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Purpose: To assess the clinical and pharmacodynamic activity of dovitinib in a treatment-resistant, molecularly enriched non–muscle-invasive urothelial carcinoma of the bladder (NMIUC) population.Experimental Design: A multi-site pilot phase II trial was conducted. Key eligibility criteria included the following: Bacillus Calmette-Guerin (BCG)-unresponsive NMIUC (>2 prior intravesical regimens) with increased phosphorylated FGFR3 (pFGFR3) expression by centrally analyzed immunohistochemistry (IHC+) or FGFR3 mutations (Mut+) assessed in a CLIA-licensed laboratory. Patients received oral dovitinib 500 mg daily (5 days on/2 days off). The primary endpoint was 6-month TURBT-confirmed complete response (CR) rate.Results: Between 11/2013 and 10/2014, 13 patients enrolled (10 IHC+ Mut−, 3 IHC+ Mut+). Accrual ended prematurely due to cessation of dovitinib clinical development. Demographics included the following: median age 70 years; 85% male; carcinoma in situ (CIS; 3 patients), Ta/T1 (8 patients), and Ta/T1 + CIS (2 patients); median prior regimens 3. Toxicity was frequent with all patients experiencing at least one grade 3–4 event. Six-month CR rate was 8% (0% in IHC+ Mut−; 33% in IHC+ Mut+). The primary endpoint was not met. Pharmacodynamically active (94–5,812 nmol/L) dovitinib concentrations in urothelial tissue were observed in all evaluable patients. Reductions in pFGFR3 IHC staining were observed post-dovitinib treatment.Conclusions: Dovitinib consistently achieved biologically active concentrations within the urothelium and demonstrated pharmacodynamic pFGFR3 inhibition. These results support systemic administration as a viable approach to clinical trials in patients with NMIUC. Long-term dovitinib administration was not feasible due to frequent toxicity. Absent clinical activity suggests that patient selection by pFGFR3 IHC alone does not enrich for response to FGFR3 kinase inhibitors in urothelial carcinoma. Clin Cancer Res; 23(12); 3003–11. ©2016 AACR.

Supplementary Table S3: Baseline Tumor pFGFR3 IHC Intensity

Supplementary Figure Legends

National and international guidelines recommend the use of 1 dose of intravesical chemotherapy immediately following surgery for nonmuscle invasive bladder cancer, which is performed infrequently on a population level. We sought to understand the importance of potential environmental and clinical dimensions involved in the decision to offer this therapy.Urologists from the Michigan Urological Surgery Improvement Collaborative (MUSIC) rated 8 distinct clinical vignettes involving patients with nonmuscle invasive bladder cancer. A ratings-based conjoint analysis method was used to evaluate the clinical vignette responses. Each vignette included 4 clinical dimensions and 2 environmental dimensions, with each dimension consisting of 2 possible attributes. The relative importance of each attribute was derived from the regression model and ranked in order.A total of 58 urologists answered the clinical vignettes which represents75% of MUSIC sites. The median age of urologists was 53, most were male, and median years in practice was 20 years post residency. An environmental attribute, having a recovery room protocol for instilling and disposing of the chemotherapy, ranked as the most influential attribute for giving postoperative chemotherapy (utility=8.6). The clinical attribute yielding the strongest preference for giving chemotherapy was tumor grade (utility=4.9). These preferences varied by different subgroups of urologists, particularly regarding the type of practice a urologist was in.This study demonstrates that urologists have clear preferences for when they offer postoperative immediate chemotherapy. Factors beyond just clinical variables play a role in this decision making process such as the structure of the recovery room.

Objective To characterize the health-related quality of life reported by patients who received an ileal conduit (IC), Indiana pouch, or neobladder urinary diversion after radical cystectomy. Materials and Methods The Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index survey was administered to patients with bladder cancer undergoing radical cystectomy and urinary diversion from 2015-2018. Surveys were completed prior to radical cystectomy and then longitudinally throughout the postoperative course. Results A total of 146 patients completed questionnaires over a median of 12.3 months, 83 (56.8%) received an IC, 31 (21.2%) an Indiana pouch, and 32 (21.9%) an orthotopic neobladder. There were no significant differences in health related quality of life among urinary diversion groups considering the Trial Outcome Index scores, general overall FACT-G assessment, or total Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index instruments. Patients who received IC were older and had higher Charlson Comorbidity Index scores (p Conclusions To our knowledge this is the first and largest quality of life analysis comparing all three methods of urinary diversion in a longitudinal fashion utilizing a standardized, validated, treatment-specific health survey. Proper preoperative counseling is critical to ensure understanding of the benefits of available urinary diversion.

