Trends in mediastinal nodal staging and its impact on unforeseen N2 and survival in lung cancer.

INTRODUCTION: Guidelines for invasive mediastinal nodal staging in resectable nonsmall cell lung cancer (NSCLC) have changed over the years. The aims of this study were to describe trends in invasive staging and unforeseen N2 (uN2) and to assess a potential effect on overall survival. METHODS: A nationwide Dutch cohort study included all clinical stage IA-IIIB NSCLC patients primarily treated by surgical resection between 2005 and 2017 (n=22 555). We assessed trends in invasive nodal staging (mediastinoscopy 2005-2017; endosonography 2011-2017), uN2 and overall survival and compared outcomes in the entire group and in clinical nodal stage (cN)1-3 patients with or without invasive staging. RESULTS: An overall increase in invasive nodal staging from 26% in 2005 to 40% in 2017 was found (p<0.01). Endosonography increased from 19% in 2011 to 32% in 2017 (p<0.01), while mediastinoscopy decreased from 24% in 2011 to 21% in 2017 (p=0.08). Despite these changes, uN2 was stable over the years at 8.7%. 5-year overall survival rate was 41% for pN1 compared to 37% in single node uN2 (p=0.18) and 26% with more than one node uN2 (p<0.01). 5-year overall survival rate of patients with cN1-3 with invasive staging was 44% versus 39% in patients without invasive staging (p=0.12). CONCLUSION: A significant increase in invasive mediastinal nodal staging in patients with resectable NSCLC was found between 2011 and 2017 in the Netherlands. Increasing use of less invasive endosonography prior to (or as a substitute for) surgical staging did not lead to more cases of uN2. Performance of invasive staging indicated a possible overall survival benefit in patients with cN1-3 disease.

Randomised controlled trial of transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND Study).

OBJECTIVE: Non-randomised studies suggest that endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM), but EMR might be more cost-effective and safer. This trial compares the clinical outcome and cost-effectiveness of TEM and EMR for large rectal adenomas. DESIGN: Patients with rectal adenomas ≥3 cm, without malignant features, were randomised (1:1) to EMR or TEM, allowing endoscopic removal of residual adenoma at 3 months. Unexpected malignancies were excluded postrandomisation. Primary outcomes were recurrence within 24 months (aiming to demonstrate non-inferiority of EMR, upper limit 10%) and the number of recurrence-free days alive and out of hospital. RESULTS: Two hundred and four patients were treated in 18 university and community hospitals. Twenty-seven (13%) had unexpected cancer and were excluded from further analysis. Overall recurrence rates were 15% after EMR and 11% after TEM; statistical non-inferiority was not reached. The numbers of recurrence-free days alive and out of hospital were similar (EMR 609±209, TEM 652±188, p=0.16). Complications occurred in 18% (EMR) versus 26% (TEM) (p=0.23), with major complications occurring in 1% (EMR) versus 8% (TEM) (p=0.064). Quality-adjusted life years were equal in both groups. EMR was approximately €3000 cheaper and therefore more cost-effective. CONCLUSION: Under the statistical assumptions of this study, non-inferiority of EMR could not be demonstrated. However, EMR may have potential as the primary method of choice due to a tendency of lower complication rates and a better cost-effectiveness ratio. The high rate of unexpected cancers should be dealt with in further studies.

MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): study protocol of a multicenter randomised controlled trial.

