Management of Upper Tract Urothelial Carcinoma.

PURPOSE OF REVIEW: We review the epidemiology, risk factors, diagnosis, and treatment of upper tract urothelial carcinoma (UTUC), with a distinction between the different risk groups. RECENT FINDINGS: Endoscopic treatment with laser ablation of tumors has an evolving role in treating low-grade UTUC including select large and multifocal tumors, along with complementary topical chemotherapeutic treatment that can reach difficult intrarenal locations. Template lymphadenectomy is recommended in patients undergoing nephroureterectomy. A recent randomized control trial showed benefit of adjuvant chemotherapy after radical nephroureterectomy for locally advanced disease. Advances in immunologic therapy have shown promise in treating metastatic UTUC, and immunologic-based therapies have been incorporated into treatment regimens. Notable progress has been made in both the surgical and medical treatment arms for UTUC, thus extending the reach of nephron-sparing therapy for those with localized disease and increasing overall survival for those with locally advanced disease.

Durability of Response to Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma Using UGN-101, a Mitomycin-Containing Reverse Thermal Gel: OLYMPUS Trial Final Report.

PURPOSE: Our goal was to evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma. MATERIALS AND METHODS: In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term followup; 23/41 patients (56%) remained in complete response after 12 months (95% CI 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs. CONCLUSIONS: Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.

Surgical and Radiological Management of Complicated Uterine Leiomyoma Aided by 3D Models in a Patient with Fibrodysplasia Ossificans Progressiva.

BACKGROUND Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of the connective tissue. Over time, patients with FOP experience decreased range of motion in the joints and the formation of a second skeleton, limiting mobility. Patients with FOP are advised to avoid any unwarranted surgery owing to the risk of a heterotopic ossification flare-up. For patients who do require a surgical procedure, a multidisciplinary team is recommended for comprehensive management of the patient's needs. CASE REPORT A 27-year-old woman with FOP underwent a hysterectomy for removal of a suspected necrotic uterine fibroid. To aid in presurgical planning and management, patient-specific 3-dimensional (3D) models of the patient's tracheobronchial tree, thorax, and lumbosacral spine were printed from the patient's preoperative computed tomography (CT) imaging. The patient required awake nasal fiberoptic intubation for general anesthesia and transversus abdominus plane block for regional anesthesia. Other anesthesia modalities, including spinal epidural, were ruled out after visualizing the patient's anatomy using the 3D model. Postoperatively, the patient was started on a multi-modal analgesic regimen and a course of steroids, and early ambulation was encouraged. CONCLUSIONS Patients with FOP are high-risk surgical patients requiring the care of multiple specialties. Advanced visualization methods, including 3D printing, can be used to better understand their anatomy and locations of heterotopic bone ossification that can affect patient positioning. Our patient successfully underwent supracervical hysterectomy and bilateral salpingectomy with no signs of fever or sepsis at follow-up.

Ergonomics in Endourology: Measurement of Force for Deflection in Contemporary Ureteroscopes.

Introduction: Few studies have examined the ergonomic hazards to endourologists during endoscopic procedures. We have evaluated the forces required to deflect different flexible ureteroscopes across a range of measurements with several different standard instruments within the working channel. Methods: Five ureteroscopes were studied: the Uscope, Neoflex, LithoVue™, URF-P6, and the Flex-X2™. A pull-force meter (Nextech DFS 500) was attached to the thumb lever to deflect the tip from 30° to 210° at 30° intervals. Measurements were made with upward and downward deflection separately. The forces were reported in Newtons (N) to the nearest 10th, as positive values regardless of the direction of the force. Measurements were made with the channel empty or containing an instrument: a 365 µm laser fiber, a 2.4F Nitinol basket, 3F biopsy forceps, or a 0.038" guidewire using the flexible or the stiff tip. Results: The maximum downward deflection force, measured at 210° of deflection, with an empty channel range from a minimum of 5.7 N in one scope to a maximum of 33.4 N in another. The force necessary for deflection ranges from 2.0 to 7.0 N (0.45-1.57 foot-pounds) at 30° to 8.5 to 25.3 N (1.8-5.69) at 180°. Maximum upward deflection shows similar results with a minimum of 7.9 N in one scope and a maximum of 43.1 N of force in another. Working instruments in the channel increased the force needed for deflection. Conclusions: Forces required for steep deflection of the tip of a flexible ureteroscope reach extremely high levels or limit the deflection capability of the scope. The force is higher with increased deflection and with instruments within the channel.

Indwelling ureteric stents: Patterns of use and nomenclature.

