Biomed Central, Dissertation Abstracts, ISI proceedings, and PubMed were searched to identify suitable studies. Data were extracted from each identified paper independently by two reviewers (B.R. and B.S.) and cross checked by a senior member of the team. The data analysis was performed using the Cochrane software Review manager version 5. Comparable data from each study was combined in a meta-analysis where possible. For dichotomous data, odds ratios with 95% confidence intervals (CIs) were estimated based on the fixed-effects model and according to an intention-to-treat analysis. If the data available were deemed not suitable for a meta-analysis it was described in a narrative fashion. One randomised control trial (RCT) and 19 observational studies comparing open nephroureterectomy (ONU) and laparoscopic NU (LNU) were identified. The RCT reported the LNU group to have statistically significantly less blood loss (104 vs 430 mL, P < 0.001) and mean time to discharge (2.30 vs 3.65 days, P < 0.001) than the ONU group. At a median follow-up of 44 months, the overall 5-year cancer-specific survival (CSS; 89.9 vs 79.8%) and 5-year metastasis-free survival rates (77.4 vs 72.5%) for the ONU were better than for LNU, respectively, although not statistically significant. A meta-analysis of the observational studies favoured LNU group for lower urinary recurrence (P < 0.001) and distant metastasis. The meta-analyses for local recurrence for the two groups were comparable. One retrospective study comparing ONU with a percutaneous approach for grade 2 disease reported no significant differences in CSS rates (53.8 vs 53.3 months). Three retrospective studies compared NSS and radical NU, and reported no significant differences in overall CSS and recurrence-free survival between the two approaches. Five retrospective studies compared various techniques of en bloc excision of the lower ureter. No technique was reported to be better (operative and oncological) than any other. This review concludes that there is a paucity of good quality evidence for the various surgical approaches for UUT-TCC. The techniques have been assessed and reported in many retrospective single-centre studies favouring LNU for better perioperative outcomes and comparable oncological safety. The reported observational studies data is further supported by one RCT.

Radulović P, Kraus O, Krušlin B
Micropapillary urothelial carcinoma of the ureter.
Cesk Patol. 2012; 48(2):100-2 [PubMed]

Micropapillary urothelial carcinoma (MPUC) is a rare aggressive variant of urothelial carcinoma, associated with advanced tumor stage, high tendency to invade lymphovascular spaces, and metastasize to lymph nodes and other organs. Therefore, it has a poor prognosis. One of the most prominent histological features is the presence of small, round empty spaces surrounding infiltrating tumor nests. If detected, even a small focus of micropapillary pattern may be therapeutically significant; the higher proportion of micropapillary component, the worse the prognosis. Radical nephroureterectomy is the treatment of choice even in the setting of superficially invasive disease. Although, MPUC has been well studied in urinary bladder, only a few cases of MPUC in upper urinary tract have been described. We are describing a case of a 79-year old woman with micropapillary urothelial carcinoma involving ureter and review the literature of this rare entity.

Harikrishnan JA, Chilka S, Jain S
Urinary tract transitional cell carcinoma and melanosis of the bladder: a case report and review of the literature.
Ann R Coll Surg Engl. 2012; 94(4):e152-4 [PubMed]

Melanosis vesica is a rare condition and thought to be benign. We report the case of a 50-year-old man who presented with haematuria and was found to have a diffusely pigmented bladder on cystoscopy and high grade transitional cell carcinoma of his upper and lower renal tract. This required a laparoscopic nephroureterectomy and pathology confirmed a diagnosis of melanosis vesica. Melanosis vesica has only been associated with high grade transitional cell carcinoma in one previous case. We recommend that any patient presenting with bladder melanosis is monitored for the development of upper or lower urinary tract transitional cell carcinoma.

Bin X, Roy OP, Ghiraldi E, et al.
Impact of tumour location and surgical approach on recurrence-free and cancer-specific survival analysis in patients with ureteric tumours.
BJU Int. 2012; 110(11 Pt B):E514-9 [PubMed]

UNLABELLED: What's known on the subject? and What does the study add? Pathological stage, lymph node metastasis and tumour grade have been established as prognostic factors for upper-tract urothelial carcinoma, but there are few studies to date assessing location within the ureter as a prognostic factor. There are also few studies comparing surgical approaches to radical nephroureterectomy (NU), partial ureterectomy and endoscopic resection (ENDO) with regard to oncological outcomes. This study did not find any prognostic significance for tumour location or surgical approach with regard to outcomes in patients with ureteric tumours. Although NU is the standard treatment for invasive ureteric tumours, partial ureterectomy and ENDO can safely be performed in selected patients. Despite the risk of a shorter time to recurrence, ENDO can be recommended in low grade, non-invasive ureteric tumours but only with close, thorough surveillance practices.
OBJECTIVE: • To assess the impact of tumour location within the ureter and the impact of surgical approach on recurrence-free survival (RFS) and cancer-specific survival (CSS) with regard to ureteric tumours.
PATIENTS AND METHODS: • Data were retrospectively reviewed from 60 patients with isolated primary ureteric tumours, treated at a single tertiary referral centre. • Patients were treated with radical nephroureterectomy (NU, n= 33), partial ureterectomy (n= 17) or endoscopic resection (ENDO, n= 10). • Kaplan-Meier curves were used for the analysis of RFS and CSS after surgery, stratified by tumour location and surgical approach.
RESULTS: • With a median follow-up of 29 months, tumour location was not associated with disease recurrence (P= 0.423). • The ENDO group had shorter time to disease recurrence. • There were no significant differences in the probability of CSS with regard to either tumour location or surgical approach (P= 0.523 and P= 0.904, respectively).
CONCLUSIONS: • Tumour location or surgical approach were not significant predictors of oncological outcomes in patients with ureteric tumours. • Although NU is standard treatment for invasive ureteric tumours, partial ureterectomy and ENDO can safely be performed in selected patients. Despite the risk of a shorter time to recurrence, ENDO can be recommended in low grade, non-invasive ureteric tumours. • All urothelium-preserving approaches require thorough surveillance.