Incontinence and impotence occur following radical prostatectomy due to injury to nerves and sphincter muscle. Preserving nerves and muscle adjacent to prostate cancer risks positive surgical margins. Advanced imaging with MRI has improved cancer localization but limitations exist.To measure the accuracy for assessing extra-prostatic extension at nerve bundles for 2 PSMA-PET tracers and to compare the PET accuracy to standard-of-care predictors including MRI and biopsy results.We studied men with PSMA-targeted PET imaging, performed prior to prostatectomy in men largely with intermediate to high-risk prostate cancer, and retrospectively evaluated for assessment of extra-prostatic extension with whole-mount analysis as reference standard. Two different PSMA-PET tracers were included:Pre-operative PSMA-PET imaging was available for 71 patients with eitherPresurgical PSMA-PET appeared useful as a tool for surgical planning, changing treatment plans in men with ≥4+3 or multi-core 3+4 prostate cancer resulting in preservation of nerve-bundles.

Objective: To compare peri-operative factors and renal function following open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN) for intermediate and high complexity tumors when contr...

The International Collaboration on Cancer Reporting (ICCR) is an alliance of major pathology organisations in Australasia, Canada, Europe, United Kingdom, and United States of America that develops internationally standardised, evidence-based datasets for the pathology reporting of cancer specimens. This dataset was developed by a multidisciplinary panel of international experts based on previously published ICCR guidelines for the production of cancer datasets. It is composed of Required (core) and Recommended (noncore) elements identified on the basis of literature review and expert consensus. The document also includes an explanatory commentary explaining the rationale behind the categorization of individual data items and provides guidance on how these should be collected and reported. The dataset includes nine required and six recommended elements for the reporting of cancers of the urinary tract in biopsy and transurethral resection (TUR) specimens. The required elements include specimen site, operative procedure, histological tumor type, subtype/variant of urothelial carcinoma, tumor grade, extent of invasion, status of muscularis propria, noninvasive carcinoma, and lymphovascular invasion (LVI). The recommended elements include clinical information, block identification key, extent of T1 disease, associated epithelial lesions, coexistent pathology, and ancillary studies. The dataset provides a structured template for globally harmonized collection of pathology data required for management of patients diagnosed with cancer of the urinary tract in biopsy and TUR specimens. It is expected that this will facilitate international collaboration, reduce duplication of effort in updating current national/institutional datasets, and be particularly useful for countries that have not developed their own datasets.

Introduction and objective: Traditionally, patients with renal masses in solitary kidneys were managed with an open partial nephrectomy. With improving techniques, robotic-assisted partial nephrectomy in the setting of a solitary kidney is increasingly utilized. The objective of this study was to compare open partial nephrectomy and robotic-assisted partial nephrectomy outcomes in solitary kidney patients. Methods: A retrospective study of 536 total patients who underwent partial nephrectomy between 2004–2016 was performed. Of these patients, 23 had a renal mass in a solitary kidney. Patient demographics, perioperative values, and surgical outcomes were analyzed using descriptive statistics to compare open partial nephrectomy to robotic-assisted partial nephrectomy. Results: Of the 23 patients in the cohort, 52% ( n=12) underwent open partial nephrectomy and 48% ( n=11) underwent robotic-assisted partial nephrectomy. Patient characteristics were not significantly different. The mean (standard deviation) nephrometry score was 6.9 (1.8) for open partial nephrectomy and 6.1 (1.9) for robotic-assisted partial nephrectomy ( p=0.290). The mean (standard deviation) pre-operative creatinine was 1.2 (0.3) in open partial nephrectomy and 1.5 (0.4) in robotic-assisted partial nephrectomy, which did not reach statistical significance ( p=0.110). No difference in postoperative kidney function, Clavien grade 3 or higher complication rate, blood loss, or hospitalization length was noted. Conclusion: Although traditionally patients with a tumor in a solitary kidney are counseled to undergo open partial nephrectomy, robotic-assisted partial nephrectomy is a safe alternative with no decrease in postoperative renal function when compared with a similar cohort of patients undergoing open partial nephrectomy in a solitary kidney. Level of evidence: Level II

HNO 70(1), 44-50 (2022). doi:10.1007/s00106-021-01029-w, Published by Springer, New York