BACKGROUND: In case of suspicious lymph nodes on computed tomography (CT) or fluorodeoxyglucose positron emission tomography (FDG-PET), advanced tumour size or central tumour location in patients with suspected non-small cell lung cancer (NSCLC), Dutch and European guidelines recommend mediastinal staging by endosonography (endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS)) with sampling of mediastinal lymph nodes. If biopsy results from endosonography turn out negative, additional surgical staging of the mediastinum by mediastinoscopy is advised to prevent unnecessary lung resection due to false negative endosonography findings. We hypothesize that omitting mediastinoscopy after negative endosonography in mediastinal staging of NSCLC does not result in an unacceptable percentage of unforeseen N2 disease at surgical resection. In addition, omitting mediastinoscopy comprises no extra waiting time until definite surgery, omits one extra general anaesthesia and hospital admission, and may be associated with lower morbidity and comparable survival. Therefore, this strategy may reduce health care costs and increase quality of life. The aim of this study is to compare the cost-effectiveness and cost-utility of mediastinal staging strategies including and excluding mediastinoscopy. METHODS/DESIGN: This study is a multicenter parallel randomized non-inferiority trial comparing two diagnostic strategies (with or without mediastinoscopy) for mediastinal staging in 360 patients with suspected resectable NSCLC. Patients are eligible for inclusion when they underwent systematic endosonography to evaluate mediastinal lymph nodes including tissue sampling with negative endosonography results. Patients will not be eligible for inclusion when PET/CT demonstrates 'bulky N2-N3' disease or the combination of a highly suspicious as well as irresectable mediastinal lymph node. Primary outcome measure for non-inferiority is the proportion of patients with unforeseen N2 disease at surgery. Secondary outcome measures are hospitalization, morbidity, overall 2-year survival, quality of life, cost-effectiveness and cost-utility. Patients will be followed up 2 years after start of treatment. DISCUSSION: Results of the MEDIASTrial will have immediate impact on national and international guidelines, which are accessible to public, possibly reducing mediastinoscopy as a commonly performed invasive procedure for NSCLC staging and diminishing variation in clinical practice. TRIAL REGISTRATION: The trial is registered at the Netherlands Trial Register on July 6th, 2017 ( NTR 6528 ).

Random biopsies taken during colonoscopic surveillance of patients with longstanding ulcerative colitis: low yield and absence of clinical consequences.

OBJECTIVES: To evaluate the yield and clinical impact of random biopsies taken during colonoscopic surveillance of patients with longstanding ulcerative colitis (UC). METHODS: Retrospective analysis of 1,010 colonoscopies performed from 1998 to 2008. Colonoscopy and pathology reports were reviewed to assess the yield and clinical impact of random biopsies. In total, 475 patients with UC who underwent colonoscopy at the Academic Medical Centre Amsterdam were included in this study. The main outcome measures are neoplasia yield per-colonoscopy and clinical impact per-patient of random biopsies. RESULTS: Of all colonoscopies, 466 were performed for surveillance (in 167 patients) during which 11,772 random biopsies were taken (median 29). Overall, neoplasia was detected in 88 colonoscopies (53 patients): in 75 colonoscopies (85%) by targeted biopsies only and in 8 (9.1%) by both targeted and random biopsies. Neoplasia was detected in random biopsies only in five (5.7%) colonoscopies in four (7.5%) patients. Two of these four patients with neoplasia detected only by random biopsies had visible neoplasia in previous colonoscopies. One patient had unifocal low-grade intraepithelial neoplasia (LGIN) that could not be confirmed in three subsequent colonoscopies. The last patient had multifocal LGIN and suspicious appearing ulcerations. Proctocolectomy confirmed the presence of neoplasia. CONCLUSIONS: The yield of random biopsies is low whereas UC-associated neoplasia is macroscopically visible in 94% of colonoscopies. During 10-year surveillance, neoplasia was detected in only random biopsies in four patients of whom only one had clinical consequences. The low yield and lack of clinical consequences from random biopsies in this high-risk population raise questions about the necessity and cost-effectiveness of their routine use during UC surveillance.

Population-based study on surgical care for primary spontaneous pneumothorax.

