Lars Konge

Correlation between human papillomavirus and p16 overexpression in oropharyngeal tumours: a systematic review

Background:A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based on diagnostic measures and definition of p16 overexpression. We evaluated means of p16 and HPV diagnostics, and quantified overexpression of p16 in HPV-positive and -negative OP-SCCs by mode of immunohistochemical staining of carcinoma cells.Methods:PubMed, Embase, and the Cochrane Library were searched from 1980 until October 2012. We applied the following inclusion criteria: a minimum of 20 cases of site-specific OP-SCCs, and HPV and p16 results present. Studies were categorised into three groups based on their definition of p16 overexpression: verbal definition, nuclear and cytoplasmatic staining between 5 and 69%, and ⩾70% staining.Results:We identified 39 studies with available outcome data (n=3926): 22 studies (n=1980) used PCR, 6 studies (n=688) used ISH, and 11 studies (n=1258) used both PCR and ISH for HPV diagnostics. The methods showed similar HPV-positive results. Overall, 52.5% of the cases (n=2062) were HPV positive. As to p16 overexpression, 17 studies (n=1684) used a minimum of 5–69% staining, and 7 studies (n=764) used ⩾70% staining. Fifteen studies (n=1478) referred to a verbal definition. Studies showed high heterogeneity in diagnostics of HPV and definition of p16. The correlation between HPV positivity and p16 overexpression proved best numerically in the group applying ⩾70% staining for p16 overexpression. The group with verbal definitions had a significantly lower false-positive rate, but along with the group applying 5–69% staining showed a worse sensitivity compared with ⩾70% staining.Conclusions:There are substantial differences in how studies diagnose HPV and define p16 overexpression. Numerically, p16 staining is better to predict the presence of HPV (i.e. larger sensitivity), when the cutoff is set at ⩾70% of cytoplasmatic and nuclear staining.

Combined endobronchial and esophageal endosonography for the diagnosis and staging of lung cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS)

This is an official guideline of the European Society of Gastrointestinal Endoscopy (ESGE), produced in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS). It addresses the benefit and burden associated with combined endobronchial and esophageal mediastinal nodal staging of lung cancer. The Scottish Intercollegiate Guidelines Network (SIGN) approach was adopted to define the strength of recommendations and the quality of evidence.The article has been co-published with permission in the European Journal of Cardio-Thoracic Surgery and the European Respiratory Journal. Recommendations 1 For mediastinal nodal staging in patients with suspected or proven non-small-cell lung cancer (NSCLC) with abnormal mediastinal and/or hilar nodes at computed tomography (CT) and/or positron emission tomography (PET), endosonography is recommended over surgical staging as the initial procedure (Recommendation grade A). The combination of endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic (esophageal) ultrasound with fine needle aspiration, with use of a gastrointestinal (EUS-FNA) or EBUS (EUS-B-FNA) scope, is preferred over either test alone (Recommendation grade C). If the combination of EBUS and EUS-(B) is not available, we suggest that EBUS alone is acceptable (Recommendation grade C).Subsequent surgical staging is recommended, when endosonography does not show malignant nodal involvement (Recommendation grade B). 2 For mediastinal nodal staging in patients with suspected or proven non-small-cell peripheral lung cancer without mediastinal involvement at CT or CT-PET, we suggest that EBUS-TBNA and/or EUS-(B)-FNA should be performed before therapy, provided that one or more of the following conditions is present: (i) enlarged or fluorodeoxyglucose (FDG)-PET-avid ipsilateral hilar nodes; (ii) primary tumor without FDG uptake; (iii) tumor size ≥ 3 cm (Fig. 3a - c) (Recommendation grade C). If endosonography does not show malignant nodal involvement, we suggest that mediastinoscopy is considered, especially in suspected N1 disease (Recommendation grade C).If PET is not available and CT does not reveal enlarged hilar or mediastinal lymph nodes, we suggest performance of EBUS-TBNA and/or EUS-(B)-FNA and/or surgical staging (Recommendation grade C). 3 In patients with suspected or proven < 3 cm peripheral NSCLC with normal mediastinal and hilar nodes at CT and/or PET, we suggest initiation of therapy without further mediastinal staging (Recommendation grade C). 4 For mediastinal staging in patients with centrally located suspected or proven NSCLC without mediastinal or hilar involvement at CT and/or CT-PET, we suggest performance of EBUS-TBNA, with or without EUS-(B)-FNA, in preference to surgical staging (Fig. 4) (Recommendation grade D). If endosonography does not show malignant nodal involvement, mediastinoscopy may be considered (Recommendation grade D). 5 For mediastinal nodal restaging following neoadjuvant therapy, EBUS-TBNA and/or EUS-(B)-FNA is suggested for detection of persistent nodal disease, but, if this is negative, subsequent surgical staging is indicated (Recommendation grade C). 6 A complete assessment of mediastinal and hilar nodal stations, and sampling of at least three different mediastinal nodal stations (4 R, 4 L, 7) (Fig. 1, Fig. 5) is suggested in patients with NSCLC and an abnormal mediastinum by CT or CT-PET (Recommendation grade D). 7 For diagnostic purposes, in patients with a centrally located lung tumor that is not visible at conventional bronchoscopy, endosonography is suggested, provided the tumor is located immediately adjacent to the larger airways (EBUS) or esophagus (EUS-(B)) (Recommendation grade D). 8 In patients with a left adrenal gland suspected for distant metastasis we suggest performance of endoscopic ultrasound fine needle aspiration (EUS-FNA) (Recommendation grade C), while the use of EUS-B with a transgastric approach is at present experimental (Recommendation grade D). 9 For optimal endosonographic staging of lung cancer, we suggest that individual endoscopists should be trained in both EBUS and EUS-B in order to perform complete endoscopic staging in one session (Recommendation grade D). 10 We suggest that new trainees in endosonography should follow a structured training curriculum consisting of simulation-based training followed by supervised practice on patients (Recommendation grade D). 11 We suggest that competency in EBUS-TBNA and EUS-(B)-FNA for staging lung cancer be assessed using available validated assessment tools (Recommendation Grade D).