ZUSAMMENFASSUNGDas akute Nierenversagen (ANV) mit Nierenersatztherapie-Pflichtigkeit ist ein häufiges Krankheitsbild auf den Intensivstationen, verbunden mit hoher Mortalität. Als Nierenersatztherapie-Verfahren werden v. a. extrakorporale Methoden eingesetzt. Untersuchungen in den letzten Jahren zeigen, dass die Peritonealdialysetherapie eine effektive, sichere und durchführbare komplementäre Alternative zu den extrakorporalen Verfahren nicht nur bei Patienten mit chronischem, sondern auch bei (intensivpflichtigen) Patienten mit ANV darstellt. Die Peritonealdialyse (PD) bietet methodische Vorteile wie die Vermeidung eines Kathetergefäßzuganges mit entsprechendem Bakteriämie- und Sepsisrisiko, einen gleichmäßigen Flüssigkeitsentzug mit geringerer hämodynamischer Instabilität, einem fehlenden Antikoagulationsbedarf und einer Fortführbarkeit der Nierenersatztherapie bei fortbestehender Dialysepflichtigkeit. Insbesondere wäre die PD zu erwägen bei Erkrankungen wie fortgeschrittener chronischer Herzinsuffizienz mit kardiorenalem Syndrom, Leberzirrhose mit refraktärem Aszites, akut auf chronischem Nierenversagen mit anzunehmender chronischer Nierenersatztherapiepflichtigkeit, bei schlechten Gefäßzugangsmöglichkeiten und bei erhöhtem Blutungsrisiko. Bei bestimmten klinischen Situationen wie Septikämien mit Katecholamin-Pflichtigkeit und möglichem peritonealem Ultrafiltrationsverlust sowie aktiven chronisch-entzündlichen Darmerkrankungen sollte jedoch den extrakorporalen Verfahren der Vorzug gegeben werden. Ein limitierender Faktor für den Einsatz der PD kann insbesondere die akute und zeitige Anlage des PD-Katheters beim kritisch kranken Patienten darstellen. Jedoch erscheint dies durch die Etablierung einer entsprechenden Vorgehensweise und Methode mit Kooperation der beteiligten Disziplinen vor Ort auch in der Akutsituation möglich.

Summary Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC., Genetic factors may distinguish who should receive active surveillance (AS) versus treatment following prostate cancer diagnosis. We undertook the first study to investigate this and report novel variants, genes, and risk scores associated with AS outcomes. These findings could help inform and individualize the decision of AS.

Winter wheat growing areas in the Northern hemisphere are regularly exposed to heavy frost. Due to the negative impact on yield, the identification of genetic factors controlling frost tolerance (FroT) and development of tools for breeding is of prime importance. Here, we detected QTL associated with FroT by genome wide association studies (GWAS) using a diverse panel of 276 winter wheat genotypes that was phenotyped at five locations in Germany and Russia in three years. The panel was genotyped using the 90K iSelect array and SNPs in FroT candidate genes. In total, 17,566 SNPs were used for GWAS resulting in the identification of 53 markers significantly associated (LOD ≥4) to FroT, corresponding to 23 QTL regions located on 11 chromosomes (1A, 1B, 2A, 2B, 2D, 3A, 3D, 4A, 5A, 5B and 7D). The strongest QTL effect confirmed the importance of chromosome 5A for FroT. In addition, to our best knowledge, seven FroT QTLs were discovered for the first time in this study comprising QTLs on chromosomes 3A, 4A, 1B, and two on chromosomes 2D, 3D, and 7D. Identification of novel FroT candidate genes will help to better understand the FroT mechanism in wheat and to develop more effective combating strategies.

High-intensity focused ultrasound (HIFU) is a noninvasive treatment option used for localized prostate cancer or salvage surgery after failed radiation therapy. Histological changes in post-treatment needle biopsies are reviewed to better understand HIFU failures. Between 2016 and 2021, 50 patients with localized prostate cancer were enrolled and treated in this study. Of these, 10 patients underwent salvage therapy after radiation failure and 7 did not have post-treatment needle biopsies available for review and were excluded. Inclusion criteria included pathologically confirmed prostate cancer and clinical stage T1/T2 disease. We describe the histological changes in post-treatment needle biopsies as part of routine follow-up. Biopsies were examined for presence, distribution and extent of residual adenocarcinoma, Gleason score, and ablative tissue changes. A total of 33 patients underwent HIFU hemi-ablation treatment of localized prostate cancer as primary treatment with post-treatment biopsies available for review. The average mean age of the patients was 64 years (range, 52-81 years). The average PSA (prostate-specific antigen) level of the patients was 6.3 ng/mL (range, 2.4-14.7 ng/mL). The Gleason scores assigned in pretreatment prostate needle biopsies are as follows: 3 + 3 (1 case, 3%), 3 + 4 (21 cases, 64%), 4 + 3 (9 cases, 27%), and 4 + 4 (2 cases, 6%). In post-treatment needle biopsies, 33 cases (100%) showed variable degrees of fibrosis ranging from mild to moderate. Twenty-four of 33 cases (73%) showed necrosis usually associated with acute and/or chronic inflammation. Histological examination of benign glands revealed glandular heterogeneity including atrophy and basal cell hyperplasia. Eight cases (24%) had residual prostatic adenocarcinoma after treatment, of which 4 cases were assigned Gleason score: ≥3 + 4. In cases with residual adenocarcinoma, 8 cases (100%) showed nuclear enlargement, 5 cases (63%), cytoplasmic vacuolization, and 1 case (13%) showed nuclear pyknosis; otherwise, no discernible effects of treatment were seen. Morphological alterations included a spectrum of changes ranging from extensive coagulative stromal necrosis secondary to thermal injury to atrophic changes in benign prostatic tissue after HIFU treatment. Our findings also support the hypothesis that HIFU failure results from inadequate targeting rather than failure within a treated zone.

