Introducción La amiloidosis AA es una complicación infrecuente de las neoplasias sólidas y se asocia habitualmente a procesos inflamatorios crónicos. La asociación con los tumores del estroma gastrointestinal (GIST) es excepcional, con escasos casos descritos en la literatura. Caso clínico Presentamos el caso de una mujer de 64 años diagnosticada de GIST duodenal metastásico con carcinomatosis peritoneal. Cuatro meses después del diagnóstico desarrolló síndrome nefrótico grave y fracaso renal agudo dependiente de hemodiálisis. La biopsia renal mostró depósitos glomerulares y vasculares de amiloide AA confirmados mediante tinción con rojo Congo e inmunohistoquímica para proteína amiloide A, asociados a necrosis tubular aguda. El estudio etiológico descartó otras causas de amiloidosis secundaria. A pesar del tratamiento con imatinib y de evidenciarse cierta respuesta radiológica tumoral, la paciente no recuperó la función renal y falleció por complicaciones infecciosas y hemorrágicas. Discusión La amiloidosis AA asociada a GIST es una entidad extremadamente rara. Los casos publicados comparten la presencia de tumores voluminosos, con áreas de necrosis y elevada actividad inflamatoria, lo que sugiere un papel relevante de la sobreproducción sostenida de proteína sérica amiloide A. La afectación renal suele ser grave y con frecuencia conduce a terapia renal sustitutiva. Conclusión El GIST debe considerarse una posible causa de amiloidosis AA en pacientes con síndrome nefrótico o deterioro renal asociado a una neoplasia sólida con importante carga tumoral e inflamación sistémica. El reconocimiento precoz de esta asociación puede facilitar el diagnóstico y el manejo de una complicación potencialmente devastadora.

BACKGROUND AND OBJECTIVE:The current European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC) categorize patients into four risk groups. In 2024, a specific follow-up schedule was introduced for intermediate-risk (IR) disease. However, recommendations are based on expert opinion and restricted to patients with IR-NMIBC who have primary low-grade or high-grade/grade 2 disease. Our aim was to identify a subgroup of patients with IR-NMIBC who may require more stringent follow-up. METHODS:We conducted a retrospective analysis of 2086 patients with IR-NMIBC classified according to the World Health Organization 1973 grading scheme. Multivariable Cox-regression models were fitted to identify predictors of recurrence, which were then used to dichotomize groups with low risk of recurrence (IR-Low) versus high risk of recurrence (IR-High). Kaplan-Meier curves were plotted to estimate recurrence-free survival (RFS) and progression-free survival (PFS). Smoothed hazard estimates of first recurrence were plotted by risk group. KEY FINDINGS AND LIMITATIONS:Multifocality and tumor size ≥3 cm were significantly associated with higher risk of first recurrence and were used to define the IR-High and IR-Low (unifocal, size <3 cm; n = 1087) groups. The 3-yr RFS rate was significantly worse for the IR-High group (51%, 95% confidence interval [CI] 48-54%) than for IR-Low (68%, 95% CI 65-71%). The risk of progression was low (5-yr PFS rate 96%) with no significant difference between the IR-High and IR-Low groups. CONCLUSIONS AND CLINICAL IMPLICATIONS:During IR-NMIBC follow-up for recurrence, tumor size and focality should be considered rather than grade. If the primary objective is to ensure prompt detection of recurrence, follow-up schedules should be tailored according to the risk of recurrence, with more stringent protocols for patients with IR-NMIBC at higher risk of recurrence.

A hybrid-three tier system with low grade (LG), high grade- G2 (HG-G2), high grade- G3 (HG-G3) has been proposed in recognition of, and to help address, the clinical heterogeneity within high grade WHO 2004/2022. We assessed interobserver reproducibility amongst international uropathologists using this three-tier approach. Papillary Ta nonmuscle invasive bladder cancer (NMIBC) specimens (n = 30) were selected and graded by two uropathologists and assessed using WHO 2004/2022 and WHO 1973 and categorized as LG (n = 15), HG-G2 (n = 8), HG-G3 (n = 7), and photographed at 10× and 20× magnification. Images were circulated via Survey Monkey to invited uropathologists who determined: (1) that image was LG or HG, and (2) if HG, assigned to G2 or G3. Model-based kappa measure of association was used to assess interrater agreement. Eighteen uropathologists:(eight North American, eight European, two other) assessed 60 images with 1076 gradings for analysis. The kappa value amongst Europeans versus North Americans was 0.663 versus 0.647 for 10× images and 0.682 versus 0.623 for 20× images. At 10×, agreement for LG, HG-G2, and HG-G3 was 74.6%, 63.6%, and 92.0%, and at 20× was 64.3%, 63.9%, and 95.2% respectively. Three-tier grading of papillary Ta NMIBC had substantial interobserver agreement amongst international uropathologists. The recognition of the HG-G3 case reached the highest concordance. North American uropathologists had comparable kappa scores (substantial agreement) to Europeans, despite being unaccustomed to separating HG cases into G2 and G3, demonstrating three-tier grading could be "quickly" adopted by genitourinary experts if endorsed and required by the relevant bodies in their jurisdiction of practice.

