Genome-wide association studies (GWAS) have identified over 300 loci associated with the inflammatory bowel diseases (IBD), but putative causal genes for most are unknown. We conducted the largest disease-focused expression quantitative trait loci (eQTL) analysis using colon tissue from 252 IBD patients to determine genetic effects on gene expression and potential contribution to IBD. Combined with two non-IBD colon eQTL studies, we identified 194 potential target genes for 108 GWAS loci. eQTL in IBD tissue were enriched for IBD GWAS loci colocalizations, provided novel evidence for IBD-associated genes such as ABO and TNFRSF14, and identified additional target genes compared to non-IBD tissue eQTL. IBD-associated eQTL unique to diseased tissue had distinct regulatory and functional characteristics with increased effect sizes. Together, these highlight the importance of eQTL studies in diseased tissue for understanding functional consequences of genetic variants, and elucidating molecular mechanisms and regulation of key genes involved in IBD.
The preoperative assessment of surgical patients, including colorectal patients, has undergone significant changes over the last 20 years. The rationale for such changes is based on evidence-based guidelines that showed a minimal clinical impact from broad base testing in healthy patients. Additionally, nonselective testing has been shown to be a large economic burden to the American health care system. As such, a tailored approach based on risk stratification is recommended rather than a “standard, one-size-fits-all” approach. This article will review current risk stratification and preoperative evaluation strategies for patients undergoing elective colorectal surgery. Emphasis will be given to areas in which preoperative optimization strategies may be employed to minimize operative risks. We will review the role and need of preoperative testing in specific patient populations and highlight situations where preoperative evaluation impacts operative timing and planning. Specifically, emphasis will be placed on strategies for mitigation of major adverse cardiac events. The aim is to provide a framework that allows for safe and responsible preoperative assessment.
This study aims to investigate the phenomenon of high-amplitude pouch contractile waves and their impact on functional results in patients undergoing ileal pouch-anal anastomosis following total proctocolectomy for ulcerative colitis. This is an observational cohort study evaluating pouch manometric data at an early (study 1, < 6 months s/p ileostomy closure) and delayed (study 2, > 5 months after study 1) time point. High-amplitude contractions were defined as peaks ≥ 20 mmHg over baseline. Pouch functional measures and quality of life outcomes were correlated with contractile amplitude and frequency. Thirty-three patients were included in this study. Contractile frequency decreased from study 1 to study 2 (0.14 vs. 0.07 contractions/min). Peristaltic contractility was absent in 18/33 patients (55
Introduction The impact of diverting ileostomy in adults with ulcerative colitis (UC) undergoing ileal pouch-anal anastomosis (IPAA) is unclear. This study uses a novel approach with population-level data to identify patients with diverting ileostomy at the time of IPAA and determine the impact of diverting ileostomy on postoperative outcomes.Methods Using the International Business Machines (IBM) MarketScan (R) database, adults (18-64 years old) with a diagnosis of UC who underwent IPAA between 2000 and 2019 were examined. Patients were assigned to the diverting ileostomy (DI) cohort or no-DI cohort based on the presence of an ostomy closure code in the 1-year following their IPAA. Rates of ileostomy formation and readmissions were quantified and outcomes between cohorts compared.Results There were 540 patients in the no-DI and 2494 in the DI cohort. There were regional differences in the rate of ostomy creation, but the overall rate of ostomy creation remained stable across years. Patients with no-DI vs DI had a longer index length of stay (LOS) (7 vs 6 days, P = .001). Adverse postoperative outcomes did not differ between cohorts. Diversion did not independently affect the likelihood of a 30-day readmission, and since 2000, readmission rates have declined for all IPAA patients.Discussion This is the first study to capture population-level data on the effect of diversion at the time of IPAA for adult UC patients. This study demonstrates that the rate of fecal diversion at the time of IPAA has remained stable over time, but readmission rates have declined.
