Development and evaluation of a virtual knowledge assessment tool for transanal total mesorectal excision.

BACKGROUND: Transanal total mesorectal excision (TATME) is difficult to learn and can result in serious complications. Current paradigms for assessing performance and competency may be insufficient. This study aims to develop and provide preliminary validity evidence for a TATME virtual assessment tool (TATME-VAT) to assess the cognitive skills necessary to safely complete TATME dissection. METHODS: Participants from North America, Europe, Japan and China completed the test via an interactive online platform between 11/2019 and 05/2020. They were grouped into expert, experienced and novice surgeons depending on the number of independently performed TATMEs. TATME-VAT is a 24-item web-based assessment evaluating advanced cognitive skills, designed according to a blueprint from consensus guidelines. Eight items were multiple choice questions. Sixteen items required making annotations on still frames of TATME videos (VCT) and were scored using a validated algorithm derived from experts' responses. Annotation (range 0-100), multiple choice (range 0-100), and overall scores (sum of annotation and multiple-choice scores, normalized to µ = 50 and σ = 10) were reported. RESULTS: There were significant differences between the expert, experienced, and novice groups for the annotation (p < 0.001), multiple-choice (p < 0.001), and overall scores (p < 0.001). The annotation (p = 0.439) and overall (p = 0.152) scores were similar between the experienced and novice groups. Annotation scores were higher in participants with 51 or more vs. 30-50 vs. less than 30 cases. Scores were also lower in users with a self-reported recent complication vs. those without. CONCLUSIONS: This study describes the development of an interactive video-based virtual assessment tool for TATME dissection and provides initial validity evidence for its use.

P338: summarizing measures of proficiency in transanal total mesorectal excision-a systematic review.

INTRODUCTION: Transanal total mesorectal excision (TaTME) is technically challenging even for experienced colorectal surgeons and there may be a higher risk of complications during learning. Determining when a surgeon is ready to safely perform this technique independently remains a matter of debate. Therefore, the objective of this study was to systematically summarize the available evidence regarding measures of proficiency in TaTME for rectal adenocarcinoma. METHODS: A systematic search of MEDLINE, Embase, PubMed Epub records, Biosis previews, Scopus, and Cochrane Library databases was performed according to PRISMA guidelines. All English and French language studies published between 2010 and 2018 that described proficiency metrics for TaTME were included. Study heterogeneity precluded meta-analysis, and therefore qualitative synthesis was performed. The primary outcomes were the methodology and measures used to define proficiency, and the number of cases needed to achieve proficiency. RESULTS: Of 994 citations, five studies met inclusion criteria. Of these, only two used objective measures to define proficiency. These studies evaluated patient outcomes and defined proficiency through cumulative sum (CUSUM) analysis of the primary outcome(s): post-operative complications and TME quality. Two studies reported expert consensus to establish recommendations using a combination of electronic survey distributed to colorectal surgeons and consensus conferences with TaTME experts from 7 to 8 different countries. One study defined the learning phase as 16 months of TaTME practice, or the first 27 cases. Stated case volumes needed to achieve proficiency varied widely. Studies using objective outcome measures reported threshold volumes of 40 and 51 cases, respectively, while expert consensus studies recommended needing 6-30 procedures. CONCLUSIONS: Significant heterogeneity exists regarding the determination of proficiency benchmarks for TaTME. Expert consensus documents recommend lower case numbers to obtain proficiency than those defined by objective measures, suggesting greater experience may be required than generally thought.

Pelvic dimensions on preoperative imaging can identify poor-quality resections after laparoscopic low anterior resection for mid- and low rectal cancer.

BACKGROUND: High-quality surgery is essential for optimal oncologic outcomes in rectal cancer, but total mesorectal excision (TME) can be difficult for mid- and low rectal cancers. Preoperative identification of patients at risk for difficult TME may change the operative approach. The objective of this study was to determine if MRI pelvimetry can predict poor-quality surgery in patients undergoing laparoscopic low anterior resection (LAR) for mid- and low rectal cancer. METHODS: All patients undergoing laparoscopic LAR for rectal cancer ≤ 9 cm from the anal verge at a single tertiary care referral center from 2011 to 2017 were retrospectively reviewed. Pelvic dimensions were measured from preoperative staging MRI on sagittal and axial views. Pelvimetry variables were all dichotomized based on median values. Exploratory factor analysis then identified the most relevant variables for regression analysis. The primary outcome was poor-quality resection, defined as an incomplete mesorectal grade, or involved circumferential (CRM) or distal (DRM) resection margins. RESULTS: There were 92 patients included in this study, of which 70% were male, the mean BMI was 26.0 kg/m2, and the mean tumor height was 6.6 cm. Preoperative (chemo)radiotherapy was administered in 70%, and the pathologic T-stage was T3/T4 in 41%. The overall incidence of poor-quality resection was 17%, including 13% incomplete TME, 7% involved CRM, and 1% involved DRM. Factor analysis identified S1-pubic symphysis and the angle between S1 and S5-bottom of symphysis (angle ABD) as relevant variables. After adjusting for pathologic T-stage, BMI, and tumor height, a S1-S5-bottom of symphysis angle > 74.3° (OR 6.19, 95% CI 1.18-32.37) independently predicted poor-quality resection. CONCLUSIONS: MRI pelvimetry can identify patients at risk for a poor-quality resection after laparoscopic proctectomy for mid- and low rectal cancer. These patients may benefit from the selective use of more advanced access methods to improve surgical resection quality.