Purpose The use of intraoperative diagnostic during ureterorenoscopy (URS) for upper tract urothelial cancer (UTUC) may assist in deciding between kidney-sparing or radical surgical approaches. We assessed the diagnostic performance of confocal microscopy (CM) using the Vivascope CM system compared to conventional histopathology. Methods This prospective feasibility cohort study included patients undergoing URS for suspected UTUC or during UTUC follow-up between May and August 2022. Each biopsy was analyzed first with the Vivascope CM, followed by conventional histopathology. The primary outcome was the UTUC detection rate with the VivaScope CM and conventional histopathological analysis, considering conventional analysis as the gold standard. Concordance between Vivascope CM and conventional histopathology in terms of high-grade UTUC was reported in terms of raw numbers and proportions. Analyses were conducted per biopsy sample and per patient. Results Ten patients underwent URS, with a total of fourteen biopsy samples. Suspicion of UTUC emerged in four (28.6%) cases because of hematuria and in four (28.6%) cases by CT-scan, while the remaining 6 cases (42.9%) underwent URS during the follow-up for UTUC. Per-biopsy analysis showed a cancer detection rate of 70% using Vivascope CM and a high-grade concordance of 50%. Among 5 CM high-grade cases, 2 were downgraded; 1 low-grade case was upgraded by conventional histopathology. Per-patient analysis showed a cancer detection rate of 77.8% using Vivascope CM and a high-grade concordance of 66.7%. Among 5 high-grade patients classified by CM, one was downgraded by conventional analysis, while one low-grade case was upgraded by conventional analysis. Vivascope CM produced artifacts that prevented histological analysis in 2 cases. The main limitation of current study is the low sample size. Conclusions VivaScope CM shows promise as an intraoperative tool for UTUC detection during URS. However, its performance in terms of tumor grading was limited in this preliminary experience. Larger, blinded studies, preferably including multiple biopsies per UTUC lesion, are needed to confirm the diagnostic accuracy of VivaScope CM and better define its potential role in clinical decision-making during URS.

Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (P < 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P = 0.001 and 16.3, 95% CI = 1.8-2151.5; P = 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

BACKGROUND:The optimal oncologic surveillance in patients with upper tract urothelial carcinoma (UTUC) elected for conservative treatment is still a matter of debate.METHODS:Patients elected for endoscopic treatment of UTUC were followed up according to EAU guidelines recommendations after treatment. Bladder cancer recurrence-free survival (BCa-RFS), UTUC recurrence-free survival (UTUC-RFS), radical nephroureterectomy-free survival (RNU-FS), and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. The crude risks of BCa and UTUC recurrences over time were estimated with the Locally Weighted Scatterplot Smoothing method.RESULTS:Overall, 54 and 55 patients had low- and high-risk diseases, respectively. Median follow-up was 46.9 (IQR: 28.7-68.7) and 36.9 (IQR: 19.8-60.1) months in low and high-risk patients, respectively. In low-risk patients, BCa recurrence risk was more than 20% at 24 months follow-up. At 60 months, time point after which cystoscopy and imaging should be interrupted, the risk of BCa recurrence and UTUC recurrence were 14% and 7%, respectively. In high-risk patients, the risk of BCa and UTUC recurrence at 36 months was approximately 40% and 10%, respectively. Conversely, at 60 months, the risk of bladder recurrence and UTUC recurrence was 28% and 8%, respectively.CONCLUSIONS:For low-risk patients, cystoscopy should be performed semi-annually until 24 months, while upper tract assessment should be obtained up to 60 months, as per current EAU guidelines recommendations. For high-risk patients, upper tract assessment should be intensified to semi-annually up to 36 months, then obtained yearly. Conversely, cystoscopy should be ideally performed semi-annually until 60 months and yearly thereafter.