Reliable and valid assessment of competence in endoscopic ultrasonography and fine-needle aspiration for mediastinal staging of non-small cell lung cancer

BACKGROUND AND STUDY AIMS Fine-needle aspiration (FNA) guided by endoscopic ultrasonography (EUS) is important in mediastinal staging of non-small cell lung cancer (NSCLC). Training standards and implementation strategies of this technique are currently under discussion. The aim of this study was to explore the reliability and validity of a newly developed EUS Assessment Tool (EUSAT) designed to measure competence in EUS - FNA for mediastinal staging of NSCLC. PATIENTS AND METHODS A total of 30 patients with proven or suspected NSCLC underwent EUS - FNA for mediastinal staging by three trainees and three experienced physicians. Their performances were assessed prospectively by three experts in EUS under direct observation and again 2 months later in a blinded fashion using digital video-recordings. Based on the assessments, intra-rater reliability, inter-rater reliability, and construct validity were explored. RESULTS The intra-rater reliability was good (Cronbachs α = 0.80), but comparison of results based on direct observations and blinded video-recordings indicated a significant bias favoring consultants (P = 0.022). Inter-rater reliability was very good (Cronbachs α = 0.93). However, one rater assessing five procedures or two raters each assessing four procedures were necessary to secure a generalizability coefficient of 0.80. The assessment tool demonstrated construct validity by discriminating between trainees and experienced physicians (P = 0.034). CONCLUSIONS Competency in mediastinal staging of NSCLC using EUS and EUS - FNA can be assessed in a reliable and valid way using the EUSAT assessment tool. Measuring and defining competency and training requirements could improve EUS quality and benefit patient care.

Assessment of performance measures and learning curves for use of a virtual‐reality ultrasound simulator in transvaginal ultrasound examination

To assess the validity and reliability of performance measures, develop credible performance standards and explore learning curves for a virtual‐reality simulator designed for transvaginal gynecological ultrasound examination.

Using virtual-reality simulation to assess performance in endobronchial ultrasound.

Background: For optimal treatment of patients with non-small cell lung carcinoma, it is essential to have physicians with competence in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). EBUS training and certification requirements are under discussion and the establishment of basic competence should be based on an objective assessment of performance. Objectives: The aims of this study were to design an evidence-based and credible EBUS certification based on a virtual-reality (VR) EBUS simulator test. Methods: Twenty-two respiratory physicians were divided into 3 groups: experienced EBUS operators (group 1, n = 6), untrained novices (group 2, n = 8) and simulator-trained novices (group 3, n = 8). Each physician performed two standardized simulated EBUS-TBNA procedures. Simulator metrics with discriminatory ability were identified and reliability was explored. Finally, the contrasting-groups method was used to establish a pass/fail standard, and the consequences of this standard were explored. Results: Successfully sampled lymph nodes and procedure time were the only simulator metrics that showed statistically significant differences of p = 0.047 and p = 0.002, respectively. The resulting quality score (QS, i.e. sampled lymph nodes per minute) showed an acceptable reliability and a generalizability coefficient of 0.67. Reliability of 0.8 could be obtained by testing in 4 procedures. Median QS was 0.24 (range 0.21-0.26) and 0.098 (range 0.04-0.21) for groups 1 and 2, respectively (p = 0.001). The resulting pass/fail standard was 0.19. Group 3 had a median posttraining QS of 0.11 (range 0-0.17). None of them met the pass/fail standard. Conclusions: With careful design of standardized tests, a credible standard setting and appropriate transfer studies, VR simulators could be an important first line in credentialing before proceeding to supervised performance on patients.

Video-assisted thoracoscopic surgery lobectomy for lung cancer is associated with a lower 30-day morbidity compared with lobectomy by thoracotomy.