OBJECTIVES: The optimal surgical strategy for primary spontaneous pneumothorax remains a matter of debate and variation in surgical practice is expected. This variation may influence clinical outcomes, such as postoperative complications and length of stay. This national population-based registry study provides an overview and extent of variability of current surgical practice and outcomes in the Netherlands. METHODS: To identify national patterns of care and between-hospital variability in the treatment of primary spontaneous pneumothorax, patients who underwent surgical pleurodesis and/or bullectomy between 2014 and 2021, were identified from the Dutch Lung Cancer Audit-Surgery database. The type of surgical intervention, postoperative complications, length of stay and ipsilateral recurrences were recorded. RESULTS AND CONCLUSIONS: Out of 4338 patients, 1851 patients were identified to have primary spontaneous pneumothorax. The median age was 25 years (interquartile range 20-31) and 82% was male. The most performed surgical procedure was bullectomy with pleurodesis (83%). The overall complication rate was 12% (Clavien-Dindo grade ≥III 6%), with the highest recorded incidence for persistent air leak >5 days (5%). Median postoperative length of stay was 4 days (interquartile range 3-6) and 0.7% underwent a repeat pleurodesis for ipsilateral recurrence. Complication rate and length of stay differed considerably between hospitals. There were no differences between the surgical procedures. In the Netherlands, surgical patients with primary spontaneous pneumothorax are preferably treated with bullectomy plus pleurodesis. Postoperative complications and length of stay vary widely and are considerable in this young patient group. This may be reduced by optimization of surgical care.

Multimodal prehabilitation in patients with non-small cell lung cancer: a feasibility study.

Background: Anatomic pulmonary resection is the preferred curative treatment in operable non-small cell lung cancer (NSCLC) but is associated with postoperative complications and inevitable compromise in functional capacity. Preoperative enhancement of functional capacity can be achieved with prehabilitation, yet the window of opportunity in NSCLC patients is small because patients are required to undergo surgery within 3 weeks from diagnosis. The goal of this study was to assess the feasibility of a prehabilitation programme in NSCLC within a 3-week timeframe and its effect on functional capacity-although the study was not powered to confirm improvements in functional capacity. Methods: Prehabilitation consisted of six interventions: exercise programme, nutritional support, mental support, smoking cessation, patient empowerment, and optimisation of respiratory status and was executed in two large teaching hospitals in the Netherlands. Assessments were scheduled at baseline (T0), end of program preoperatively (T1), and 6 weeks postoperatively (T2). Feasibility was defined as ≥80% of participants completing ≥80% of the programme. Functional capacity [6-minute walk test (6MWT), steep ramp test (SRT), one repetition maximum (1RM), maximal inspiratory pressure (MIP), and hand grip strength (HGS)] was evaluated on T1 and T2 compared to T0 using mixed model analyses. Results: In total, 24 patients were included. In 95.8% of patients, the program proved feasible and preoperative functional capacity significantly improved in all pre-specified tests on T1. 1RM sustained improved at T2. Conclusions: Multimodal prehabilitation for lung surgery is feasible within a timeframe of 3 weeks. Even though this study was not powered to confirm it, prehabilitation may improve preoperative functional capacity.

The role of high-resolution endoscopy and narrow-band imaging in the evaluation of upper GI neoplasia in familial adenomatous polyposis.

BACKGROUND: The Spigelman classification stratifies cancer risk in familial adenomatous polyposis (FAP) patients with duodenal adenomatosis. High-resolution endoscopy (HRE) and narrow-band imaging (NBI) may identify lesions at high risk. OBJECTIVE: To compare HRE and NBI for the detection of duodenal and gastric polyps and to characterize duodenal adenomas harboring advanced histology with HRE and NBI. DESIGN: Prospective, nonrandomized, comparative study. Retrospective image evaluation study. SETTING: Tertiary-care center. PATIENTS: Thirty-seven FAP patients undergoing surveillance upper endoscopies. INTERVENTION: HRE endoscopy was followed by NBI. The number of gastric polyps and Spigelman staging were compared. Duodenal polyp images were systematically reviewed in a learning and validation phase. MAIN OUTCOME MEASUREMENTS: Number of gastric and duodenal polyps detected by HRE and NBI and prevalence of specific endoscopic features in duodenal adenomas with advanced histology. RESULTS: NBI did not identify additional gastric polyps but detected more duodenal adenomas in 16 examinations, resulting in upgrades of the Spigelman stage in 2 cases (4.4%). Pictures of 168 duodenal adenomas (44% advanced histology) were assessed. In the learning phase, 3 endoscopic features were associated with advanced histology: white color, enlarged villi, and size ≥1 cm. Only size ≥1 cm was confirmed in the validation phase (odds ratio 3.0; 95% confidence interval, 1.2-7.4). LIMITATIONS: Nonrandomized study, scant number of high-grade dysplasia adenomas. CONCLUSION: Inspection with NBI did not lead to a clinically relevant upgrade in the Spigelman classification and did not improve the detection of gastric polyps in comparison with HRE. The only endoscopic feature that predicted advanced histology of a duodenal adenoma was size ≥1 cm.