Introduction: Suspicious bilateral upper tract urinary cancer (bUTUC) is a challenging scenario both for diagnosis and treatment reasons.1–3 We evaluated the feasibility and safety of synchronous bilateral endoscopic treatment for UTUC.

We evaluated the prevalence of homologous recombination deficiencies (HRD) to determine the efficacy of different techniques and clinical characteristics of patients. This retrospective study included patients with metastatic prostate cancer who underwent molecular testing at our hospital between 2016 and 2022. We used tumor tissue, ctDNA, and lymphocytes for somatic or germline testing. We analyzed the clinical characteristics and survival outcomes. 144 patients were tested (113 somatic, 21 germline, and 10 both). Technical issues prevented the analysis of 23 prostatic samples (18.7

PURPOSE:Genitourinary (GU) multidisciplinary tumour boards (GUMTBs) are key components of patient care, as they might lead to changes in treatment plan, improved survival, and increased adherence to guidelines. However, there are no guidelines on how GUMTBs should operate or how to assess their quality of performance.METHODS:A systematic literature review was conducted to identify criteria and indicators to evaluate quality in GUMTBs. A scientific committee-comprising 12 GU cancer specialists from seven disciplines-proposed a list of criteria and developed indicators, evaluated in two rounds of Delphi method. Appropriateness and utility of indicators were scored using a 9-point Likert scale. Consensus was defined as at least two-thirds of Delphi respondents selecting a score sub-category that encompassed the median score of the group.RESULTS:Forty-five criteria were selected to evaluate the quality of GUMTBs covering five dimensions: organisation, personnel, protocol and documentation, resources, and interaction with patients. Then, 33 indicators were developed and evaluated in the first round of Delphi, leading to a selection of 26 indicators in two dimensions: function, governance and resources, and GUMTB sessions. In the second round, consensus was reached on the appropriateness of all 26 indicators and on the utility of 24 of them. Index cards for criteria and indicators were developed to be used in clinical practice.CONCLUSIONS:Criteria and indicators were developed to evaluate the quality of GUMTBs, aiming to serve as a guide to improve quality of care and health outcomes in patients with GU cancer.

General Urology and Endourology cases during their chief year. More research is needed to determine if lack of exposure to general urology and endourology during chief year translate into decreased prepared- ness for independent practice.

