Efficacy and Safety of Mitomycin Gel (UGN-101) as an Adjuvant Therapy After Complete Endoscopic Management of Upper Tract Urothelial Carcinoma.

PURPOSE: We describe a novel application of the reverse thermal polymer gel of mitomycin C (UGN-101) as adjuvant therapy after complete endoscopic ablation of upper tract urothelial carcinoma. MATERIALS AND METHODS: We retrospectively reviewed patients treated with UGN-101 from 15 high-volume centers. Adjuvant therapy was defined as treatment administered following visually complete endoscopic ablation. Response at primary endoscopic evaluation was defined as no visual tumor or negative biopsy. Ipsilateral disease-free and progression-free survival were estimated by the Kaplan-Meier method. Ureteral stenosis and other adverse events were abstracted from the medical records. Ureteral stenosis was defined as a condition requiring ureteral stent or nephrostomy, or that would typically warrant stent or nephrostomy. RESULTS: Adjuvant UGN-101 after complete endoscopic ablation was used in 52 of 115 (45%) renal units in the oncologic analysis. At first endoscopic evaluation, 36/52 (69%) were without visible disease. At 6.8 months' median follow-up, the ipsilateral disease-free rate was 63%. Recurrence after adjuvant UGN-101 therapy was more likely in multifocal tumors compared to unifocal (HR 3.3, 95% CI 1.07-9.91). Compared with UGN-101 treatment for chemoablation of measurable disease, there were significantly fewer disease detections with adjuvant therapy (P < .001). Ureteral stenosis after UGN-101 was diagnosed in 10 patients (19%) undergoing adjuvant therapy compared to 17 (29%) undergoing chemoablative therapy (P = .28). CONCLUSIONS: In patients being considered for UGN-101, maximal endoscopic ablation prior to UGN-101 treatment may result in fewer patients with disease at first endoscopy and possibly fewer adverse events than primary chemoablative therapy. Longer follow-up is needed to determine if UGN-101 after complete endoscopic ablation will lead to durable disease-free interval.

Concomitant vs Staged Therapeutic Inguinal Lymphadenectomy in Clinically Node Positive Penile Squamous Cell Carcinoma: Does It Make a Difference?

PURPOSE: Inguinal lymph node dissection within 3 months of primary tumor resection in penile cancer has been associated with longer recurrence-free and cancer-specific survival. However, the optimal timing and effect of lymphadenectomy performed concurrently at the time of primary lesion management on oncologic outcomes in clinically lymph node positive penile squamous cell carcinoma remains unknown. MATERIALS AND METHODS: An international, multicenter cohort of 966 penile cancer cases was queried for penile squamous cell carcinoma management after the year 2000, clinically lymph node positive status, and performance of penile surgery and inguinal lymph node dissection. Cohorts were stratified as concomitant if inguinal lymph node dissection and penile surgery occurred on the same date or staged when inguinal lymph node dissection was performed after penile resection. Rates and patterns of penile squamous cell carcinoma recurrence were reported. Distant recurrence-free, cancer-specific, and overall survival were estimated using Kaplan-Meier analyses and groups compared with log-rank testing. RESULTS: Of 253 contemporary men with clinically lymph node positive penile squamous cell carcinoma, 96 (38%) underwent concomitant inguinal lymph node dissection and 157 (62%) had inguinal lymph node dissection performed in a staged manner. Penile cancer was most likely to recur distantly (19%) followed by in the groin (14%) or pelvis (5%). There were no differences in distant recurrence-free, cancer-specific, or overall survival between management strategies. Multivariable analysis adjusting for stage, treatment center, and perioperative chemoradiation also demonstrated no recurrence-free, cancer-specific, or overall survival benefit between management strategies. CONCLUSIONS: Inguinal lymph node dissection performed concurrently with excision of the penile tumor for clinically node positive penile squamous cell carcinoma is not associated with differences in recurrence-free, cancer-specific, or overall survival compared to staged lymph node dissection.

Antegrade administration of mitomycin gel for upper tract urothelial carcinoma via percutaneous nephrostomy tube: a multi-institutional retrospective cohort study.

