Ureteral Tumors Research Articles

Spontaneous ureteral rupture and review of the literature

IntroductionSpontaneous ureteral rupture is defined as non-traumatic urinary leakage from the ureter. This is a diagnosis that, although uncommon, is important for emergency physicians to know about. The literature is relatively sparse. Materials and MethodsThis was a retrospective review of patients who were diagnosed with spontaneous ureteral rupture. From 2006 to 2012, 18 patients were diagnosed by radiography (computed tomography or intravenous urogram) with spontaneous ureteral rupture. These cases all showed extravasation of the contrast outside the excretory system. We evaluated underlying causes, diagnostic and therapeutic procedures, and outcomes. ResultsThere were 9 men and 9 women with a median age of 59 years (range, 22-82 years). In 56% of patients, a ureteral stone was the cause; in 17% of, a ureteral stricture; in 1 patient, a ureteral tumor; and in the remaining 22%, no cause was identified. In 13 patients (72.2%), primary ureteroscopy to place D-J stents was performed. The average duration of ureteral catheter stenting was 21 days (range, 8-45 days). The other 5 patients (27.8%) were managed conservatively with antibiotic treatment and the outcome was good. ConclusionsUreteral stones most commonly cause spontaneous ureteral rupture. In our experience, most patients received ureteroscopy and Double-J stenting. Conservative management with antibiotics also had good outcomes. Most patients had sudden onset of abdominal or flank pain. Spontaneous ureteral rupture should be kept in the differential diagnosis of patients with acute abdominal or flank pain in the emergency department.

V11-12 ROBOT-ASSISTED LAPAROSCOPIC DISTAL TUMOR-URETERECTOMY, PSOAS HITCH AND BOARI-FLAP URETERAL RECONSTRUCTION.

INTRODUCTION AND OBJECTIVES: Reconstruction of the lower ureter can be achieved by a Boari-flap either by open surgery or a laparoscopic procedure. Robot assisted surgery offers multiple intraoperative advantages including wristed movements with additional degrees of freedom and three dimensional visualization with magnification. The video shows a robot-assisted approach for ureteric resection according to a malignant ureteral tumor, the creation of a Boari-flap and the ureteral reimplantation. METHODS: We used 4 robot and 2 assistant trocars similar to radical cystectomy in a 10 degree Trendelenburg position. The distal ureter (10cm) was resected, the distal part of the remaining ureter sent for frozen section. After filling the bladder with saline, the Boari-flap was created and fixed at the psoas-fascia in a psoas-hitch manner. Then the antirefluxive ureteral reimplanatation was performed intraabdominally. RESULTS: Recovery was uneventful. Histologic examination of the specimen revealed a transitional carcinoma of the ureter pT2, high grade, R0 L0 V0. There was no leakage at the time of removal of the ureteric splint on the 10th postoperative day. Follow up at 14 months showed no recurrence of the tumor. CONCLUSIONS: Robot assisted oncological surgery of ureter and bladder is a safe and effective alternative to open and conventional laparoscopic surgery. It offers fast and uncomplicated recovery, minimal blood loss and optimal cosmesis.