The International Collaboration on Cancer Reporting (ICCR) is a not-for-profit organisation sponsored by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Association of Pathologists in association with the Canadian Partnership Against Cancer, the European Society of Pathology, the American Society of Clinical Pathology and the Faculty of Pathology, Royal College of Physicians of Ireland. Its goal is to produce standardised, internationally agreed-upon, evidence-based datasets for cancer pathology reporting throughout the world. This paper describes the development of a cancer dataset by the multidisciplinary ICCR expert panel for the reporting of carcinoma of the urethra in urethrectomy specimens. The dataset is composed of 'required' (mandatory) and 'recommended' (non-mandatory) elements, which are based on a review of the most recent evidence and supported by explanatory commentary. Fourteen required elements and eight recommended elements were agreed by the international dataset authoring committee to represent the essential/required (core) and recommended (non-core) information for the reporting of carcinoma of the urethra in urethrectomy specimens. Use of an internationally agreed, structured pathology dataset for reporting carcinoma of the urethra (in urethrectomy specimens) will provide the necessary information for optimal patient management, will facilitate consistent data collection and will provide valuable data for research and international benchmarking. The dataset will be valuable for those countries and institutions that are not in a position to develop their own datasets.

The novel Rfm3 locus causing undesired fertility restoration in the msm1 cytoplasm of winter barley is located on the short arm of chromosome 6H. Undesired fertility restoration of cytoplasmic male sterile (CMS) mother lines in absence of the functional Rfm1 restorer gene is a significant problem for hybrid breeding in winter barley. Here, we describe that a novel restorer locus on the short arm of chromosome 6H, designated Rfm3, is closely linked to two mitochondrial transcription termination factor family (mTERF) protein coding genes. Genome-wide association studies in a multiparental mapping population revealed that two of the most significantly associated markers are located very close to these genes, with one marker lying directly within one mTERF gene sequence. Sequences of the candidate genes in the parental lines, segregating individuals and an independent set of breeding lines clearly revealed haplotypes discriminating completely sterile, partially fertile and Rfm1-restorer lines. The haplotypes segregate for several single nucleotide polymorphisms, a 6 bp insertion-deletion (InDel) polymorphism and another 2 bp InDel. CMS-unstable genotypes carrying haplotypes associated with undesired fertility restoration showed significantly higher grain setting on bagged spikes when plants were subjected to elevated temperatures during anthesis, indicating a temperature influence on pollen fertility. SNPs associated with desirable Rfm3 haplotypes can be implemented in marker-assisted selection of stable CMS mother lines.

INTRODUCTION: The intravesical instillation of mitomycin C immediately following surgery for non-muscle invasive bladder cancer has been shown to be efficacious in reducing cancer recurrence. As a result, the American Urological Association adopted guidelines for non-muscle invasive bladder cancer care to support its use in low to intermediate risk patients. Despite this, urologists’ use of this drug following transurethral resection of a bladder tumor (TURBT) has been reported as low as 5% or less. Our study objective was to better understand the barriers urologists experience in using mitomycin C. METHODS: Semi-structured interviews were conducted with 13 practicing urologists at 4 geographically distinct practice locations throughout Indiana between 2017 and 2018. Cognitive task analysis was used to explore factors that influenced their clinician decision-making about Mitomycin C use following TURBT in specific patient cases. Interview transcripts were coded and analyzed using immersion/crystallization to identify emergent themes. RESULTS: The median age of the urologists interviewed was 44 (IQR 40–48). Eighty-five percent were male. Approximately 30% had completed urologic fellowship training; 62% were in private practice. Three major themes related to the use of mitomycin C emerged: cumbersome workflow processes, urologists’ fears of side effects, and issues of identifying patients most likely to benefit. CONCLUSION: Workflow, fear, and value are key factors and also represent complexities of translating efficacy into effectiveness for a drug with known benefits to patients. Areas of potential intervention development to improve the use of mitomycin C to reduce recurrence of bladder cancer are suggested. Alternatives such as gemcitabine may also help overcome these barriers.