Objectives: To evaluate ureteric stenting practice patterns amongst a range of academic and community urologists, and to examine the nomenclature used to identify an indwelling ureteric stent from both our questionnaire and from a review of the literature. Subjects and methods: A 16-question, peer-reviewed online survey was distributed to members of the Mid-Atlantic American Urological Association. Responses were collected over a 1-month period. Questions included demographics, ureteric stenting practice patterns, and utilization of stenting nomenclature. Inappropriate use of nomenclature was defined as a mismatch between the visually depicted stents and the written description amongst urologists. Trends in ureteric stenting and nomenclature usage were tabulated and analyzed. Results: Of 863 members, 105 (12.2%) responded to the survey. There was a wide variety of practice settings, with the single-specialty group (44.2%) and academic/university (27.9%) being the two most common. Most providers used both cystoscopy and fluoroscopy to place stents (87.5%) as compared to fluoroscopy alone (12.5%). Most urologists (63.5%) removed stents with cystoscopy as compared to using a stent string (36.5%). While about half (51.0%) of the respondents left stents in situ for ≤3 months, many respondents (43.3%) felt comfortable with maximum dwell times of up to 6 months. The most commonly placed stent was the double pigtail stent (80.8%). However, most respondents inappropriately described this stent design as a Double J stent (72.1%). In the recent literature, 80% of articles clearly defined as using double pigtail stents, incorrectly identified their stent as a 'Double J'. Conclusions: Variations in ureteric stenting practice patterns exist amongst community and academic urologists. Although most urologists utilize double pigtail ureteric stents, the majority inaccurately identified this stent design as a Double J. We propose use of the term 'indwelling ureteric stent' (IUS) unless describing any specific stent design.

How I Do It: Anticoagulation management for common urologic procedures.

Appropriate perioperative management of antithrombotic medications is critical; for every patient, the risk of bleeding must be balanced against individual risk of thrombosis. There has been a rapid influx of new antithrombotic therapies in the past 5 years, yet there is a lack of clear and concise guidelines on the management of anticoagulant and antiplatelet therapy during urologic surgery. Here we describe our approach to perioperative antithrombotic counseling, including the timing of stopping and restarting these medications. These practice guidelines have been developed in consultation with the Vascular Medicine service at our institution as well as after a review of current literature, and apply to common urologic procedures. Many cases are complex and require medical consultation or a multidisciplinary approach to management. We believe that by presenting our systematic method of antithrombotic management, including when to involve other discplines, we can increase knowledge and comfort amongst urologists in managing these medications in the perioperative period.

Ureteroscopic biopsy of upper tract urothelial carcinoma and role of urinary biomarkers.

Ureteroscopic biopsy is an integral part of diagnosis of urothelial carcinoma of the upper urinary tract. It can be a technical challenge, but diagnostic rates have improved remarkably with refinements in surgical technique and specimen processing. Cytology aids with diagnosis and other urinary biomarkers continue to evolve, which may help further stratify patients for treatment. The current literature on the ureteroscopic biopsy and role of urinary biomarkers is reviewed and summarized below.

Long term outcomes of ureteroscopic management of upper tract urothelial carcinoma.

OBJECTIVES: Upper tract urothelial carcinoma (UTUC) is relatively rare. While nephroureterectomy is considered the gold standard for treatment, endoscopic nephron- sparing techniques have emerged for select cases with equivalent cancer specific survival (CSS). We present the largest series with longest follow-up to date of retrograde ureteroscopy as the primary treatment of UTUC. METHODS: A retrospective review was performed of 258 patients diagnosed with UTUC who were initially evaluated and managed by a single surgeon. Patients were followed from 1994 to 2017. Clinical records were evaluated for patient and tumor characteristics, operative parameters and outcomes. Statistical analysis was performed to identify risk of recurrence, progression, cancer and overall survival. RESULTS: Following exclusion criteria, 168 patients were evaluated. Average tumor size on initial excision was 16.8mm. Mean age of the cohort was 70 years, with mean follow-up of 5.53 years. The 5-year overall survival was 80.9%, but CSS was 92.6%. Recurrence free survival was 30% with average tumor size on recurrence of 6.39mm. Progression free survival was 75% with a renal preservation rate of 71.4%. CONCLUSIONS: Ureteroscopic management of UTUC is a successful alternative to nephroureterectomy in select cases of UTUC. With strict surveillance protocols to manage frequent local recurrence rates, it is possible to achieve high renal preservation rates with acceptable CSS, even in the long-term.

