Quality-of-life outcomes of the ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial.

OBJECTIVES: To comprehensively compare quality-of-life (QoL) outcomes between open partial nephrectomy (OPN) and robot-assisted PN (RAPN) from the randomised ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial, as QoL data comparing OPN and RAPN are virtually non-existent, especially not from randomised controlled trials (RCTs). PATIENTS AND METHODS: The ROBOCOP II was a single-centre, open-label RCT between OPN and RAPN. The pre-planned analyses of QoL outcomes are presented. Data were analysed descriptively in a modified intention-to-treat population. RESULTS: A total of 50 patients underwent surgery. At postoperative Day 90 (POD90), there was no significant difference for the Kidney Disease Quality of Life-Short Form questionnaire score (mean [sd] OPN 72 [20] vs RAPN 76 [15], P = 0.850), while there were advantages for RAPN in the subdomains of 'Pain' (P = 0.006) and 'Physical functioning' (P = 0.011) immediately after surgery. For the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core there were overall advantages directly after surgery (mean [sd] score OPN 63 [20] vs RAPN 75 [17], P = 0.031), as well as for the subdomains 'Fatigue' (P = 0.026), 'Pain' (P = 0.002) and 'Constipation' (P = 0.045) but no differences at POD90. There were no differences for the EuroQoL five Dimensions five Levels questionnaire at POD90 (mean [sd] score OPN 70 [22] vs RAPN 72 [17], P = 1.0) or at any other time point. Finally, no significant differences were found for the overall Convalescence and Recovery Evaluation questionnaire score at POD90 (mean [sd] OPN 84 [13] vs RAPN 86 [10], P = 0.818) but less pain in the RAPN group (P = 0.017) directly after surgery. CONCLUSIONS: Pain and physical functioning as subdomains of QoL are improved after RAPN compared to OPN in the early postoperative course, while there are no differences anymore after 3 months.

Robotic-assisted versus laparoscopic bowel anastomoses: randomized crossover in vivo experimental study.

BACKGROUND: Initial learning curves are potentially shorter in robotic-assisted surgery (RAS) than in conventional laparoscopic surgery (LS). There is little evidence to support this claim. Furthermore, there is limited evidence how skills from LS transfer to RAS. METHODS: A randomized controlled, assessor blinded crossover study to compare how RAS naïve surgeons (n = 40) performed linear-stapled side-to-side bowel anastomoses in an in vivo porcine model with LS and RAS. Technique was rated using the validated anastomosis objective structured assessment of skills (A-OSATS) score and the conventional OSATS score. Skill transfer from LS to RAS was measured by comparing the RAS performance of LS novices and LS experienced surgeons. Mental and physical workload was measured with the NASA-task load index (NASA-Tlx) and the Borg-scale. OUTCOMES: In the overall cohort, there were no differences between RAS and LS for surgical performance (A-OSATS, time, OSATS). Surgeons that were naïve in both LS and RAS had significantly higher A-OSATS scores in RAS (Mean (Standard deviation (SD)): LS: 48.0 ± 12.1; RAS: 52.0 ± 7.5); p = 0.044) mainly deriving from better bowel positioning (LS: 8.7 ± 1.4; RAS: 9.3 ± 1.0; p = 0.045) and closure of enterotomy (LS: 12.8 ± 5.5; RAS: 15.6 ± 4.7; p = 0.010). There was no statistically significant difference in how LS novices and LS experienced surgeons performed in RAS [Mean (SD): novices: 48.9 ± 9.0; experienced surgeons: 55.9 ± 11.0; p = 0.540]. Mental and physical demand was significantly higher after LS. CONCLUSION: The initial performance was improved for RAS versus LS for linear stapled bowel anastomosis, whereas workload was higher for LS. There was limited transfer of skills from LS to RAS.

Pancreatic surgery with or without drainage: propensity score-matched study.

