Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.

Utilization and Timing of Cystoscopy for Hematuria Evaluation by Advanced Practice Providers and Urologists.

OBJECTIVE: To characterize differences between urologists and advanced practice providers (APPs) in the utilization of cystoscopy for hematuria. METHODS: We identified patients initially evaluated for hematuria by a urologist or urology APP between 2015 and 2020 in the MarketScan Research Databases. We determined whether they received a cystoscopy within 6 months of their urology visit and the number of days until cystoscopy. We used multivariable regression to analyze the association between these outcomes and whether the urology clinician was an advanced practice registered nurse (APRN), physician assistant (PA), or urologist. RESULTS: We identified 34,470 patients with microscopic hematuria and 17,328 patients with gross hematuria. Patients evaluated by urologists more often received a same-day cystoscopy than those evaluated by APPs (13% vs 5.8%). The odds that patients evaluated for microscopic and gross hematuria received a cystoscopy were 46.2% and 26.2% lower, respectively, if they were evaluated by an APRN vs a urologist. Patients seeing an APRN for microscopic and gross hematuria also waited approximately 7 and 14 days longer for their cystoscopy, respectively. No differences were observed for patients evaluated by PAs vs urologists. CONCLUSION: Patients evaluated for hematuria by an APRN were less likely to receive a cystoscopy and had a longer wait until the procedure compared to those evaluated by a urologist; however, no differences were observed between PAs and urologists. Better understanding APP integration into urology clinics is warranted.

Necrotizing granulomatous epididymo-orchitis post intravesical BCG administration after brachytherapy for prostate cancer.

Urothelial carcinoma of the bladder remains a challenging disease to treat. Intravesical instillation of BCG has demonstrated tremendous efficacy in preventing recurrence. BCG related necrotizing granulomatous epididymo-orchitis is rare and has not been previously linked to brachytherapy for adenocarcinoma of the prostate. We hypothesize that prior brachytherapy has a deleterious effect on the verumontanum that can result in retrograde transmission of BCG particles leading to granulomatous epididymo-orchitis. This is the first case report of necrotizing granulomatous epididymo-orchitis related to BCG in a patient status post brachytherapy for adenocarcinoma of the prostate.

Standardization of the evaluation and surveillance of patients with BCG unresponsive high grade non-muscle invasive bladder cancer clinical trials.

There are multiple ongoing and planned clinical trials that are evaluating novel therapies to treat patients with BCG-unresponsive high grade nonmuscle invasive bladder cancer (NMIBC). Importantly, there is considerable variation in surveillance strategies between these clinical trials, specifically with regards to the use of advanced imaging, enhanced cystoscopy, and mandatory biopsies, which could impact landmark efficacy assessments of investigational agents. To present guideline recommendations for the standardization of cystoscopic evaluation, surveillance, and efficacy assessments for patients with BCG-unresponsive NMIBC participating in clinical trials. On September 29, 2023 at the annual meeting of the International Bladder Cancer Network, a breakout session was convened, during which representatives from various disciplines discussed potential guidance statements with opportunity for discussion and comment. A set of statements regarding use of white light and enhanced cystoscopy were developed to help guide a pragmatic approach to surveillance and efficacy assessments of patients in clinical trials. The use of "for cause" and "mandatory" biopsies was also addressed. A standard approach to evaluation of patients within the context of clinical trials is necessary to accurately assess the efficacy of novel agents, especially within single arm trials that lack an appropriate comparator. Additionally, the utilization and timing of mandatory biopsies is critical, as these biopsies may impact both disease evaluations and the determination of duration of response.

Functional and oncologic outcomes of prostate capsule-sparing radical cystectomy: A systematic review and meta-analysis.

