Background: We sought to investigate the association between surgical opioid prescriptions and the risk of opioid initiation among opioid-naive spouses. Methods: Patients who underwent surgery for breast or gastrointestinal cancer were identified from the IBM Marketscan database. Multivariable regression analysis was performed to examine the association between surgical opioid prescription and opioid initiation among opioid-na & iuml;ve patient spouses. Results: Among the 9365 individuals included in the analytic cohort, 77.9 % (n 1/4 7300) filled a perioperative opioid prescription. Of note, spouses of patients who received a surgical opioid prescription (6.7 % vs. 4.5 %; p < 0.001) were more likely to begin using opioids. On multivariable analysis, surgical opioid prescription was associated with 61 % (1.61, 95%CI 1.28-2.03) higher odds of opioid initiation among opioid-naive spouses. Conclusion: Surgical opioid prescriptions are associated with an increased risk of opioid initiation among opioidnaive spouses. These findings underscore the importance of counseling on safe opioid use, storage, and disposal for the family.

BACKGROUND:Inflammatory bowel disease may affect the pathogenesis and clinicopathologic course of colorectal cancer. We sought to characterize the impact of inflammatory bowel disease on outcomes after colectomy and/or proctectomy for a malignant indication. METHODS:Patients diagnosed with colorectal cancer as well as a pre-existing comorbid diagnosis of Crohn's disease or ulcerative colitis between 2018 and 2021 were identified from Medicare claims data. The postoperative textbook outcome was defined as the absence of complications, as well as no extended hospital stay, 90-day readmission, or mortality. Postdischarge disposition and expenditures were also examined. RESULTS:Among 191,684 patients with colorectal cancer, 4,770 (2.5%) had a pre-existing diagnosis of inflammatory bowel disease. Patients with inflammatory bowel disease-associated colorectal cancer were less likely to undergo surgical resection (no inflammatory bowel disease: 47.6% vs inflammatory bowel disease: 42.1%; P < .001). Among patients who did undergo colorectal surgery, individuals with inflammatory bowel disease were less likely to achieve a textbook outcome (odds ratio 0.64 [95% confidence interval 0.58-0.70]). In particular, patients with inflammatory bowel disease had higher odds of postoperative complications (odds ratio 1.24 [1.12-1.38]), extended hospital stay (odds ratio 1.41 [1.27-1.58]), and readmission within 90 days (odds ratio 1.56 [1.42-1.72]) (all P < .05). Patients with inflammatory bowel disease-associated colorectal cancer were less likely to be discharged to their home under independent care (odds ratio 0.77 [0.68-0.87]) and had 12.2% higher expenditures, which correlated with whether the patient had a postoperative textbook outcome. CONCLUSION:One in 40 patients with colorectal cancer had concomitant inflammatory bowel disease. Inflammatory bowel disease was associated with a lower probability of achieving ideal postoperative outcomes, higher postdischarge expenditure, as well as worse long-term survival after colorectal cancer resection.

Supplementary fig 1 Flowchart for trial design

Supplementary fig 4 Baseline p-ERK score in Tumor Tissue Correlated to RAS/RAF Mutation Status

Supplementary fig 2 Schema for trial design

Supplementary fig 3 Tumor Regression Grade versus Baseline p-ERK score in Tumor Tissue

Introduction: Rater-based assessment and objective assessment play an important role in evaluating residents’ clinical competencies. We hypothesize that a cumulative sum (CUSUM) chart of operative time is a complement to the assessment of chief general surgery residents’ competencies with ACGME Milestones, aiding residency programs’ determination of graduating residents’ practice readiness. Study Design: We extracted ACGME milestone evaluations of performance of operations and procedures (POP) and three objective metrics (operative time, case type, and case complexity) from three procedures (cholecystectomy, colectomy, and inguinal hernia) performed by three cohorts of residents (N=15) during their PGY4-5. CUSUM charts were computed for each resident on each procedure type. A learning plateau was defined as at least four cases consistently locating around the centerline (target performance) at the end of a CUSUM chart with minimal deviations (range 0-1). Results: All residents reached the ACGME graduation targets for the overall POP by the end of chief year. A total of 2446 cases were included (cholecystectomy N=1234, colectomy N=507, and inguinal hernia N=705). Three CUSUM chart patterns emerged: skewed distribution, bimodal distribution, and peaks-and-valleys distribution. Analysis of CUSUM charts reveal surgery residents’ development process in the OR towards a learning plateau vary and only 46.7% residents reach a learning plateau in all three procedures upon graduation. Conclusions: CUSUM charts of operative time is a complement to the ACGME Milestones evaluations. The use of both may enable residency programs to holistically determine graduating residents’ practice readiness and provide recommendations for their upcoming career/practice transition.