OBJECTIVES: To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC) with the aim of decreasing morbidity associated with therapy. PATIENTS AND METHODS: Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centres between 2020 and 2022. The primary outcome was safety profile, as graded by Common Terminology Criteria for Adverse Events (v5.0). Post-therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy. RESULTS: Thirty-two patients received at least one dose of mitomycin gel via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen patients (41%) had residual tumour present prior to induction therapy. At a median of 15.0 months following first dose of induction therapy, ureteric stenosis occurred in three patients (9%), all of whom were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%) and haematuria (8%). No patients had impaired renal function during follow-up and there were no treatment-related deaths. Seventeen patients (59%) had no evidence of disease at PDE and have not experienced recurrence at a median follow-up of 13.0 months post induction. CONCLUSIONS: Administration of mitomycin gel via a PCNT offers a low rate of ureteric stenosis, demonstrates a favourable safety profile, and is administered without general anaesthesia.

Contemporary Management of Chylous Ascites after Retroperitoneal Surgery: Development of an Evidence-Based Treatment Algorithm.

PURPOSE: Chylous ascites (CA) is an uncommon complication that occurs from traumatic disruption of lymphatic channels after retroperitoneal surgery. The purpose of this study was to generate an evidence-based management strategy for CA by reviewing the current literature and available treatment modalities. MATERIALS AND METHODS: A MEDLINE® literature review was performed for "chylous ascites." Individual patient data were extracted from case series and reports to create an efficacy analysis. Treatment modality, drain output, time to escalation of care and time to resolution were recorded. The efficacy analysis was utilized to generate a data-driven treatment algorithm. RESULTS: The literature review yielded 1,953 articles, from which 146 studies contributed data for 523 patients. The efficacy analysis included 245 patients, 168 (69%) of whom were managed successfully with conservative management (CM), at a median time to resolution of 11 days. Forty-eight patients underwent lymphangiography±embolization after CM, with a success rate of 85%. Thirty-one (12%) patients underwent surgical exploration. When treating CA, the patients who underwent stepwise management with CM followed by lymphangiography if CM failed experienced a resolution rate of 96.7%. An evidence-based treatment algorithm was created to guide treatment selection and duration of therapy before escalating to additional forms of therapy. CONCLUSIONS: In this report, we describe the largest conglomeration of iatrogenic CA cases from a literature review (523 cases) and efficacy analysis (245 cases), and created the first evidence-based treatment algorithm for this condition. Treatment success is substantial when using a stepwise combination of CM followed by lymphangiography±embolization.

Effect of intracorporeal urinary diversion on the incidence of benign ureteroenteric stricture after cystectomy.

OBJECTIVES: To compare ureteroenteric stricture rates after radical cystectomy in patients who undergo an intracorporeal urinary diversion versus other surgical approaches. METHODS: We retrospectively reviewed health records of all patients who underwent cystectomy with urinary diversion at Mayo Clinic Hospital (Phoenix, AZ, USA) from 1 January 2007 through 1 January 2018. Ureteroenteric stricture was identified by surveillance imaging. Patients were stratified by surgical approach: open radical cystectomy, robot-assisted radical cystectomy with extracorporeal urinary diversion and robot-assisted radical cystectomy-intracorporeal urinary diversion. A Cox proportional hazards model was fitted that included independent predictors of stricture development. RESULTS: Of the 573 cystectomies assessed, 236 (41.2%) were carried out robotically. In the robot-assisted radical cystectomy cohort, 39 patients (16.5%) underwent intracorporeal urinary diversion. The median follow-up period was 55, 70 and 71 months for the open radical cystectomy, robot-assisted radical cystectomy-extracorporeal urinary diversion and robot-assisted radical cystectomy-intracorporeal urinary diversion groups, respectively. Subgroup stricture rates were as follows: open radical cystectomy, 8.0%; robot-assisted radical cystectomy-extracorporeal urinary diversion, 9.6%; and robot-assisted radical cystectomy-intracorporeal urinary diversion, 2.6% (P = 0.33). The median time to stricture was 5 months (interquartile range 3.3-11.5 months). In the bivariable analysis, factors that were associated with the development of ureteroenteric stricture were postoperative urinary leak (hazard ratio 3.177, 95% confidence interval 1.129-8.935; P = 0.03) and body mass index (hazard ratio 1.078, 95% confidence interval 1.027-1.132; P = 0.002). On multivariable logistic regression analysis, intracorporeal urinary diversion approach was not associated with the development of ureteroenteric stricture (hazard ratio 0.272, 95% confidence interval 0.036-2.066; P = 0.21). CONCLUSIONS: Ureteroenteric stricture is a complication that typically occurs within the first postoperative year. Although our results did not support major differences in outcomes between intracorporeal urinary diversion and extracorporeal urinary diversion, the small sample size did not exclude the possibility of a type 2 statistical error.

