Oncological Outcomes of Thulium-Yttrium-Aluminum-Garnet (Tm:YAG) Laser Ablation for Penile Cancer.

OBJECTIVE: To report oncological outcomes after thulium-yttrium-aluminum-garnet (Tm:YAG) laser ablation for penile cancer patients. MATERIALS AND METHODS: We retrospectively analyzed 71 patients with ≤cT1 penile cancer (2013-2022). All patients underwent Tm:YAG ablation with a RevoLix 200W continuous-wave laser. First, Kaplan-Meier plots and multivariable Cox regression models tested local tumor recurrence rates. Second, Kaplan-Meier plots tested progression-free survival (≥T3 and/or N1-3 and/or M1). RESULTS: Median (interquartile range) follow-up time was 38 (22-58) months. Overall, 33 (50.5%) patients experienced local tumor recurrence. Specifically, 19 (29%) vs 9 (14%) vs 5 (7.5%) patients had 1 vs 2 vs 3 recurrences over time. In multivariable Cox regression models, a trend for higher recurrence rates was observed for G3 tumors (hazard ratio:6.1; P = .05), relative to G1. During follow-up, 12 (18.5%) vs 4 (6.0%) vs 2 (3.0%) men were retreated with 1 vs 2 vs 3 Tm:YAG laser ablations. Moreover, 11 (17.0%) and 3 (4.5%) patients underwent glansectomy and partial/total penile amputation. Last, 5 (7.5%) patients experienced disease progression. Specifically, TNM stage at the time of disease progression was: (1) pT3N0; (2) pT2N2; (3) pTxN3; (4) pT1N1 and (5) pT3N3, respectively. CONCLUSION: Tm:YAG laser ablation provides similar oncological results as those observed by other penile-sparing surgery procedures. In consequence, Tm:YAG laser ablation should be considered a valid alternative for treating selected penile cancer patients.

Spatio-temporal layers based intra-operative stereo depth estimation network via hierarchical prediction and progressive training.

BACKGROUND AND OBJECTIVE: Safety of robotic surgery can be enhanced through augmented vision or artificial constraints to the robotl motion, and intra-operative depth estimation is the cornerstone of these applications because it provides precise position information of surgical scenes in 3D space. High-quality depth estimation of endoscopic scenes has been a valuable issue, and the development of deep learning provides more possibility and potential to address this issue. METHODS: In this paper, a deep learning-based approach is proposed to recover 3D information of intra-operative scenes. To this aim, a fully 3D encoder-decoder network integrating spatio-temporal layers is designed, and it adopts hierarchical prediction and progressive learning to enhance prediction accuracy and shorten training time. RESULTS: Our network gets the depth estimation accuracy of MAE 2.55±1.51 (mm) and RMSE 5.23±1.40 (mm) using 8 surgical videos with a resolution of 1280×1024, which performs better compared with six other state-of-the-art methods that were trained on the same data. CONCLUSIONS: Our network can implement a promising depth estimation performance in intra-operative scenes using stereo images, allowing the integration in robot-assisted surgery to enhance safety.

Penile-Sparing Surgery for Tumour Recurrence after Previous Glansectomy/Partial Penectomy: Treatment Feasibility and Oncological Outcomes.

We tested the feasibility and oncological outcomes after penile-sparing surgery (PSS) for local recurrent penile cancer after a previous glansectomy/partial penectomy. We retrospectively analysed 13 patients (1997-2022) with local recurrence of penile cancer after a previous glansectomy or partial penectomy. All patients underwent PSS: circumcision, excision, or laser ablation. First, technical feasibility, treatment setting, and complications (Clavien-Dindo) were recorded. Second, Kaplan-Meier plots depicted overall and local recurrences over time. Overall, 11 (84.5%) vs. 2 (15.5%) patients were previously treated with glansectomy vs. partial penectomy. The median (IQR) time to disease recurrence was 56 (13-88) months. Six (46%) vs. two (15.5%) vs. five (38.5%) patients were treated with, respectively, local excision vs. local excision + circumcision vs. laser ablation. All procedures, except one, were performed in an outpatient setting. Only one Clavien-Dindo 2 complication was recorded. The median follow-up time was 41 months. Overall, three (23%) vs. four (30.5%) patients experienced local vs. overall recurrence, respectively. All local recurrences were safely treated with salvage surgery. In conclusion, we reported the results of a preliminary analysis testing safety, feasibility, and early oncological outcomes of PSS procedures for patients with local recurrence after previous glansectomy or partial penectomy. Stronger oncological outcomes should be tested in other series to optimise patient selection.