Palliative Endoscopic Treatment of Metastatic Uveal Melanoma to the Upper and Lower Urinary Tract.

We report a rare case of uveal melanoma demonstrating simultaneous metastatic foci to the upper and lower urinary tract. A 60-year-old woman, with metastatic uveal melanoma, was referred for incidental right hydronephrosis. Diagnostic cystoscopy and ureteroscopy confirmed the diagnosis of metastatic malignant melanoma to the bladder and kidney. Both tumor resection and coagulation were possible with the neodymium/holmium laser combination. The goals of treatment in metastatic patients should be cessation of hematuria and relief of obstruction with preservation of functional renal reserve while minimizing morbidity.

Ureteroscopic Management of Large ≥2 cm Upper Tract Urothelial Carcinoma: A Comprehensive 23-Year Experience.

OBJECTIVE: To evaluate the effectiveness of ureteroscopy (URS) with laser ablation as an alternative treatment for upper tract urothelial carcinoma (UTUC) lesions larger than 2 cm. Traditionally, patients with large UTUC are treated with radical nephroureterectomy (RNU). However, in patients with pre-existing renal disease, a solitary kidney, or those who decline RNU, management of UTUC may prove challenging METHODS: An institutional database review identified 80 patients with biopsy proven low-grade UTUC who had at least one lesion larger than 2 cm. We collected clinical data including demographics, operative parameters, and pathologic features. Follow-up for all patients was standardized and included cystoscopy and URS every 3 months until clear, every 6 months through the fifth year, and yearly thereafter. We calculated rates of recurrence, progression, and overall survival. RESULTS: In total, 86 unique lesions ≥2cm were identified in the 80 qualifying patients; mean tumor size was 3.04 cm. Median follow-up was 43.6 months. During follow-up of patients treated curatively, 90.5% of tumors had ipsilateral recurrence and 31.7% progressed in grade at a median of 26.3 months. RNU was performed in 16 patients (20%); mean time to surgery was 23.2 months. Overall survival was 75%, and cancer specific survival was 84% at 5-year follow-up. CONCLUSION: Under strict surveillance, ureteroscopic management of large (≥ 2cm) UTUC lesions is a viable treatment alternative to RNU. While recurrence is common, URS can potentially preserve renal units in patients with large lesions.

Simultaneous Bilateral Ureteral Calculi: A New Paradigm for Management.

OBJECTIVE: To define the need for emergent intervention between patients with simultaneous bilateral ureteral calculi (SBUC) compared to unilateral ureteral calculi (UUC). Patients with SBUC represent a potential urological emergency due to possible anuria or electrolyte imbalance. While conventional practice mandates immediate intervention in these patients, little data exist to define the rate of these events. METHODS: Records of all patients with ureteral stones treated ureteroscopically over an 11-year period were reviewed to identify those with SBUC. Patient presenting characteristics, time from diagnosis to intervention, and postoperative outcomes were noted. To determine the need for emergent intervention, we compared metabolic and infectious parameters between SBUC patients and age- and sex-matched patients with UUC. RESULTS: A total of 3800 patients presented with ureteral calculi including 42 (1.1%) with SBUC. Two-thirds of patients with SBUC had an established diagnosis of nephrolithiasis. Among the 42 patients with SBUC, 11 (26.2%) were considered emergent due to metabolic (5 of 11, 45.5%), infectious (1 of 11, 9.1%), or both metabolic and infectious indications (5 of 11, 45.5%). No patients required acute dialysis before surgical intervention. Compared to patients with UUC, those with SBUC were significantly more likely to require emergent management (P = .03, odds ratio 2.3). Univariate and multivariate analyses showed this to be due to anuria (P = .001) and acidosis (P = .003). CONCLUSION: SBUC is an uncommon condition and, in this series, only the minority of patients presented emergently. Therefore, patients with SBUC can often be managed electively if counseled on clinical signs warranting emergent medical attention. Appropriately selected patients have excellent outcomes following single stage bilateral ureteroscopy.

Retrograde Ureteroscopic Management of Large Renal Calculi: A Single Institutional Experience and Concise Literature Review.