Does bladder stone composition predict kidney stone composition?

INTRODUCTION Bladder stones have historically been associated with urinary stasis secondary to bladder outlet obstruction (BOO). Recent studies indicate that the role of BOO in bladder stone formation is minor. We evaluate the role of urinary lithogenic factors in bladder stone formation by comparing the compositions of bladder stones and kidney stones in patients with multi-site urinary calculi. MATERIALS AND METHODS: We identified patients who were treated for concomitant bladder stones and kidney stones between 2008-2019, and had both stone compositions available. Patients with bladder stone size < 10 mm, urinary foreign bodies, encrusted stents or tumors were excluded. Data regarding urinary symptoms, residual volumes, stone composition and 24-hours urine data were collected. RESULTS: We identified 40 males with a median age of 72 years (IQR 6-14), median residual volume of 76 mL (IQR 41-200), and a median prostate volume of 52 mL (IQR 32-102). Bladder outlet procedures were performed concomitantly with cystolitholapaxy in 21 (53%) patients. The most common bladder stone and kidney stone compositions were CaOx (47.5% and 65%), uric acid (32.5% and 22.5%), calcium phosphate (15% and 10%), and struvite (5% and 2.5%), respectively. Bladder stone and kidney stone compositions were identical in 70% of patients. Bladder stone composition was predictive of kidney stone composition, regardless of the PVR, bladder stone size, or whether an outlet procedure was performed. CONCLUSION: We found a high concordance between bladder stone and kidney stone composition, suggesting that metabolic abnormalities have a significant role in bladder stone formation. Bladder stone composition can be used to guide surgical and medical treatment for kidney stones in metabolically active stone patients.

Plasticity of phenotype and heteroblasty in contrasting populations of Acacia koa.

BACKGROUND AND AIMS: Heteroblastic plant species, whose morphology or growth habit changes suddenly during development, offer unique opportunities to investigate the role of selection in canalizing development or increasing the adaptive importance of plasticity. Leaf forms of the Hawaiian tree Acacia koa (koa) change morphologically and physiologically during the first year of growth, providing time to study abiotic factors influencing transition rates relative to other Acacia species. METHODS: The roles of light and water availability in triggering transition to the mature leaf form in contrasting (wet/dry) ecotypes of koa were investigated using a novel modelling technique to distinguish between chronological and ontogenetic controls in triggering transition. A light quality treatment was included to test interactions of heterophylly (the presence of multiple leaf forms) with heteroblastic processes on the resulting phenotype at transition. KEY RESULTS: Increased light intensity increased transition rates, but reduced red to far-red light (R:FR) ratios did not affect transition rates, solidifying the current paradigm of heteroblasty. However, evidence was found for earlier transition ontogenetically under water stress, which is not part of the current paradigm and could differentiate the role of heteroblasty in some Acacia species versus other heteroblastic species. Ecotypic responses also indicate that plasticity of development could vary across koa's range and the adaptive significance of heteroblasty could be marginalized or amplified dependent on the disparate selective pressures present across koa's range. CONCLUSIONS: The use of novel survival functions and a species with an elongated transition time helped to elucidate abiotic modifiers of ontogenetic trajectories. Differences in ontogenetic trajectories between contrasting ecotypes suggest that ongoing climate and land use change will have non-uniform effects on koa regeneration and establishment dynamics across its range.

Role of robot-assisted retroperitoneal lymph node dissection in malignant mesothelioma of the tunica vaginalis: case series and review of the literature.

