Complementary routes towards precision urologic surgery: image guidance technologies and standardized training programmes

The studies presented in this thesis focus on the introduction in urology of novel imaging technologies that allow surgical guidance and on the need for standardized, quality assured, certified training pathways in robotic surgery in order to achieve higher level of precision urologic procedures and guarantee patients’ safety.In the first part of this thesis we demonstrated that:- SPECT/CT and ICG-99mTc-nanocolloid represent a valid optional dynamic sentinel node biopsy protocol for penile cancer patients candidate to dynamic sentinel node biopsy;- A novel hybrid radioactive tracer (i.e. 99mTc-EuK-(SO3)Cy5-mas3) provides adeguate fluorescence imaging for intraoperative guidance during prostate cancer surgery;- Sentinel node biopsy with ICG-99mTc-nanocolloid should always be combined with extended pelvic lymph node dissection to improve detection of positive nodes and potentially reduce the risk of recurrence in surgically treated prostate cancer patients;- The application of a robotic-tailored radioguidance modalities (i.e. DROP-IN gamma probe) in prostate cancer surgery helps to extend the pelvic lymph node dissection template in a personalised manner, enables more efficient intraoperative identification of sentinel nodes and when combined with fluorescence imaging allows for a complementary optical confirmation of node localisations.The second part of this thesis focused on the need for standardized, validated training programmes in robotic surgery in order to achieve higher level of precision urologic procedures, to guide surgeons during the learning process of a specific robotic procedure and protect patients from suboptimal outcomes. The available evidence on the disposable standardized and validated robotic training curricula was presented and the first structured training program for robot-assisted radical cystectomy with intracorporeal ileal conduit in male patients was developed.LUMC / Geneeskund

Dataset for multimodal fake news detection and verification tasks

The proliferation of online disinformation and fake news, particularly in the context of breaking news events, demands the development of effective detection mechanisms. While textual content remains the predominant medium for disseminating misleading information, the contribution of other modalities is increasingly emerging within online outlets and social media platforms. However, multimodal datasets, which incorporate diverse modalities such as texts and images, are not very common yet, especially in low-resource languages. This study addresses this gap by releasing a dataset tailored for multimodal fake news detection in the Italian language. This dataset was originally employed in a shared task on the Italian language. The dataset is divided into two data subsets, each corresponding to a distinct sub-task. In sub-task 1, the goal is to assess the effectiveness of multimodal fake news detection systems. Sub-task 2 aims to delve into the interplay between text and images, specifically analyzing how these modalities mutually influence the interpretation of content when distinguishing between fake and real news. Both sub-tasks were managed as classification problems. The dataset consists of social media posts and news articles. After collecting it, it was labeled via crowdsourcing. Annotators were provided with external knowledge about the topic of the news to be labeled, enhancing their ability to discriminate between fake and real news. The data subsets for sub-task 1 and sub-task 2 consist of 913 and 1350 items, respectively, encompassing newspaper articles and tweets

Objective assessment of intraoperative skills for robot-assisted radical prostatectomy (RARP): results from the ERUS Scientific and Educational Working Groups Metrics Initiative

Objective: To develop and seek consensus from procedure experts on the metrics that best characterise a reference robot-assisted radical prostatectomy (RARP) and determine if the metrics distinguished between the objectively assessed RARP performance of experienced and novice urologists, as identifying objective performance metrics for surgical training in robotic surgery is imperative for patient safety. Materials and methods: In Study 1, the metrics, i.e. 12 phases of the procedure, 81 steps, 245 errors and 110 critical errors for a reference RARP were developed and then presented to an international Delphi panel of 19 experienced urologists. In Study 2, 12 very experienced surgeons (VES) who had performed >500 RARPs and 12 novice urology surgeons performed a RARP, which was video recorded and assessed by two experienced urologists blinded as to subject and group. Percentage agreement between experienced urologists for the Delphi meeting and Mann–Whitney U- and Kruskal–Wallis tests were used for construct validation of the newly identified RARP metrics. Results: At the Delphi panel, consensus was reached on the appropriateness of the metrics for a reference RARP. In Study 2, the results showed that the VES performed ~4% more procedure steps and made 72% fewer procedure errors than the novices (P = 0.027). Phases VIIa and VIIb (i.e. neurovascular bundle dissection) best discriminated between the VES and novices. Limitations: VES whose performance was in the bottom half of their group demonstrated considerable error variability and made five-times as many errors as the other half of the group (P = 0.006). Conclusions: The international Delphi panel reached high-level consensus on the RARP metrics that reliably distinguished between the objectively scored procedure performance of VES and novices. Reliable and valid performance metrics of RARP are imperative for effective and quality assured surgical training