What is the best time for postoperative radiation therapy in pN1 prostate cancer?

We retrospectively compared long-term biochemical recurrence rates (BCR) in pN1 PCa patients that underwent adjuvant radiotherapy (aRT) vs. no aRT/early salvage (esRT) after robot-assisted radical prostatectomy and extended pelvic lymphadenectomy. All PCa pN1 M0 patients treated at a single high-volume center between 2010 and 2020 were analyzed. Patients with <10 LNs yield, or >10 positive LNs, or persistently detectable PSA after RARP were excluded. Kaplan-Meier (KM) plots depicted BCR rates. Multivariable Cox regression models (MCRMs) focused on predictors of BCR. The cumulative incidence plot depicted BCR rates after propensity score (PS) matching (ratio 1:1). 220 pN1 patients were enrolled, 133 (60.4%) treated with aRT and 87 (39.6%) with no-aRT/esRT. aRT patients were older, with higher rates of postoperative ISUP grade group 4-5, and higher rates of pT3b stage. The actuarial BCR was similar (aRT 39.8% vs. no-aRT/esRT 40.2%; p=1). Median time to BCR was 62 vs. 38 months in aRT vs. no-aRT/esRT patients (p=0.001). In MCRMs, patients managed with no-aRT/esRT were associated with higher rates of BCR over time (hazard ratio [HR]: 3.27, p<0.001). ISUP grade group 5 (HR: 2.18, p<0.01) was an independent predictor of BCR. In PS-matched cumulative incidence plots, the BCR rate was significantly higher in the aRT group (76.4 vs. 40.4%; p<0.01). Patients managed with no-aRT/esRT experienced BCR approximately two years before the aRT group. Despite, the important BCR benefit after aRT, this treatment strategy is underused in daily practice.

FRSR: Framework for real-time scene reconstruction in robot-assisted minimally invasive surgery.

3D reconstruction of the intra-operative scenes provides precise position information which is the foundation of various safety related applications in robot-assisted surgery, such as augmented reality. Herein, a framework integrated into a known surgical system is proposed to enhance the safety of robotic surgery. In this paper, we present a scene reconstruction framework to restore the 3D information of the surgical site in real time. In particular, a lightweight encoder-decoder network is designed to perform disparity estimation, which is the key component of the scene reconstruction framework. The stereo endoscope of da Vinci Research Kit (dVRK) is adopted to explore the feasibility of the proposed approach, and it provides the possibility for the migration to other Robot Operating System (ROS) based robot platforms due to the strong independence on hardware. The framework is evaluated using three different scenarios, including a public dataset (3018 pairs of endoscopic images), the scene from the dVRK endoscope in our lab as well as a self-made clinical dataset captured from an oncology hospital. Experimental results show that the proposed framework can reconstruct 3D surgical scenes in real time (25 FPS), and achieve high accuracy (2.69 ± 1.48 mm in MAE, 5.47 ± 1.34 mm in RMSE and 0.41 ± 0.23 in SRE, respectively). It demonstrates that our framework can reconstruct intra-operative scenes with high reliability of both accuracy and speed, and the validation of clinical data also shows its potential in surgery. This work enhances the state of art in 3D intra-operative scene reconstruction based on medical robot platforms. The clinical dataset has been released to promote the development of scene reconstruction in the medical image community.

Safety and Diagnostic Accuracy of the Transnasal Approach for Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA).