INTRODUCTION: The management of malignant mesothelioma of the tunica vaginalis (MMTVT) is not clearly defined. Retroperitoneal lymph node dissection has been reported as a potential management option. Herein we present our experience with robot-assisted retroperitoneal lymph node dissection (RARPLND) in our series of patients with MMTVT. MATERIALS AND METHODS: The Mayo Clinic cancer registry was queried from 1972-present for all patients who had a diagnosis of MMTVT. Six patients were identified, five of whom were treated with RPLND, where four underwent RARPLND. RESULTS: In five patients who underwent RPLND, the median age was 50 years (IQR 34-51). Four patients originally presented with right sided symptomatic hydroceles, while one presented with right sided chronic epididymitis. Orchiectomy (one simple, two inguinal radical) was performed in three patients prior to presentation. Preoperative cross-sectional imaging, including PET-CT scan in three patients, was negative for lymphadenopathy or metastasis. RARPLND was performed in 4/5 (80%) cases and concomitant hemiscrotectomy in 4/5 (80%) cases. Full bilateral template was performed in three patients and right modified template was performed in the remaining two. Median lymph node yield was 29 (IQR 22-32) and median blood loss was 275 cc (IQR 200-300). Positive retroperitoneal lymph nodes were found in 3/5 (60%) cases. All patients who underwent RARPLND were discharged home on postoperative day one. Mean follow up was 27 months (range 3-47). No patients recurred. CONCLUSIONS: Regardless of the approach, RPLND may provide a diagnostic benefit in patients who present with MMTVT, with the robotic approach affording a potentially expedited recovery.

Single-dose perioperative mitomycin-C versus thiotepa for low-grade noninvasive bladder cancer.

INTRODUCTION: Mitomycin-C (MMC) and thiotepa are intravesical agents effective in reducing the recurrence of low-grade noninvasive bladder cancer when instilled perioperatively. No studies have compared these agents as a single-dose perioperative instillation. This study tests whether there is a difference in recurrence-free survival in patients with low-grade noninvasive bladder cancer who received intravesical MMC versus thiotepa. MATERIALS AND METHODS: A retrospective review was performed of patients who underwent cystoscopic excision of a bladder mass identified as a small, low-grade, treatment-naïve, noninvasive, wild-type urothelial carcinoma of the bladder and who received either intravesical thiotepa (30 mg/15 cc) or MMC (40 mg/20 cc) between January 1, 2002, and January 1, 2016. Data were collected for demographic characteristics, comorbid conditions, operative information, surveillance, and recurrence. The primary outcome was disease-free survival. Cohorts were compared via the doubly robust estimation approach, which used logistic regression to model the probability of recurrence. RESULTS: Of 154 total patients, 84 received intravesical MMC; 70, thiotepa. No statistical differences were shown between groups for age, sex, race, body mass index, smoking status, or baseline comorbid conditions; mass size, tumor multifocality, or tumor grade; and unadjusted recurrence rates (MMC, 36.0%; thiotepa, 46.0%; p = .33) at similar median follow up (MMC, 20.4; thiotepa, 22.8 months; p = .46). The robust logistic regression analysis yielded no differences in recurrence rates between MMC and thiotepa (OR, 0.65 [95% CI, 0.33-1.31]; p = .23). No episodes of myelosuppression or frozen pelvis were identified. CONCLUSIONS: As single-dose perioperative agents, both thiotepa and MMC were associated with similar recurrence-free survival rates.

Comparative Effectiveness of Neoadjuvant Pembrolizumab Versus Cisplatin-based Chemotherapy or Upfront Radical Cystectomy in Patients with Muscle-invasive Urothelial Bladder Cancer.

