Proposal for a 10-high-power-fields scoring method for the assessment of tumor budding in colorectal cancer

Although tumor budding is linked to adverse prognosis in colorectal cancer, it remains largely unreported in daily diagnostic work due to the absence of a standardized scoring method. Our aim was to assess the inter-observer agreement of a novel 10-high-power-fields method for assessment of tumor budding at the invasive front and to confirm the prognostic value of tumor budding in our setting of colorectal cancers. Whole tissue sections of 215 colorectal cancers with full clinico-pathological and follow-up information were stained with cytokeratin AE1/AE3 antibody. Presence of buds was scored across 10-high-power fields at the invasive front by two pathologists and two additional observers were asked to score 50 cases of tumor budding randomly selected from the larger cohort. The measurements were correlated to the patient and tumor characteristics. Inter-observer agreement and correlation between observers' scores were excellent (P<0.0001; intraclass correlation coefficient=0.96). A test subgroup of 65 patients (30%) was used to define a valid cutoff score for high-grade tumor budding and the remaining 70% of the patients were entered into the analysis. High-grade budding was defined as an average of ≥10 buds across 10-high-power fields. High-grade budding was associated with a higher tumor grade (P<0.0001), higher TNM stage (P=0.0003), vascular invasion (P<0.0001), infiltrating tumor border configuration (P<0.0001) and reduced survival (P<0.0001). Multivariate analysis confirmed its independent prognostic effect (P=0.007) when adjusting for TNM stage and adjuvant therapy. Using 10-high-power fields for evaluating tumor budding has independent prognostic value and shows excellent inter-observer agreement. Like the BRE and Gleason scores in breast and prostate cancers, respectively, tumor budding could be a basis for a prognostic score in colorectal cancer.

Affinity retardation chromatography: characterization of the method and its application. The description of low affinity laminin self-interactions.

Affinity retardation chromatography (ARC), a method for the examination of low-affinity interactions, is mathematically described in order to characterize the method itself and to estimate binding coefficients of self-assembly domains of basement membrane protein laminin. Affinity retardation was determined by comparing the elutions on a "binding" and on a "nonreacting" column. It depends on the binding coefficient, the concentrations of both ligands, and the nonbinding elution position. Half maximal binding of the NH2-terminal domain of laminin B1-short arm to the A- and/or B2-short arms was estimated to occur at 10-17 microM for noncooperative and at < or = 3 microM for cooperative binding. A model of the laminin polymerization, postulating two levels of cooperative binding behavior, is described.

Virtual tissue alignment and cutting plane definition--a new method to obtain optimal longitudinal histological sections.

Histomorphometric evaluation of the buccal aspects of periodontal tissues in rodents requires reproducible alignment of maxillae and highly precise sections containing central sections of buccal roots; this is a cumbersome and technically sensitive process due to the small specimen size. The aim of the present report is to describe and analyze a method to transfer virtual sections of micro-computer tomographic (CT)-generated image stacks to the microtome for undecalcified histological processing and to describe the anatomy of the periodontium in rat molars. A total of 84 undecalcified sections of all buccal roots of seven untreated rats was analyzed. The accuracy of section coordinate transfer from virtual micro-CT slice to the histological slice, right-left side differences and the measurement error for linear and angular measurements on micro-CT and on histological micrographs were calculated using the Bland-Altman method, interclass correlation coefficient and the method of moments estimator. Also, manual alignment of the micro-CT-scanned rat maxilla was compared with multiplanar computer-reconstructed alignment. The supra alveolar rat anatomy is rather similar to human anatomy, whereas the alveolar bone is of compact type and the keratinized gingival epithelium bends apical to join the junctional epithelium. The high methodological standardization presented herein ensures retrieval of histological slices with excellent display of anatomical microstructures, in a reproducible manner, minimizes random errors, and thereby may contribute to the reduction of number of animals needed.

Development and validation of a quantitative method to assess pedicle screw loosening in posterior spine instrumentation on plain radiographs.

PURPOSE Currently, the diagnosis of pedicle screw (PS) loosening is based on a subjectively assessed halo sign, that is, a radiolucent line around the implant wider than 1 mm in plain radiographs. We aimed at development and validation of a quantitative method to diagnose PS loosening on radiographs. METHODS Between 11/2004 and 1/2010 36 consecutive patients treated with thoraco-lumbar spine fusion with PS instrumentation without PS loosening were compared with 37 other patients who developed a clinically manifesting PS loosening. Three different angles were measured and compared regarding their capability to discriminate the loosened PS over the postoperative course. The inter-observer invariance was tested and a receiver operating characteristics curve analysis was performed. RESULTS The angle measured between the PS axis and the cranial endplate was significantly different between the early and all later postoperative images. The Spearman correlation coefficient for the measurements of two observers at each postoperative time point ranged between 0.89 at 2 weeks to 0.94 at 2 months and 1 year postoperative. The angle change of 1.9° between immediate postoperative and 6-month postoperative was 75% sensitive and 89% specific for the identification of loosened screws (AUC = 0.82). DISCUSSION The angle between the PS axis and the cranial endplate showed good ability to change in PS loosening. A change of this angle of at least 2° had a relatively high sensitivity and specificity to diagnose screw loosening.