BACKGROUND: A recent RCT has shown that routine intraoperative drain placement after pancreatoduodenectomy (PD) is not necessary. The aim was to confirm this in real-world conditions. METHODS: A propensity score-matched (PSM) analysis of patients with and without drainage after PD or distal pancreatectomy (DP) at a high-volume centre was undertaken. Main outcomes were complications and duration of hospital stay. Multivariable regression analysis was used to assessed which factors led to intraoperative drainage after the standard was changed from drain to no drain. RESULTS: Of 377 patients who underwent PD, 266 were included in PSM analysis. No drain was associated with fewer major complications (42 (31.6 per cent) versus 62 (46.6 per cent); P = 0.017), shorter duration of hospital stay (mean(s.d.) 14.7(8.5) versus 19.6(14.9) days; P = 0.001), and required fewer interventional drain placements (8.4 versus 19.8 per cent; P = 0.013). In PSM analysis after DP (112 patients), no drainage was associated with fewer clinically relevant postoperative pancreatic fistulas (9 versus 18 per cent; P = 0.016), fewer overall complications (mean(s.d.) comprehensive complication index score 15.9(15.4) versus 24.8(20.4); P = 0.012), and a shorter hospital stay (9.3(7.0) versus 13.5(9.9) days; P = 0.011). Multivisceral resection (OR 2.80, 95 per cent c.i. 1.10 to 7.59; P = 0.034) and longer operating times (OR 1.56, 1.04 to 2.36; P = 0.034) influenced the choice to place a drain after PD. Greater blood loss was associated with drainage after DP (OR 1.14, 1.02 to 1.30; P = 0.031). CONCLUSION: Standard pancreatic resections can be performed safely without drainage. Surgeons were more reluctant to omit drainage after complex pancreatic resections.

Pancreatic surgery has traditionally relied on the use of drains placed during surgery that should facilitate outflow of fluids from the operating site. This principle has recently been challenged by specially designed studies showing that patients who do not receive a drain may have fewer complications. The present study has demonstrated that these results also apply to routine clinical settings outside the constraints of surgical trials.

Laparoscopic Versus Open Pancreaticoduodenectomy: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To compare perioperative outcomes of laparoscopic pancreaticoduodenectomy (LPD) to open pancreaticoduodenectomy (OPD) using evidence from randomized controlled trials (RCTs). BACKGROUND: LPD is used more commonly, but this surge is mostly based on observational data. METHODS: We searched CENTRAL, Medline and Web of Science for RCTs comparing minimally invasive to OPD for adults with benign or malignant disease requiring elective pancreaticoduodenectomy. Main outcomes were 90-day mortality, Clavien-Dindo ≥3 complications, and length of hospital stay (LOS). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), bile leak, blood loss, reoperation, readmission, oncologic outcomes (R0-resection, lymph nodes harvested), and operative times. Data were pooled as odds ratio (OR) or mean difference (MD) with a random-effects model. Risk of bias was assessed using the Cochrane Tool and the GRADE approach (Prospero registration ID: CRD42019120363). RESULTS: Three RCTs with a total of 224 patients were included. Meta-analysis showed there were no significant differences regarding 90-day mortality, Clavien-Dindo ≥3 complications, LOS, POPF, DGE, PPH, bile leak, reoperation, readmission, or oncologic outcomes between LPD and OPD. Operative times were significantly longer for LPD {MD [95% confidence interval (CI)] 95.44 minutes (24.06-166.81 minutes)}, whereas blood loss was lower for LPD [MD (CI) -150.99 mL (-168.54 to -133.44 mL)]. Certainty of evidence was moderate to very low. CONCLUSIONS: At current level of evidence, LPD shows no advantage over OPD. Limitations include high risk of bias and moderate to very low certainty of evidence. Further studies should focus on patient safety during LPD learning curves and the potential role of robotic surgery.

Relevance of Positive Surgical Margins in Localized Renal Cell Carcinoma After Surgical Resection: Predictive Factors and Survival Implications.