BACKGROUND: Recent progresses in the use of immune checkpoint inhibitor (ICI) have challenged the therapeutic standards in patients with muscle-invasive urothelial bladder carcinoma (MIBC). OBJECTIVE: To compare neoadjuvant pembrolizumab followed by radical cystectomy (RC) versus neoadjuvant chemotherapy (NAC) and RC or upfront RC, according to cisplatin eligibility. DESIGN, SETTING, AND PARTICIPANTS: We conducted two separate analyses for cisplatin-eligible and cisplatin-ineligible cT2-4N0M0 MIBC patients. We used a propensity score adjustment that relied on inverse probability of treatment-weighting (IPTW). INTERVENTION: Pembrolizumab within the PURE-01 trial, and NAC and RC or upfront RC from a high-volume tertiary care referral center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint in both analyses was event-free survival (EFS), defined as freedom from recurrence, and/or death from any cause indexed from the date of treatment initiation or RC. The secondary endpoints included EFS in propensity score-matched patients, pathologic response rate, and recurrence-free survival (RFS) after RC. RESULTS AND LIMITATIONS: A total of 458 patients who underwent RC, with or without NAC, at Moffitt Cancer Center between October 2005 and October 2020, and 146 patients enrolled in PURE-01 were analyzed. In cisplatin-ineligible patients, EFS was superior in those receiving pembrolizumab (p < 0.001). The estimated 3-yr EFS was 77.8% (95% confidence interval [CI]: 63.5-95.2) for pembrolizumab and RC, and 36.1% (95% CI: 28.6-45.5) for upfront RC. EFS remained superior in those receiving neoadjuvant ICI (NICI) following IPTW (p < 0.001). In cisplatin-eligible patients, EFS was superior in those receiving pembrolizumab and RC (p < 0.001). The estimated 3-yr EFS was 86.9% (95% CI: 80.9-93.3) for pembrolizumab and 63.5% (95% CI: 56.5-71.4) for NAC. EFS remained superior in those receiving NICI following IPTW (p < 0.001). Pathologic responses and RFS in pembrolizumab-treated patients were also superior to those in NAC-treated patients. Results are limited by the retrospective nature of the study. CONCLUSIONS: In the first ever reported comprehensive comparison of outcomes between neoadjuvant ICI and NAC, followed by RC, or upfront RC, we report increased responses and improved oncologic outcomes with neoadjuvant ICI in patients with MIBC. PATIENT SUMMARY: We compared the results obtained from the use of pembrolizumab and radical cystectomy with standard-of-care treatments in patients with bladder carcinoma infiltrating the muscle layer. We reported increased response and survival rates possibilities with the use of immunotherapy, anticipating the possibility to set new therapeutic standards in these patients, pending the results of ongoing randomized studies.

First analysis of the safety and efficacy of UGN-101 in the treatment of ureteral tumors.

OBJECTIVE: UGN-101 has been approved for the chemoablation of low-grade upper tract urothelial cancer (UTUC) involving the renal pelvis and calyces. Herein is the first reported cohort of patients with ureteral tumors treated with UGN-101. PATIENTS AND METHODS: We performed a retrospective review of patients treated with UGN-101 for UTUC at 15 high-volume academic and community centers focusing on outcomes of patients treated for ureteral disease. Patients received UGN-101 with either adjuvant or chemo-ablative intent. Response rates are reported for patients receiving chemo-ablative intent. Adverse outcomes were characterized with a focus on the rate of ureteral stenosis. RESULTS: In a cohort of 132 patients and 136 renal units, 47 cases had tumor involvement of the ureter, with 12 cases of ureteral tumor only (8.8%) and 35 cases of ureteral plus renal pelvic tumors (25.7%). Of the 23 patients with ureteral involvement who received UGN-101 induction with chemo-ablative intent, the complete response was 47.8%, which did not differ significantly from outcomes in patients without ureteral involvement. Fourteen patients (37.8%) with ureteral tumors had significant ureteral stenosis at first post-treatment evaluation, however, when excluding those with pre-existing hydronephrosis or ureteral stenosis, only 5.4% of patients developed new clinically significant stenosis. CONCLUSIONS: UGN-101 appears to be safe and may have similar efficacy in treating low-grade urothelial carcinoma of the ureter as compared to renal pelvic tumors.

Novel Use of Circulating Tumor DNA to Identify Muscle-invasive and Non-organ-confined Upper Tract Urothelial Carcinoma.