Berod AA, Colin P, Yates DR, et al.
The role of American Society of Anesthesiologists scores in predicting urothelial carcinoma of the upper urinary tract outcome after radical nephroureterectomy: results from a national multi-institutional collaborative study.
BJU Int. 2012; 110(11 Pt C):E1035-40 [PubMed]

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.

Cutress ML, Stewart GD, Wells-Cole S, et al.
Long-term endoscopic management of upper tract urothelial carcinoma: 20-year single-centre experience.
BJU Int. 2012; 110(11):1608-17 [PubMed]

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Endoscopic management of small, low-grade, non-invasive upper tract urothelial cell carcinoma (UTUC) is a management option for selected groups of patients. However, the long-term survival outcomes of endoscopically-managed UTUC are uncertain because only four institutions have reported outcomes of more than 40 patients beyond 50 months of follow-up. Moreover, there is significant variance in the degree of underlying UTUC pathology verification in some of these reports, which precludes an analysis of disease-specific survival outcomes. The present study represents one of the largest endoscopically managed series of patients with UTUC, with a long-term follow-up. The degree of verification of underlying UTUC pathology is one of the highest, which allows a grade-stratified analysis of different outcomes, including upper-tract recurrence-free survival, intravesical recurrence-free survival, renal unit survival and disease-specific survival. These outcomes provide further evidence suggesting that endoscopic management of highly selected, low-grade UTUC can provide effective oncological control, as well as renal preservation, in experienced centres.
OBJECTIVE: • To report the long-term outcomes of patients with upper tract urothelial cell carcinoma (UTUC) who were treated endoscopically (either via ureteroscopic ablation or percutaneous resection) at a single institution over a 20-year period.
PATIENTS AND METHODS: • Departmental operation records were reviewed to identify patients who underwent endoscopic management of UTUC as their primary treatment. • Outcomes were obtained via retrospective analysis of notes, electronic records and registry data. • Survival outcomes, including overall survival (OS), UTUC-specific survival (disease-specific survival; DSS), upper-tract recurrence-free survival, intravesical recurrence-free survival, renal unit survival and progression-free survival, were estimated using Kaplan-Meier methods and grade-stratified differences were analyzed using the log-rank test.
RESULTS: • Between January 1991 and April 2011, 73 patients underwent endoscopic management of UTUC with a median age at diagnosis of 67.7 years. • All patients underwent ureteroscopy and biopsy-confirmation of pathology was obtained in 81% (n = 59) of the patients. In total, 14% (n = 10) of the patients underwent percutaneous resection. • Median (range; mean) follow-up was 54 (1-223; 62.8) months. • Upper tract recurrence occurred in 68% (n = 50). Eventually, 19% (n = 14) of the patients proceeded to nephroureterectomy. • The estimated OS and DSS were 69.7% and 88.9%, respectively, at 5 years, and 40.3% and 77.4%, respectively, at 10 years. The estimated mean and median OS times were 119 months and 107 months, respectively. The estimated mean DSS time was 190 months.
CONCLUSIONS: • The present study represents one of the largest reported series of endoscopically-managed UTUC, with high pathological verification and long-term follow-up. • Upper-tract recurrence is common, which mandates regular ureteroscopic surveillance. • However, in selected patients, this approach has a favourable DSS, with a relatively low nephroureterectomy rate, and therefore provides oncological control and renal preservation in patients more likely to die eventually from other causes.

Kates M, Badalato GM, Gupta M, McKiernan JM
Secondary bladder cancer after upper tract urothelial carcinoma in the US population.
BJU Int. 2012; 110(9):1325-9 [PubMed]