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT). Materials and methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy. Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p

Salivary gland stones, or sialoliths, are the most common cause of the obstruction of salivary glands. Symptomatic sialolithiasis has a prevalence of 0.45% in the general population, is characterized by recurrent painful periprandial swelling of the affected gland and often results in sialadenitis with the need for surgical intervention. The mechanism behind the formation of sialoliths has been elusive. Here we show that neutrophil extracellular traps (NETs) initiate the formation and growth of sialoliths. The deposition of neutrophil granulocyte extracellular DNA around small crystals results in their dense aggregation, and the subsequent mineralization creates alternating layers of dense mineral, predominantly calcium salt deposits and DNA. Further agglomeration and appositional growth of these structures promotes the development of macroscopic sialoliths that finally occlude the efferent ducts of the salivary glands, causing clinical symptoms and salivary gland dysfunction. These findings provide an entirely novel insight into the mechanism of sialolithogenesis in which an immune system mediated response essentially participates in the physico-chemical process of concrement formation and growth.

OBJECTIVE To assess predictors of prostate-specific membrane antigen (PSMA) expression in a genomic database; positron emission tomography with PSMA-targeted radiopharmaceuticals is increasingly being utilized. METHODS The de-identified Decipher Biosciences database, which includes expression for more than 46,000 coding and noncoding genes per patient, was queried for expression of FOLH1 (PSMA). Prostate cancer patients who underwent radical prostatectomy and received the Decipher Test were included in the analysis. PSMA expression was compared to the Gleason Grade Group, Decipher risk category (a validated 22 biomarker genomic score), basal versus luminal molecular subtype, and androgen receptor activity. Multivariable regression analyses were performed. RESULTS The Decipher de-identified Decipher Biosciences database contained 16,807 men who underwent prostatectomy with the average age being 65-year old and most being Gleason Grade Group 2 (35%) or 3 (27%). Higher Grade Group was associated with higher PSMA expression except in Grade Group 5 [Grade group: 1 (0.66), 2 (0.84), 3 (0.99), 4 (1.07), 5 (0.99), P

The purpose of this study was to evaluate the effect of neoadjuvant chemotherapy (NACT) on squamous variant (SV) bladder cancer by investigating patients presenting with SV histology at the time of transurethral resection (TUR), stratified by their receipt of NACT.The records of 71 patients with muscle-invasive bladder cancer and SV in the TUR specimen who underwent cystectomy between 2008 and 2018 were reviewed. Our primary outcome was pathologic response at time of cystectomy. Secondary outcomes included recurrence-free survival and overall survival stratified by receipt of NACT. A subgroup analysis was then conducted on the patients with defined SV% on TUR stratified by % involvement (50% SV vs. ≥ 50% SV).The median age of the NACT and no-NACT groups was 60.2 and 70 years, respectively (P = .003). The complete response rate at cystectomy was 60% versus 13.7% for the NACT and no-NACT groups, respectively (P .001). The non-organ-confined disease rate at time of radical cystectomy was 35% for the NACT group and 68.6% for the no-NACT group (P = .01). The NACT group had fewer recurrences than the no-NACT group (10% vs 47.1%; P = .003). In the subgroup analysis, the lower rate of non-organ-confined disease persisted for the patients who underwent NACT at the lower SV percentage but failed to remain significant at greater percentage involvement. This was also true for overall survival.The effect of NACT in variant histology bladder cancer is variable. In patients with SV, these results favor the recommendation in favor of NACT administration, particularly when the primary tumor has 50% involvement by the variant histology.

INTRODUCTION AND OBJECTIVE:Complication rates following cystectomy range from 40-80% with 75% of complications being related to the urinary diversion. Reported complication following continent cuta...

INTRODUCTION AND OBJECTIVE:MRI-guided transurethral ultrasound ablation (TULSA) is a novel minimally-invasive procedure for prostate ablation. We report two-year outcomes from the pivotal TULSA-PRO...