INTRODUCTION: The implications of positive surgical margins (PSM) after surgery for renal cell carcinoma (RCC) remain subject of discussion. This study aimed to identify risk factors for PSM, assess its effect on overall survival (OS), and determine predictors of OS. PATIENTS AND METHODS: Data from RCC surgeries at Mannheim University Medical Center between 2010 and 2023 was analyzed. Propensity score matching balanced PSM and control groups using age, surgical approach, tumor stage, histological subtype, and American Association of Anesthesiologists (ASA) score. Logistic and cox regression models predict PSM and OS, respectively. Kaplan-Meier analysis compared OS of PSM patients and controls. RESULTS: A total of 1066 RCC patients were included. Propensity score matching yielded 32 PSM patients and 96 controls. Multivariable logistic regression identified tumor stage ≥ T3a (odds ratio [OR] = 2.74, 95% confidence interval [CI] = 1.0-6.8, P = .04) and chromophobe, compared to clear cell, RCC (OR = 3.19, 95% CI = 1.0-8.7, P = .03) as independent predictors of PSM. Multivariable cox regression found age > 65 years (hazard ratio [HR] = 2.65, 95% CI = 1.7-4.2, P < .01) and tumor stage ≥ T3a (HR = 2.25, 95% CI = 1.4-3.7, P < .01) to predict shorter OS. Partial vs. radical nephrectomy was associated with improved OS (HR = 0.49, 95% CI = 0.3-0.9, P = .02). Kaplan-Meier analysis revealed no OS difference between PSM patients and controls (P = .49) over a 45-month median follow-up. CONCLUSION: PSM is not a primary determinant of inferior survival, while age and tumor stage play a more prominent role. A well-calibrated follow-up protocol for PSM patients, combining PSM with coinciding factors such as tumor stage, grade, size, or PSM extent, is crucial for adequate surveillance while preventing excessive interventions.

Endotracheal Intubation via Tracheotomy and Subsequent Thoracotomy in Rats for Non-Survival Applications.

Endotracheal intubation and subsequent ventilation are often basic requirements for translational research in rat models for various interventions that require controlled or high ventilation pressures or access to the thoracic cavity and organs. Conventional endoorotracheal intubation using the anatomically existing route through the mouth is well suited for survival experiments. However, this procedure poses some challenges, including generally higher levels of the required experience and technical skill, more advanced equipment, and greater time effort with relevant intubation failure rates and complications such as tracheal perforation, temporary systemic hypooxygenation, and relevant aerial leakage. This manuscript, therefore, presents a detailed step-by-step protocol for endotracheal intubation through tracheotomy in non-survival rat models when guaranteed intubation success, constant oxygenation levels, high ventilation pressures, or open thoracotomy are required. The protocol emphasizes the importance of meticulous surgical technique to ensure consistent and reliable outcomes, especially for researchers who are inexperienced or lack routine in the technique of endoorotracheal intubation via direct laryngoscopy. This procedure is, therefore, expected to minimize animal suffering and unnecessary animal losses.

IDEAL-D Phase 0 Evaluation of the Avatera System in Robot-Assisted Prostate, Bladder and Renal Surgery.

Purpose: To evaluate the utilization of novel Avatera system in urological operations according to the IDEAL-D framework recommendations for high-risk invasive surgical devices. Materials and Methods: Three surgeons attempted to perform 23 upper and lower urinary tract operations on human cadavers and in live porcine models using the Avatera system. Total operative time and the duration of the substeps were evaluated. Surgical performance was assessed with the Global Evaluative Assessment of Robotic Skills (GEARS) score. Suturing was rated using the technical checklist for the assessment of suturing in robotic surgery. Attending surgeons rated their satisfaction with the Avatera system on a scale of 1-5. Results and Limitation: Seventeen out of 18 operations performed on cadavers were completed, while one pyeloplasty was discontinued. All five operations performed in porcine models were completed. Although 1 pig was euthanized on the fifth postoperative day, its symptoms were unrelated to surgery. Mean GEARS and Suturing scores in the upper urinary tract were 29 ± 0.7 and 29.5 ± 0.95, respectively, and in the lower urinary 28.5 ± 1.2 and 29.5 ± 0.5, respectively. Surgeons' satisfaction was high or very high for all procedures. Conclusions: The Avatera system was associated with good surgical performance and high surgeons' satisfaction rates. All urological procedures performed were shown to be feasible, with comparable risks to other robot-assisted surgery systems.