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and accurate diagnostic procedure used for investigating mediastinal pathologies. It is usually performed using an oral approach. The nasal route has been proposed but not extensively investigated. With the aim to report the use of linear EBUS through the nasal route and compare its accuracy and safety with the oral one, we conducted a retrospective analysis of the subjects who underwent an EBUS-TBNA procedure at our center. From January 2020 to December 2021, 464 subjects underwent an EBUS-TBNA, and in 417 patients, EBUS was performed through the nose or mouth. Nasal insertion of the EBUS bronchoscope was performed in 58.5% of the patients. No difference between the two insertion routes was observed in terms of location or number of stations sampled per subject. Procedure complications were mild and similar between the two groups (10.2% for the nasal group vs. 9.8% for the oral group). Minor epistaxis occurred in five subjects in the nasal group. Comparing the two groups, the rates of adequate specimens were similar (95.1% vs. 94.8%), as were the proportions of diagnostic specimens (84% vs. 82%). In conclusion, the nasal route for EBUS-TBNA is a valid alternative to the oral one.

Conditional survival of patients with low-risk prostate cancer: Temporal changes in active surveillance permanence over time.

PURPOSE: To determine risk categories for patients with prostate cancer (PCa) in active surveillance (AS) and to test the conditional survival (CS) that examined the effect of event-free survival since AS-entrance. MATERIALS AND METHODS: From January 2012 to December 2020 we analyzed 606 patients with PCa enrolled in our AS program. Kaplan-Meier (KM) plots depicted AS-exit rate. Multivariable Cox regression models (MCRMs) tested for AS-exit rate independent predictors to determine risk categories. CS estimates were used to calculate overall AS-exit rate after event-free survival intervals of 1, 2, 3, and 5 years, and after stratification according to risk categories. RESULTS: At MCRMs PSAd ≥ 0.15 (HR: 1.43; P-value 0.04), PI-RADS 4-5 (HR: 2.56; P-value <0.001) and number of biopsy positive cores ≥ 2 (HR: 1.75; P-value <0.001) were independent predictors of AS-exit. These variables were used to determine risk categories: low-, intermediate- and high-risk. Overall, according to CS-analyses, 5-year AS-exit free rate increased from 59.7% at baseline, to 67.3%, 74.7%, and 89.4% in patients who remained in AS respectively ≥1, ≥2, ≥3 and ≥5 years. After stratification according to risk categories, in those patients who remained in AS ≥ 5 years, 5-year AS-exit free rates increased from 76.3% to 100% in patients with a low-risk, from 62.7% to 83.7% in patients with an intermediate-risk and from 42.3% to 87.5% in patients with a high-risk. CONCLUSIONS: CS models showed a direct relationship between event-free survival duration and subsequent AS permanence in overall PCa patients and after stratification according to risk categories.

Semi-Supervised Bladder Tissue Classification in Multi-Domain Endoscopic Images.

OBJECTIVE: Accurate visual classification of bladder tissue during Trans-Urethral Resection of Bladder Tumor (TURBT) procedures is essential to improve early cancer diagnosis and treatment. During TURBT interventions, White Light Imaging (WLI) and Narrow Band Imaging (NBI) techniques are used for lesion detection. Each imaging technique provides diverse visual information that allows clinicians to identify and classify cancerous lesions. Computer vision methods that use both imaging techniques could improve endoscopic diagnosis. We address the challenge of tissue classification when annotations are available only in one domain, in our case WLI, and the endoscopic images correspond to an unpaired dataset, i.e. there is no exact equivalent for every image in both NBI and WLI domains. METHOD: We propose a semi-surprised Generative Adversarial Network (GAN)-based method composed of three main components: a teacher network trained on the labeled WLI data; a cycle-consistency GAN to perform unpaired image-to-image translation, and a multi-input student network. To ensure the quality of the synthetic images generated by the proposed GAN we perform a detailed quantitative, and qualitative analysis with the help of specialists. CONCLUSION: The overall average classification accuracy, precision, and recall obtained with the proposed method for tissue classification are 0.90, 0.88, and 0.89 respectively, while the same metrics obtained in the unlabeled domain (NBI) are 0.92, 0.64, and 0.94 respectively. The quality of the generated images is reliable enough to deceive specialists. SIGNIFICANCE: This study shows the potential of using semi-supervised GAN-based bladder tissue classification when annotations are limited in multi-domain data.