The role of multi-parametric MRI (mpMRI) in the diagnosis and management of prostate cancer (PCa) has evolved rapidly over the previous decade. At present, it includes the following indications: prior negative biopsies with ongoing clinical concern for underlying malignancy, presurgical planning, active surveillance, and local recurrence after prostatectomy. In this review, we will begin by discussing the role of mpMRI at time of initial diagnosis, both in the biopsy-naive and prior biopsy setting. We will discuss its use in active surveillance (AS), both in confirmatory biopsy and ongoing surveillance. Finally, we will review the role prior to local (or surgical) therapy of known PCa.

Prostate cancer is poorly visualized on ultrasonography (US) so that current biopsy requires either a templated technique or guidance after fusion of US with magnetic resonance imaging. Here we determined the ability for photoacoustic tomography (PAT) and US followed by texture-based image processing to identify prostate biopsy targets. K-means clustering feature learning and testing was performed on separate datasets comprised of 1064 and 1197 nm PAT and US images of intact, ex vivo human prostates. 1197 nm PAT was found to not contribute to the feature learning, and thus, only 1064 nm PAT and US images were used for final feature testing. Biopsy targets, determined by the tumor-assigned pixels’ center of mass, located 100% of the primary lesions and 67% of the secondary lesions. In conclusion, 1064 nm PAT and US texture-based feature analysis provided successful prostate biopsy targets. Keywords: Photoacoustic imaging, Prostate, Targeted biopsy, K-means clustering, Texture image processing

Environmental factors that play a role in the urothelial carcinogenesis have been well characterized. Current research is continuously exploring potential heritable forms of bladder cancer. Lynch syndrome is a well-known inheritable disease that increases the risk for a variety of cancers, including urothelial carcinomas. Screening of patients with known Lynch syndrome is important to evaluate for development of new primary tumors. Further study may provide more information on what level of follow-up each patient needs. Recent data suggest that mismatch repair mutations confer a greater risk for urothelial cancer. Additional large patient series as well as advancement of molecular testing may provide triage for Lynch syndrome patients in regards to the frequency and type of screening best suited for individual patient.

With the advancement of early detection tools for prostate cancer and ability to better localize disease, there has been increased interest in focal or targeted therapies that carry less morbidity than traditional whole-gland treatments. The Sonablate

To evaluate the long-term (5 years) health-related quality of life (HRQOL) outcomes following radical cystectomy, comparing Indiana pouch (IP), neobladder (NB), and ileal conduit (IC).The departmental radical cystectomy database was queried to identify patients who underwent radical cystectomy and urinary diversion for bladder cancer between 1991 and 2009 and had not died. Three hundred patients were identified and sent the validated Bladder Cancer Index instrument.A total of 128 (43%) patients completed the survey. When adjusted for gender, age at surgery, surgeon, and time since surgery, IC and IP patients had significantly better urinary function than NB patients (P = .0013). Sexual bother was less in NB than IP (P = .0387). Among men ≥65 years of age, IC patients had significantly better urinary function (P = .0376) than NB patients (91.6 vs 49.4, respectively). Among men 65 years of age, IC and IP patients (76.0 and 82.8, respectively) had significantly better urinary function than NB patients (50.7) (P = .0199). Among women greater than 65 years, bowel bother was significantly better (P = .0095) for IC patients than IP patients (44.8 vs 69.5, respectively).Urinary diversion type after radical cystectomy affects HRQOL differently in long-term survivors. Age and gender at surgery influenced HRQOL based on diversion procedure. Urinary function but not urinary bother was significantly better in IC and IP compared to NB diversions. Prospective longitudinal studies using validated HRQOL tools will further help guide preoperative diversion choice decisions between patient and surgeon.

Background Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Materials and Methods Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. Results A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19-13.98; P = .025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = .055) and OS (104.5 vs. 152.3 months; P = .091) outcomes similar to those for the pCR patients. Conclusion The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.

Radial forearm flap donor side defects can be treated by vacuum therapy and conventional wound dressing. The aim of this study was to compare different wound management considering wound healing, including risk factors and cost effectiveness.Retrospective study including patients treated with radial flaps in the Department of Head and Neck Surgery in Erlangen from January 2005 to August 2013. Wound healing was assessed regarding complications considering several risk factors and comorbidities. Data were analyzed comparing conventional dressing and vacuum therapy, including a calculation of costs.The study included 138 patients (n = 55 conventional dressing; n = 83 vacuum dressing). The incidence of wound complications in the vacuum group was 50.6 and 32.7% in the conventional dressing group (p = .058). The presence of risk factors and comorbidities did not have significant impact on the occurrence of complications. Costs for vacuum therapy turned out to be at least five times higher.In view of the current state of research, these results show that using vacuum dressings has no significant benefit in the wound management of forearm donor side defect covered with full-thickness skin grafts. If the costs and economical aspects are also considered, conventional wound dressing may be preferred.