Radical cystectomy (RC) is the gold standard treatment for patients with organ-confined bladder cancer. However, despite the success of this treatment, many men who undergo orthotopic neobladder substitution develop significant erectile dysfunction and urinary symptoms, including daytime and nighttime urinary incontinence. Prostate-capsule-sparing radical cystectomy (PCS-RC) with orthotopic neobladder (ONB) has been described in the literature as a surgical technique to improve functional outcomes in appropriately selected patients. We performed a systematic review and meta-analysis of manuscripts on PCS-RC with ONB published after 2000. We included retrospective and prospective studies with more than 25 patients and compared PCS-RC with nerve-sparing or conventional RC. Studies in which the entire prostate was spared (including the transitional zone) were excluded. Comparative studies were analyzed to assess rates of daytime continence, nighttime continence, and satisfactory erectile function in patients undergoing PCS-RC compared with those undergoing conventional RC. Fourteen reports were included in the final review. Our data identify high rates of daytime (83%-97%) and nighttime continence (60%-80%) in patients undergoing PCS-RC with ONB. In comparative studies, meta-analysis results demonstrate no difference in daytime continence (RR:1.12; 95% CI: 0.72-1.73) in those undergoing PCS-RC compared to those undergoing conventional RC. Similarly, nighttime continence was similar between the 2 groups (RR:1.85; 95% CI: 0.57-6.00. Erectile function was improved in those undergoing PCS-RC (RR 5.35; 95% CI: 1.82-15.74) in the PCS-RC series. Bladder cancer margin positivity and recurrence rates were similar to those reported in the literature with conventional RC with an average weighted follow-up of 52.2 months. While several studies utilized different prostate cancer (CaP) screening techniques, the rates of CaP were low (incidence 0.02; 95% CI:0.01-0.04), and oncologic outcomes were similar to standard RC. PCS-RC is associated with improved nighttime continence and erectile function compared to conventional RC techniques. Further work is needed to standardize CaP screening before surgery, but the data suggest low rates of CaP with similar oncologic outcomes when compared to RC.

Bladder-Preserving Trimodality Therapy With Capecitabine.

INTRODUCTION: Many patients with muscle-invasive bladder cancer are poor candidates for radical cystectomy or trimodality therapy with maximal transurethral resection of bladder tumor (TURBT) and chemoradiotherapy with cisplatin or mitomycin C. Given the benefit of chemotherapy in bladder-preserving therapy, less-intense concurrent chemotherapy regimens are needed. This study reports on efficacy and toxicity for patients treated with trimodality therapy using single-agent concurrent capecitabine. MATERIALS AND METHODS: Patients deemed ineligible for radical cystectomy or standard chemoradiotherapy by a multidisciplinary tumor board and patients who refused cystectomy were included. Following TURBT, patients received twice-daily capecitabine (goal dose 825 mg/m2) concurrent with radiotherapy to the bladder +/- pelvis depending on nodal staging and patient risk factors. Toxicity was evaluated prospectively in weekly on-treatment visits and follow-up visits by the treating physicians. Descriptive statistics are provided. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival were estimated using the Kaplan-Meier method. RESULTS: Twenty-seven consecutive patients met criteria for inclusion from 2013 to 2023. The median age was 79 with 9 patients staged cT3-4a and 7 staged cN1-3. The rate of complete response in the bladder and pelvis was 93%. Overall, progression-free, cancer-specific, distant metastasis-free, and bladder recurrence-free survival at 2 years were estimated as 81%, 65%, 91%, 75%, and 92%, respectively. There were 2 bladder recurrences, both noninvasive. There were 7 grade 3 acute hematologic or metabolic events but no other grade 3+ toxicities. CONCLUSION: Maximal TURBT followed by radiotherapy with concurrent capecitabine offers a high rate of bladder control and low rates of acute and late toxicity.

Effective population size in simple infectious disease models.

Almost all models used in analysis of infectious disease outbreaks contain some notion of population size, usually taken as the census population size of the community in question. In many settings, however, the census population is not equivalent to the population likely to be exposed, for example if there are population structures, outbreak controls or other heterogeneities. Although these factors may be taken into account in the model: adding compartments to a compartmental model, variable mixing rates and so on, this makes fitting more challenging, especially if the population complexities are not fully known. In this work we consider the concept of effective population size in outbreak modelling, which we define as the size of the population involved in an outbreak, as an alternative to use of more complex models. Effective population size is an important quantity in genetics for estimation of genetic diversity loss in populations, but it has not been widely applied in epidemiology. Through simulation studies and application to data from outbreaks of COVID-19 in China, we find that simple SIR models with effective population size can provide a good fit to data which are not themselves simple or SIR.

Purple urine bag syndrome: An unusual manifestation of urinary tract infection, our experience at a tertiary care center.