UNLABELLED: Study Type - Prognosis (cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? It is known that a certain percentage of patients treated for upper tract urothelial carcinoma (UTUC) will go on to develop a secondary bladder cancer; however, the risk factors for developing a secondary bladder tumour have not been studied in a population-based setting. Given the large changes in how UTUC has been diagnosed and managed in recent years, this study aimed to evaluate the natural history of UTUC in the US population over a 30-year period, with a particular emphasis on the development of secondary bladder cancer.
OBJECTIVE: • To assess the natural history of upper tract urothelial carcinoma (UTUC) and the development of lower tract secondary cancer.
PATIENTS AND METHODS: • Patients diagnosed with UTUC between 1975 and 2005 were identified within nine Surveillance, Epidemiology and End Results registries. • Baseline characteristics of patients with and without secondary bladder cancer were compared. • A multivariate logistic regression model was fitted to test if the year of diagnosis predicted the likelihood of developing a secondary bladder cancer.
RESULTS: • Of the 5212 patients with UTUC, 242 (4.6%) had a secondary bladder cancer (range: 1.7-8.2%). • There was a mean interval of 26.5 (95% CI: 22.2-30.8) months between cancer diagnoses. • Compared with those without secondary tumours, patients with secondary bladder malignancy were more likely to present with larger tumours (4.2 vs 3.1 cm, P < 0.001) and with tumours located in the ureter (P < 0.001). • Year of diagnosis was not a predictor of the likelihood of having a secondary bladder malignancy in a multivariate analysis controlling for demographic and tumour characteristics (odds ratio: 0.99; 95% CI: 0.95-1.03)
CONCLUSIONS: • Patients with larger urothelial tumours located in the ureter were those most likely to develop a secondary lower tract tumour. • No longitudinal changes in the rate of secondary bladder cancer were noted among patients with UTUC over the 30-year study period.

Kondo T, Tanabe K
Role of lymphadenectomy in the management of urothelial carcinoma of the bladder and the upper urinary tract.
Int J Urol. 2012; 19(8):710-21 [PubMed]

The role of lymphadenectomy has been controversial in urological malignancies. Urothelial carcinoma of the bladder and upper urinary tract has a high potential to spread through the lymphatic network compared with other malignancies, including renal cell carcinoma or prostate cancer. In urothelial carcinoma of the bladder, lymphadenectomy of pelvic nodes had been considered as the standard procedure when radical cystectomy was carried out. Recently, many investigators have examined the influence of its extent, and the majority of the studies have supported the beneficial role of extended lymphadenectomy in accurate staging or in improving patient survival. Although randomized controlled trials are required to establish a greater level of evidence, more urological surgeons have already noticed the necessity for extended lymphadenectomy in bladder cancer. In contrast to bladder cancer, there have been far fewer studies on urothelial carcinoma of the upper urinary tract. This might be because of the smaller number of the patients with urothelial carcinoma of the upper urinary tract and the lack of understanding of regional nodes. However, studies of lymph node mapping and the retrospective analyses with respect to the benefit of lymphadenectomy have been carried out in urothelial carcinoma of the upper urinary tract by some investigators, although the results are still controversial. However, the results from multi-institutional studies by high volume centers have supported the beneficial role of lymphadenectomy in urothelial carcinoma of the upper urinary tract, as it has been proposed in bladder cancer. Thus, lymphadenectomy for urothelial carcinoma of the bladder and the upper urinary tract might have a potential role in staging and improving the oncological outcomes.

Chen CH, Dickman KG, Moriya M, et al.
Aristolochic acid-associated urothelial cancer in Taiwan.
Proc Natl Acad Sci U S A. 2012; 109(21):8241-6 [PubMed] Free Access to Full Article

Aristolochic acid, a potent human carcinogen produced by Aristolochia plants, is associated with urothelial carcinoma of the upper urinary tract (UUC). Following metabolic activation, aristolochic acid reacts with DNA to form aristolactam (AL)-DNA adducts. These lesions concentrate in the renal cortex, where they serve as a sensitive and specific biomarker of exposure, and are found also in the urothelium, where they give rise to a unique mutational signature in the TP53 tumor-suppressor gene. Using AL-DNA adducts and TP53 mutation spectra as biomarkers, we conducted a molecular epidemiologic study of UUC in Taiwan, where the incidence of UUC is the highest reported anywhere in the world and where Aristolochia herbal remedies have been used extensively for many years. Our study involves 151 UUC patients, with 25 patients with renal cell carcinomas serving as a control group. The TP53 mutational signature in patients with UUC, dominated by otherwise rare A:T to T:A transversions, is identical to that observed in UUC associated with Balkan endemic nephropathy, an environmental disease. Prominent TP53 mutational hotspots include the adenine bases of (5')AG (acceptor) splice sites located almost exclusively on the nontranscribed strand. A:T to T:A mutations also were detected at activating positions in the FGFR3 and HRAS oncogenes. AL-DNA adducts were present in the renal cortex of 83% of patients with A:T to T:A mutations in TP53, FGFR3, or HRAS. We conclude that exposure to aristolochic acid contributes significantly to the incidence of UUC in Taiwan, a finding with significant implications for global public health.

Alva AS, Matin SF, Lerner SP, Siefker-Radtke AO
Perioperative chemotherapy for upper tract urothelial cancer.
Nat Rev Urol. 2012; 9(5):266-73 [PubMed]

Upper tract urothelial cancer (UTUC) is an aggressive disease associated with significant morbidity and mortality. Radical nephroureterectomy (RNU) with bladder cuff removal is considered the standard of care for most invasive UTUCs but distant relapses after surgery for locally advanced, high-grade disease are common. Although multimodality treatment with perioperative chemotherapy has been investigated thoroughly in recent years, adjuvant chemotherapy has primarily been analyzed in small retrospective uncontrolled studies and a clear benefit for this treatment modality is yet to be established. It is likely that the high incidence of renal insufficiency after surgery substantially limits the applicability of adjuvant chemotherapy with cisplatin-based regimens. Neoadjuvant cisplatin-based chemotherapy has several practical advantages over adjuvant therapy, including better patient tolerance in the preoperative setting when a patient has two kidneys rather than one and the obtainment of prognostic information from pathological downstaging. Although, some academic centers have adopted neoadjuvant chemotherapy as a de facto treatment standard for patients with high-grade locally advanced UTUC, this treatment approach has not been prospectively validated or adopted in general urologic practice. A multicenter trial of neoadjuvant chemotherapy for locally advanced high-grade UTUC could further define the role of neoadjuvant chemotherapy in treating UTUC.