BACKGROUND: Optimal patient selection for neoadjuvant chemotherapy prior to surgical extirpation is limited by the inaccuracy of contemporary clinical staging methods in high-risk upper tract urothelial carcinoma (UTUC). OBJECTIVE: To investigate whether the detection of plasma circulating tumor DNA (ctDNA) can predict muscle-invasive (MI) and non-organ-confined (NOC) UTUC. DESIGN, SETTING, AND PARTICIPANTS: Plasma cell-free DNA was prospectively collected from chemotherapy-naïve, high-risk UTUC patients undergoing surgical extirpation and sequenced using a 152-gene panel and low-pass whole-genome sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: To test for concordance, whole-exome sequencing was performed on matching tumor samples. The performance of ctDNA for predicting MI/NOC UTUC was summarized using the area under a receiver-operating curve, and a variant count threshold for predicting MI/NOC disease was determined by maximizing Youden's J statistic. Kaplan-Meier methods estimated survival, and Mantel-Cox log-rank testing assessed the association between preoperative ctDNA positivity and clinical outcomes. RESULTS AND LIMITATIONS: Of 30 patients enrolled prospectively, 14 were found to have MI/NOC UTUC. At least one ctDNA variant was detected from 21/30 (70%) patients, with 52% concordance with matching tumor samples. Detection of at least two panel-based molecular alterations yielded 71% sensitivity at 94% specificity to predict MI/NOC UTUC. Imposing this threshold in combination with a plasma copy number burden score of >6.5 increased sensitivity to 79% at 94% specificity. Furthermore, the presence of ctDNA was strongly prognostic for progression-free survival (PFS; 1-yr PFS 69% vs 100%, p < 0.001) and cancer-specific survival (CSS; 1-yr CSS 56% vs 100%, p = 0.016). CONCLUSIONS: The detection of plasma ctDNA prior to extirpative surgery was highly predictive of MI/NOC UTUC and strongly prognostic of PFS and CSS. Preoperative ctDNA demonstrates promise as a biomarker for selecting patients to undergo neoadjuvant chemotherapy prior to nephroureterectomy. PATIENT SUMMARY: Here, we show that DNA from upper tract urothelial tumors can be detected in the blood prior to surgical removal of the kidney or ureter. This circulating tumor DNA can be used to predict that upper tract urothelial carcinoma is invasive into the muscular lining of the urinary tract and may help identify those patients who could benefit from chemotherapy prior to surgery.

Neoadjuvant platinum-based chemotherapy and lymphadenectomy for penile cancer: an international, multi-institutional, real-world study.

INTRODUCTION: This study investigated the efficacy and safety of neoadjuvant chemotherapy for locally advance penile squamous cell carcinoma for which current evidence is lacking. METHODS: Included patients had locally advanced penile squamous cell carcinoma with clinical lymph node metastasis treated with at least 1 dose of neoadjuvant chemotherapy prior to planned consolidative lymphadenectomy. Objective response rates were assessed using Response Evaluation Criteria in Solid Tumors v1.1. The primary and secondary outcomes were overall survival and progression-free survival, estimated by the Kaplan-Meier method. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events v5.0. RESULTS: A total of 209 patients received neoadjuvant chemotherapy for locally advanced and clinically node-positive penile squamous cell carcinoma. The study population consisted of 7% of patients with stage II disease, 48% with stage III, and 45% with stage IV. Grade 2 treatment-related adverse events occurred in 35 (17%) patients, and no treatment-related mortality was observed. Of the patients, 201 (97%) completed planned consolidative lymphadenectomy. During follow-up, 106 (52.7%) patients expired, with a median overall survival of 37.0 months (95% confidence interval [CI] = 23.8 to 50.1 months) and median progression-free survival of 26.0 months (95% CI = 11.7 to 40.2 months). Objective response rate was 57.2%, with 87 (43.2%) having partial response and 28 (13.9%) having a complete response. Patients with objective response to neoadjuvant chemotherapy had a longer median overall survival (73.0 vs 17.0 months, P < .01) compared with those who did not. The lymph node pathologic complete response rate was 24.8% in the cohort. CONCLUSION: Neoadjuvant chemotherapy with lymphadenectomy for locally advanced penile squamous cell carcinoma is well tolerated and active to reduce the disease burden and improve long-term survival outcomes.

An Exercise Prescription To Improve Posture, Minimize Injury, and Improve Career Longevity in Surgeons.

A contemporary exercise and strength regimen can improve posture, minimize injury, and improve career longevity in surgeons. By targeting core stability, neck posture, and thoracoscapular strength, surgeons and operating room teams can minimize neck and lower back pain.