Background: Purple urine bag syndrome (PUBS) is an unusual condition in which a purple discoloration of urine and bag occurs in people with urinary catheters. People with purple urine usually do not complain of any symptoms. The purple discoloration of the urine bag is often the only finding, frequently noted by caregivers. Materials and methods: This prospective observational study was conducted at our tertiary care institute from June 2018 to May 2020. A total of 46 patients with PUBS were included in this study. The objective of our study was to record the prevalence of each predisposing factor and to correlate the pathological mechanism through which the PUBS is manifested. Results: The mean age of PUBS patients was 67.4years and 67.4% were males. Most patients of PUBS (60.9%) had a urethral catheter, while there was percutaneous nephrostomy in 26.1% patients and 13% patients had a percutaneous suprapubic cystostomy catheter. Among the patients, 69.65% were bedridden or in an institutionalized situation, 73.9% were suffering from chronic constipation, 21.7% were associated with dementia, and 47.8% were cerebrovascular accidents with hemiparesis patients. In addition, 93.5% of patients presented with alkaline urine and 3 patients with acidic urine. The most common bacteria isolated in urine culture were E coli and Pseudomonas. Conclusions: Urinary catheter associated urinary tract infection and PUBS is most commonly documented in females, but our study showed that it is more common in males. The appearance of a purple bag does not depend on the material and type of the catheter or the catheterization method. In addition, no correlation was found between the microorganisms isolated from the environment and patients' urine.

The "Wind Surf" Deformity-Correcting Fixed Flexion Deformity and Hyperextension in Bilateral CAS TKA.

Severe knee arthritis can result in complex coronal and sagittal angular deformities. Windswept deformity is used to describe a varus deformity and contralateral valgus deformity. We recognized a new sagittal pattern at the time of computer-assisted surgery (CAS) in total knee arthroplasty (TKA) in which one knee has a fixed flexion deformity (FFD), while the contralateral knee has a hyperextension deformity. We propose to define it as "wind surf" deformity mimicking the opposite pull of the wind and a surfer. The incidence of "wind surf" deformity in this series was 0.96% among a cohort of 2,291 bilateral TKAs performed between 2013 and 2018. Twenty-two patients were identified with an FFD of 5° to 20° on one knee and recurvatum of -5° to -20° on the contralateral knee. Additional bone resection and soft-tissue releases were performed for the FFD with a goal to maintain residual 1° to 3° of flexion. Minimal bone resection and soft-tissue disruption were performed on the knee with hyperextension with a goal to maintain 5° to 7° of flexion. These opposite strategies applied with the help of CAS prevented recurrence resulting in satisfactory clinical results at 2-year follow-up. The "wind surf" deformity variant should be identified in patients presenting with severe knee arthritis to guide surgical treatment, prevent recurrence, and obtain favorable clinical patient outcomes.

Management of Lateral Femoral Condyle Non-union with Autogenous Bone Graft in CAS Total Knee Arthroplasty.

Introduction: Neglected distal femur fractures often present with significant uncontained bone defects of the lateral femoral condyle (LFC) leading to a valgus deformity and lateral compartment arthritis. Case Report: Bone defect can be managed with the help of autogenous bone graft harvested from a distal femur cut and shaped in the form of an augment. The objective of using bone graft along with the primary femur was to restore bone stock in a young patient and prevent the use of an augment with a revision femur and intramedullary rod. Conclusion: The use of computer navigation helped in getting accurate components and overall alignment thus facilitating compression at the bone graft site and early union.

IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

IL-15 Superagonist NAI in BCG-Unresponsive NMIBCIn this trial, patients with BCG-unresponsive bladder CIS with or without Ta/T1 papillary disease or BCG-unresponsive high-grade Ta/T1 papillary NMIBC were treated with intravesical NAI, an IL-15 superagonist, plus BCG. Primary end points were CR at 3 or 6 months for patients with CIS disease and DFS rate at 12 months for those with high-grade Ta/T1 disease. CR rate was 71% (58 of 82 patients), and the DFS rate was 55.4%.

Model-based intensification of CHO cell cultures: One-step strategy from fed-batch to perfusion.

There is a growing interest in continuous processing of the biopharmaceutical industry. However, the technology transfer from traditional batch-based processes is considered a challenge as protocol and tools still remain to be established for their usage at the manufacturing scale. Here, we present a model-based approach to design optimized perfusion cultures of Chinese Hamster Ovary cells using only the knowledge captured during small-scale fed-batch experiments. The novelty of the proposed model lies in the simplicity of its structure. Thanks to the introduction of a new catch-all variable representing a bulk of by-products secreted by the cells during their cultivation, the model was able to successfully predict cellular behavior under different operating modes without changes in its formalism. To our knowledge, this is the first experimentally validated model capable, with a single set of parameters, to capture culture dynamic under different operating modes and at different scales.