Partial nephrectomy (PN) reduces the risk of postoperative chronic renal insufficiency (CRI). However, some patients still develop CRI after PN, and may eventually require dialysis. Being able to predict renal function before PN helps in counseling patients and managing expectations. We aimed to construct nomograms that predict estimated glomerular filtration rates (eGFRs), defined by the modification of diet in renal disease (MDRD) and the chronic kidney disease epidemiology collaboration (CKD-EPI) formulae, at 1 year after PN, using only preoperative covariates as predictors.We identified patients who underwent PN in our institution between 2004 and 2016, with known postoperative serum creatinine levels at 1 year. The preoperative covariates included patients' demographics, chronic comorbid conditions, tumor characteristics, and preoperative renal status. The endpoints were eGFRs at 1 year after PN, calculated using the MDRD and the CKD-EPI formulae. We first identified preoperative covariates with significant associations with the endpoints by Pearson correlation and independent samples t-test. Suitable covariates were then included in two multivariate linear regression models, for constructing and internally validating two nomograms.461 patients were eligible for analysis. The percentage of patients with eGFR below 60 mL/min/1.73 mWe constructed and internally validated two nomograms to predict eGFRs at 1 year after PN, using only preoperative covariates as predictors.

Introduction This study was performed to estimate the human radiation dosimetry for [ 68 Ga]Ga-HBED-CC (PSMA-11) ( 68 Ga PSMA-11). Methods Under an RDRC-approved research protocol, we evaluated the biodistribution and pharmacokinetics of 68 Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical [ 11 C]acetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0–10min post-injection with the pelvis in the field-of-view. Whole-body images were acquired, pelvis-to-head, at 15, 60, and 90-min post-injection. Additional images of the pelvis were acquired at 40-min and 115-min, and voided urine collected from each subject at 48-min and 120-min post-injection. Radiation dosimetry estimates were calculated from these data using the OLINDA software package. Results Renal uptake was high and relatively invariant, ranging from 11% to 14% of the injected dose between 15 and 90-min post-injection. Radioactivity collected in the voided urine accounted for 14% of the injected dose over a period of 120-min. Lymph nodes and skeletal metastases suspicious for prostate cancer recurrence were detected in a greater number of patients using 68 Ga PSMA-11 than using 11 C-acetate. Conclusion Kidneys are the critical organ following 68 Ga PSMA-11 administration, receiving an estimated dose of 0.413mGy/MBq. Advances in knowledge and implications for patient care This study confirms that the kidneys will be the critical organ following intravenous administration of 68 Ga PSMA-11, and provided data consistent with the expectation that 68 Ga PSMA-11 will be superior to [ 11 C]acetate for defining sites of recurrence in prostate cancer patients presenting with biochemical relapse.

Background It is unknown whether early intervention with low-dose erythropoiesis-stimulating agents (ESAs) in non-anaemic patients delays progression of chronic kidney disease (CKD). Methods In a single-blind, 24-month trial, adults with estimated glomerular filtration rate (eGFR) 30–59 mL/min/1.73 m2 and either Type 2 diabetes mellitus or previous kidney transplantation were randomized to low-dose continuous erythropoiesis receptor activator (CERA; monthly dose 30–75 µg; n = 115) or placebo (n = 120). The primary endpoint was the annual change in eGFR (abbreviated Modification of Diet in Renal Disease formula). Results Mean (standard deviation) eGFR was 40.7 (9.8) mL/min/1.73 m2 versus 39.8 (9.2) mL/min/1.73 m2 at baseline for CERA and placebo, respectively, and 39.0 (11.6) g/dL versus 39.7 (10.6) g/dL at the final visit. The median (interquartile range) annual reduction in eGFR was 0.5 (−2.2, 3.8) mL/min/1.73 m2 with CERA versus 0.4 (−2.0, 3.2) mL/min/1.73 m2 with placebo (P = 0.657). No significant difference in the annual change in eGFR was observed between treatment groups in the subpopulations with Type 2 diabetes or kidney transplant. Adverse events with a suspected relation to study drug occurred in 22.0% and 16.2% of patients randomized to CERA or placebo, respectively, and adverse events led to study drug discontinuation in 11.0% and 8.5% of patients. Conclusions Patients with moderate CKD and Type 2 diabetes or previous kidney transplantation showed stable renal function that was unaffected by administration of low-dose ESA. In addition, there was no clinically meaningful effect of 2-year low-dose ESA treatment on albuminuria, an important surrogate marker of kidney injury.