Table showing next generation sequencing of tumor samples

OBJECTIVE:To determine whether an electronic health record (EHR) system can be used to identify cases of aspirin-exacerbated respiratory disease (AERD) in an area outside of a regional referral center with low rates of aspirin desensitization therapy.STUDY DESIGN:Retrospective chart review single academic tertiary care hospital.SETTING:Single-site academic tertiary care hospital.METHODS:Using Epic's SlicerDicer function, an algorithm was created and applied to all patient charts from 2013 to 2021. The algorithm was as follows: "Allergy/Contraindication to NSAIDs OR aspirin" AND "Diagnosis of Nasal polyp AND "Diagnosis of Asthma." Clinical data including demographics, NSAID reaction, and specialist involvement was collected.RESULTS:A total of 54 potential cases of AERD were identified. Thirty-two were determined to have AERD after chart review, yet 12 of these patients (37.5%) had no mention of AERD within the chart. The 54 patients were stratified into 2 cohorts based on reaction to NSAIDs: respiratory (n = 29) or unspecified (n = 25). Of the patients in the respiratory reaction group, 26 were found to have clinical AERD, demonstrating a positive predictive values (PPV) of 89.7%. The overall PPV was 59.3%. Those with a respiratory reaction to NSAIDS listed in the EHR were more likely to have clinical AERD (odds ratio 27.44; confidence interval 6.08-123.85; p < 0.0001). Only 2 patients (6.3%) underwent aspirin desensitization.CONCLUSION:AERD remains under-diagnosed in the study population. The informatics algorithm presented here has a high positive predictive value for identifying clinical AERD patients in a geographical area with low rates of aspirin desensitization and may aid in identifying candidates for expanded treatment options.

Supplementary fig 5 Degree of Reduction (%) in Tumor pERK Levels From Baseline to After Trametinib Monotherapy and Correlation With pCR

Introduction: We have previously reported using a resident’s learning curve based on operative time (OT) plateau could determine their procedural proficiency. In this study we hypothesize case volume in the chief resident (CR) year would influence whether a CR could achieve reproducible procedural proficiency based on OT. Methods: We extracted laparoscopic cholecystectomy (LCh), laparoscopic colectomy (LCo), laparoscopic inguinal hernia (LIH) and open inguinal hernia (OIH) performed by general surgery residents in the CR year from 7/2016 to 6/2020 through hospital records with OT, patient type, and case complexity assessed by DRG. We used variance component analyses as well as generalizability and decision studies (D-Study) to determine number of cases needed to achieve desired reliability (> 0.80). Results: In total 1514 cases (LCh=776, LCo=339, LIH=158, OIH=241) were included. On average, CR overall completed 38.3 LCh, 16.9 LCo, 7.8 LIH, and 11.8 OIH. After controlling for CR effect, case complexity (r=0.004) and procedure type (r<0.0001) significantly influenced OT. To achieve stable/reproducible OT in each procedure upon graduation, our CRs (N = 6) were estimated to perform on average 25 LCh, 30 LCo, 26 LIH, and 17 OIH per person. Individual CR had minimal impact on the estimation of case needed. Conclusion: The case volume needed to achieve stable procedural proficiency in LCo, LIH and OIH exceeds average CR case number in our program. This might be also true in other programs. Prospective measurement of OT may allow for individualized CR case assignments and enhance CR readiness for independent practice in general surgery.