Diagnosis and treatment strategy of primary ureteral fibroepithelial polyp

Objective To summarize the diagnosis and treatment strategy of primary ureteral fibroepithelial polyp.Methods The Clinico-pathological data of 44 primary ureteral fibroepithelial polyp cases (27 males and 17 females) treated from Jan.1998 to Mar.2013 were analyzed retrospectively.The mean age was 37 (12-67) years.Patients were admitted with flank-abdominal pain (63.6％),painless gross hematuria (18.2％) and hydronephrosis (9.1％) with a mean history of 4 (1 week-20 years) yrs.CT scan of the 38 cases revealed hydronephrosis (68.4％) and ureter tumor (63.2％).Of the 16 cases with retrograde urography,13 demonstrated filling-defects in ureter (81.3％),among whom,10 revealed long strip-shaped filling-defects suspect of ureter polyp (62.5％).Ureteroscopy was performed in 25 cases and discovered ureter polyp in 19 patients.Partial ureterectomy was performed on 28 patients,endoscopic procedure was performed on 11 cases and the left 5 patients were treated with nephroureterectomy.Results 40 patients were followed-up for 6 mon to 15 years.Of the 35 patients with the kidney reserved,31 were fully recovered with no symptoms and with no hydronephrosis or polyp recurring,3 cases with hydronephrosis were relieved,1 patient lost the affected kidney after 3 years because of severe hydronephrosis.Conclusions Primary ureteral fibroepithelial polyp should be suspected in younger patients with long term intermittent flank or abdominal pain and/or gross hematuria.CT scan and retrograde urography are the main diagnostic imaging studies.Ureteroscopy plays a pivotal role in the diagnosis and decision of treatment strategy,especially to avoid undertaking nephroureterectomy in suspicious of ureteral carcinoma.Resection of the polyp under ureteroscopy is safe and effective. Key words: Ureter; Fibroepithelial polyp; Primary; Diagnosis; Therapeutics

BK Virus–Associated Urothelial Carcinoma of a Ureter Graft in a Renal Transplant Recipient: A Case Report

BackgroundUrothelial carcinomas of ureter grafts in renal transplant patients are rare. Here we report our experience with a case of BK virus–associated urothelial carcinoma in a ureter graft. Case ReportA 47-year-old man developed chronic renal failure secondary to diabetes mellitus and started maintenance hemodialysis in September 2007. Two months later, the patient received a renal transplant from his 70-year-old mother. The patient developed BK virus–associated nephropathy 1 year after transplantation and presented with a decline in renal function and hydronephrosis in the transplanted kidney 4 years 6 months after transplantation. Cystoscopy and retrograde pyelography revealed an irregular filling defect in the ureter graft. Cytologic diagnosis of his urine revealed a high-grade urothelial carcinoma. Computerized tomography showed a cT2 ureteral tumor and no involvement of other organs. The patient subsequently underwent a transplant nephroureterectomy with bladder cuff resection. Histopathologic findings revealed a high-grade urothelial carcinoma, pT2, in the ureter graft with SV40-positive staining. The patient was closely observed without adjuvant chemotherapy therapy and remained disease free 1 year after surgery. Renal transplant recipients with BK virus infection are at high risk of developing urologic malignancies. Close attention is necessary to diagnose post-transplantation urologica malignancies as early as possible.

Metastasis of renal cell carcinoma to the contralateral ureter

We herein report a rare case of renal cell carcinoma (RCC) that metastasized to the contralateral ureter. A 55-year-old man with a past history of right radical nephrectomy due to G3 pT1b clear cell RCC one year earlier presented to our department with a complaint of gross hematuria. On computed tomography, a ureteral tumor was found in both the left distal ureter and left hydronephrosis. The ureteral tumor was pathologically diagnosed by ureteroscopic biopsies as metastatic RCC, consistent with the primary renal tumor. Partial ureterectomy and end-to-end uretero-ureterostomy were performed. Pathologic examination of the resected tumor confirmed metastatic RCC. The post-operative course has been uneventful, and to date, the patient has remained disease-free.

Isolated ureteric endometriosis presenting as a ureteric tumor

A 32 year old lady presented with recurrent left flank pain for 4 weeks and chronic lower back pain. CT without contrast showed no stones and mild left hydronephrosis. CT of the spine suggested an inflammatory process at L5-S1 vertebra. The diagnosis was supported by a bone scan. Incidentally, the scan showed nonfunctioning left kidney. Diuretic renography confirmed poor perfusion and no excretion. A retrograde study showed narrowing of the ureter at the pelvic brim. Ureteroscopy showed a papillary mass in the lumen of the ureter from which multiple cold cup biopsies were taken. The pathology however was not conclusive. A robotic nephroureterectomy was carried out. Definitive pathology showed intrinsic endometriosis of the ureter. We conclude that endometriosis should be considered in the differential diagnosis of unexplained ureteric obstruction and ureteric lumen filling defects in young women.