Comparing Oncological and Perioperative Outcomes of Open versus Laparoscopic versus Robotic Radical Nephroureterectomy for the Treatment of Upper Tract Urothelial Carcinoma: A Multicenter, Multinational, Propensity Score-Matched Analysis.

OBJECTIVES: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). METHODS: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990-2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien-Dindo > 3) were assessed between groups. RESULTS: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan-Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22-2.28, p = 0.001 and HR 1.73, 95%CI 1.22-2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta -1.1, 95% CI -2.2-0.02, p = 0.047 and beta -6.1, 95% CI -7.2-5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31-0.79, p = 0.003 and OR 0.27, 95% CI 0.16-0.46, p < 0.001, respectively). CONCLUSIONS: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

Biological and prognostic implications of biopsy upgrading for high-grade upper tract urothelial carcinoma at nephroureterectomy.

OBJECTIVES: Technical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated. METHODS: Patients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low-grade on URS biopsy) versus same grade (high-grade on URS biopsy) for high-grade UTUC tumors on radical nephroureterectomy (RNU) specimens. RESULTS: This study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy-based low- and high-grade tumors, respectively. Median follow-up was 27.3 months. Patients with high-grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high-grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10-2.75; p = 0.018), cancer-specific (HR 1.94; 95% CI, 1.07-3.52; p = 0.03), and recurrence-free survival (HR 1.80; 95% CI, 1.13-2.87; p = 0.013). In subgroup analyses of patients with pT2-T4 and/or positive LN, its significant association retained. Furthermore, high-grade biopsy in clinically non-muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (≥pT2) compared to low-grade biopsy. CONCLUSIONS: High tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low-grade UTUC that becomes upgraded to high-grade might carry a better prognosis than high-grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high-grade on RNU.

The DEpth of Endoscopic Perforation scale to assess intraoperative perforations during transurethral resection of bladder tumor: subgroup analysis of a randomized controlled trial.

PURPOSE: Bladder perforation (BP) is the most important intraoperative adverse event of transurethral resection of bladder tumor (TURBT). It is frequently underreported despite its impact on the postoperative course. There is no standardized classification of BP. The study aims to develop a classification of the depth of endoscopic bladder perforation during TURBT. METHODS: This is a sub-analysis of a prospective randomized trial enrolling 248 patients submitted to en-bloc vs conventional TURBT from 03/2018 to 06/2021. The DEpth of Endoscopic Perforation (DEEP) scale is as follows: "0" visible muscular layer with no perivesical fat; "1" visible muscle fibers with spotted perivesical fat; "2" exposition of perivesical fat; "3" intraperitoneal perforation. Logistic and linear regression models were used to investigate predictors of high-grade perforations (DEEP 2-3) and to assess whether the DEEP scale independently predicted patients' postoperative outcomes. RESULTS: A total of 146/248 (58.9%), 56/248 (22.6%), 41/248 (16.5%), 5/248 (2.0%) patients presented DEEP grade 0, 1, 2, and 3, respectively. Female gender [B coeff. 0.255 (95% CI 0.001-0.513); p = 0.05], tumor location [B coeff. 0.188 (0.026-0.339); p = 0.015], and obturator-nerve reflex [B coeff. 0.503 (0.148-0.857); p = 0.006] were independent predictors of DEEP. The scale predicted independently major complications [Odd Ratio (OR) 2.221 (1.098-4.495); p = 0.026], no post-operative chemotherapy intravesical instillation [OR 9.387 (2.434-36.200); p = 0.001], longer irrigation time [B coeff. 0.299 (0.166-0.441); p < 0.001] and hospital stay [B coeff. 0.315 (0.111-0.519); p = 0.003]. CONCLUSION: The DEEP scale provides a visual tool for grading bladder perforation during TURBT, which can help physicians standardize complication reporting and plan postoperative management accordingly.