Randomized Controlled Feasibility Trial of Robot-assisted Versus Conventional Open Partial Nephrectomy: The ROBOCOP II Study.

BACKGROUND: There is no evidence from randomized controlled trials (RCTs) comparing robot-assisted partial nephrectomy (RAPN) and open partial nephrectomy (OPN). OBJECTIVE: To assess the feasibility of trial recruitment and to compare surgical outcomes between RAPN and OPN. DESIGN, SETTING, AND PARTICIPANTS: ROBOCOP II was designed as single-center, open-label, feasibility RCT. Patients with suspected localized renal cell carcinoma referred for PN were randomized at a 1:1 ratio to either RAPN or OPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the feasibility of recruitment, assessed as the accrual rate. Secondary outcomes included perioperative and postoperative data. Data were analyzed descriptively in a modified intention-to-treat population consisting of randomized patients who underwent surgery. RESULTS AND LIMITATIONS: A total of 50 patients underwent RAPN or OPN (accrual rate 65%). In comparison to OPN, RAPN had lower blood loss (OPN 361 ml, standard deviation [SD] 238; RAPN 149 ml, SD 122; difference 212 ml, 95% confidence interval [CI] 105-320; p < 0.001), less need for opioids (OPN 46%; RAPN 16%; difference 30%, 95% CI 5-54; p = 0.024), and fewer complications according to the mean Comprehensive Complication Index (OPN 14, SD 16; RAPN 5, SD 15; difference 9, 95% CI 0-18; p = 0.008). OPN has a shorter operative time (OPN 112 min, SD 29; RAPN 130 min, SD 32; difference -18 min, 95% CI -35 to -1; p = 0.046) and warm ischemia time (OPN 8.7 min, SD 7.1; RAPN 15.4 min, SD 7.0; difference 6.7 min, 95% CI -10.7 to -2.7; p = 0.001). There were no differences between RAPN and OPN regarding postoperative kidney function. CONCLUSIONS: This first RCT comparing OPN and RAPN met the primary outcome of the feasibility of recruitment; however, the window for future RCTs is closing. Each approach has advantages over the other, and both remain safe and effective options. PATIENT SUMMARY: For patients with a kidney tumor, open surgery and robot-assisted keyhole surgery are both feasible and safe approaches for partial removal of the affected kidney. Each approach has known advantages. Long-term follow-up will explore differences in quality of life and cancer control outcomes.

Robot-assisted Versus Conventional Laparoscopic Radical Prostatectomy: A Systematic Review and Meta-analysis of Randomised Controlled Trials.