Association between metabolic syndrome, obesity, diabetes mellitus and oncological outcomes of bladder cancer. A systematic review

Metabolic syndrome is a cluster of several metabolic abnormalities, its prevalence is increasing worldwide. To summarize the most recent evidence regarding the relationship between metabolic syndrome, its components and the oncological outcomes in bladder cancer patients, a National Center for Biotechnology Information PubMed search for relevant articles either published or e-published up to March 2014 was carried out by combining the following Patient population, Intervention, Comparison, Outcome terms: metabolic syndrome, obesity, body mass index, hyperglycemia, insulin resistance, diabetes, hypertension, dyslipidemia, bladder cancer, risk, mortality, cancer specific survival, disease recurrence and progression. Metabolic syndrome is a complex, highly prevalent disorder, and central obesity, insulin resistance, dyslipidemia and hypertension are its main components. Published findings would suggest that metabolic syndrome per se might be associated with an increased risk of bladder cancer in male patients, but it did not seem to confer a risk of worse prognosis. Considering the primary components of metabolic syndrome (hypertension, obesity and dyslipidemia), available data are uncertain, and it is no possible to reach a conclusion yet on either a direct or an indirect association with bladder cancer risk and prognosis. Only with regard to type 2 diabetes mellitus, available data would suggest a potential negative correlation. However, as the evaluation of bladder cancer risk and prognosis in patients with metabolic disorders is certainly complex, further studies are urgently required to better assess the actual role of these metabolic disorders

Usefulness of the Indocyanine Green (ICG) immunofluorescence in laparoscopic and robotic partial nephrectomy

The trend towards the organ sparing and robotic assisted surgeries is clear and is going to expand in the future. Hence, the tools surgeons need to facilitate such minimallly invasive approaches are going to be even more important. The Indocyanine green (ICG) is a water-soluble, relatively hydrophobic dye which bounds to plasma protein and can be used intraoperatively as real time contrast agent. Near infrared fluorescence (NIRF) helps in differentiating the renal planes, and the most common reagent used for the NIRF is ICG. The combination is used frequently during nephron sparing surgery in urology to ensure the ischemia of the kidney after clamping the renal artery, moreover it can help to identify the arterial blood supply to the tumor allowing selective clamping and thus minimizing the ischemia time. Several studies assessed the role of ICG in nephron-sparing surgery and provided evidence that its use allows to improve perioperative and oncological outcomes. This review provides an overview of the articles published regarding the use of ICG during partial nephrectomy, about the oncological outcomes and safety

The role of intraoperative indocyanine green in robot-assisted partial nephrectomy: results from a large, multi-institutional series