Aspirin-exacerbated respiratory disease (AERD) presents with a triad of nasal polyps, asthma, and aspirin and nonsteroidal anti-inflammatory drug sensitivity. It is characterized by often recalcitrant type 2 inflammation with dysregulated arachidonic acid metabolism, mast cell activation, and blood and airway eosinophilia.1 In addition to characteristic respiratory reactions with cyclooxygenase-1 (COX-1) inhibitors, patients with AERD often have alcohol sensitivity. Up to 75% of patients with AERD have upper airway symptoms (sneezing, rhinorrhea, nasal congestion) whereas 51% have lower respiratory symptoms (wheezing, dyspnea)2 that are not specific to the type or amount of alcohol ingested.

PURPOSE Hereditary cancer syndromes infer high cancer risks and require intensive surveillance. Identification of high-risk individuals among patients with colorectal cancer (CRC) needs improvement. METHODS Three thousand three hundred ten unselected adults who underwent surgical resection for primary invasive CRC were prospectively accrued from 51 hospitals across Ohio between January 1, 2013, and December 31, 2016. Universal Tumor screening (UTS) for mismatch repair (MMR) deficiency was performed for all, and pathogenic germline variants (PGVs) were identified using multigene panel testing (MGPT) in those who met at least one inclusion criterion: MMR deficiency, diagnosed < 50 years, multiple primary tumors (CRC or endometrial cancer), or with a first-degree relative with CRC or endometrial cancer. RESULTS Five hundred twenty-five patients (15.9%) had MMR deficiency. Two hundred thirty-four of 3,310 (7.1%; 16% of the 1,462 who received MGPT) had 248 PGVs in cancer susceptibility genes. One hundred forty-two (4.3%) had a PGV in an MMR gene, and 101 (3.1%) had a PGV in a non-MMR gene. Ten with Lynch syndrome (LS) also had a non-MMR PGV and were included in both groups. Two (0.06%) had constitutional MLH1 hypermethylation. Of unexplained MMR-deficient patients, 88.4% (76 of 86) had double somatic MMR mutations. Testing for only MMR genes in MMR-deficient patients would have missed 18 non-MMR gene PGVs (7.3% of total PGVs identified). Had UTS been the only method used to screen for hereditary cancer syndromes, 38.6% (91 of 236) would have been missed, including 6.3% (9 of 144) of those with LS. These results have treatment implications as 5.3% (175 of 3,310) had PGVs in genes with therapeutic targets. CONCLUSION UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. At a minimum, 7.1% of individuals with CRC have a PGV and pan-cancer MGPT should be considered for all patients with CRC.

Purpose: The RAS/RAF/MEK/ERK signaling pathway is critical to the development of colorectal cancers, and KRAS, NRAS, and BRAF mutations foster resistance to radiation. We performed a phase I trial to determine the safety of trametinib, a potent MEK1/2 inhibitor, with 5-fluorouracil (5-FU) chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC). Patients and Methods: Patients with stage II/III rectal cancer were enrolled on a phase I study with 3+3 study design, with an expansion cohort of 9 patients at the MTD. Following a 5-day trametinib lead-in, with pre- and posttreatment tumor biopsies, patients received trametinib and CRT, surgery, and adjuvant chemotherapy. Trametinib was given orally daily at 3 dose levels: 0.5 mg, 1 mg, and 2 mg. CRT consisted of infusional 5-FU 225 mg/m(2)/day and radiation dose of 28 daily fractions of 1.8 Gy total 50.4 Gy). The primary endpoint was to identify the MTD and recommended phase II dose. IHC staining for phosphorylated ERK (pERK) and genomic profiling was performed on the tumor samples. Results: Patients were enrolled to all dose levels, and 18 patients were evaluable for toxicities and responses. Treatment was well tolerated, and there was one dose-limiting toxicity of diarrhea, which was attributed to CRT rather than trametinib. At the 2 mg dose level, 25% had pathologic complete response. IHC staining confirmed dose-dependent decrease in pERK with increasing trametinib doses. Conclusions: The combination of trametinib with 5-FU CRT is safe and well tolerated, and may warrant additional study in a phase II trial, perhaps in a RAS/RAF-mutant selected population.

Lansing, Shan S. MS; Abdel-Rasoul, Mahmoud MS, MPH; Griffiths, Claire BS; Diaz, Kayla BA; Arnold, Mark W. MD, FACS; Eldon Harzman, Alan MD, FACS; Huang, Emily S. MD, MAEd; Linnell Traugott, Amber MD; Husain, Syed MD Author Information