Energy source comparison in en-bloc resection of bladder tumors: subanalysis of a single-center prospective randomized study.

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.

Diagnosis of Organizing Pneumonia with an Ultrathin Bronchoscope and Cone-Beam CT: A Case Report.

Organizing pneumonia (OP) is a pulmonary disease histopathologically characterized by plugs of loose connective tissue in distal airways. The clinical and radiological presentations are not specific and they usually require a biopsy confirmation. This paper presents the case of a patient with a pulmonary opacity sampled with a combined technique of ultrathin bronchoscopy and cone-beam CT. A 64-year-old female, a former smoker, was admitted to the hospital of Reggio Emilia (Italy) for exertional dyspnea and a dry cough without a fever. The history of the patient included primary Sjögren Syndrome interstitial lung disease (pSS-ILD) characterized by a non-specific interstitial pneumonia (NSIP) radiological pattern; this condition was successfully treated up to 18 months before the new admission. The CT scan showed the appearance of a right lower lobe pulmonary opacity of an uncertain origin that required a histological exam for the diagnosis. The lung lesion was difficult to reach with traditional bronchoscopy and a percutaneous approach was excluded. Thus, cone-beam CT, augmented fluoroscopy and ultrathin bronchoscopy were chosen to collect a tissue sample. The histopathological exam was suggestive of OP, a condition occurring in 4-11% of primary Sjögren Syndrome cases. This case showed that, in the correct clinical and radiological context, even biopsies taken with small forceps can lead to a diagnosis of OP. Moreover, it underlined that the combination of multiple advanced technologies in the same procedure can help to reach difficult target lesions, providing proper samples for a histological diagnosis.

Diagnosis and Pattern Identification of Intrathoracic Malignant Melanoma Metastasis: A Retrospective Single Center Analysis.

The lung is a frequent site of secondary malignancies. Melanoma is a malignant tumor originating from melanocytes, that accounts for the majority of death related to skin cancers. In advanced stages, it can also present with intrathoracic metastasis, particularly in the lungs, but infrequent intrathoracic manifestations are possible. A retrospective analysis of the cases referred to the pulmonary endoscopy unit of the hospital of Reggio Emilia in the last 10 years (since December 2012) was carried out, discovering 17 cases of melanoma metastasis with thoracic localizations, either with or without a diagnosis of primary melanoma. Four repetitive patterns of clinical-radiological presentation have been identified and described through the same number of paradigmatic clinical cases: nodal involvement (35%), lung mass(es) (41%), diffuse pulmonary involvement (12%), and pleural involvement (12%). These different presentations imply the use of different diagnostic techniques, with an overall high diagnostic yield (87.5%). Finally, a brief analysis of survival based on the pattern of presentation has been performed, finding no statistically significant differences between the four groups at metastasis diagnosis (p-value = 0.06, median survival of respectively 54, 8, 9, and 26 months from metastasis diagnosis), while there is a significant difference considering patients with lung involvement versus nodal/pleural involvement (p = 0.01).

Efficacy and Safety of Omalizumab Treatment Over a 16-Year Follow-Up: When a Clinical Trial Meets Real-Life.

Purpose: Treatment of severe asthma has made great strides thanks to rapid progress in understanding immune response and inflammatory pathways. This led to the advent of the first biologic for severe allergic asthma (SAA), omalizumab. Although the long-term efficacy and safety of omalizumab has been confirmed, increasingly longer follow-up data can further reinforce this evidence and potentially provide new ones, for example on any loss of efficacy or the appearance of unexpected side effects. This study reports omalizumab treatment-related outcomes after 16 years of follow-up. Patients and Methods: In this real-life retrospective study, an extension of a previous 9-year follow-up study on patients initially recruited in a clinical trial, we enrolled 8 adult patients with SAA followed-up from November 2005 to December 2021. Study subjects were selected based on omalizumab eligibility criteria. Results: Exacerbation rate significantly decreased from 3.6 ± 2.1 events in year before index date to 0.1 ± 0.4 after 32 weeks of treatment (p < 0.0001). Mean annual number of mild-to-moderate exacerbations at 16 years was 0.88 compared with 1.8 in the year before the index date and 1.1 at 32 weeks. No hospitalizations were documented during the 16-year follow-up compared to 0.3 hospitalizations/patient in the year before the index date. Respiratory function also progressively and significantly improved. Regarding patient-reported outcomes (PROs), The AQLQ and ACT significantly improved from baseline throughout the follow-up, particularly up to 9 years of follow-up. During the study, an overall reduction in doses of asthma medications was observed, with a significant OCS-sparing effect. Conclusion: Our study, the longest clinical follow-up on patients treated with anti-IgE, confirms and amplifies the results of the studies carried out so far, as they are maintained over a very long interval of time without drops in efficacy without any type of side effect.