Assessing distractors and teamwork during surgery: developing an event-based method for direct observation

OBJECTIVE: To develop a behavioural observation method to simultaneously assess distractors and communication/teamwork during surgical procedures through direct, on-site observations; to establish the reliability of the method for long (>3 h) procedures. METHODS: Observational categories for an event-based coding system were developed based on expert interviews, observations and a literature review. Using Cohen's κ and the intraclass correlation coefficient, interobserver agreement was assessed for 29 procedures. Agreement was calculated for the entire surgery, and for the 1st hour. In addition, interobserver agreement was assessed between two tired observers and between a tired and a non-tired observer after 3 h of surgery. RESULTS: The observational system has five codes for distractors (door openings, noise distractors, technical distractors, side conversations and interruptions), eight codes for communication/teamwork (case-relevant communication, teaching, leadership, problem solving, case-irrelevant communication, laughter, tension and communication with external visitors) and five contextual codes (incision, last stitch, personnel changes in the sterile team, location changes around the table and incidents). Based on 5-min intervals, Cohen's κ was good to excellent for distractors (0.74-0.98) and for communication/teamwork (0.70-1). Based on frequency counts, intraclass correlation coefficient was excellent for distractors (0.86-0.99) and good to excellent for communication/teamwork (0.45-0.99). After 3 h of surgery, Cohen's κ was 0.78-0.93 for distractors, and 0.79-1 for communication/teamwork. DISCUSSION: The observational method developed allows a single observer to simultaneously assess distractors and communication/teamwork. Even for long procedures, high interobserver agreement can be achieved. Data collected with this method allow for investigating separate or combined effects of distractions and communication/teamwork on surgical performance and patient outcomes.

Computer-based summative assessment of clinical reasoning in clerkships: A mixed-method comparison of key feature problems with case-based multiple choice questions

Background: It is yet unclear if there are differences between using electronic key feature problems (KFPs) or electronic case-based multiple choice questions (cbMCQ) for the assessment of clinical decision making. Summary of Work: Fifth year medical students were exposed to clerkships which ended with a summative exam. Assessment of knowledge per exam was done by 6-9 KFPs, 9-20 cbMCQ and 9-28 MC questions. Each KFP consisted of a case vignette and three key features (KF) using “long menu” as question format. We sought students’ perceptions of the KFPs and cbMCQs in focus groups (n of students=39). Furthermore statistical data of 11 exams (n of students=377) concerning the KFPs and (cb)MCQs were compared. Summary of Results: The analysis of the focus groups resulted in four themes reflecting students’ perceptions of KFPs and their comparison with (cb)MCQ: KFPs were perceived as (i) more realistic, (ii) more difficult, (iii) more motivating for the intense study of clinical reasoning than (cb)MCQ and (iv) showed an overall good acceptance when some preconditions are taken into account. The statistical analysis revealed that there was no difference in difficulty; however KFP showed a higher discrimination and reliability (G-coefficient) even when corrected for testing times. Correlation of the different exam parts was intermediate. Conclusions: Students perceived the KFPs as more motivating for the study of clinical reasoning. Statistically KFPs showed a higher discrimination and higher reliability than cbMCQs. Take-home messages: Including KFPs with long menu questions into summative clerkship exams seems to offer positive educational effects.

Computerbasierte Prüfung von klinischem Denken in der klinischen Ausbildung: Ein Mixed-Method Vergleich von Key Feature Problemen mit fallbasierten Multiple Choice Typ A Fragen

Fragestellung/Einleitung: Es ist unklar inwiefern Unterschiede bestehen im Einsatz von Key Feature Problemen (KFP) mit Long Menu Fragen und fallbasierten Typ A Fragen (FTA) für die Überprüfung des klinischen Denkens (Clinical Reasoning) in der klinischen Ausbildung von Medizinstudierenden. Methoden: Medizinstudierende des fünften Studienjahres nahmen an ihrer klinischen Pädiatrie-Rotation teil, die mit einer summativen Prüfung endete. Die Überprüfung des Wissen wurde pro Prüfung elektronisch mit 6-9 KFP [1], [3], 9-20 FTA und 9-28 nichtfallbasierten Multiple Choice Fragen (NFTA) durchgeführt. Jedes KFP bestand aus einer Fallvignette und drei Key Features und nutzen ein sog. Long Menu [4] als Antwortformat. Wir untersuchten die Perzeption der KFP und FTA in Focus Gruppen [2] (n of students=39). Weiterhin wurden die statistischen Kennwerte der KFP und FTA von 11 Prüfungen (n of students=377) verglichen. Ergebnisse: Die Analyse der Fokusgruppen resultierte in vier Themen, die die Perzeption der KFP und deren Vergleich mit FTA darstellten: KFP wurden als 1. realistischer, 2. schwerer, und 3. motivierender für das intensive Selbststudium des klinischen Denkens als FTA aufgenommen und zeigten 4. insgesamt eine gute Akzeptanz sofern gewisse Voraussetzungen berücksichtigt werden. Die statistische Auswertung zeigte keinen Unterschied im Schwierigkeitsgrad; jedoch zeigten die KFP eine höhere Diskrimination und Reliabilität (G-coefficient) selbst wenn für die Prüfungszeit korrigiert wurde. Die Korrelation der verschiedenen Prüfungsteile war mittel. Diskussion/Schlussfolgerung: Die Studierenden erfuhren die KFP als motivierenden für das Selbststudium des klinischen Denkens. Statistisch zeigten die KFP eine grössere Diskrimination und höhere Relibilität als die FTA. Der Einbezug von KFP mit Long Menu in Prüfungen des klinischen Studienabschnitts erscheint vielversprechend und einen „educational effect“ zu haben.