Background: In recent years, novel technologies have been implemented in order to improve the surgical outcomes of robot-assisted partial nephrectomy (RAPN). Intraoperative administration of indocyanine green (ICG) has been proposed to assess kidney perfusion intraoperatively.Objective: To confirm, on a large scale, the effectiveness of near-infrared fluorescence ICG-guided RAPN in leading the surgeon strategy and to provide hints to the use of this tool. Design, setting, and participants: The Transatlantic Robotic Nephron-sparing Surgery (TRoNeS) study group collected data from 737 patients subjected to RAPN between 2010 and 2016 at three tertiary care referral centers. Of them, 318 had complete demographic and clinical data, and underwent ICG-guided RAPN for clinically localized kidney cancer.Surgical procedure: Patients were subjected to RAPN with intraoperative intravenous ICG injection.Measurements: Optimal surgical outcomes, defined according to both the margin, ischemia, and complication (MIC), and the trifecta score, were assessed.Results and limitations: A total of 194 (61%) patients were male and 124 (39%) were female. The median patient age was 61 yr and median preoperative tumor size was 30 mm. Median operative time, estimated blood loss, and warm ischemia time were, respectively, 162 min, 100 ml, and 17 min. In total, 228 (71.7%) and 254 (79.9%) individuals, respectively, were selected as optimal surgical patients defined according to MIC and trifecta. The univariate and multivariable logistic regression models showed that tumor complexity nephrometry scores were independent predictors of both trifecta and MIC. The main limitation of this study is the lack of a control group. Conclusions: We report the largest population of patients who underwent ICG-guided RAPN. Intraprocedural ICG administration represents a useful tool where the vascular anatomy is challenging, and it could be implemented to maximize the adoption of RAPN.Patient summary: We demonstrated that indocyanine green (ICG) is a reliable tool for guiding the surgeon strategy during robot-assisted partial nephrectomy. ICG may help in procedure tailoring, especially in cases with challenging vascularization or impaired renal function. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.</p

The role of metabolic syndrome in high grade prostate cancer: development of a clinical nomogram

BACKGROUND: The aim of our study is to develop a clinical nomogram including metabolic syndrome status for the prediction of high-grade prostate cancer (HG PCa).METHODS: A series of men at increased risk of PCa undergoing prostate biopsies were enrolled in a single center. Demographic and clinical characteristics of the patients were recorded. Metabolic syndrome was defined according to the adult treatment panel III. A nomogram was generated based on the logistic regression model and used to predict high grade prostate cancer defined as grade group >= 3 (ISUP 2014). ROC curves, calibration plots and decision curve analysis were used to evaluate the performance of the nomogram.RESULTS: Overall, 738 patients were enrolled. Greater than or equal to 294/738 (40%) of the patients presented PCa and of those patients, 84/294 (39%) presented high grade disease (Grade Group >= 3). On multivariate analysis, DRE (OR: 3.24, 95% CI: 1.80-5.84), PSA (OR: 1.10, 95% CI: 1.05-1.16), PV (OR: 0.98, 95% CI: 0.97-0.99) and MetS (OR: 2.02, 95% CI: 1.13-3.59) were predictors of HG PCa. The nomogram based on the model presented good discrimination (AUC: 0.76), good calibration (Hosmer-Lemeshow Test, P>0.05) and a net benefit in the range of probabilities between 10% and 70%.CONCLUSIONS: Metabolic syndrome is highly prevalent in patients at risk of prostate cancer and is particularly associated with high-grade prostate cancer. Our nomogram offers the possibility to include metabolic status in the assessment of patients at risk of prostate cancer to identify men who may have a high-grade form of the disease. External validation is warranted before its clinical implementation

Objective assessment of intraoperative skills for robot-assisted radical prostatectomy (RARP): results from the ERUS Scientific and Educational Working Groups Metrics Initiative

Objective To develop and seek consensus from procedure experts on the metrics that best characterise a reference robot-assisted radical prostatectomy (RARP) and determine if the metrics distinguished between the objectively assessed RARP performance of experienced and novice urologists, as identifying objective performance metrics for surgical training in robotic surgery is imperative for patient safety.Materials and methods In Study 1, the metrics, i.e. 12 phases of the procedure, 81 steps, 245 errors and 110 critical errors for a reference RARP were developed and then presented to an international Delphi panel of 19 experienced urologists. In Study 2, 12 very experienced surgeons (VES) who had performed >500 RARPs and 12 novice urology surgeons performed a RARP, which was video recorded and assessed by two experienced urologists blinded as to subject and group. Percentage agreement between experienced urologists for the Delphi meeting and Mann-Whitney U- and Kruskal-Wallis tests were used for construct validation of the newly identified RARP metrics.Results At the Delphi panel, consensus was reached on the appropriateness of the metrics for a reference RARP. In Study 2, the results showed that the VES performed similar to 4% more procedure steps and made 72% fewer procedure errors than the novices (P = 0.027). Phases VIIa and VIIb (i.e. neurovascular bundle dissection) best discriminated between the VES and novices. Limitations: VES whose performance was in the bottom half of their group demonstrated considerable error variability and made five-times as many errors as the other half of the group (P = 0.006).Conclusions The international Delphi panel reached high-level consensus on the RARP metrics that reliably distinguished between the objectively scored procedure performance of VES and novices. Reliable and valid performance metrics of RARP are imperative for effective and quality assured surgical training