DiabetesWise: An innovative approach to promoting diabetes device awareness.

BACKGROUND: DiabetesWise is an unbranded, data-driven online resource that tailors device recommendations based on preferences and priorities of people with insulin-requiring diabetes. The objective of this study is to examine whether DiabetesWise increases uptake of diabetes devices, which are empirically supported to improve glycemic and psychosocial outcomes. METHODS: The sample included 458 participants (Mage = 37.1, SD = 9.73; 66% female; 81% type 1 diabetes) with insulin-requiring diabetes and minimal diabetes device use at enrollment. Participants used DiabetesWise and completed online surveys. Chi-square and t tests evaluated requests for a device prescription, receiving a prescription, and starting a new device at 1 and 3 months post use. Baseline predictors of these variables and past use of continuous glucose monitors (CGMs) and changes in diabetes distress post use were also examined. RESULTS: Within the first month of interacting with DiabetesWise 19% of participants asked for a prescription for a diabetes device. This rate rose to 31% in the first 3 months. These requests resulted in 16% of the sample starting a new device within the first 3 months. Whereas several factors were associated with prior CGM use, receiving a prescription, and starting a new device, more diabetes distress (t(343) = -3.13, p = .002) was the only factor associated with asking for a prescription. Diabetes distress decreased after interacting with DiabetesWise within 1 month (t(193) = 3.51, p < .001) and 3 months (t(180) = 5.23, p < .001). CONCLUSIONS: Within 3 months of interacting with DiabetesWise, one in three participants had requested a prescription for a new diabetes device and average distress levels were reduced, indicating benefit from this low-intensity online platform.

Mitomycin Gel (UGN-101) as a Kidney-sparing Treatment for Upper Tract Urothelial Carcinoma in Patients with Imperative Indications and High-grade Disease.

BACKGROUND: Intracavitary UGN-101 is approved for the treatment of low-grade noninvasive upper tract urothelial carcinoma (UTUC). Post-commercialization studies underscore the benefit of UGN-101 administration for patients with imperative indications for whom radical nephroureterectomy (RNU) is not a viable option. OBJECTIVE: To describe the use, efficacy, and safety of UGN-101 in patients with UTUC with imperative indications for renal preservation, including high-grade disease. DESIGN, SETTING, AND PARTICIPANTS: Patients receiving UGN-101 with imperative indications were retrospectively analyzed using a multicenter centralized registry from 15 high-volume academic and community centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We defined imperative indications as patients with a solitary kidney, the presence of chronic kidney disease (CKD) with a glomerular filtration rate <30 ml/min, bilateral UTUC, and patients unfit for or unwilling to undergo surgical extirpation. Tumor characteristics, disease progression/recurrence, and adverse events were recorded on a per-renal-unit basis. RESULTS AND LIMITATIONS: UGN-101 was instilled into 52 renal units (38%) in 48 patients for imperative indications, including 29 patients (56%) with a solitary kidney, 11 kidneys (21%) in the setting of bilateral UTUC, six patients (12%) with CKD, and six patients (12%) who were unfit for or unwilling to undergo RNU. Twelve renal units had biopsy-proven high-grade papillary disease. Tumors were completely ablated before induction therapy in 34% of cases, while 66% had tumor present. Following induction therapy, 17 patients (40%) had no evidence of disease (NED) on ureteroscopy, 88% of whom maintained this status at median follow-up of 10.8 mo. In the cohort with high-grade disease, five patients (45%) had NED at initial post-induction primary disease evaluation. Adverse events included pyelonephritis (8%), ureteral stenosis (8%), anemia (6%), and acute renal failure (4%). Limitations include the retrospective study design, the lack of long-term follow up, and patient selection bias. CONCLUSIONS: Intracavitary therapy with UGN-101 in patients with UTUC and imperative indications shows promise as a kidney-sparing treatment modality. While long-term follow-up is needed, this intracavitary treatment may help in prolonging time to RNU and delaying the morbidity of hemodialysis in this comorbid population. PATIENT SUMMARY: We reviewed results for patients with cancer in the upper urinary tract and an additional condition that would not allow kidney removal who received treatment with a gel called UGN-101. Our results suggest that UGN-101 shows promise as a kidney-sparing treatment. It may delay the time until kidney removal is needed in these patients and avoid the negative effects associated with dialysis.