INTRODUCTION: Advances in flexible ureteroscope design and accessory instrumentation have allowed for more challenging cases to be treated ureteroscopically. Here, we evaluate our experience with ureteroscopy (URS) for the management of large renal calculi (≥2 cm) and provide a concise review of recent reports. METHODS: A retrospective review was undertaken of all URS cases between 2004 and 2014 performed by the endourologic team at a single academic tertiary care institution. We identified patients with at least one stone ≥2 cm managed with retrograde URS. Stone size was defined as the largest linear diameter of the index stone. Small diameter flexible ureteroscopes were used primarily with holmium laser. Patient demographics, intraoperative data, and postoperative outcomes were evaluated. RESULTS: We evaluated 167 consecutive patients who underwent URS for large renal stones ≥2 cm. The initial reason for choosing URS included patient preference (29.5%), failure of other therapies (8.2%), anatomic considerations/body habitus (30.3%), and comorbidities (28.8%). Mean patient age was 55.5 years (22-84). The mean stone size was 2.75 cm with mean number of procedures per patient of 1.65 (1-6). The single session stone-free rate was 57.1%, two-stage procedure stone-free rate was 90.2% and three-stage stone-free rate was 94.0%. Access sheaths were used in 47% of patients. An association was identified between stone size and patient outcomes; smaller stones correlated with decreased number of procedures. Postoperative complications were minor. CONCLUSIONS: Single or multi-stage retrograde ureteroscopic lithotripsy is a safe and effective mode of surgical management of large renal calculi. Total stone burden is a reliable predictor of the need for a staged procedure and of stone-free rate.

Fluorescence in situ hybridization (FISH) in the diagnosis of bladder and upper tract urothelial carcinoma: the largest single-institution experience to date.

INTRODUCTION: We evaluated the UroVysion (Abbott Molecular, IL, USA) fluorescence in situ hybridization (FISH) assay for the diagnosis of urothelial cancer in patients diagnosed with or suspected to have bladder, upper tract urothelial carcinoma (UTUC), and combined upper and lower tract urothelial carcinoma (BC). MATERIALS AND METHODS: A single institution retrospective analysis comparing sensitivity, specificity, positive predictive value, and negative predictive values for FISH and urinary cytology. FISH within 6 months of endoscopic evaluation were obtained from outpatient voided urine samples. Our institutional pathology department confirmed pathologic disease from specimens obtained during endoscopic evaluations for lower tract disease. For upper tract disease, disease was confirmed by retrograde ureteroscopy, biopsies of visual lesions, and site-specific upper tract cytology. RESULTS: A total of 415 patients submitted FISH specimens. Overall, FISH was more sensitive than cytology 54.9% in comparison with cytology 42.2% (p = 0.01), specificity favored cytology 92.9% compared to 73.5% with FISH (p < 0.01). For BC only patients, the same significant finding of increased sensitivity and decreased specificity was identified, but for UTUC alone and combined UTUC and BC, there was no significant difference. Cytology had improved positive predictive value (PPV) over FISH, 76.9% in comparison to 64.6% (p = 0.02). Negative predictive value (NPV) also favored cytology 74.2% versus 64.9% (p = 0.02). When analyzing individual cohorts, cytology had improved PPV for BC alone patients. UTUC showed no difference for PPV and NPV. For both UTUC and BC, NPV was slightly favored for FISH over cytology 93.2% versus 91.2% (p = 0.03). CONCLUSIONS: Voided urine FISH testing does offer a higher detection of urothelial carcinoma for BC compared to voided cytology; however, specificity was worse. FISH does not appear to improve detection of urothelial carcinoma in patients with either UTUC only or both BC and UTUC.

Endoscopic Treatment of Upper Tract Urothelial Carcinoma.

PURPOSE OF REVIEW: This study aims to make the reader be aware of recent trends regarding the endoscopic management of upper tract urothelial carcinoma (UTUC) via review of the urologic literature over the past 5 years. Given the rare incidence of this disease, and the lack of level 1 evidence, systematic reviews and meta-analyses were also evaluated. Studies of importance are also considered and outlined in the annotated reference section. RECENT FINDINGS: The PubMed database was queried using the following medical subject headings (MeSH terms): "carcinoma, transitional cell," "ureter," "ureteral neoplasms," "kidney pelvis," "endoscopy," "laser therapy," "ureteroscopy," "urologic surgical procedures," and "ureteroscopes." MeSH terms were linked together in varying combinations and limited to human studies in English. Given the relatively rare nature of upper tract urothelial carcinoma (UTUC), level 1 evidence regarding the efficacy of endoscopic treatment does not exist, even after 30+ years of experience. Rather, the literature available mostly is in the form of single institutional retrospective series consisting of relatively small numbers of patients with short to intermediate follow-up. Only within the last 3 years have published series with larger numbers of patients and mean follow-up over 5 years been made available. Even with these more robust experiences, comparisons among series are difficult given variable treatment and follow-up approaches. Most endoscopically managed UTUC will locally recur, especially with longer follow-up. Renal preservation rate is high, however, approaching 80% with follow-up well over 3 years. Patients with high-grade disease often fare poorly regardless of treatment modality. As such, endoscopic management for high-grade urothelial carcinoma should only be used in exceptional circumstances (i.e., in those patients medically unfit for NU or those with solitary kidneys wishing to avoid the morbidity of dialysis). No level 1 evidence exists for the routine use of intraluminal adjuvant therapy for UTUC (i.e., BCG and Mitomycin C) and multiple retrospective observational series claim there is no overt benefit. The recent formation of multiple international groups with interest in UTUC may eventually lead to the production of level 1 studies regarding optimal treatment; however, uniformity in treatment approach will likely still offer challenges.