You have accessJournal of UrologyCME1 Apr 2023MP69-14 THE IMPLEMENTATION OF SYSTEMATIC BIOPSIES IN THE ENDOSCOPIC MANAGEMENT OF UPPER TRACT UROTHELIAL CANCER Andrea Gallioli, Angelo Territo, Basile Giuseppe, Pietro Diana, Paolo Verri, Francesco Sanguedolce, Josep Maria Gaya, Pavel Gavrilov, Alessandro Uleri, Sofia Fontanet, Paula Izquierdo, Jordi Huguet, Ferran Algaba, Joan Palou, and Alberto Breda Andrea GallioliAndrea Gallioli More articles by this author , Angelo TerritoAngelo Territo More articles by this author , Basile GiuseppeBasile Giuseppe More articles by this author , Pietro DianaPietro Diana More articles by this author , Paolo VerriPaolo Verri More articles by this author , Francesco SanguedolceFrancesco Sanguedolce More articles by this author , Josep Maria GayaJosep Maria Gaya More articles by this author , Pavel GavrilovPavel Gavrilov More articles by this author , Alessandro UleriAlessandro Uleri More articles by this author , Sofia FontanetSofia Fontanet More articles by this author , Paula IzquierdoPaula Izquierdo More articles by this author , Jordi HuguetJordi Huguet More articles by this author , Ferran AlgabaFerran Algaba More articles by this author , Joan PalouJoan Palou More articles by this author , and Alberto BredaAlberto Breda More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003332.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Diagnosis of upper tract urothelial cancer (UTUC) is crucial. In this regard, uretheral systematic biopsies (USB) have never been considered. We aim to investigate the safety and usefulness of USB in the diagnosis of UTUC and its impact on disease management. METHODS: We relied on a prospectively maintained database of patients who underwent diagnostic ureteroscopy (URS) for UTUC between 2015-21. USB included at least 2 biopsies in each UT portion: pelvis, proximal, medium, and distal ureter. Perioperative complications were graded using the Clavien-Dindo (CD) classification. We assessed the surgical safety and diagnostic impact of USB and estimated the 2-yr nephroureterectomy free-survival (NFU-FS) according to USB results. Then, we investigated the added value of USB over high-risk tumor variables according to EAU prognostic model. Finally, uni and multivariable logistic regression (MLR) analyses investigated preoperative predictors of positive USB. RESULTS: Overall, 91/360 (25.3%) patients underwent USB. Compared to patients who did not undergo USB, USB did not increase the risk of perioperative and major (CD >3a) complications, nor the risk of readmission (all p>0.05). USB was positive in 43 (47.25%) cases, negative in 30 (33%) patients. 58/300 (19.3%) biopsies were not diagnostic. In 36 (39.5%) patients both USB and biopsy of a suspicious lesion were performed. In 7 (19.4%) cases, USB outperformed the biopsy of the lesion in detecting UTUC. 11 (12%) patients were diagnosed with a distal ureter tumor. In 5 (45.4%) cases USB detected UTUC in other upper tract portions. The 2-yr NFU-FS rates were 87.7% (95CI%: 78.1-98.5) vs 53% (95%CI: 39.4-71.2) (p=0.001) for negative vs positive USB patients. At Cox-regression model accounting for predefined variables, patients with positive USB (vs. negative) had a higher risk of being treated with NFU [Hazard ratio: 3.38, 95%CI: 1.46-7.80, p=0.004)]. At MLR analysis, after adjusting for age, pre-operative positive cytology, smoking status, previous bladder cancer and previous UTUC, patients with negative pre-operative CT scan had a higher probability of having a positive USB (Odds ratio: 8.36, 95%CI: 1.57-71.18, p=0.02). CONCLUSIONS: USB is a safe procedure and detected a non-visible tumor at URS in one over five patients. Positive USB increases the risk of radical treatment and possibly changes the treatment algorithm in almost 50% of the patients with distal ureteral tumor candidates to conservative management. When UTUC is suspected, patients with preoperative negative CT scan may benefit the most from USB. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e969 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrea Gallioli More articles by this author Angelo Territo More articles by this author Basile Giuseppe More articles by this author Pietro Diana More articles by this author Paolo Verri More articles by this author Francesco Sanguedolce More articles by this author Josep Maria Gaya More articles by this author Pavel Gavrilov More articles by this author Alessandro Uleri More articles by this author Sofia Fontanet More articles by this author Paula Izquierdo More articles by this author Jordi Huguet More articles by this author Ferran Algaba More articles by this author Joan Palou More articles by this author Alberto Breda More articles by this author Expand All Advertisement PDF downloadLoading ...

Primary upper tract carcinoma in situ (UTcis) is a rare disease whose diagnosis and natural history are poorly understood. Radical nephroureterectomy is the standard of care but in imperatives or selected cases, topical instillations of Bacillus Calmette-Guérin (BCG) may represent a good alternative. The aim of this study was to report the histologic response to BCG instillations for the treatment of biopsy-proven UTcis and to systematically assess the current evidence on topical BCG instillation for the treatment of UTcis. This is a retrospective analysis of patients with biopsy-proven UTcis treated with BCG instillation between 1995 and 2020 in an expert center. The initial diagnosis was performed by a standardized random biopsy scheme during ureterorenoscopy (URS) in patients with positive cytology but negative CT and bladder biopsies. BCG course consisted of 6 weekly instillation of 81 mg Immucyst (Sanofi Pasteur MSD AG, Baar, Switzerland). Administration techniques were single-J, double-J and nephrostomy tube. The primary outcome was the rate of complete histological response at the 3-month 2nd-look-URS. Kaplan-Meier analysis curves assessed recurrence- and progression-free survival. A total of 22 patients (23 renal units) were included. Twenty-one (91.3%) patients completed the planned 6-week instillation cycle. Only one major complication was recorded (renal tuberculosis). Twenty patients had a 3-month 2nd-look-URS, with a complete histological response achieved in 17/20 cases (85%). After a median time of follow-up of 40 months (30–62), 8/20 patients harbored disease recurrence, including 5 cases of disease progression (≥pT2). The main limitations are the retrospective and non-comparative design of the study. Our systematic review (CRD42022324876) identified 15 studies (289 renal units). UTcis suffers from the lack of a standardized definition, and considerable heterogeneity has been found in making the diagnosis and assessing the response to treatment. Our study is the first to propose a histological diagnosis of UTcis as well as a histological re-evaluation of the response to treatment. Topical instillations of BCG appear to be a promising alternative, avoiding radical treatment in the majority of cases.