CONTEXT: Robot-assisted radical prostatectomy (RARP) has largely replaced conventional laparoscopic radical prostatectomy (LRP) even though the costs are significantly higher. Justification for this change is the hope for better postoperative functional results because of better dissection of the neurovascular bundle. OBJECTIVE: To perform a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing RARP and LRP for the primary outcome of continence (use of 0 pads or 1 safety pad) at 12 mo after surgery. EVIDENCE ACQUISITION: We searched the CENTRAL, MEDLINE, and Web of Science databases for RCTs comparing RARP versus LRP for adults with localised prostate cancer (PC). Where possible, individual-patient data were obtained. Secondary outcomes were potency for patients potent at baseline; a trifecta of patients continent and potent and no recurrence/further treatment; positive surgical margins; biochemical recurrence; and further treatment for PC. The systematic review was registered prospectively (reviewregistry1190 on www.researchregistry.com/). EVIDENCE SYNTHESIS: Five RCTs were identified. Three trial teams provided data. For another trial, only published data were available. The fifth trial was terminated prematurely because of insufficient recruitment and thus could not be included. Overall, data for 1205 randomised patients were available. At 12 mo, there was no significant difference between the two groups regarding continence (odds ratio [OR] 1.95, 95% confidence interval [CI] 0.67-5.62). However, at 3 mo and 6 mo there were significant differences in favour of RARP. Significantly more patients who were potent at baseline and underwent a robot-assisted nerve-sparing approach were potent at 12 mo (OR 4.05, 95% CI 1.63-10.09). CONCLUSION: At 12 mo after surgery there are no differences in continence between RARP and LRP. Short-term continence benefits of RARP were observed. Potent patients undergoing RARP consistently show better potency postoperatively. PATIENT SUMMARY: We analysed differences between robot-assisted removal of the prostate and conventional keyhole surgery for removal of the prostate. At 12 mo after surgery, there were no differences in continence outcomes between the two approaches. However, patients who were potent at baseline and underwent robot-assisted surgery were more likely to be potent at 12 mo.

HeiPorSPECTRAL - the Heidelberg Porcine HyperSPECTRAL Imaging Dataset of 20 Physiological Organs.

Hyperspectral Imaging (HSI) is a relatively new medical imaging modality that exploits an area of diagnostic potential formerly untouched. Although exploratory translational and clinical studies exist, no surgical HSI datasets are openly accessible to the general scientific community. To address this bottleneck, this publication releases HeiPorSPECTRAL ( https://www.heiporspectral.org ; https://doi.org/10.5281/zenodo.7737674 ), the first annotated high-quality standardized surgical HSI dataset. It comprises 5,758 spectral images acquired with the TIVITA® Tissue and annotated with 20 physiological porcine organs from 8 pigs per organ distributed over a total number of 11 pigs. Each HSI image features a resolution of 480 × 640 pixels acquired over the 500-1000 nm wavelength range. The acquisition protocol has been designed such that the variability of organ spectra as a function of several parameters including the camera angle and the individual can be assessed. A comprehensive technical validation confirmed both the quality of the raw data and the annotations. We envision potential reuse within this dataset, but also its reuse as baseline data for future research questions outside this dataset. Measurement(s) Spectral Reflectance Technology Type(s) Hyperspectral Imaging Sample Characteristic - Organism Sus scrofa.

ICG-augmented hyperspectral imaging for visualization of intestinal perfusion compared to conventional ICG fluorescence imaging: an experimental study.

BACKGROUND: Small bowel malperfusion (SBM) can cause high morbidity and severe surgical consequences. However, there is no standardized objective measuring tool for the quantification of SBM. Indocyanine green (ICG) imaging can be used for visualization, but lacks standardization and objectivity. Hyperspectral imaging (HSI) as a newly emerging technology in medicine might present advantages over conventional ICG fluorescence or in combination with it. METHODS: HSI baseline data from physiological small bowel, avascular small bowel and small bowel after intravenous application of ICG was recorded in a total number of 54 in-vivo pig models. Visualizations of avascular small bowel after mesotomy were compared between HSI only (1), ICG-augmented HSI (IA-HSI) (2), clinical evaluation through the eyes of the surgeon (3) and conventional ICG imaging (4). The primary research focus was the localization of resection borders as suggested by each of the four methods. Distances between these borders were measured and histological samples were obtained from the regions in between in order to quantify necrotic changes 6 h after mesotomy for every region. RESULTS: StO2 images (1) were capable of visualizing areas of physiological perfusion and areas of clearly impaired perfusion. However, exact borders where physiological perfusion started to decrease could not be clearly identified. Instead, IA-HSI (2) suggested a sharp-resection line where StO2 values started to decrease. Clinical evaluation (3) suggested a resection line 23 mm (±7 mm) and conventional ICG imaging (4) even suggested a resection line 53 mm (±13 mm) closer towards the malperfused region. Histopathological evaluation of the region that was sufficiently perfused only according to conventional ICG (R3) already revealed a significant increase in pre-necrotic changes in 27% (±9%) of surface area. Therefore, conventional ICG seems less sensitive than IA-HSI with regards to detection of insufficient tissue perfusion. CONCLUSIONS: In this experimental animal study, IA-HSI (2) was superior for the visualization of segmental SBM compared to conventional HSI imaging (1), clinical evaluation (3) or conventional ICG imaging (4) regarding histopathological safety. ICG application caused visual artifacts in the StO2 values of the HSI camera as values significantly increase. This is caused by optical properties of systemic ICG and does not resemble a true increase in oxygenation levels. However, this empirical finding can be used to visualize segmental SBM utilizing ICG as contrast agent in an approach for IA-HSI. Clinical applicability and relevance will have to be explored in clinical trials. LEVEL OF EVIDENCE: Not applicable. Translational animal science. Original article.