Multimodal treatment in focal therapy for localized prostate cancer using concomitant short-term androgen deprivation therapy: the ENHANCE prospective pilot study

Focal therapy (FT) for localized prostate cancer (PCa) is emerging to reduce adverse effects of radical treatments, while maintaining comparable oncological outcomes. However, an area for improvement still exists and a gap in cancer control needs to be filled by complementing FT with additional forms of treatment to minimize failures. Part of the recurrences/persistences after FT may be related to PCa microenvironment favouring tumorigenesis of benign tissue or indolent PCa left untreated. FT-induced inflammation may alter microenvironment in a pro-tumorigenic fashion. On the contrary, androgen deprivation therapy (ADT) modifies PCa microenvironment and suppresses PCa tumorigenesis. So far, ADT has proven effective in combination with radiotherapy, has been evaluated in the context of AS and to reduce prostate volume in the context of whole-gland high-intensity focused ultrasound (HIFU). However, no prospective data exist evaluating FT/ADT combination in terms of cancer control for the treatment of localized PCa. We will perform the ENHANCE pilot study (EvaluatioN of HIFU Hemiablation and short-term AndrogeN deprivation therapy Combination to Enhance prostate cancer control). Twenty men with localized unilateral csPCa will receive HIFU hemi-ablation and concomitant short-term ADT. Oncologic efficacy will be assessed 1-year post-treatment considering the persistence/recurrence of csPCa. Complications and functional outcomes will be evaluated using internationally validated questionnaires. If the hypothesis of an oncological benefit together with no relevant additional toxicity is confirmed, the ENHANCE study will allow an evidence-based starting point for a large randomized controlled trial against the standard of care and/or HIFU hemiablation alone

A DROP-IN gamma probe for robot-assisted radioguided surgery of lymph nodes during radical prostatectomy

Background: The DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the DROP-IN promotes the implementation of radioguided surgery in the robotic setting.Objective: To confirm the utility and safety profile of the DROP-IN gamma probe and to perform a comparison with the traditional laparoscopic gamma probe and fluorescence guidance.Design, setting, and participants: Twenty-five prostate cancer patients were scheduled for a robot-assisted sentinel lymph node (SN) procedure, extended pelvic lymph node dissection, and prostatectomy at a single European centre.Surgical procedure: After intraprostatic injection of indocyanine green (ICG)-Tc-99m-nanocolloid (n = 12) or Tc-99m-nanocolloid + ICG (n = 13), SN locations were defined using preoperative imaging. Surgical excision of SNs was performed under image guidance using the DROP-IN gamma probe, the traditional laparoscopic gamma probe, and fluorescence imaging.Measurements: Intraoperative SN detection was assessed for the different modalities and related to anatomical locations. Patient follow-up was included (a median of 18 mo).Results and limitations: Overall, 47 SNs were pursued in vivo by the DROP-IN gamma probe, of which 100% were identified. No adverse events related to its use were observed. In vivo fluorescence imaging identified 91% of these SNs. The laparoscopic gamma probe identified only 76% of these SNs, where the detection inaccuracies appeared to be related to specific anatomical regions.Conclusions: Owing to improved manoeuvrability, the DROP-IN probe yielded improved SN detection rates compared with the traditional gamma probe and fluorescence imaging. These findings underline that the DROP-IN technology provides a valuable tool for radioguided surgery in the robotic setting.Patient summary: Radioguided robot-assisted surgery with the novel DROP-IN gamma probe is feasible and safe. It enables more efficient intraoperative identification of sentinel lymph nodes than can be achieved with a traditional laparoscopic gamma probe. The use of the DROP-IN probe in combination with fluorescence imaging allows for a complementary optical confirmation of node localisations. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.Oncologic Imagin