Supplementary figure S5. Progression-free survival curves in all patients for (A) EAU risk category, (B) FGFR3, (C) GATA2 and (D) TBX3. Progressive disease is defined as progression to stage T2 or higher stage disease. P-values (log-rank test) are indicated in each figure.

Purpose Different energy sources are employed to perform en-bloc transurethral resection of bladder tumor (ERBT). No study compared different energy sources in ERBT. The aim is to compare the different ERBT sources in terms of pathological, surgical and postoperative outcomes. Methods This is a sub-analysis of a prospective randomized trial enrolling patients submitted to ERBT vs conventional TURBT from 03/2018 to 06/2021 (NCT04712201). 180 patients enrolled in ERBT group were randomized 1:1:1 to receive monopolar (m-ERBT), bipolar (b-ERBT) or thulium laser (l-ERBT). Endpoints were the comparison between energies in term of pathological analysis, intra, and post-operative outcomes. Results 49 (35%) m-ERBT, 45 (32.1%) b-ERBT, and 46 (32.9%) l-ERBT were included in final analysis. The rate of detrusor muscle (DM) presence was comparable between the energies used ( p = 0.796) or the location of the lesion ( p = 0.662). Five (10.2%), 10 (22.2%) and 0 cases of obturator nerve reflex (ONR) were recorded in m-ERBT, b-ERBT and I-ERBT groups, respectively ( p = 0.001). Conversion to conventional TURBT was higher for lesions located in the anterior wall/dome/neck ( p < 0.001), irrespective from the energy used. The presence of artifact in the pathological specimen was higher for lesions at the posterior wall ( p = 0.03) and trigone ( p = 0.03). Conclusions In our study, no difference in staging feasibility among energies was found. Laser energy might be beneficial in lateral wall lesions to avoid ONR. Since there is an increased risk of ERBT conversion to conventional TURBT for lesions of the anterior wall, electrocautery might be preferred over laser to avoid waste of material.

The purpose of the study was to evaluate the effect of second-look ureteroscopy (SU) in the endoscopic operative work-up of patients with upper tract urothelial carcinoma (UTUC). Patients with UTUC who underwent SU between 2016 and 2021 were included. Cancer detection rate (CDR) at SU was defined as endoscopic visualization of tumor. The effect of SU on recurrence-free survival (RFS), radical nephroureterectomy-free survival (RNU-FS), bladder cancer-free survival (BC-FS), and cancer-specific survival (CSS) was estimated using the Kaplan–Meier method. Multivariate logistic regression analysis (MLR) assessed predictors of negative SU. Finally, we evaluated the effect of SU timing on oncological outcomes, classifying SUs as “early” (≤ 8 weeks) and “late” (> 8 weeks). Overall, 85 patients underwent SU. The CDR at SU was 44.7

Supplementary figure S6. Progression-free survival curves in EAU high risk patients for (A) Intravesical instillations, (B) Grade, (C) FGFR3 and (D) GATA2. Progressive disease is defined as progression to stage T2 or higher stage disease. P-values (log-rank test) are indicated in each figure.

p53 immunohistochemistry (IHC) has been proposed as a surrogate for TP53 mutations in penile squamous cell carcinomas (PSCC). We aimed to evaluate the performance of a pattern-based evaluation of p53 IHC in PSCC. Human papilloma virus (HPV) DNA testing, p16 and p53 IHC, and whole exome sequencing were performed in a series of 40 PSCC. p53 IHC was evaluated following a pattern-based framework and conventional p53 IHC evaluation. Out of 40 PSCC, 12 (30.0%) were HPV-associated, and 28 (70.0%) were HPV-independent. The agreement between the p53 IHC pattern-based evaluation and TP53 mutational status was almost perfect (k = 0.85). The sensitivity and accuracy of the pattern-based framework for identifying TP53 mutations were 95.5% and 92.5%, respectively, which were higher than the values of conventional p53 IHC interpretation (54.5% and 70.0%, respectively), whereas the specificity was the same (88.9%). In conclusions, the pattern-based framework improves the accuracy of detecting TP53 mutations in PSCC compared to the classical p53 IHC evaluation.