Metabolic profiling of synovial fluid in a unilateral ovine model of anterior cruciate ligament reconstruction of the knee suggests biomarkers for early osteoarthritis.

Joint injuries and subsequent osteoarthritis (OA) are the leading causes of chronic joint disease. In this work, we explore the possibility of applying magnetic resonance spectroscopy-based metabolomics to detect host responses to an anterior cruciate ligament (ACL) reconstruction injury in synovial fluid in an ovine model. Using multivariate statistical analysis, we were able to distinguish post-injury joint samples (ACL and sham surgery) from the uninjured control samples, and as well the ACL surgical samples from sham surgery. In all samples there were 65 metabolites quantified, of which six could be suggested as biomarkers for early post-injury degenerative changes in the knee joints: isobutyrate, glucose, hydroxyproline, asparagine, serine, and uridine. Our results raise a cautionary note indicating that surgical interventions into the knee can result in metabolic alterations that need to be distinguished from those caused by the early onset of OA. Our findings illustrate the potential application of metabolomics as a diagnostic and prognostic tool for detection of injuries to the knee joint. The ability to detect a unique pattern of metabolic changes in the synovial fluid of sheep offers the possibility of extending the approach to precision medicine protocols in patient populations in the future.

Sleeve gastrectomy and gastroesophageal reflux disease.

Bariatric surgery, when combined with lifestyle and medical interventions, is a common and successful treatment modality in the obese patient. Laparoscopic sleeve gastrectomy is one such procedure that has increased in popularity as a definitive bariatric operation. Although laparoscopic sleeve gastrectomy has been shown to be effective in producing weight loss and improving type 2 diabetes mellitus, its effect on gastroesophageal reflux disease (GERD) has been inconsistent. This paper aims to summarize the available literature regarding GERD prevalence following laparoscopic sleeve gastrectomy, 8 studies demonstrate increased GERD prevalence, and 5 demonstrate decreased GERD prevalence following laparoscopic sleeve gastrectomy. The relationship between GERD and SG is complex and no clear relationship exists. The anatomic and physiologic changes caused by laparoscopic sleeve gastrectomy are discussed in the context of these inconsistent results.

Cyclic Tritrpticin Analogs with Distinct Biological Activities.

Tritrpticin is a Trp-, Arg-, and Pro-rich cathelicidin peptide with promising antimicrobial activity. Cyclic analogs of tritrpticin were designed using two different approaches: circularization of the backbone by a head-to-tail peptide bond (TritrpCyc) or disulfide bridging between two Cys residues introduced at the termini of the peptide (TritrpDisu). Compared to the parent peptide, TritrpCyc has greatly improved therapeutic potential, showing stronger bactericidal activities and diminished hemolytic activity. Unexpectedly, the opposite effect was observed for TritrpDisu, which has lost its antimicrobial activity and is very hemolytic. In a membrane mimetic environment, NMR spectra show that TritrpDisu adopts an amphipathic turn-turn structure similar to linear tritrpticin. The structure of membrane-bound TritrpCyc has some similarity to that of TritrpDisu; however, the lipid interactions were not sufficient to restrain the structure of the former peptide in a single well-defined conformation. To help explain the distinct biological properties of the analogs, experiments investigating alternative antimicrobial targets were pursued: the membrane bilayer, lipopolysaccharides, and DNA. Although the hemolytic activity of TritrpDisu can be explained by the peptide's ability to induce higher leakage from the model mammalian membranes, TritrpCyc and TritrpDisu show no significant differences in these functional assays. Overall, our studies show that TritrpCyc holds great promise as a candidate for further development toward antimicrobial therapy.

Serum stabilities of short tryptophan- and arginine-rich antimicrobial peptide analogs.

BACKGROUND: Several short antimicrobial peptides that are rich in tryptophan and arginine residues were designed with a series of simple modifications such as end capping and cyclization. The two sets of hexapeptides are based on the Trp- and Arg-rich primary sequences from the "antimicrobial centre" of bovine lactoferricin as well as an antimicrobial sequence obtained through the screening of a hexapeptide combinatorial library. METHODOLOGY/PRINCIPAL FINDINGS: HPLC, mass spectrometry and antimicrobial assays were carried out to explore the consequences of the modifications on the serum stability and microbicidal activity of the peptides. The results show that C-terminal amidation increases the antimicrobial activity but that it makes little difference to its proteolytic degradation in human serum. On the other hand, N-terminal acetylation decreases the peptide activities but significantly increases their protease resistance. Peptide cyclization of the hexameric peptides was found to be highly effective for both serum stability and antimicrobial activity. However the two cyclization strategies employed have different effects, with disulfide cyclization resulting in more active peptides while backbone cyclization results in more proteolytically stable peptides. However, the benefit of backbone cyclization did not extend to longer 11-mer peptides derived from the same region of lactoferricin. Mass spectrometry data support the serum stability assay results and allowed us to determine preferred proteolysis sites in the peptides. Furthermore, isothermal titration calorimetry experiments showed that the peptides all had weak interactions with albumin, the most abundant protein in human serum. CONCLUSIONS/SIGNIFICANCE: Taken together, the results provide insight into the behavior of the peptides in human serum and will therefore aid in advancing antimicrobial peptide design towards systemic applications.