Robotic-assisted Versus Laparoscopic Radical Prostatectomy: 12-month Outcomes of the Multicentre Randomised Controlled LAP-01 Trial.

BACKGROUND: Recently, our LAP-01 trial demonstrated superiority of robotic-assisted laparoscopic radical prostatectomy (RARP) over conventional laparoscopic radical prostatectomy (LRP) with respect to continence at 3 mo. OBJECTIVE: To compare the continence, potency, and oncological outcomes between RARP and LRP in the 12-mo follow-up. DESIGN, SETTING, AND PARTICIPANTS: In this multicentre, randomised, patient-blinded controlled trial, patients referred for radical prostatectomy to four hospitals in Germany were randomly assigned (3:1) to undergo either RARP or LRP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Continence was assessed as a patient-reported outcome through validated questionnaires. Secondary endpoints included potency and oncological outcomes. Data were statistically analysed by bivariate tests and multivariable models. RESULTS AND LIMITATIONS: At 12 mo, follow-up data were available for 701 of 782 patients. Continence at 6 and 12 mo after surgery was better in RARP patients, however no longer statistically significant (p = 0.068 and 0.38, respectively). Patients who were potent at baseline and underwent nerve-sparing surgery reported significantly higher potency after RARP, as defined by the capability to maintain an erection sufficient for intercourse at 3 (p = 0.005), 6 (p = 0.018), and 12 mo (p = 0.013). There were no statistically significant differences in oncological outcomes at 12 mo. It is a limitation that the influence of different anastomotic techniques was not investigated in this study. CONCLUSIONS: Both LRP and RARP offer a high standard of therapy for prostate cancer patients. However, robotic assistance offers better functional outcomes in specific areas such as potency and early continence in patients who are eligible for nerve-sparing RP. PATIENT SUMMARY: We compared outcomes 12 mo after radical prostatectomy between robotic-assisted and conventional laparoscopy. Both methods were equivalent with respect to oncological outcomes. Better recovery of continence in patients with robotic-assisted surgery, which was observed at 3 mo, blurred up to 12 mo. A benefit of robotic-assisted surgery was also observed in potency.

Spectral organ fingerprints for machine learning-based intraoperative tissue classification with hyperspectral imaging in a porcine model.