Effectiveness of perioperative chemotherapy and radical cystectomy in treating bladder cancer.

BACKGROUND: Despite abundant evidence supporting the use of perioperative chemotherapy from clinical trials, no study to date has comprehensively evaluated its use in the treatment of muscle-invasive bladder cancer (MIBC) in the real-world setting. Little is known regarding the impact of pretreatment disease stage and real-world factors such as patient comorbidities preventing timely completion of therapy on its effectiveness. This study aims to assess the usage of perioperative chemotherapy and examines its impact on pathologic downstaging rates and recurrence free survival in patients undergoing radical cystectomy. METHODS: A retrospective review was conducted in 805 patients with muscle invasive bladder cancer undergoing radical cystectomy with no perioperative chemotherapy, 761 with presurgical chemotherapy followed by radical cystectomy, and 134 radical cystectomy followed by adjuvant chemotherapy. Relevant clinicopathologic features were reviewed. Recurrence-free survival and Overall Survival probability estimates were calculated using the Kaplan-Meier method and compared using the Log-rank or Gehan-Breslow tests. The prognostic effects of presurgical chemotherapy and adjuvant chemotherapy regimens were evaluated by estimating hazard ratio and 95% confidence interval from an adjusted Cox proportional hazards model. Statistical tests were 2-sided, and significance was defined as P-value < 0.05. RESULTS: In this contemporary, real-world cohort, 5-yr RFS was found to be 65.6% in pT0, 59.1%in pT2, and 10.8% in pN+ patients. Presurgical chemotherapy increased pathologic downstaging rates from 27.5% to 41.1% in patients with ≥cT2 BCa. Stratified by clinical T-stage, only cT2 patients derived recurrence-free survival (Median 45.3 months vs. 29.0 months, P < 0.01) and overall survival (Median 62.3 months vs. 41.9 months, P < 0.001) benefits.  In patients with adverse pathologic features (≥pT3 or pN+), adjuvant chemotherapy improved recurrence-free survival (Median 22.8 months vs. 10.0 months, P < 0.0001) and overall survival (Median OS 32.4 months vs. 16.3 months, P < 0.0001). CONCLUSIONS: We report real-world outcomes from a large cohort of muscle-invasive bladder cancer patients undergoing surgical treatment with/out perioperative chemotherapy. Pathologic response rates to pre-surgical chemotherapy were modest and led to clinical benefit only in cT2 patients. Adjuvant chemotherapy provided survival benefit for pathologically advanced MIBC patients irrespective of pT/N staging.

A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma In Situ of the Bladder.

PURPOSE: Immune checkpoint blockade holds promise for treating bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal antibody, against BCG-unresponsive carcinoma in situ (CIS). PATIENTS AND METHODS: Patients with BCG-unresponsive CIS-containing NMIBC received durvalumab IV at 1,500 mg every 4 weeks for up to 12 months. The primary endpoint was complete response (CR) rate at month 6, defined by negative cystoscopy, urine cytology, and absence of high-grade recurrence on bladder mapping biopsy. The null hypothesis specified a CR rate of 18% and alternative hypothesis of 40%. According to the Simon two-stage design, if ≤3/13 patients achieved CR during stage 1, the trial is stopped due to futility. RESULTS: Between March 8, 2017, and January 24, 2020, 17 patients were accrued whereas 4 withdrew from study treatment after bladder biopsy at month 3 was positive for CIS. Two of 17 (12%) achieved a CR at month 6, with duration of response of 10 and 18 months, respectively. A single grade 3 lipase elevation was attributed to durvalumab, and immune-related adverse events were observed in 7/17 (41%) patients. Only 1/17 patients had high programmed death-ligand 1 expression pretreatment. On RNA sequencing, complement activation genes were elevated posttreatment, along with enrichment of tumor-associated macrophage signature. CONCLUSIONS: Durvalumab monotherapy conferred minimal efficacy in treating BCG-unresponsive CIS of the bladder, with 6-month CR of 12%. Complement activation is a potential mechanism behind treatment resistance.