In this review, we discuss the types of liquid biopsies currently available, and their recent and potential clinical applications, especially as they relate to the detection of molecular biomarkers of bladder cancer. The advances in research using high-throughput next-generation genomic techniques have identified a number of promising molecular biomarkers of bladder urothelial carcinoma. Liquid biopsy has recently received enormous attention as a potential tool for real-time monitoring of disease status in cancer patients, and genomic profiles are reported to closely match those of corresponding tumors. It is noninvasive and easily repeated, and allows monitoring during treatment and detection of different genomic alterations that are potentially accessible to targeted therapy or are associated with treatment resistance in bladder cancer patients. Moreover, liquid biopsy is a tool that allows rapid access to biomarker assessment in patients for whom solid biopsies are not available. Liquid biopsy will be widely applied to daily clinical practice and serve as an important tool for the screening, surveillance, prediction of outcomes, and selection of effective targeted therapies in bladder carcinoma.

Bladder cancer is the sixth most common cancer in the United States, and it exhibits an alarming 70% recurrence rate. Thus, the development of more efficient antibladder cancer approaches is a high priority. Accordingly, this work provides the basis for a transformative anticancer strategy that takes advantage of the unique characteristics of the bladder. Unlike mucin-shielded normal bladder cells, cancer cells are exposed to the bladder lumen and overexpress EGFR. Therefore, we used an EGF-conjugated anthrax toxin that after targeting EGFR was internalized and triggered apoptosis in exposed bladder cancer cells. This unique agent presented advantages over other EGF-based technologies and other toxin-derivatives. In contrast to known agents, this EGF-toxin conjugate promoted its own uptake via receptor microclustering even in the presence of Her2 and induced cell death with a LC(50) < 1 nM. Furthermore, our data showed that exposures as short as ≈3 min were enough to commit human (T24), mouse (MB49) and canine (primary) bladder cancer cells to apoptosis. Exposure of tumor-free mice and dogs with the agent resulted in no toxicity. In addition, the EGF-toxin was able to eliminate cells from human patient tumor samples. Importantly, the administration of EGF-toxin to dogs with spontaneous bladder cancer, who had failed or were not eligible for other therapies, resulted in ~30% average tumor reduction after one treatment cycle. Because of its in vitro and in vivo high efficiency, fast action (reducing treatment time from hours to minutes) and safety, we propose that this EGF–anthrax toxin conjugate provides the basis for new, transformative approaches against bladder cancer.

The International Collaboration on Cancer Reporting (ICCR) is a not for profit organisation whose goal is to produce standardised internationally agreed and evidence-based datasets for pathology reporting. With input from pathologists worldwide, the datasets are intended to be uniform and structured. They include all items necessary for an objective and accurate pathology report which enables clinicians to apply the best treatment for the patient. This dataset has had input from a multidisciplinary ICCR expert panel. The rationale for some items being required and others recommended is explained, based on the latest literature. The dataset incorporates data from the World Health Organization (WHO) 2016, and also from the latest (8th edition) TNM staging system of the American Joint Committee on Cancer (AJCC). Fifteen required elements and eight recommended items are described. This dataset provides all the details for a precise and valuable pathology report required for patient management and prognostication. This dataset is intended for worldwide use, and should facilitate the collection of standardised comparable data on bladder carcinoma at an international level.

We evaluated which lesions are detected and missed on [Patients undergoing radical prostatectomy were enrolled in this prospective observational study. Patients underwent [On whole mount analysis 30 cancerous lesions were found in a total of 15 patients, including 4, 15, 4, 1 and 6 which were Grade Group 1, 2, 3, 4 and 5, respectively. PSMA-positron emission tomography detected 100% of primary/index lesions and 8 of 11 (82%) secondary lesions. All Grade Group 3-5 lesions were detected vs 12 of 15 Grade Group 2 lesions. When comparing Grade Group 2 vs 3-5, lesion size was similar (p=0.48) but the standardized uptake value was lower for Grade Group 2 vs 3-5 (5.3 vs 7.9, p=0.03). The 3 missed lesions showed 10% or less of pattern 4 and a Gleason pattern 4/5 volume of less than 0.1 cmPSMA positron emission tomography detected 100% of primary/index lesions in this study. The 3 missed secondary lesions were small and had a low percent of pattern 4. This argues for further study to better understand what defines clinically significant prostate cancer, which would assist in determining whether small lesions that become challenging to detect by [