Age and Gender Relation in Ureterial Tumors Detected with Transurethral Resection

Bladder tumors are biologically and chemically hazardous tumors that still remains as high morbidity and mortality rates even though the improvements of diagnosis and treatment in clinical field. Ureteral tumors constitutes about 90% of all bladder tumors and their biological behaviour vary from benign lesions to agressive cancers. In our study 66 diagnosed bladder biopsy and transureteral resection material were analysed retrospectively through the database of pathology department of Iskenderun State Hospital between january 2011 and November 2013.When only the bladder tumor cases were examined, 26 (59.65%) male and 3 (10.35%) female patients were detected. The age average of these tumor cases was 63.86±14.84 and ages were varied from 28-84. The 29 patients of tumor cases were consisted of 1 (1.52%) carcinoma in situ, 2 methastathic cancers, 1 papilloma, 2 low malignity potential papillary neoplasia, 14 low grade papillary carcinoma and 9 high grade papillary carcinoma. We observed that urothelial papilloma and low malignant potential papillary carcinoma has low rates and the percentage of low grade papillary carcinoma has high rates according to smilar studies. Unlikely the other studies, we found that the high grade papillary ureteral carcinoma can seen in further ages than low grade papillary ureteral carcinoma.In the light of our study, we recommend to keep in mind that malignant tumors of ureterium can be seen in all age groups and gender.

MDCT Evaluation of Ureteral Tumors: Advantages of 3D Reconstruction and Volume Visualization

This article reviews the use of CT urography in diagnosing ureteral transitional cell carcinomas, different CT urography protocols, CT findings suggestive of ureteral malignancy, and the importance of 3D reconstructions. The ureters can be problematic to evaluate on CT, partly because of difficulties in obtaining adequate ureteral distention and opacification. Proper diagnosis hinges not only on appropriate interpretation of the axial images but also on the utilization of a 3D technique (volume rendering or maximum intensity projection) as an ancillary tool.

Laparoendoscopic single-site nephroureterectomy for morbid obese patients

Since the first laparoendoscopic single-site (LESS) surgery report in urology in 2007 (1) (Rane A e Cadeddu JA), the few reports of LESS extraperitoneal access in the literature were mainly described for less complex cases. The aim of this video is to demonstrate the feasibility of LESS extraperitoneal access in a morbid obese patient presenting a malignant tumor in the renal pelvis. The patient is positioned in 90-degree lateral decubitus. An incision is made below the abdominal skin crease on the left side of the patient and the anterior rectus fascia is vertically incised with manual dissection of the extra/retroperitoneal space. We use an Alexis® retractor to retract the skin maximizing the incision orifice. Three trocars (12, 10 and 5 mm) are inserted through a sigle-port. The pedicle was controlled "en bloc" with a vascular stapler and the bladder cuff treated by the conventional open approach through the same incision. Operative time was 126 minutes with minimal blood loss. The pathology reported high grade papillary urothelial carcinoma in the pelvis (pT3N0M0) and in the ureter (pTa). LESS extraperitoneal nephroureterectomy is feasible and safe, even in more complex cases. It is a good alternative for morbid obese patients and for patients with synchronous distal ureteral tumors for whom an open approach to the bladder cuff is proposed to avoid incisions in two compartments of the abdominal wall.

Metastatic Behavior of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: Association with Primary Tumor Location

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). 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. 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). 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.

Alpha-fetoprotein and carbohydrate antigen 19-9 producing advanced adenocarcinoma of renal pelvis and ureter

Tumour markers producing primary adenocarcinoma of upper urinary tract is extremely rare. We report a case of advanced adenocarcinoma of renal pelvis and ureter with highly elevated serum levels of alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9). This 66-year-old man was diagnosed with left renal pelvic and ureteral tumours with para-aortic lymph node swelling, with no evidence of abnormality in his digestive or reproductive system. He was successfully treated with left nephroureterectomy and lymph node dissection followed by gemcitabine/carboplatin chemotherapy and the serum levels of AFP and CA19-9 decreased to normal. Pathological examination revealed a moderately or poorly differentiated intestinal-type adenocarcinoma with para-aortic lymph node metastasis. The patient was followed up for 11 months after surgery without recurrence.