OBJECTIVES Lung cancer is the most common cause of cancer-related deaths worldwide. Survival is highly dependent on surgery. Video-assisted thoracoscopic surgery (VATS) is increasingly chosen over open thoracotomy (OT) because of the possible benefits of the minimally invasive approach. Consequently, our aim was to compare the 30-day morbidity and mortality for lung cancer patients operated by VATS lobectomy or lobectomy by OT. METHOD Data were obtained from prospective national and regional databases, including patients who underwent lobectomy for lung cancer in the eastern part of Denmark from 1 January 2005 to 31 December 2011. All patients operated before 2009 were re-staged according to the latest International Association for the Study of Lung Cancer lung cancer classification. Patient characteristics, comorbidities, pathology and operative data were assessed using an independent samples t-test, Pearsons χ(2), Fishers exact test and Mann-Whitney test. Morbidity was assessed using multinomial logistic regression adjusted for gender, age, cancer stage, forced expiratory volume in 1 s (FEV1), year of surgery and Charlson comorbidity score. RESULTS In total, 1379 patients underwent lobectomy, 785 patients via VATS and 594 patients via thoracotomy. The two groups were similar in gender and FEV1. The patients operated by VATS were older (P < 0.001), and had a lower Charlson comorbidity score (P = 0.034), higher frequency of adenocarcinomas (P < 0.001) and lower cancer stage (P < 0.001). Among the VATS patients, 285 (36.3%) and among the thoracotomy patients, 288 (48.5%) had minor complications (P < 0.001); and 157 (20.0%) VATS patients and 212 (35.7%) thoracotomy patients had major complications (P < 0.001). The 30-day mortality rate was 1% in the VATS group and 1.5% in the thoracotomy group (P = 0.47). Multinomial logistic regression analysis showed that the prevalence of both minor [odds ratio (OR) = 1.51; 95% confidence interval (Cl) = 1.18-1.96] and major complications (OR = 1.91, 95% Cl = 1.44-2.53) was significantly higher for patients who underwent lobectomy via thoracotomy compared with VATS. CONCLUSION Patients undergoing lobectomy via VATS were less likely to have at least one minor complication within the first 30 postoperative days and less likely to have at least one major complication, compared with patients operated by thoracotomy. These findings remained after adjusting for gender, age, FEV1, cancer stage, year of surgery and Charlson comorbidity score.

Combined endobronchial and oesophageal endosonography for the diagnosis and staging of lung cancer. European Society of Gastrointestinal Endoscopy (ESGE) Guideline, in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS)

New guidelines for combined endobronchial and oesophageal mediastinal nodal staging of lung cancer http://ow.ly/MwM4H

The Simulation Centre at Rigshospitalet, Copenhagen, Denmark

The Simulation Centre at Rigshospitalet was officially inaug-urated in December 2013 as part of the Centre for ClinicalEducation (CEKU) in Copenhagen. The advanced technicalsimulations, which constitute the bulk of the activities, havebeen developed gradually since 2006. CEKU is a research,development, and service provider for the pregraduate andpostgraduate health educations at the University of Copenha-gen and the postgraduate medical training at the CapitalRegion. The mission of CEKU, founded in 1995, was to trainmedical students in basic clinical skills as a preparation fortheir clerkships. The courses included basic procedural skills,resuscitation skills, and patient encounter skills trained usingsimulated patients. Over the years, the repertoire of clinicalskills was widened to include a variety of physical examinationskills, ultrasound skills, resuscitation at various levels, inter-professional skills, and patient communication skills, allcourses tailored to students’ academic years.

Simulation-based certification for cataract surgery

To evaluate the EyeSi™ simulator in regard to assessing competence in cataract surgery. The primary objective was to explore all simulator metrics to establish a proficiency‐based test with solid evidence. The secondary objective was to evaluate whether the skill assessment was specific to cataract surgery.

Gender differences in the acquisition of surgical skills: a systematic review

BackgroundFemales are less attracted than males to surgical specialties, which may be due to differences in the acquisition of skills. The aim of this study was to systematically review studies that investigate gender differences in the acquisition of surgical skills.MethodsWe performed a comprehensive database search using relevant search phrases and MeSH terms. We included studies that investigated the role of gender in the acquisition of surgical skills.ResultsOur search yielded 247 studies, 18 of which were found to be eligible and were therefore included. These studies included a total of 2,106 study participants. The studies were qualitatively synthesized in five categories (studies on medical students, studies on both medical students and residents, studies on residents, studies on gender differences in needed physical strength, and studies on other gender-related training conditions). Male medical students tended to outperform females, while no gender differences were found among residents. Gaming experience and interest in surgery correlated with better acquisition of surgical skills, regardless of gender. Although initial levels of surgical abilities seemed lower among females, one-on-one training and instructor feedback worked better on females and were able to help the acquisition of surgical skills at a level that negated measurable gender differences. Female physicians possess the required physical strength for surgical procedures, but may face gender-related challenges in daily clinical practice.ConclusionMedical students are a heterogeneous group with a range of interests and experiences, while surgical residents are more homogeneous perhaps due to selection bias. Gender-related differences are more pronounced among medical students. Future surgical curricula should consider tailoring personalized programs that accommodate more mentoring and one-on-one training for female physicians while giving male physicians more practice opportunities in order to increase the output of surgical training and acquisition of surgical skills.