Bing-bing S, Cheng C, Han-zhong L, et al.
Correlation between surgical modality and clinicopathologic characteristics for ureteral transitional cell carcinoma.
Clin Transl Oncol. 2012; 14(4):312-6 [PubMed]

PURPOSE: To investigate the relationship between surgical modality and clinicopathologic features for ureteral transitional cell carcinoma.
METHODS: The correlation between surgical modality and clinicopathology characteristics of 146 patients with ureteral carcinoma having undergone surgery was evaluated using univariate analysis by a general linear model.
RESULTS: 43.8%, 51.4% and 4.8% of patients experienced nephroureterectomy, renal conservation management and palliative operations, respectively, with a mean survival time of 97.3, 101.3 and 51.0 months (p=0.069) accordingly. Univariate analysis by general linear model indicated that the size of lesions, pathologic stage and tumour grade had a statistically significant impact on surgical modality (p=0.000, p=0.001 and p=0.017, respectively).
CONCLUSION: Tumour stage and grade, as well as tumour size, correlate with surgical modality.

Grasso M, Fishman AI, Cohen J, Alexander B
Ureteroscopic and extirpative treatment of upper urinary tract urothelial carcinoma: a 15-year comprehensive review of 160 consecutive patients.
BJU Int. 2012; 110(11):1618-26 [PubMed]

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UTUC) have historically been treated with radical, extirpative surgery, primarily nephroureterectomy with bladder-cuff excision. In general, there has been growing interest in renal preservation, as evidenced by the broadening application of nephron-sparing surgery for renal parenchymal tumours. Beyond imperative reasons such as tumour in a solitary kidney, bilateral disease, or comorbidities preventing radical surgery, there is a growing role for endoscopic management of upper tract tumours. The aim has been to obtain similar oncological results to those of extirpative surgery, while preserving long-term renal function. Properly selecting patients for these therapies, designing specific treatments based on a complex presentation, and general information with regard to outcomes and risks for patient counselling have been based historically on results from relatively small series without long-term follow-up. This study reflects all patients with UTUC treated by a single tertiary referral surgeon, accrued prospectively over 15 years using the same surgical techniques and treatment algorithms throughout the entire study period, with 10-year survival data. The consecutively accrued nature and size of the study groups, uniformity in treatments, statistical review and long-term follow-up provide baseline oncological data that could help frame future study.
OBJECTIVE: • To present long-term oncological outcomes of all patients treated surgically for upper urinary tract urothelial carcinoma (UTUC) over a 15-year period.
PATIENTS AND METHODS: • All patients (N = 160) treated from January 1996 to August 2011 were prospectively studied and placed into three distinct groups after initial diagnostic ureteroscopy (URS): Group 1: low grade lesions treated with URS (n = 66); Group 2: high grade lesions palliatively treated with URS (n = 16); and Group 3: extirpative surgery (nephroureterectomy [NU]; n = 80). • Statistical analysis was performed using Kaplan-Meier methodology to calculate overall (OS), cancer-specific (CSS) and metastasis-free survival (MFS).
RESULTS: • The median patient age at presentation was 73 years, and the mean (range) follow-up time was 38.2 (1-185) months. At initial diagnostic URS, 71 (44.4%) patients presented with high grade and 89 (55.6%) patients presented with low grade disease. • The 2-, 5- and 10-year CSS rates were 98, 87 and 81% for patients with low grade disease, and 97, 87 and 78% for patients treated with URS (Group 1), not significantly different from those patients with low grade disease treated with NU (Group 3), (P = 0.54). • Of the patients treated with URS for low grade disease, 10 (15.2%) progressed to high grade disease at a mean time of 38.5 months. • Patients with high grade disease treated with NU had a 2-, 5-, and 10-year CSS of 70, 53 and 38%, with a MFS of 55, 45 and 35%. • Median survival of patients with high grade disease treated with palliative URS was 29.2 months with a 2-year OS of 54%. • On multivariate analysis only high grade lesion on initial presentation was found to be a significant factor (P < 0.001; hazard ratio = 7.27).
CONCLUSIONS: • Grade is the most significant predictor of OS and CSS in those with UTUC, regardless of treatment method. • Ureteroscopic and extirpative therapy are acceptable options for those with low grade disease showing excellent long-term CSS. • Extirpative therapy was found to result in relatively poor long-term CSS in patients with high grade disease, underscoring the need for adjuvant or neoadjuvant therapies.

Huguet J
Transitional cell carcinoma of the upper urinary tract after cystectomy.
Arch Esp Urol. 2012; 65(2):227-36 [PubMed]

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.