Electric-field control of nonlinear THz spintronic emitters.

Energy-efficient spintronic technology holds tremendous potential for the design of next-generation processors to operate at terahertz frequencies. Femtosecond photoexcitation of spintronic materials generates sub-picosecond spin currents and emission of terahertz radiation with broad bandwidth. However, terahertz spintronic emitters lack an active material platform for electric-field control. Here, we demonstrate a nonlinear electric-field control of terahertz spin current-based emitters using a single crystal piezoelectric Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) that endows artificial magnetoelectric coupling onto a spintronic terahertz emitter and provides 270% modulation of the terahertz field at remnant magnetization. The nonlinear electric-field control of the spins occurs due to the strain-induced change in magnetic energy of the ferromagnet thin-film. Results also reveal a robust and repeatable switching of the phase of the terahertz spin current. Electric-field control of terahertz spintronic emitters with multiferroics and strain engineering offers opportunities for the on-chip realization of tunable energy-efficient spintronic-photonic integrated platforms.

Flat intraurothelial lesions of the urinary bladder-do hyperplasia, dysplasia, and atypia of unknown significance need to exist as diagnostic entities? and how to handle in routine clinical practice.

Classification of the putative flat preneoplastic and neoplastic lesions of the urothelium with features subthreshold for urothelial carcinoma in situ remains a challenging, indeed, vexing problem in diagnostic surgical pathology. This area, subtending lesions including flat urothelial hyperplasia, urothelial dysplasia, and atypia of unknown significance, has struggled under evolving classifications, changing criteria, and limited clinical actionability, all confounded by the recognized lack of diagnostic reproducibility. Herein, we review the state of the literature around these lesions, reviewing contemporary criteria and definitions, assessing the arguments in favor and against of retaining hyperplasia, dysplasia, and atypia of unknown significance as diagnostic entities. We clarify the intent of the original definitions for dysplasia as a lesion felt to be clearly neoplastic but with morphologic features that fall short of the threshold of urothelial carcinoma in situ. While several pathologists, including some experts in the field, conflate the term dysplasia with urothelial atypia of unknown significance, the latter is defined as a descriptive diagnosis term to express diagnostic uncertainty of a lesion of whether it is clearly reactive or neoplastic. Both molecular studies and clinical needs are considered, as we outline our approach on diagnosing each of these lesions in clinical practice. Recommendations are made to guide consistency and interoperability in future scholarship, and the place of these lesions in context of evolving trends in the field is considered.

Incidence of Preoperative Antibiotic Use and Its Association with Postoperative Infectious Complications after Radical Cystectomy.

OBJECTIVE: To determine exposure rates to antibiotics prior to radical cystectomy and determine if there is correlation with post-operative infections. METHODS AND MATERIALS: 2248 patients were identified in the 2016 SEER-Medicare linkage who underwent radical cystectomy between 2008 and 2014 with complete prescription information. An outpatient prescription for an antibiotic within 30 days prior to cystectomy was considered exposure. Antibiotic class and combinations were recorded. Postoperative infectious diagnoses and readmissions were tabulated within 30 days of cystectomy. RESULTS: Fifty one percent of patients (n = 1149) were prescribed an outpatient antibiotic prior to cystectomy. Patients receiving antibiotics were more likely to be female (31% vs 25%, P < .01) and had been diagnosed with an infection (17% vs 11%, P < .01). Antibiotic bowel prophylaxis was prescribed to 42% of patients receiving antibiotics. Postoperatively, the exposure group had higher rates of any infection, (56% vs 51% P < .01) and UTI (36% vs 31% P < .01). All-cause readmission within 30 days was higher in the exposure cohort (26% vs 22%, P = .02) Multivariable logistic regression showed outpatient preoperative antibiotics were an independent risk factor for any infection (HR 1.19, P < .05) and readmission (hazards ratio 1.24, P = .03) in the 30 days after radical cystectomy. CONCLUSION: Outpatient antibiotic use prior to radical cystectomy is common and may be associated with increased risk of postoperative infection and readmission. Antibiotic use prior to radical cystectomy should be examined as a modifiable factor to decrease post-operative morbidity.

