Sentinel lymph node biopsy in women over 70: Evaluation of rates of axillary staging and impact on adjuvant therapy in elderly women.

BACKGROUND: The 2016 Society of Surgical Oncology Choosing Wisely guidelines recommended against routine sentinel lymph node biopsy in women ≥70 years old with favorable, early-stage breast cancer, as sentinel lymph node biopsy does not decrease recurrence or mortality in these patients. This study's objective was to evaluate the use of sentinel lymph node biopsy and its effect on management in elderly patients. METHODS: A retrospective analysis of female patients ≥70 years old with stage I-II, clinically node-negative, hormone-receptor positive, HER2-negative disease undergoing upfront breast cancer surgery between 2017 and 2019. Primary outcome was rate of sentinel lymph node biopsy. Secondary outcome was effect of sentinel lymph node biopsy on adjuvant therapy. RESULTS: In total, 142 patients were included. Median age was 76 (interquartile range 73-81), and 71.8% underwent lumpectomy. On final pathology, 57.7% had invasive ductal carcinoma, and median tumor size was 15 mm (interquartile range 10-24.3). A total of 118 patients (83.1%) underwent sentinel lymph node biopsy; of these, 27 (22.9%) were positive for N1mi (7 patients) or N1a disease (20 patients). On multivariate regression analysis, patients undergoing sentinel lymph node biopsy were more likely to be younger (odds ratio 0.87, 95% confidence interval 0.78-0.95). The major risk factor for sentinel lymph node biopsy positivity was lymphovascular invasion (odds ratio 13.4, 95% confidence interval 4.57-40.1). Patients with sentinel lymph node biopsy positivity were more likely to receive local adjuvant radiation therapy (odds ratio 4.66, 95% confidence interval 1.49-16.8) and tended to receive more adjuvant regional radiation therapy (75.0% if sentinel lymph node biopsy positive compared with 15.3% if sentinel lymph node biopsy negative, P < .001). CONCLUSION: Despite the 2016 Choosing Wisely guidelines, more than 80% of patients ≥70 years old underwent sentinel lymph node biopsy at our institution. If sentinel lymph node biopsy was positive, this is associated with over 4-fold higher rates of adjuvant radiation therapy.

Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial.

Importance: The overprescription of opioids to surgical patients is recognized as an important factor contributing to the opioid crisis. However, the value of prescribing opioid analgesia (OA) vs opioid-free analgesia (OFA) after postoperative discharge remains uncertain. Objective: To investigate the feasibility of conducting a full-scale randomized clinical trial (RCT) to assess the comparative effectiveness of OA vs OFA after outpatient general surgery. Design, Setting, and Participants: This parallel, 2-group, assessor-blind, pragmatic pilot RCT was conducted from January 29 to September 3, 2020 (last follow-up on October 2, 2020). at 2 university-affiliated hospitals in Montreal, Quebec, Canada. Participants were adult patients (aged ≥18 years) undergoing outpatient abdominal (ie, cholecystectomy, appendectomy, or hernia repair) or breast (ie, partial or total mastectomy) general surgical procedures. Exclusion criteria were contraindications to drugs used in the trial, preoperative opioid use, conditions that could affect assessment of outcomes, and intraoperative or early complications requiring hospitalization. Interventions: Patients were randomized 1:1 to receive OA (around-the-clock nonopioids and opioids for breakthrough pain) or OFA (around-the-clock nonopioids with increasing doses and/or addition of nonopioid medications for breakthrough pain) after postoperative discharge. Main Outcomes and Measures: Main outcomes were a priori RCT feasibility criteria (ie, rates of surgeon agreement, patient eligibility, patient consent, treatment adherence, loss to follow-up, and missing follow-up data). Secondary outcomes included pain intensity and interference, analgesic intake, 30-day unplanned health care use, and adverse events. Between-group comparison of outcomes followed the intention-to-treat principle. Results: A total of 15 surgeons were approached; all (100%; 95% CI, 78%-100%) agreed to have patients recruited and adhered to the study procedures. Rates of patient eligibility and consent were 73% (95% CI, 66%-78%) and 57% (95% CI, 49%-65%), respectively. Seventy-six patients were randomized (39 [51%] to OA and 37 [49%] to OFA) and included in the intention-to-treat analysis (mean [SD] age, 55.5 [14.5] years; 50 [66%] female); 40 (53%) underwent abdominal surgery, and 36 (47%) underwent breast surgery. Seventy-five patients (99%; 95% CI, 93%-100%) adhered to the allocated treatment; 1 patient randomly assigned to OFA received an opioid prescription. Seventeen patients (44%) randomly assigned to OA consumed opioids after discharge. Seventy-three patients (96%; 95% CI, 89%-99%) completed the 30-day follow-up. The rate of missing questionnaires was 37 of 3724 (1%; 95% CI, 0.7%-1.4%). All the a priori RCT feasibility criteria were fulfilled. Conclusions and Relevance: The findings of this pilot RCT support the feasibility of conducting a robust, full-scale RCT to inform evidence-based prescribing of analgesia after outpatient general surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04254679.