Acute pain management after thoracoscopic lung resection: a systematic review and explorative meta-analysis.

OBJECTIVES: Pain after thoracoscopic surgery may increase the incidence of postoperative complications and impair recovery. Guidelines lack consensus regarding postoperative analgesia. We performed a systematic review and meta-analysis to determine the mean pain scores of different analgesic techniques (thoracic epidural analgesia, continuous or single-shot unilateral regional analgesia and only systemic analgesia) after thoracoscopic anatomical lung resection. METHODS: Medline, Embase and Cochrane databases were searched until 1 October 2022. Patients undergoing at least >70% anatomical resections through thoracoscopy reporting postoperative pain scores were included. Due to a high inter-study variability an explorative meta-analysis next to an analytic meta-analysis was performed. The quality of evidence has been evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: A total of 51 studies comprising 5573 patients were included. Mean 24, 48 and 72 h pain scores with 95% confidence interval on a 0-10 scale were calculated. Length of hospital stay, postoperative nausea and vomiting, additional opioids and the use of rescue analgesia were analysed as secondary outcomes. A common-effect size was estimated with an extreme high heterogeneity for which pooling of the studies was not appropriate. An exploratory meta-analysis demonstrated acceptable mean pain scores of Numeric Rating Scale <4 for all analgesic techniques. CONCLUSIONS: This extensive literature review and attempt to pool mean pain scores for meta-analysis demonstrates that unilateral regional analgesia is gaining popularity over thoracic epidural analgesia in thoracoscopic anatomical lung resection, despite great heterogeneity and limitations of current studies precluding such recommendations. PROSPERO REGISTRATION: ID number 205311.

Colorectal Pulmonary Metastases: Pulmonary Metastasectomy or Stereotactic Radiotherapy?

BACKGROUND: Pulmonary metastasectomy and stereotactic ablative radiotherapy (SABR) are both guideline-recommended treatments for selected patients with oligometastatic colorectal pulmonary metastases. However, there is limited evidence comparing these local treatment modalities in similar patient groups. METHODS: We retrospectively reviewed records of consecutive patients treated for colorectal pulmonary metastases with surgical metastasectomy or SABR from 2012 to 2019 at two Dutch referral hospitals that had different approaches toward the local treatment of colorectal pulmonary metastases, one preferring surgery, the other preferring SABR. Two comparable patient groups were identified based on tumor and treatment characteristics. RESULTS: The metastasectomy group comprised 40 patients treated for 69 metastases, and the SABR group had 60 patients who were treated for 90 metastases. Median follow-up was 38 months (IQR: 26-67) in the surgery group and 46 months (IQR: 30-79) in the SABR group. Median OS was 58 months (CI: 20-94) in the metastasectomy group and 70 months (CI: 29-111) in the SABR group (p = 0.23). Five-year local recurrence-free survival (LRFS) was 44% after metastasectomy and 30% after SABR (p = 0.16). Median progression-free survival (PFS) was 15 months (CI: 3-26) in the metastasectomy group and 10 months (CI: 6-13) in the SABR group (p = 0.049). Local recurrence rate was 12.5/7.2% of patients/metastases respectively after metastasectomy and 38.3/31.1% after SABR (p < 0.001). Lower BED Gy10 was correlated with an increased likelihood of recurrence (p = 0.025). Clavien Dindo grade III-V complication rates were 2.5% after metastasectomy and 0% after SABR (p = 0.22). CONCLUSION: In this retrospective cohort study, pulmonary metastasectomy and SABR had comparable overall survival, local recurrence-free survival, and complication rates, despite patients in the SABR group having a significantly lower progression-free survival and local control rate. These data would support a randomized controlled trial comparing surgery and SABR in operable patients with radically resectable colorectal pulmonary metastases.