Colin P, Ouzzane A, Pignot G, et al.
Comparison of oncological outcomes after segmental ureterectomy or radical nephroureterectomy in urothelial carcinomas of the upper urinary tract: results from a large French multicentre study.
BJU Int. 2012; 110(8):1134-41 [PubMed]

UNLABELLED: What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UUT-UCs) are rare tumours. Because of the aggressive pattern of UC, radical nephroureterectomy (RNU) with bladder cuff removal remains the 'gold-standard' treatment. However, conservative strategies, such as segmental ureterectomy (SU) or endourological management, have also been developed in patients with imperative indications. Some teams are now advocating the use of conservative management more commonly in cases of elective indications of UUT-UCs. Due to the paucity of cases of UUT-UC, only limited data are available on the oncological outcomes afforded by conservative management. We retrospectively investigated the oncological outcomes after SU and RNU in a large multi-institutional database. Overall, 52 patients were treated with SU and 416 with RNU. There was no statistical difference between the RNU and SU groups for the 5-year probability of cancer-specific survival, recurrence-free survival and metastasis-free survival. The type of surgery was not a significant prognostic factor in univariate analysis. The results were the same in a subgroup analysis of only unifocal tumours of the distal ureter with a diameter of <2 cm and of low stage (≤T2). Our results suggest that oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT-UC in select cases.
OBJECTIVE: To compare recurrence-free survival (RFS), metastasis-free survival (MFS) and cancer-specific survival (CSS) after segmental ureterectomy (SU) vs radical nephroureterectomy (RNU) for urothelial carcinoma (UC) of the upper urinary tract (UUT-UC) located in the ureter.
PATIENTS AND METHODS: We performed a multi-institutional retrospective review of patients with UUT-UC who had undergone RNU or SU between 1995 and 2010. Type of surgery, Tumour-Node-Metastasis status, tumour grade, lymphovascular invasion and positive surgical margin were tested as prognostic factors for survival.
RESULTS: In all, 52 patients were treated with SU and 416 with RNU. The median (range) follow-up was 26 (10-48) months. The 5-year probability of CSS, RFS and MFS for SU and RNU were 87.9% and 86.3%, respectively (P = 0.99); 37% and 47.9%, respectively (P = 0.48); 81.9% and 85.4%, respectively (P = 0.51). In univariable analysis, type of surgery (SU vs RNU) failed to affect CSS, RFS and MFS (P = 0.94, 0.42 and 0.53, respectively). In multivariable analyses, pT stage and pN stage achieved independent predictor status for CSS (P = 0.005 and 0.007, respectively); the positive surgical margin and pT stage were independent prognostic factors of RFS and MFS (P = 0.001, 0.04, 0.009 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of the disease.
CONCLUSIONS: Short-term oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT-UC in select cases and should be considered an option. In every other case, RNU still represents the 'gold standard' for the treatment of UUT-UC.

Coskuner E, Cevik I, Ozkan A, et al.
In the cystoscopic follow-up of non-muscle-invasive transitional cell carcinoma, NMP-22 works for high grades, but unreliable in low grades and upper urinary tract tumors.
Int Urol Nephrol. 2012; 44(3):793-8 [PubMed]

INTRODUCTION AND OBJECTIVES: Two percent of the bladder non-muscle-invasive (NMI) transitional cell carcinomas (TCC) are associated with upper urinary tract (UUT) TCC. We evaluated the role of nuclear matrix protein-22 (NMP-22) (BladderChek) test in the diagnosis of lower urinary tract and UUT-TCC.
METHODS: From March 2009 to June 2011, 122 patients with bladder NMI-TCC underwent 205 control cystoscopy. A total of 95 (78 men and 17 women, mean age 60.7 years, range, 27-88) patients who were followed regularly with NMP-22 test and with follow-up cystoscopies (145 episodes; min. 1-max. 5) were included in this study. For routine monitoring of the UUT, IVU or CT urography was used once a year for high grades (HG), and once in every other year for low grades (LG). The sensitivity and specificity of NMP-22 were evaluated by ROC curves, and sensitivity, specificity, and positive and negative predictive values were calculated. Chi-square test was used for the differences between the subgroups.
RESULTS: Cystoscopy and NMP-22 results of the patients included in the study revealed the sensitivity (44.4%) of the test was very low and the specificity (98.4%) was quite high (p < 0.001). Among the 10 cystoscopies where NMP-22 was negative, but cystoscopy was positive for tumor, 8 had LG and 2 had HG TCC. NMP-22 was never positive in low-grade tumors, in other words, all of the NMP-22-positive 8 tumors were high grade. On the other hand, in 20% (2/10) of the cases, NMP-22 can be negative although the tumor was high grade. Two (2.1%) HG UUT-TCC were detected in 95 patients. These 2 patients were within the 125 cystoscopies (75 patients) where both NMP-22 and cystoscopy were negative for tumor.
CONCLUSIONS: Nuclear matrix protein-22 cannot detect LG TCC. However, it detects overwhelming majority of HG TCC. For this reason, positive NMP-22 test largely indicates HG TCC. NMP-22 is also not reliable in UUT-TCC, even in HG tumors.