Robotic Nerve Sheath Tumor Resection With Intraoperative Neuromonitoring: Case Series and Systematic Review.

BACKGROUND: Retroperitoneal nerve sheath tumors present a surgical challenge. Despite potential advantages, robotic surgery for these tumors has been limited. Identifying and sparing functional nerve fascicles during resection can be difficult, increasing the risk of neurological morbidity. OBJECTIVE: To review the literature regarding robotic resection of retroperitoneal nerve sheath tumors and retrospectively analyze our experience with robotic resection of these tumors using a manual electromyographic probe to identify and preserve functional nerve fascicles. METHODS: We retrospectively analyzed the clinical courses of 3 patients with retroperitoneal tumors treated at the National Institutes of Health by a multidisciplinary team using the da Vinci Xi system. Parent motor nerve fascicles were identified intraoperatively with a bipolar neurostimulation probe inserted through a manual port, permitting tumor resection with motor fascicle preservation. RESULTS: Two patients with neurofibromatosis type 1 underwent surgery for retroperitoneal neurofibromas located within the iliopsoas muscle, and 1 patient underwent surgery for a pelvic sporadic schwannoma. All tumors were successfully resected, with no complications or postoperative neurological deficits. Preoperative symptoms were improved or resolved in all patients. CONCLUSION: Resection of retroperitoneal nerve sheath tumors confers an excellent prognosis, although their deep location and proximity to vital structures present unique challenges. Robotic surgery with intraoperative neurostimulation mapping is safe and effective for marginal resection of histologically benign or atypical retroperitoneal nerve sheath tumors, providing excellent visibility, increased dexterity and precision, and reduced risk of neurological morbidity.

EZR-ROS1 fusion renal cell carcinoma mimicking urothelial carcinoma: report of a previously undescribed gene fusion in renal cell carcinoma.

A subset of renal cell carcinomas harbor gene fusions, and we report the first case of an EZR-ROS1 fusion in renal cell carcinoma. A 47-year-old female presented with hematuria and a mass involving the renal pelvis. Renal biopsy revealed a tumor with solid and tubular architecture that was diffusely positive for PAX8, CK7, and vimentin; retained expression of INI1; focally positive for P504S; and negative for GATA3 and TFE3. Partial nephrectomy was performed, and histologically, the tumor had solid and tubular architecture with mucin-like content within tubules. The nuclei corresponded to WHO/ISUP grade 2 and 3. The morphology was neither specific nor diagnostic, and a final diagnosis of unclassified renal cell carcinoma with solid and tubular architecture was rendered. Molecular sequencing revealed an EZR-ROS1 fusion: a fusion that has never been reported in renal cell carcinoma. Recognition of this fusion is of significance if the tumor becomes metastatic as treatment with crizotinib may be considered.

Association between Industry Payments and Published Position on Use of Devices for the Treatment of Lower Urinary Tract Symptoms.

OBJECTIVE: To determine the impact of industry payments to authors of opinion articles on the Urolift and Rezum devices. We also examined the extent to which authors omitted acknowledgements of financial conflicts-of-interest. METHODS: We searched Google Scholar for all articles that cite either of the respective pivotal trials for these devices. 2 blinded urologists coded the articles as favorable or neutral. A separate blinded researcher recorded industry payments from the manufacturers using the Open Payments Program database. RESULTS: We identified 29 articles written by 27 unique authors from an initial screening list of 235 articles. Of these articles, 15 (52%) were coded as positive and 14 (48%) were coded as neutral. 20 (74%) authors have accepted payments from the manufacturer of the device. Since 2014, these authors have collectively received $270,000 from NeoTract and $314,000 from Boston Scientific. Of the 20 authors with payments, 9 (45%) received more than $10,000 from either manufacturer. Of authors with payments, 65% (13/20) contributed to only positive articles. Authors who received payments had more than 4 times the number of article contributions than did authors without payments (42 vs 10). Authors of at least one favorable article were more likely to have received payments from the device manufacturers than authors of neutral articles (P = .014, Chi-squared test). Most (80%, 16/20) authors with payments did not report a relevant conflict-of-interest within any of their articles. CONCLUSION: These data suggest a relationship between payments from a manufacturer and positive published position on that company's device. There may be a critical lack of published editorial pieces by authors without financial conflicts of interest.