DNA Methylation Urine Biomarkers Test in the Diagnosis of Upper Tract Urothelial Carcinoma: Results from a Single-Center Prospective Clinical Trial.

PURPOSE: The correct risk categorization and staging of upper tract urothelial cancer (UTUC) is key for disease management. Computerized tomography urography and urinary cytology have limited accuracy for risk stratification of UTUC. Ureteroscopy may increase the risk of bladder cancer recurrence. Recently, Bladder EpiCheckTM (EpiCheck) showed a high accuracy in the detection of bladder cancer. The aim of the study is to investigate the diagnostic accuracy of EpiCheck in the clinical management of UTUC and to compare it with urinary cytology. MATERIALS AND METHODS: In this single-arm, blinded, prospective, single-center study (February 2019-December 2020), all patients who were candidates for ureteroscopy for suspicion of UTUC were included. Bladder and upper urinary tract (UUT) samples were collected before ureteroscopy to test for cytology and Epicheck. EpiCheck accuracy was calculated in bladder and UUT samples and compared to cytology. RESULTS: EpiCheck resulted diagnostic in 83/86 (97%) and 73/75 (97%) of UUT and bladder samples. Histology was positive in 47/83 (57%) and 42/73 (58%) cases, respectively. In UUT samples, EpiCheck yielded a sensitivity/specificity/ negative predictive value (NPV)/positive predictive value of 83%/79%/77%/84% vs 59%/88%/61%/87% of cytology. The sensitivity/NPV for high-grade tumors was 96%/97% for EpiCheck vs 71%/86% for cytology. EpiCheck indicated ureteroscopy in 45/80 (56%) patients, missing 17%/4% of all/high-grade UTUC with 9% of unnecessary ureteroscopy. In bladder samples, the sensitivity/NPV for high-grade tumors was 71%/88% for EpiCheck and 59%/87% for cytology. CONCLUSIONS: Epicheck may be an important tool to decrease the number of unnecessary ureteroscopy. The clinical implementation of EpiCheck in UTUC warrants further investigation in multicentric prospective randomized trials.

En Bloc Versus Conventional Transurethral Resection of Bladder Tumors: A Single-center Prospective Randomized Noninferiority Trial.