Mouracade P, Velten M, Gigante M, et al.
Factors impacting survival in patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy.
Can J Urol. 2012; 19(1):6105-10 [PubMed]

INTRODUCTION: This study aims to assess the influence of different prognostic factors on survival of upper tract urothelial carcinoma (UTUC) managed by nephroureterectomy and to investigate whether these factors have an independent prognostic significance.
MATERIALS AND METHODS: A retrospective review of institutional databases from two teaching hospitals identified 269 consecutive patients with UTUC managed with nephroureterctomy between 1985 and 2005. Mean follow up was 80.6 months (median 70.3 months). Follow up was completed until January 2009. Tumor location and other clinicopathological variables were analyzed regarding survival. Data accrued included age, gender, tumor characteristics (pT stage, grade, lymph node status), tumor location, use of chemotherapy and period of diagnosis. Tumor location was divided into two groups (renal pelvis and ureter) based on the location of the tumor.
RESULTS: Five year and 10 year overall survival estimates for this cohort were 71.3% and 40.0% respectively. According to tumor location, survival was 73.6% and 47.0% for the renal pelvis versus 67.8% and 32.3% for the ureter, respectively (log rank test: p = 0.027). In multivariate analysis, among the clinicopathological variables, T stage was the most significant prognostic factor (p < 0.001). Nodal involvement (p = 0,005), high grade (p < 0.001), first period of diagnosis (p < 0.001) and ureteral tumor location (p = 0.003) were significantly associated with lower survival rates. Prognosis of UTUC improved over time: survival was significantly better during the last period of diagnosis (2001-2005) (p < 0.002).
CONCLUSIONS: Tumor location and diagnostic period should be considered as an independent prognostic factor for upper tract transitional cell carcinoma.

Godfrey MS, Badalato GM, Hruby GW, et al.
Prognostic indicators for upper tract urothelial carcinoma after radical nephroureterectomy: the impact of lymphovascular invasion.
BJU Int. 2012; 110(6):798-803 [PubMed]

UNLABELLED: What's known on the subject? and What does the study add? In an array of urological and non-urological malignancies, lymphovascular invasion (LVI) is a pathological feature known to be associated with adverse outcomes for recurrence and survival. For some cancers, LVI has therefore been incorporated into American Joint Committee on Cancer TNM staging algorithms. This study presents an analysis of the impact of LVI in upper urinary tract urothelial carcinoma (UTUC) treated at our institution over a 20-year period. In addition to known associations with features of aggressive disease and overall survival, we were able to show that LVI-positive status upsets the TNM staging for UTUC. Namely, patients with superficial stage and LVI-positive disease have overall survival outcomes similar to those of patients with muscle-invasive LVI-negative carcinoma. Such evidence may support the addition of LVI to future TNM staging algorithms for UTUC.
OBJECTIVE: To assess the impact of lymphovascular invasion (LVI) on the prognosis of patients with upper urinary tract urothelial cell carcinoma (UTUC) treated with radical nephroureterectomy (RNU).
PATIENTS AND METHODS: The Columbia University Medical Center Urologic Oncology database was queried and 211 patients undergoing RNU for UTUC between 1990 and 2010 were identified. These cases were retrospectively reviewed, and the prognostic significance of relevant clinical and pathological variables was analysed using log-rank tests and Cox proportional hazards regression models. Actuarial survival curves were calculated using the Kaplan-Meier method.
RESULTS: LVI was observed in 68 patients (32.2%). The proportion of LVI increased with advancing stage, high grade, positive margin status, concomitant carcinoma in situ, and lymph node metastases. The 5- and 10-year overall survival rates were 74.7% and 53.1% in the absence of LVI, and 35.7% and 28.6% in the presence of LVI, respectively. In multivariate analysis, age, race and LVI were independent predictors of overall survival.
CONCLUSIONS: The presence of LVI on pathological review of RNU specimens was associated with worse overall survival in patients with UTUC. LVI status should be included in the pathological report for RNU specimens to help guide postoperative therapeutic options. With confirmation from large international studies, inclusion of LVI in the tumour-node-metastasis staging system for UTUC should be considered.

Rogers A, Ng JK, Glendinning J, Rix D
The management of transitional cell carcinoma (TCC) in a European regional renal transplant population.
BJU Int. 2012; 110(2 Pt 2):E34-40 [PubMed]

UNLABELLED: In the West, transitional cell carcinoma (TCC) in renal transplant patients is uncommon, but aggressive. Conversely, it appears to be frequent in the Far East, necessitating aggressive surgical approaches such as prophylactic nephroureterectomy. There are few European case series to date. TCC in the present population was predominantly low-grade and superficial, with no progression in patients with those tumours. Endoscopic management was sufficient for most patients. The behaviour of TCC in the present population was much less aggressive than that described in the Far East. Altering immunosuppression regimes may have a role to play in managing bladder cancer in renal transplant patients.
OBJECTIVE: To examine the clinical characteristics, management and long-term outcomes of patients with transitional cell carcinoma (TCC) who also have had renal transplantation.
PATIENTS AND METHODS: A retrospective case note review was performed for the 15-year period 1995-2009. Searches from three different urological centres in the UK, using multiple sources, yielded 1647 patients with renal transplants, 12 of whom had TCC. Eight cases were identified who developed de novo TCC after transplantation (0.48%). Four patients had pre-existing TCC who then had renal transplantation. The current literature was reviewed.
RESULTS: In the eight de novo TCC cases, the bladder was the site in all with no upper tract TCC; seven were superficial (pTa/T1) and five were low grade (G1/2). The mean time to development of TCC after transplant was 5 years, with a mean follow-up of 11 years. There was no progression in low-grade superficial disease that was managed endoscopically. The 5- and 10-year overall survival was 83% and 72%, respectively. In patients with pre-existing TCC prophylactic bilateral nephroureterectomy before transplantation was performed once. There was progression of superficial disease whilst on immunosuppression in one patient. Sirolimus was used in patients with TCC and reports suggest this may have a role to play in modifying malignancy in this setting. The number of patients involved in studies particularly focusing on TCC in renal transplantation is small (136 patients), with 60% from China/Taiwan where there is a high incidence of upper tract TCC and high-grade muscle-invasive disease.
CONCLUSIONS: Although this is one of the largest European case series of renal transplant patients with TCC, the numbers are small making clear conclusions difficult. The frequency of TCC in our renal transplant population is low, consistent with previous studies. However, contrary to prior studies, TCC after renal transplantation in this European population was predominantly superficial, low-grade, non-progressive and confined to the bladder. Altering immunosuppression regimes in patients with TCC may have a role to play, although further work is required to clarify and substantiate this.