Visual discrimination of tissue during surgery can be challenging since different tissues appear similar to the human eye. Hyperspectral imaging (HSI) removes this limitation by associating each pixel with high-dimensional spectral information. While previous work has shown its general potential to discriminate tissue, clinical translation has been limited due to the method's current lack of robustness and generalizability. Specifically, the scientific community is lacking a comprehensive spectral tissue atlas, and it is unknown whether variability in spectral reflectance is primarily explained by tissue type rather than the recorded individual or specific acquisition conditions. The contribution of this work is threefold: (1) Based on an annotated medical HSI data set (9059 images from 46 pigs), we present a tissue atlas featuring spectral fingerprints of 20 different porcine organs and tissue types. (2) Using the principle of mixed model analysis, we show that the greatest source of variability related to HSI images is the organ under observation. (3) We show that HSI-based fully-automatic tissue differentiation of 20 organ classes with deep neural networks is possible with high accuracy (> 95%). We conclude from our study that automatic tissue discrimination based on HSI data is feasible and could thus aid in intraoperative decisionmaking and pave the way for context-aware computer-assisted surgery systems and autonomous robotics.

ROBOCOP II (ROBOtic assisted versus conventional open partial nephrectomy) randomised, controlled feasibility trial: clinical trial protocol.

INTRODUCTION: Randomised controlled trials comparing robotic-assisted partial nephrectomy (RAPN) and open PN (OPN) are lacking. Therefore, we aim to report the study protocol and a trial update for a randomised controlled feasibility trial comparing RAPN versus OPN for renal neoplasms. METHODS AND ANALYSIS: The ROBOtic assisted versus conventional Open Partial nephrectomy II trial is designed as a single-centre, randomised, open-label, feasibility trial. Participation will be offered to patients with renal neoplasms and deemed feasible for both, OPN and RAPN. We aim to enrol 50 patients within 15 months using a 1:1 allocation ratio. The primary endpoint of the trial is feasibility of recruitment and will be successful if one third of eligible patients agree to participate. Secondary endpoints include perioperative results, health-related quality of life, inflammatory response as well as surgical ergonomics of the operating team. If the primary outcome, feasibility of recruitment, is successful, the secondary results of the trial will be used for planning a confirmative phase III trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from the local institutional review board (Ethik-Kommission II at Heidelberg University: 2020-542N). Results will be made publicly available in peer-reviewed scientific journals and presented at appropriate congresses and social media. TRIAL REGISTRATION NUMBER: NCT04534998.

Process Evaluation of a Medical Student-Delivered Smoking Prevention Program for Secondary Schools: Protocol for the Education Against Tobacco Cluster Randomized Trial.

BACKGROUND: Most smokers start smoking during their early adolescence under the impression that smoking entails positive attributes. Given the addictive nature of cigarettes, however, many of them might end up as long-term smokers and suffering from tobacco-related diseases. To prevent tobacco use among adolescents, the large international medical students' network Education Against Tobacco (EAT) educates more than 40,000 secondary school students per year in the classroom setting, using evidence-based self-developed apps and strategies. OBJECTIVE: This study aimed to evaluate the long-term effectiveness of the school-based EAT intervention in reducing smoking prevalence among seventh-grade students in Germany. Additionally, we aimed to improve the intervention by drawing conclusions from our process evaluation. METHODS: We conduct a cluster-randomized controlled trial with measurements at baseline and 9, 16, and 24 months postintervention via paper-and-pencil questionnaires administered by teachers. The study groups consist of randomized schools receiving the 2016 EAT curriculum and control schools with comparable baseline data (no intervention). The primary outcome is the difference of change in smoking prevalence between the intervention and control groups at the 24-month follow-up. Secondary outcomes are between-group differences of changes in smoking-related attitudes and the number of new smokers, quitters, and never-smokers. RESULTS: A total of 11,268 students of both sexes, with an average age of 12.32 years, in seventh grade of 144 secondary schools in Germany were included at baseline. The prevalence of cigarette smoking in our sample was 2.6%. The process evaluation surveys were filled out by 324 medical student volunteers, 63 medical student supervisors, 4896 students, and 141 teachers. CONCLUSIONS: The EAT cluster randomized trial is the largest school-based tobacco-prevention study in Germany conducted to date. Its results will provide important insights with regards to the effectiveness of medical student-delivered smoking prevention programs at school. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13508.