Pain management after pneumothorax surgery: intercostal nerve block or thoracic epidural analgesia.

OBJECTIVES: In patients undergoing video-assisted thoracoscopic surgery for pneumothorax, the benefits and risks of single-shot intercostal nerve block as loco-regional analgesia are not well known. We retrospectively compared the effectiveness of intercostal nerve blocks as a viable alternative to thoracic epidural analgesia (TEA) regarding pain control and enhanced recovery. METHODS: A retrospective multicentre analysis with single-centre propensity score matching was performed in patients undergoing video-assisted thoracoscopic surgery for pneumothorax receiving either TEA or intercostal nerve block. The primary outcome was a proportion of pain scores ≥4 (scale 0-10) until postoperative day (POD) 3. Secondary outcomes included variation in pain over time, additional opioid use, length of stay, mobility, complications and recurrence rate. RESULTS: In 218 patients, TEA was compared to intercostal nerve block and showed no difference in the proportion of pain scores ≥4 {14.3% [interquartile range (IQR) 0.0-33.3] vs 11.1% (IQR 0.0-27.3) respectively, P = 0.24}, more frequently needed additional opioids on the day of surgery (18% vs 48%) and first POD (20% vs 42%), had a shorter length of stay (4.0 days [IQR 3.0-7.0] vs 3.0 days [IQR 2.8-4.0]) and were significantly more mobile until POD 3, while having similar recurrences. Intercostal nerve block had higher pain scores early in the course whereas TEA had higher late (rebound) pain scores. CONCLUSIONS: In a multimodal analgesic setting with additional opioids, intercostal nerve block shows comparable moments of unacceptable pain from POD 0-3 compared to TEA and is linked to improved mobility. Results require randomized confirmation.

Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer: A Randomized Clinical Trial.

PURPOSE: Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking. METHODS: Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior < .0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality. RESULTS: Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior = .0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior = .0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P = .4940). CONCLUSION: On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.

Endoscopic trimodal imaging detects colonic neoplasia as well as standard video endoscopy.

BACKGROUND & AIMS: Endoscopic trimodal imaging (ETMI) is a novel endoscopic technique that combines high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) that has only been studied in academic settings. We performed a randomized, controlled trial in a nonacademic setting to compare ETMI with standard video endoscopy (SVE) in the detection and differentiation of colorectal lesions. METHODS: The study included 234 patients scheduled to receive colonoscopy who were randomly assigned to undergo a colonoscopy in tandem with either ETMI or SVE. In the ETMI group (n=118), first examination was performed using HRE, followed by AFI. In the other group, both examinations were performed using SVE (n=116). In the ETMI group, detected lesions were differentiated using AFI and NBI. RESULTS: In the ETMI group, 87 adenomas were detected in the first examination (with HRE), and then 34 adenomas were detected during second inspection (with AFI). In the SVE group, 79 adenomas were detected during the first inspection, and then 33 adenomas were detected during the second inspection. Adenoma detection rates did not differ significantly between the 2 groups (ETMI: 1.03 vs SVE: 0.97, P=.360). The adenoma miss-rate was 29% for HRE and 28% for SVE. The sensitivity, specificity, and accuracy of NBI in differentiating adenomas from nonadenomatous lesions were 87%, 63%, and 75%, respectively; corresponding values for AFI were 90%, 37%, and 62%, respectively. CONCLUSIONS: In a nonacademic setting, ETMI did not improve the detection rate for adenomas compared with SVE. NBI and AFI each differentiated colonic lesions with high levels of sensitivity but low levels of specificity.

Oncological and functional outcomes of transanal total mesorectal excision in a teaching hospital in the Netherlands.