Incidental Lymphoma Discovered During Surveillance for Low-Grade Upper Tract Urothelial Carcinoma Treated Ureteroscopically: A Case Report Series.

Two cases of incidentally found follicular lymphoma during surveillance for ureteroscopically treated upper tract urothelial carcinoma with cross-sectional imaging are described. Multiple independent primary malignancies should be considered in this population.

Ureteral Avulsion Associated with Ureteroscopy: Insights from the MAUDE Database.

BACKGROUND: Flexible and semirigid ureteroscopy (URS) are widely performed for the treatment of upper tract calculi and tumors. Ureteral avulsion is a rare, but devastating complication of endoscopic stone removal having multiple possible etiologies. Awareness and avoidance of this rare complication depend on identifying responsible mechanisms. This study examines the situations in which ureteral avulsion occurs as described anonymously in the Manufacturer and User facility Device Experience (MAUDE) database. MATERIALS AND METHODS: The MAUDE database was systematically reviewed to account for all reported complications of flexible and semirigid URS. Keywords "ureteroscopy, injury, death, malfunction and other" were entered in the database and medical device reports were reviewed to capture any cases resulting in ureteral avulsion. Attention was paid to the type of ureteroscope involved and the mechanism for avulsion. RESULTS: A total of 104 entries were found detailing the reported complications of flexible and semirigid URS. Ureteral avulsion was clearly noted in six reports with flexible (2) and semirigid ureteroscopes (4). Potential mechanisms included locked deflection of a flexible ureteroscope (1), bunching of the distal bending rubber in a flexible ureteroscope (1), scabbard avulsion (3), and stone basketing (1). CONCLUSIONS: Although the incidence of ureteral avulsion cannot truly be determined from this study, some potentially novel mechanisms for this rare complication are observed. This may target future educational efforts to maximize awareness and avoidance of this complication.

Locked Deflection During Flexible Ureteroscopy: Incidence and Elucidation of the Mechanism of an Underreported Complication.

BACKGROUND AND PURPOSE: Flexible ureteroscopy (URS) is widely implemented with a well-defined safety profile and low complication rates. Although rare, locked deflection of a flexible ureteroscope in the upper tract is a potentially serious complication with poorly understood etiology and is likely underreported. MATERIALS AND METHODS: We attempted to capture all cases of locked deflection during URS by performing an anonymous, online computer survey targeting members of the Endourological Society. The Manufacturer and User Facility Device Experience (MAUDE) database and published literature were queried to find additional cases. The indication for URS, method of ureteroscope removal, patient outcomes, incident reporting, and explanations provided by the manufacturer or third party repair service were obtained whenever possible. RESULTS: In total, 10 cases of locked deflection during flexible URS were identified. Survey responses were obtained from 250/2424 (10.3%) endourologists polled. Locked deflection was noted by 8/250 (3.2%). The reported literature and MAUDE database identified one case each. Successful removal was noted in four using retrograde manipulation techniques while a percutaneous approach was used in three patients. Open surgery was needed in two cases because of resultant ureteral avulsion, and in one case, an open ureterotomy was needed for ureteroscope extraction. According to our survey, locked deflection was reported to the patient in 4/8 cases, the hospital in 3/8 cases, and the Food and Drug Administration (FDA) 0/8 cases. The two cases reported outside of our survey both notified the FDA. The minority of respondents (2/8), including our group, felt improper surgical technique was responsible for resultant locked deflection. Specifically, removal of a completely deflected ureteroscope through a stenotic infundibulum should be avoided. Rather, in such a situation, the ureteroscope should be straightened under fluoroscopy before being withdrawn. CONCLUSIONS: Locked deflection of a flexible ureteroscope is rare and underreported. Some cases are attributed to surgical technique, and awareness is crucial for avoidance of this complication.