Frozen Section Analysis of Ureteral Margins in Patients Undergoing Radical Cystectomy for Bladder Cancer: Differential Impact of Carcinoma in situ in the Bladder on Reliability and Impact on Tumour Recurrence in the Upper Urinary Tract

Background: Patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) are at risk for upper urinary tract recurrence (UUTR), especially in case of carcinoma in situ (CIS). Data on the impact of CIS in the urinary bladder on ureteral tumour involvement or UUTR are conflicting. We presently evaluate the accuracy of intraoperative frozen section analysis (FSA) of the ureteral margin, the incidence of ureteral tumour involvement and their impact on UUTR in patients undergoing RC for UCB with versus without CIS of the bladder. Material and Methods: Between 2003 and 2007, 243 patients underwent RC in our department. 176 of these for UCB, either without CIS (n = 117, group I) or solitary/concomitant CIS (n = 59, group II). FSA was performed. Patients were followed up for UUTR. Results: Overall, 403 ureteral margins - including re-resections - were analysed (group I, n = 232; group II, n = 171). One patient (0.85%) in group I and 21 patients (35.6%) in group II had tumour involvement of the ureter (p < 0.0001) at the time of RC. The false-negative rate of FSA compared to final histopathology was 0.4% (1/232) for group I and 2.9% (5/171) for group II, respectively. Mean duration of follow-up was 26 months (1-72). In group II, 2 patients (1.1%) had UUTR in the follow-up; both had initially positive and subsequently false-negative FSA. Conclusions: Tumour involvement of the ureter is found significantly more often in solitary or concomitant CIS of the bladder. Intraoperative ureteral FSA is accurate and should be recommended in these patients. Ureteral tumour involvement predisposes to UUTR especially with initial positive margins mandating careful follow-up.

Oncological impact of endoscopic bladder cuff management during nephroureterectomy varies according to upper urinary tract tumor location

To compare the oncological outcome between extravesical excision and transurethral excision for bladder cuff management in patients undergoing nephroureterectomy with upper urinary tract urothelial cancer. From January 2005 to December 2010, 396 patients were enrolled in the present retrospective study. Nephroureterectomy was carried out either by endoscopic or extravesical bladder cuff excision. The oncological outcome between these two procedures was analyzed in patients with different tumor locations. The average age of the patients was 66.41 ± 10.52 years, and the median follow-up duration was 40.65 ± 23.84 months. For upper urinary tract urothelial cancer management, extravesical bladder cuff excision was carried out in 240 patients, whereas the endoscopic method was carried out in 156 patients. Previous bladder cancer is still the most independent predictor for bladder recurrence (P < 0.001). In addition, endoscopic bladder cuff management for low ureteral tumor was also independently associated with more bladder tumor recurrence (P = 0.017). Non-organ confined pathological stage still independently predicted metastasis (P < 0.001) and cancer-specific death (P < 0.001). There are similar oncological outcomes after nephroureterectomy combined with extravesical or endoscopic bladder cuff management for patients with upper urinary tract urothelial cancer above the low ureter. However, there is a higher incidence of bladder tumor recurrence for the low ureteral tumor after nephroureterectomy with endoscopic bladder cuff excision.