PURPOSE: Transanal total mesorectal excision (TaTME) was developed to overcome surgical difficulties experienced in distal pelvic dissection. Concerns have been raised about potential worse postoperative functional outcomes after TaTME. Also, the oncological safety was questioned. This study aimed to describe the functional, surgical, oncological outcomes and quality of life (QoL) after TaTME. METHODS: All consecutive TaTME cases for rectal cancer without disseminated disease between December 2016 and April 2019 were included. The Wexner incontinence score, low anterior resection syndrome (LARS) score, fecal incontinence-related QoL, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-core questionnaire and 29-item module (EORTC QLQ-C30/CR29) were collected. Kaplan-Meier analysis was used to calculate local recurrence-free survival. RESULTS: Thirty patients were eligible for analysis of which 23 received questionnaires. Response rate was 74%. After a median follow-up of respectively 20.0 and 23.0 months for functional and oncological outcomes, the median (interquartile range) of Wexner incontinence and LARS scores were 9.0 (7.0-12.0) and 33.1 (25.0-39.0). Major LARS was present in 73.3%. Fecal incontinence, general and colorectal-specific QoL subdomains that are associated with poor bowel function scored in line with previously reported data. The 2-year actuarial cumulative local recurrence rate was 3.7% (95% confidence interval, 2.4%-5.0%). CONCLUSION: TaTME may lead to significant functional impairments. Patients should receive preoperative counseling on this topic and be fully aware of the potential consequences of their treatment. Oncological data were in line with other short- to moderate-term data and did not show alarming results.

Thoracic surgery in the Netherlands.

The purpose of this article, part of the Thoracic Surgery Worldwide series, is to provide a descriptive review of how thoracic surgery is organized in the Netherlands. General information is provided on the Dutch healthcare system, as well as on how Dutch thoracic surgeons are organized and trained. Additionally, this study provides information on our national quality surveillance system, an overview of the most common thoracic surgeries performed in our country, and details of academic research conducted by Dutch medical specialists. Furthermore, we discuss current challenges and future perspectives. In the Netherlands general thoracic surgical procedures are performed by approximately 110 general thoracic surgeons and 25 of the 135 cardiothoracic surgeons. Dutch thoracic surgeons provide minimally invasive lung surgery, chest wall surgery, thymic and mediastinal surgery, and surgical diagnosis and treatment of pleural disorders. Some recently published data on hospital mortality and postoperative adverse events of thoracic surgeries are reported. Furthermore, the structure of the thoracic surgical education and training program is discussed, highlighting the particular structure of two educational programs for thoracic surgery via a general thoracic and cardiothoracic surgery program. To assure high-quality surgical care, the Netherlands has a well-structured national quality surveillance system, involving frequent site visits and mandatory participation in the national lung cancer surgery registry for all hospitals. In terms of academic research, the Netherlands ranked 14th worldwide on number of clinical trials conducted across all medical disciplines in 2021. Furthermore, several thoracic-related (inter-)national multicenter randomized trials which are currently performed and initiated by Dutch hospital research groups are mentioned. Finally, future challenges and advances of Dutch thoracic surgery are addressed, including the implementation of lung cancer screening, imbalanced labor market, and centralization of care.

Patients' Preferences Regarding Invasive Mediastinal Nodal Staging of Resectable Lung Cancer.

BACKGROUND: Variability in practice and ongoing debate on optimal invasive mediastinal staging of patients with resectable non-small cell lung cancer (NSCLC) are widely described in the literature. Patients' preferences on this topic have, however, been underexposed so far. METHODS: An internet-based questionnaire was distributed among MEDIASTrial participants (NTR6528, randomization of patients to mediastinoscopy or not in the case of negative endosonography). Literature, expert opinion and patient interviews resulted in five attributes: the risk of a futile lung resection (oncologically futile in case of unforeseen N2 disease), the length of the staging period, resection of the primary tumor, complications of staging procedures and the mediastinoscopy scar. The relative importance (RI) of each attribute was assessed by using adaptive conjoint analysis and hierarchical Bayes estimation. A treatment trade-off was used to examine the acceptable proportion of avoided futile lung resections to cover the burden of confirmatory mediastinoscopy. RESULTS: Ninety-seven patients completed the questionnaire (57%). The length of the staging period was significantly the most important attribute (RI 26.24; 95% CI: 25.05-27.43), followed by the risk of a futile surgical lung resection (RI 23.44; 95% CI: 22.28-24.60) and resection of the primary tumor (RI 22.21; 95% CI: 21.09-23.33). Avoidance of 7% (IQR 1- >14%) futile lung resections would cover the burden of confirmatory mediastinoscopy, with a dichotomy among patients always (39%) or never (38%) willing to undergo confirmatory mediastinoscopy after N2 and N3-negative endosonography. CONCLUSION: Although a strong dichotomy among patients always or never willing to undergo confirmatory mediastinoscopy was found, the length of the staging period was the most important attribute in invasive mediastinal staging according to patients with resectable NSCLC. TRIAL REGISTRATION: Not applicable.

MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): a statistical analysis plan.

BACKGROUND: Invasive mediastinal nodal staging is recommended by guidelines in selected patients with resectable non-small cell lung cancer (NSCLC). Endosonography is recommended as initial staging technique, followed by confirmatory mediastinoscopy in case of negative N2 or N3 cytology after endosonography. Confirmatory mediastinoscopy however is under debate owing its limited additional diagnostic value, its associated morbidity and its delay in the start of lung cancer treatment. The MEDIASTrial examines whether confirmatory mediastinoscopy can be safely omitted after negative endosonography in mediastinal nodal staging of NSCLC. The present work is the proposed statistical analysis plan of the clinical consequences of omitting mediastinoscopy, which is submitted before closure of the MEDIASTrial and before knowledge of any results was done to enhance transparency of scientific behaviour. METHODS: The primary outcome measure of this non-inferiority trial will be unforeseen N2 disease resulting from lobe-specific mediastinal lymph node dissection. For non-inferiority, the upper limit of the 95% confidence interval of the unforeseen N2 rate in the group without mediastinoscopy should not exceed 14.3% in order to probably have no negative impact on survival. Since this is a non-inferiority trial, both an intention to treat (ITT) and a per protocol (PP) analyses will be done. The ITT and the PP analyses should both indicate non-inferiority before the diagnostic strategy omitting mediastinoscopy will be interpreted as non-inferior to the strategy with mediastinoscopy. Secondary outcome measures include 30-day major morbidity and mortality, the total number of days of hospital care, overall and disease free 2-year survival, generic and disease-specific health related quality of life and cost-effectiveness and cost-utility of staging strategies with and without mediastinoscopy. DISCUSSION: The MEDIASTrial will determine if confirmatory mediastinoscopy can be omitted after tumour negative systematic endosonography in invasive mediastinal staging of patients with resectable NSCLC. TRIAL REGISTRATION: Netherlands Trial Register NL6344/NTR6528 . Registered on 2017 July 06.

Randomized, blinded comparison of transgastric, transcolonic, and laparoscopic peritoneoscopy for the detection of peritoneal metastases in a human cadaver model.

BACKGROUND: Natural orifice transluminal endoscopic surgery peritoneoscopy may be able to replace laparoscopic peritoneoscopy (LAP) for staging of GI malignancies if it is proven to be equally accurate and safe. OBJECTIVE: To compare transgastric peritoneoscopy (TGP) and transcolonic peritoneoscopy (TCP) to LAP, pairwise, in a randomized, blinded (to location and number of beads) human cadaver model with simulated peritoneal metastases. DESIGN: Metastases were simulated by 2.5-mm, color-coded beads, which were placed into the peritoneal cavity via an open approach. In previous porcine experiments, LAP resulted in a yield of 95%. By using a noninferiority design with a margin of equivalence of 15%, we needed a sample size of 34 beads for 80% power. Randomization was performed for number and location of beads. Eighteen experiments were performed on 6 fresh-frozen human cadavers. SETTING: Experimental surgical laboratory. INTERVENTION: LAP, TGP, and TCP were performed in randomized order by one of two surgeons/endoscopists blinded for location and number of beads. MAIN OUTCOME MEASUREMENTS: Number of beads detected and touched. RESULTS: LAP found and touched 33 beads (yield 97%), TGP 26 beads (76%; difference in yield vs LAP was -20.5 [95% CI, -26.3 to -9.27]), and TCP 29 beads (85%; difference in yield vs LAP was -11.8 [95% CI, -14.6 to 4.98]). Beads that were missed were mostly located at the inferior liver surface: TGP missed 6 of 9 of these beads (67%), TCP 4 of 9 (44%). LIMITATIONS: Cadaver model. CONCLUSION: In this prospective, blinded, comparative trial in a human cadaver model, TCP was comparable to LAP in detecting simulated metastases. TGP was inferior to LAP. Future development should focus on improved visualization of the inferior surface of the liver.