Yang WH, Ou CH
A muscle-sparing modified Gibson incision for hand-assisted retroperitoneoscopic nephroureterectomy and bladder cuff excision--an approach through a window behind the rectus abdominis muscle.
Urology. 2012; 79(2):470-4 [PubMed]

OBJECTIVE: To report our technique using a modified muscle-sparing Gibson incision for hand-assisted retroperitoneoscopic nephroureterectomy (HARN) and open bladder cuff excision.
MATERIALS AND METHODS: Thirty-four patients with upper tract transitional cell carcinoma received HARN and open bladder cuff excision using the modified muscle-sparing Gibson incision-an approach through a window behind the rectus abdominis muscle with the patient in a supine position with the legs extended and abducted at 45-60° with the surgeon standing between the legs of the patient. The window behind the rectus muscle was identified with ease. HARN and open bladder cuff excision were performed uneventfully using this incision. Mean estimated blood loss was 119 mL. Mean operation time was 139 minutes. Morphine was required for pain relief for 1-3 days (mean 16.5 mg). Mean time to oral intake was 1.5 days and to ambulation was 2.1 days. No lower abdominal bulge was found during a 15.4-month follow-up.
CONCLUSION: This modified muscle-sparing Gibson incision for retroperitoneal hand-assisted laparoscopic nephrectomy has the benefit of easier retroperitoneal approach of the Gibson incision. Iliohypogastric nerves can be spared under direct vision. By merely retracting and not incising or splitting the rectus abdominis muscle, this incision may decrease wound-related morbidity. This window could be an important portal for hand-assisted laparoscopic surgeries.

Clements T, Messer JC, Terrell JD, et al.
High-grade ureteroscopic biopsy is associated with advanced pathology of upper-tract urothelial carcinoma tumors at definitive surgical resection.
J Endourol. 2012; 26(4):398-402 [PubMed]

BACKGROUND AND PURPOSE: Accurate assessment of upper-tract urothelial carcinoma (UTUC) pathology may guide use of endoscopic vs extirpative therapy. We present a multi-institutional cohort of patients with UTUC who underwent surgical resection to characterize the association of ureteroscopic (URS) biopsy features with final pathology results.
PATIENTS AND METHODS: URS biopsy data were available in 238 patients who underwent surgical resection of UTUC. Biopsies were performed using a brush biopsy kit, mechanical biopsy device, or basket. Stage was classified as a positive brush, nonmuscle-invasive (RESULTS: On URS biopsy, 88/238 (37%) patients had a positive brush, 140 (59%) had a diagnosis of non-MI, and 10 (4%) had MI disease. Biopsy results showed low-grade cancer in 140 (59%) and high-grade cancer in 98 (41%). Pathologic evaluation at surgical resection demonstrated non-MI tumors in 140 (59%) patients, MI in 98 (41%), and high-grade disease in 150 (63%). On univariate analysis, high URS biopsy grade was associated with high-grade (positive predictive value [PPV] 92%, P<0.0001) and MI (PPV 60%, P<0.0001) UTUC at surgery. URS biopsy stage, however, was associated with surgical pathology grade (P=0.005), but not MI (P=0.16) disease. On multivariate analysis, high URS grade, but not biopsy stage, was associated with high final pathology grade (hazard ratio [HR] 16.6, 95% confidence interval [CI] 7.0-39.5, P<0.0001) and MI UTUC (HR 3.6, 95% CI 2.1-6.8, P<0.0001).
CONCLUSION: High URS biopsy grade, but not stage, is associated with adverse tumor pathology. This information may play a valuable role for risk stratification and in the appropriate selection of endoscopic management vs surgical extirpation for UTUC.