Prediction of Intravesical Recurrence After Radical Nephroureterectomy: Development of a Clinical Decision-making Tool

BackgroundIntravesical recurrence after radical nephroureterectomy (RNU) is a frequent event requiring intense cystoscopic surveillance. Recently, a prospective randomized clinical trial has shown that a single intravesical postoperative dose of mitomycin C (MMC) reduces the absolute risk of intravesical recurrence after RNU. ObjectiveThe aim of the current study was to identify predictors of intravesical recurrence and to develop a tool to allow a risk-stratified approach supporting patient counseling for cystoscopic surveillance and postoperative intravesical MMC administration. Design, setting, and participantsWe performed a retrospective analysis of 1839 patients with upper tract urothelial carcinoma (UTUC). The data set was split into a development cohort of 1261 patients from North America and a validation cohort of 578 patients from Europe. InterventionsRNU with bladder cuff excision was performed. The surgical approach was open in 1424 patients (77.4%) and laparoscopic in 415 patients (22.6%). Outcome measurements and statistical analysesUnivariable and multivariable Cox regression models addressed time to intravesical recurrence after RNU. We developed a nomogram for prediction of the probability of intravesical recurrence at 3, 6, 9, 12, 18, 24, and 36 mo. Predictive accuracy was quantified using the concordance index. Decision curve analysis was performed to evaluate the clinical benefit associated with the use of our nomograms. Results and limitationsWith a median follow-up of 45 mo, intravesical recurrence occurred in 577 patients (31%). The probability of intravesical recurrence-free survival at 6, 12, 24, and 36 mo was 85%±1%, 78%±1%, 68%±1%, and 47%±2%, respectively. In multivariable Cox regression analysis, advanced age, male gender, ureteral tumor location, laparoscopic surgical technique, endoscopic distal ureteral management, previous bladder cancer, higher tumor stage, concomitant carcinoma in situ, and lymph node involvement were all significantly associated with intravesical recurrence (p values ≤0.04). The nomograms were highly accurate for predicting intravesical recurrence in the external validation cohort (concordance index of 67.8% and 69.0% for the reduced model and the full model, respectively), and calibration plots revealed only minor overestimation beyond 24 mo. If one decided to perform postoperative instillation based on the risk of intravesical recurrence of 15% at 24 mo, one would spare 23% of the patients while not preventing only 0.3% of intravesical recurrences. The lack of information on the stage and grade of the intravesical recurrences is the main limitation of the study. ConclusionsIntravesical recurrence after RNU is a common event in patients with UTUC. We developed nomograms that predict intravesical recurrence after RNU with reasonable accuracy. Such nomograms could improve the clinical decision-making process with regard to cystoscopic surveillance scheduling and postoperative intravesical instillations of MMC after RNU.

Predictive factors for worse pathological outcomes of upper tract urothelial carcinoma: experience from a nationwide high‐volume centre in China

To analyse the predictive factors for worse pathological outcome (muscle invasive pT2+, non-organ-confined pT3+ or N+ and histological Grade 3) of upper tract urothelial carcinoma (UTUC) in a Chinese population from a nationwide high-volume centre in China. Predictors were studied by retrospectively reviewing the clinicopathological data of 729 consecutive patients with UTUC treated in our centre from January 2002 to December 2010. Univariate and multivariate logistic regression analyses were used. There were more female patients (56.4%) than males and more tumours were located in the ureter (52.7%) than in the pelvis. In multivariate analysis, male gender (hazard ratio [HR] 1.898, P = 0.001), sessile architecture (HR 3.249, P < 0.001), high grade (HR 5.007, P < 0.001), ipsilateral hydronephrosis (HR 4.768, P < 0.001), renal pelvis location (HR 2.620, P < 0.001) and tumour without multifocality (HR 1.639, P = 0.028) were predictive factors for muscle-invasive UTUC. Male gender (HR 2.132, P < 0.001), renal pelvis location (HR 3.466, P < 0.001), tumour without multifocality (HR 2.532, P = 0.001), sessile tumour architecture (HR 3.274, P < 0.001), and high grade (HR 3.019, P < 0.001) were predictive factors for non-organ-confined disease. Chronological old age (HR 1.047, P < 0.001), sessile tumour architecture (HR 25.192, P < 0.001), ipsilateral hydronephrosis (HR 1.689, P = 0.024), and positive urinary cytology (HR 1.997, P = 0.006) were predictive factors for histological Grade 3 UTUC. There was a predominance of female patients and ureteric tumours in UTUCs of this Chinese population. Male gender, sessile architecture, tumour location, tumour without multifocality, high histological grade and preoperative ipsilateral hydronephrosis were independent predictive factors for worse pathological outcome of UTUCs.