Adherence to the mediastinal staging guideline and unforeseen N2 disease in patients with resectable non-small cell lung cancer: Nationwide results from the Dutch Lung Cancer Audit - Surgery.

OBJECTIVES: Invasive mediastinal staging is advised by guidelines in patients with resectable non-small cell lung cancer (NSCLC) and suspicious lymph nodes (cN1-3) or for central, FDG-non-avid or peripheral tumours >3 cm. Our objective was to assess current guideline adherence and consequent unforeseen N2 disease (uN2) in NSCLC patients having various indications for mediastinal staging. MATERIALS AND METHODS: We analysed the Dutch Lung Cancer Audit - Surgery data of all patients who underwent a primary lung resection with lymph node dissection for NSCLC in 2017-2018. Based on the 2015 ESTS-ERS-ESGE guideline we assessed the use of initial endosonography and confirmatory mediastinoscopy as well as uN2 rates. RESULTS: A total of 2238 patients were analysed. 43 % (95 %-CI: 41-45) underwent initial endosonography followed by a confirmatory mediastinoscopy in 44 % (95 %-CI:40-47) of them, resulting in a 19 % (95 %-CI: 17-20) rate of properly staged patient according to the guidelines. uN2 was demonstrated in 12.5 % (95 %-CI: 9.7-16.0) of correctly staged patients compared to 10.9 % (95 %-CI: 9.6-12.4) who were not (p = .36). The highest uN2 rate was found in cN1-3 patients who were not staged (23.0 %, 95 %-CI: 16.4-31.2) compared to 13.0 % (95 %-CI: 9.7-17.1) who were (p = .01). CONCLUSION: Guideline adherence in Dutch NSCLC patients with an indication for invasive mediastinal staging is poor. The highest uN2 rate was found in unstaged cN1-3 patients, suggesting that this subgroup may benefit from an appropriate staging conform guidelines.

Clinical evaluation of endoscopic trimodal imaging for the detection and differentiation of colonic polyps.

BACKGROUND & AIMS: Endoscopic trimodal imaging (ETMI) incorporates high-resolution endoscopy (HRE) and autofluorescence imaging (AFI) for adenoma detection, and narrow-band imaging (NBI) for differentiation of adenomas from nonneoplastic polyps. The aim of this study was to compare AFI with HRE for adenoma detection and to assess the diagnostic accuracy of NBI for differentiation of polyps. This was a randomized trial of tandem colonoscopies. The study was performed at the Academic Medical Center in Amsterdam. METHODS: One hundred patients underwent colonoscopy with ETMI. Each colonic segment was examined twice for polyps, once with HRE and once with AFI, in random order per patient. All detected polyps were assessed with NBI for pit pattern and with AFI for color, and subsequently removed. Histopathology served as the gold standard for diagnosis. The main outcome measures of this study were adenoma miss-rates of AFI and HRE, and diagnostic accuracy of NBI and AFI for differentiating adenomas from nonneoplastic polyps. RESULTS: Among 50 patients examined with AFI first, 32 adenomas were detected initially. Subsequent inspection with HRE identified 8 additional adenomas. Among 50 patients examined with HRE first, 35 adenomas were detected initially. Successive AFI yielded 14 additional adenomas. The adenoma miss-rates of AFI and HRE therefore were 20% and 29%, respectively (P = .351). The sensitivity, specificity, and overall accuracy of NBI for differentiation were 90%, 70%, and 79%, respectively; corresponding figures for AFI were 99%, 35%, and 63%, respectively. CONCLUSIONS: The overall adenoma miss-rate was 25%; AFI did not significantly reduce the adenoma miss-rate compared with HRE. Both NBI and AFI had a disappointing diagnostic accuracy for polyp differentiation, although AFI had a high sensitivity.