Silberstein JL, Power NE, Savage C, et al.
Renal function and oncologic outcomes of parenchymal sparing ureteral resection versus radical nephroureterectomy for upper tract urothelial carcinoma.
J Urol. 2012; 187(2):429-34 [PubMed]

PURPOSE: We compared renal function and oncologic outcomes of parenchymal sparing ureteral resection with radical nephroureterectomy for the treatment of upper tract urothelial carcinoma confined to the ureter.
MATERIALS AND METHODS: Review of a large institutional database identified 367 patients treated for primary upper tract urothelial carcinoma with radical nephroureterectomy or parenchymal sparing ureteral resection from 1994 to 2009. Patients with known renal pelvis tumors, muscle invasive urothelial carcinoma, prior cystectomy, contralateral upper tract urothelial carcinoma, metastatic disease or chemotherapy were excluded, leaving 120 patients for analysis. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Recurrence-free, cancer specific and overall survival were estimated using Kaplan-Meier analysis.
RESULTS: Radical nephroureterectomy was performed in 87 patients and parenchymal sparing ureteral resection in 33. Median age at surgery was 73 years in the radical nephroureterectomy group (IQR 64-76) vs 70 years (IQR 59-77) in the parenchymal sparing ureteral resection group (p = 0.5). The radical nephroureterectomy and parenchymal sparing ureteral resection cohorts had several disparate clinicopathological variables including preoperative hydronephrosis (80% vs 45%, p = 0.0006), stage (pT3 or greater 26% vs 9%, p = 0.01) and baseline estimated glomerular filtration rate (51 vs 63 ml/minute/1.73 m(2), p = 0.009). Patients who underwent radical nephroureterectomy experienced a significantly greater decrease in estimated glomerular filtration rate after surgery (median -7 vs 0 ml/minute/1.73 m(2), p <0.001). Median followup was 4.2 years. Of the patients 79 experienced cancer recurrence and 44 died (28 of upper tract urothelial carcinoma). There were no obvious differences in the rates of recurrence, cancer specific death or overall death by procedure type. However, due to the limited number of events we cannot exclude the possibility that there are large differences in oncologic outcomes by procedure type.
CONCLUSIONS: Parenchymal sparing ureteral resection is associated with superior postoperative renal function. However, the impact on cancer control cannot be determined conclusively due to the small sample size and putative selection bias.

Rouprêt M, Drouin SJ, Cancel-Tassin G, et al.
Genetic variability in 8q24 confers susceptibility to urothelial carcinoma of the upper urinary tract and is linked with patterns of disease aggressiveness at diagnosis.
J Urol. 2012; 187(2):424-8 [PubMed]

PURPOSE: Upper urinary tract urothelial carcinoma is rare. Evidence shows that it behaves differently from urothelial bladder tumors. A polymorphism located at the T allele of rs9642880 on chromosome 8q24 is linked to an enhanced risk of bladder tumors. We explored the association of this polymorphism with susceptibility to upper urinary tract urothelial carcinoma.
MATERIALS AND METHODS: We genotyped the constitutional DNA of 261 patients with upper urinary tract urothelial carcinoma and 261 healthy controls matched for age, gender, smoking habit and ethnicity. Polymorphisms at rs9642880 on chromosome 8q24 were determined using the 5' nuclease polymerase chain reaction method with specific primers and probes. Frequencies were compared between cases and controls. Genotypes were in Hardy-Weinberg equilibrium for cases and controls.
RESULTS: Mean patient age was 68.7 years. The T/T genotype resulted in a significantly higher risk of upper urinary tract urothelial carcinoma (OR 1.72, 95% CI 1.1-2.8, p = 0.028). Using single polytomous regression analysis the T/T genotype was also associated with aggressive tumors when stratified by stage (p = 0.003), or grade G2 (p = 0.04) or G3 (p = 0.01).
CONCLUSIONS: Our results strongly suggest that the T/T rs9642880 genotype is a risk factor for upper urinary tract urothelial carcinoma, as previously shown for bladder tumors. In contrast to bladder carcinoma, for upper urinary tract urothelial carcinoma the T/T genotype is associated with aggressiveness.

Adamis S, Varkarakis J
Minimally invasive approach in the management of upper- urinary-tract tumours.
Scand J Urol Nephrol. 2011; 45(6):381-7 [PubMed]

OBJECTIVE: Nephroureterectomy with bladder cuff excision has been the gold standard treatment for upper tract transitional cell carcinoma (UTTCC) for more than 60 years. However, endoscopic treatment of urothelial tumours of renal pelvis and ureter is gaining acceptance as a conservative treatment modality.
MATERIAL AND METHODS: A review in the English language of the Medline and Pub Med databases was performed using the keywords upper urinary tract transitional cell carcinoma and endoscopic management. There was a particular emphasis on treatment outcomes from published series.
RESULTS: Endoscopic treatment of UTTCC alone for high-grade tumours is not advised owing to high rates of both local recurrence and disease progression, while many authors do not recommend primary endoscopic management of UTTCC in elective situations if pathological analysis and tumour grade cannot be obtained.
CONCLUSION: Endourological management of UTTCC has become an accepted treatment option in highly selected patients, provided long-term close surveillance to detect and treat recurrences is ensured.

Weight CJ, Gettman MT
The emerging role of lymphadenectomy in upper tract urothelial carcinoma.
Urol Clin North Am. 2011; 38(4):429-37, vi [PubMed]

Within the last decade, there has been an increased focus on lymphadenectomy or lymph node dissection (LND) in patients with upper tract urothelial carcinoma (UTUC). Although the data with regards to LND in UTUC are sparse, investigators are beginning to evaluate the role and define the anatomy to understand how LND may affect outcomes in patients with UTUC. This article reviews the history of LND for UTUC, outlines the relative anatomy, and evaluates the arguments and evidence for, and against, LND in patients with UTUC.