Long-term follow-up of patients with tumours of the renal pelvis and ureter: How often is a bladder tumour diagnosed after five tumour-free years?

Objective. It is not known when cystoscopy follow-up should be terminated after surgery for tumours of the renal pelvis and ureter [upper urinary tract tumours (UUTTs)]. The aim of this study was to investigate the length of the interval from surgery to diagnosis of the first bladder tumour. Material and methods. A review was performed of all 930 patients who were diagnosed with a UUTT from 1971 to 1998 in western Sweden. The time to the first bladder tumour was estimated using Kaplan--Meier analyses. Univariate and multivariate analyses of potential risk factors for bladder recurrence were performed. Results. In total, 614 patients were treated surgically for a renal pelvic or ureteral tumour and underwent cystoscopy at least 3 months afterwards. Of these 614 patients,192 (31.3%) patients developed a bladder tumour after the upper tract surgery. The majority, 157 out of 192 patients (81.8%), were diagnosed during the first 2 years, an additional 24 patients (12.5%) during years 3--5 and 11 patients (5.7%) between years 5 and 20. A history of bladder tumours, large tumour diameter, carcinoma in situ and UUTT diagnosed during the last part of the study period were significant risk factors for bladder recurrence after upper tract surgery. Conclusion. Cystoscopy should be performed at short intervals during the first 2 years after surgery for a UUTT, in particular among patients with a history of bladder tumours. Late bladder recurrences are unusual; therefore, as a rule, follow-up cystoscopy should be terminated after 5 tumour-free years.

Laparoscopic Anderson-Hynes procedure as a treatment of ureteropelvic junction obstruction caused by fibroepithelial polyp.

Fibroepithelial polyps (FEPs) are rare benign ureteral neoplasms of mesodermal origin. As an intrinsic cause of ureteropelvic junction obstruction (UPJO) they are very uncommon. Excretory urography and diuretic renography used by many urologists to diagnose a UPJO may not detect the ureteral polyp. We present a case of ureteropelvic junction obstruction caused by a fibroepithelial polyp, which was not diagnosed preoperatively. The patient underwent successful laparoscopic excision of the polyp with Anderson-Hynes pyeloplasty. We believe that laparoscopy is a useful, minimally invasive operative technique in the treatment of FEPs and may be considered a procedure of choice in large polyps, in which cases the endoscopic procedure is difficult or impossible to perform.

Follow-up after radical cystectomy based on patterns of tumor recurrence and its risk factors

ContextFollowing cystectomy, approximately 50% of patients will present tumor recurrence. A recurrence may be local, systemic or occur in the urethra or upper urinary tract. ObjectiveTo analyze the characteristics, risk factors and outcomes of patients with tumor recurrence following cystectomy so as to subsequently propose a cancer follow-up protocol. Acquisition of evidenceAnalysis of original articles and reviews related to tumor recurrence and follow-up after radical cystectomy for urothelial tumor. Articles were obtained from Pubmed searches. Summary of the evidenceSystemic and local recurrences following cystectomy appear in 20–35% and 5–15% of cases, respectively. Some 80–90% are diagnosed in the first 3 years, with the majority concentrated in the first 24 months. Common factors related to an increased risk of local and systemic recurrence are a pathologic stage ≥pT3, the presence of positive margins and the extension of the lymphadenectomy. The incidence of recurrence in the upper urinary tract and urethra is 2–6% and 4–6%, respectively. Both types of recurrence may appear late and share risk factors such as signs of multifocal disease, a history of non-muscle-invasive bladder cancer, multiplicity, presence of ISC, urinary tract tumors and prostatic urethral tumors. Tumors in the distal ureteral cystectomy specimen and tumors in the prostatic urethra are also risk factors related to the appearance of tumors in the urinary tract and urethra, respectively. ConclusionUnderstanding the natural history of urothelial bladder carcinoma and the risk factors related to the appearance of tumor recurrence following cystectomy are essential for designing an appropriate follow-up protocol. The follow-up of patients with risk factors for local or systemic recurrence will achieve maximum efficiency during the first 3 years. The follow-up should be extended for patients with risk factors for presenting upper urinary tract or urethral tumors.