Development of a formative feedback tool for transanal total mesorectal excision.

INTRODUCTION: Transanal total mesorectal excision (TaTME) is a novel procedure in the treatment of rectal cancer. Current training models for TaTME suggest a period of proctored cases, but no structured feedback tool exists to guide operators during the learning phase. The objective of this study therefore was to develop a formative feedback tool for the critical steps of the transanal portion of TaTME. METHODS: A two-round Delphi study by TaTME experts was conducted to determine the items to be included in the formative feedback tool. Participants rated each step from a prepared list using a Likert scale from 1 (Not relevant) to 5 (Very relevant) with the option to suggest additional steps. Responses to the first round were presented in the second round, where participants rated the revised list of steps. Consensus was defined as > 80% of participants rating the step as 4 or 5 (out of 5). Items were combined when appropriate to avoid redundancy. Rating anchors describing performance (on a 5-point scale) were then developed for each step. The final tool was recirculated and participants rated the finished product on its feasibility and usefulness. RESULTS: Twenty-six TaTME experts were contacted for participation. Fifteen experts (58%) participated in the first round of the study, and eleven (42%) participated in the second round. The majority (14, 93%) had completed fellowship training in colorectal surgery. The first round of the Delphi study contained 34 items, and 32 items met inclusion criteria after the second round. Redundant items were combined into 15 items that comprised the final tool. Out of eight respondents to the feasibility survey, all believed the feedback tool enhances the feedback of learners and would use it for training purposes if available. CONCLUSION: This work describes the development of a novel consensus-based formative feedback tool specific to TaTME.

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.

Discovery, optimization and validation of an optimal DNA-binding sequence for the Six1 homeodomain transcription factor.

The Six1 transcription factor is a homeodomain protein involved in controlling gene expression during embryonic development. Six1 establishes gene expression profiles that enable skeletal myogenesis and nephrogenesis, among others. While several homeodomain factors have been extensively characterized with regards to their DNA-binding properties, relatively little is known of the properties of Six1. We have used the genomic binding profile of Six1 during the myogenic differentiation of myoblasts to obtain a better understanding of its preferences for recognizing certain DNA sequences. DNA sequence analyses on our genomic binding dataset, combined with biochemical characterization using binding assays, reveal that Six1 has a much broader DNA-binding sequence spectrum than had been previously determined. Moreover, using a position weight matrix optimization algorithm, we generated a highly sensitive and specific matrix that can be used to predict novel Six1-binding sites with highest accuracy. Furthermore, our results support the idea of a mode of DNA recognition by this factor where Six1 itself is sufficient for sequence discrimination, and where Six1 domains outside of its homeodomain contribute to binding site selection. Together, our results provide new light on the properties of this important transcription factor, and will enable more accurate modeling of Six1 function in bioinformatic studies.