BACKGROUND: It has been proposed that en bloc resection of bladder tumor (ERBT) improves the quality of tumor resection. A recent international collaborative consensus statement on ERBT underlined the lack of high-quality prospective studies precluding the achievement of solid conclusion on ERBT. OBJECTIVE: To compare conventional transurethral resection of bladder tumor (cTURBT) and ERBT. DESIGN, SETTING, AND PARTICIPANTS: This study (NCT04712201) was a prospective, randomized, noninferiority trial enrolling patients diagnosed with bladder cancer (BC) undergoing endoscopic intervention. Inclusion criteria were: tumor size ≤3 cm, three or fewer lesions, and no sign of muscle invasion and/or ureteral involvement. For a noninferiority rate in BC staging of 5% (α risk 2.5%; ß risk 20%), a total of 300 subjects were randomized to ERBT treatment at a 1:1.5 allocation ratio. INTERVENTION: TURBT and ERBT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the presence of detrusor muscle at final histology. Secondary outcomes include BC staging, T1 substaging, artifacts, complications, the rate of adjuvant treatment, and oncological outcomes. RESULTS AND LIMITATIONS: From April 2018 to June 2021, 300 patients met the inclusion criteria. Of these, 248 (83%) underwent the assigned intervention: 108 patients (44%) underwent cTURBT and 140 (57%) underwent ERBT. The rate of detrusor muscle presence for ERBT was noninferior to that for TURBT (94% vs 95%; p = 0.8). T1 substaging was feasible in 80% of cTURBT cases versus 100% of ERBT cases (p = 0.02). Complication rates, rates of postoperative adjuvant treatment, catheterization time, and hospital stay were comparable between the two groups (p > 0.05). The recurrence rate at median follow-up of 15 mo (interquartile range 7-28) was 18% for cTURBT versus 13% for ERBT (p = 0.16). Limitations include the single high-volume institution and the short-term follow-up. CONCLUSIONS: Our study has the highest level of evidence for comparison of ERBT versus TURBT. ERBT was noninferior to TURBT for BC staging. The rate of T1 substaging feasibility was significantly higher with ERBT. PATIENT SUMMARY: We compared two techniques for removing tumors from the bladder. The en bloc technique removes the tumor in one piece and is not inferior to the conventional method in terms of the quality of the surgical resection and cancer staging assessment.

Pentafecta for Radical Nephroureterectomy in Patients with High-Risk Upper Tract Urothelial Carcinoma: A Proposal for Standardization of Quality Care Metrics.

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.

Home-based treatment of biologics for asthma: who, what, where, when and why.

INTRODUCTION: The advent of biologic therapies for severe asthma has profoundly changed the management of this pathology. The introduction of home administration is therefore an important innovation to optimize the patients' management, even if there are many aspects that need to be clarified and pointed out. AREAS COVERED: This review summarizes the path that led to the possibility of self-administration of biologics, and what the pandemic has changed in the management of these patients. EXPERT OPINION: The growing understanding of asthma phenotypes and endotypes is enabling the careful selection of patients suitable for biologics. In this context, the availability of reliable and simple self-injection devices is important in implementing self-administration. The transition to self-injection is also possible thanks to the high safety profile of biologics. With attention, most patients may potentially be suitable for self-administration. The transition process from hospital to home administration can therefore be carried out correctly by clinicians with adequate expertise in the field of severe asthma and biologic therapies, with the support of other health professionals, pharmacists, and general practitioners. Home administration is probably the best way to guarantee high adherence and high-level satisfaction of patients, even in the long term.

Predictive factors of clinical outcomes in patients with COVID-19 treated with tocilizumab: A monocentric retrospective analysis.

OBJECTIVE: The aim of this retrospective observational study is to analyse clinical, serological and radiological predictors of outcome in patients with COVID-19 pneumonia treated with tocilizumab, providing clinical guidance to its use in real-life. METHOD: This is a retrospective, monocentric observational cohort study. All consecutive patients hospitalized between February the 11th and April 14th 2020 for severe COVID-19 pneumonia at Reggio Emilia AUSL and treated with tocilizumab were enrolled. The patient's clinical status was recorded every day using the WHO ordinal scale for clinical improvement. Response to treatment was defined as an improvement of one point (from the status at the beginning of tocilizumab treatment) during the follow-up on this scale. Bivariate association of main patients' characteristics with outcomes was explored by descriptive statistics and Fisher or Kruskal Wallis tests (respectively for qualitative or quantitative variables). Each clinically significant predictor was checked by a loglikelihood ratio test (in univariate logistic models for each of the considered outcomes) against the null model. RESULTS: A total of 173 patients were included. Only hypertension, the use of angiotensin-converting enzyme inhibitors, PaO2/FiO2, respiratory rate and C-reactive protein were selected for the multivariate analysis. In the multivariable model, none of them was significantly associated with response. CONCLUSIONS: Evaluating a large number of clinical variables, our study did not find new predictors of outcome in COVID19 patients treated with tocilizumab. Further studies are needed to investigate the use of tocilizumab in COVID-19 and to better identify clinical phenotypes which could benefit from this treatment.