Cytogenomics and gene expression in a case of metachronous bilateral renal cell carcinomas with drop metastasis: Resolving a diagnostic dilemma with molecular technologies

Metachronous bilateral renal cell carcinomas (RCCs) are rare but well known. We present a case of metachronous bilateral RCCs with a ureter orifice metastasis, for which the pathological diagnosis was confirmed with single nucleotide polymorphism microarray (SNP-M) and gene expression assay (GEA). A 53-year-old man presented with a right ureteral obstruction. A cystoscopy showed a large pedunculated tumor emanating from the right ureteral orifice, consistent with a drop metastasis, which was biopsied. He had a history of a clear cell RCC (ccRCC) 1.5 years prior and a right renal pelvic mass found 8 months later. Histologically, the biopsied right ureteral tumor demonstrated sheets of poorly differentiated cancer cells composed of a mixture of spindled and focal clear cell components. The main differential diagnosis was metastatic RCC versus urothelial carcinoma, but the immunohistochemical profile was not contributory. SNP-M revealed a genomic profile consistent with a metastatic ccRCC with loss of chromosome 3p. GEA showed a gene expression pattern consistent with kidney origin. The cytogenomic array also identified chromosome copy number patterns that were shared between both kidney tumors. This finding suggests that both tumors had a common origin, and thus, the metachronous ccRCC in the contralateral kidney represents a metastasis.

Phase I clinical trial of external hyperthermia and intravesical mitomycin C to treat BCG-refractory bladder cancer.

e15560 Background: Patients with non-muscle-invasive bladder cancer (NMIBC) that fail intravesical bacillus Calmette-Guérin (BCG) are at high risk for progression. Radical cystectomy is an effective but morbid treatment option. We tested the safety and efficacy of combined intravesical mitomycin C (MMC) and external deep regional hyperthermia (HT) as a bladder-sparing approach for BCG-refractory NMIBC. Methods: Patients with BCG-refractory NMIBC were eligible for this phase I clinical trial. Treatment consisted of intravesical MMC (40 mg in 40 mL) with concurrent HT with target temperature of 42°C. MMC dwell time was 60-120 min and heating time was 40-60 min. HT was delivered using a BSD2000 device and temperatures monitored with skin, bladder and rectal probes. Treatment was given weekly for 6 weeks (induction) then monthly for 4 months (maintenance). The primary endpoint was toxicity which was assessed using CTCAE 3.0. Secondary endpoints included recurrence-free survival (RFS), progression-free survival (PFS), cystectomy, and overall survival (OS) which were assessed at 3 month intervals with cystoscopy and cytology for 2 years. Results: Fifteen patients were eligible and consented to the clinical trial. Median age was 66 years and 87% were male. Median follow-up was 2.85 years. One patient did not tolerate supine position, two completed induction but recurred prior to maintenance, one recurred after 3 maintenance treatments, and 11 patients received all 10 treatments. The 2 year RFS was 33% (median RFS = 15.4 mos). Six patients (40%) required cystectomy (median time = 20.1 mos). No patient had bladder progression but two patients developed ureteral tumors (not present on baseline imaging). Two patients died, one from ureteral cancer and one of cardiovascular disease, for a 3-year OS of 83% (median OS not reached). No grade III toxicities were observed. Common toxicities were abdominal pain (36%), cystitis (22%), pruritis and urinary tract infection (14%). Conclusions: The combination of MMC and HT for BCG refractory NMIBC was safe and associated with low grade toxicity. While recurrence was common, progression did not occur, and recurrent patients were safely salvaged with cystectomy. Clinical trial information: NCT00734994.