OBJECTIVES:This study aimed to determine if immune inflammatory markers (neutrophil lymphocyte ratio [NLR], platelet lymphocyte ratio [PLR], and prognostic nutritional index [PNI]) correlate with anal cancer risk in people living with HIV and to compare these markers with the CD4/CD8 ratio. MATERIALS AND METHODS:This is a regional retrospective cohort study of veterans living with HIV who were screened for or diagnosed with anal neoplasia or cancer from 2001 to 2019. The NLR, PLR, PNI, and CD4/CD8 ratio within 1 year of anal pathology results were computed. Patients with anal cancer were compared to patients without anal cancer. Regression modeling was used to estimate the odds of developing anal cancer. RESULTS:Three hundred thirty-four patients were included (37 with anal cancer, 297 without anal cancer). In patients with anal cancer, NLR and PLR were higher (2.17 vs 1.69, p = .04; 140 vs 110, p = .02, respectively), while PNI and CD4/CD8 ratio were lower (44.65 vs 50.01, p < .001; 0.35 vs 0.80, p < .001, respectively). On multivariate logistic regression modeling, only PNI (odds ratio, 0.90; p = .001) and CD4/CD8 ratio (odds ratio, 0.05; p < .001) were associated with increased anal cancer risk. CONCLUSIONS:Although NLR and PLR independently correlate with anal cancer risk, when controlling for other risk predictors, only PNI and CD4/CD8 ratio were statistically significant biomarkers for anal cancer. The CD4/CD8 ratio is the strongest immune inflammatory marker that predicts risk of anal cancer among veterans living with HIV.
Surgical margins following rectal cancer resection impact oncologic outcomes. We examined the relationship between margin status and race, ethnicity, region of care, and facility type. Patients undergoing resection of a stage II–III locally advanced rectal cancer (LARC) between 2004 and 2018 were identified through the National Cancer Database. Inverse probability of treatment weighting (IPTW) was performed, with margin positivity rate as the outcome of interest, and race/ethnicity and region of care as the predictors of interest. In total, 58,389 patients were included. After IPTW adjustment, non-Hispanic Black (NHB) patients were 12% (p = 0.029) more likely to have margin positivity than non-Hispanic White (NHW) patients. Patients in the northeast were 9% less likely to have margin positivity compared to those in the south. In the west, NHB patients were more likely to have positive margins than NHW patients. Care in academic/research centers was associated with lower likelihood of positive margins compared to community centers. Within academic/research centers, NHB patients were more likely to have positive margins than non-Hispanic Other patients. Our results suggest that disparity in surgical management of LARC in NHB patients exists across regions of the country and facility types. Further research aimed at identifying drivers of this disparity is warranted.
BACKGROUND:IPAA is considered the procedure of choice for restorative surgery after total colectomy for ulcerative colitis. Previous studies have examined the rate of IPAA within individual states but not at the national level in the United States. OBJECTIVE:This study aimed to assess the rate of IPAA after total colectomy for ulcerative colitis in a national population and identify factors associated with IPAA. DESIGN:This was a retrospective cohort study. SETTINGS:This study was performed in the United States. PATIENTS:Patients who were aged 18 years or older and who underwent total colectomy between 2009 and 2019 for a diagnosis of ulcerative colitis were identified within a commercial database. This database excluded patients with public insurance, including all patients older than 65 years with Medicare. MAIN OUTCOME MEASURES:The primary outcome was IPAA. Multivariable logistic regression was used to assess the association between covariates and the likelihood of undergoing IPAA. RESULTS:In total, 2816 patients were included, of whom 1414 (50.2%) underwent IPAA, 928 (33.0%) underwent no further surgery, and 474 (16.8%) underwent proctectomy with end ileostomy. Younger age, lower comorbidities, elective case, and laparoscopic approach in the initial colectomy were significantly associated with IPAA but socioeconomic status was not. LIMITATIONS:This retrospective study included only patients with commercial insurance. CONCLUSIONS:A total of 50.2% of patients who had total colectomy for ulcerative colitis underwent IPAA, and younger age, lower comorbidities, and elective cases are associated with a higher rate of IPAA placement. This study emphasizes the importance of ensuring follow-up with colorectal surgeons to provide the option of restorative surgery, especially for patients undergoing urgent or emergent colectomies. See Video Abstract . FACTORES ASOCIADOS CON LA REALIZACIN DE ANASTOMOSIS ANALBOLSA ILEAL DESPUS DE UNA COLECTOMA TOTAL POR COLITIS ULCEROSA:ANTECEDENTES:La anastomosis ileo-anal se considera el procedimiento de elección para la cirugía reparadora tras la colectomía total por colitis ulcerosa. Estudios previos han examinado la tasa de anastomosis ileo-anal dentro de los estados individuales, pero no a nivel nacional en los Estados Unidos.OBJETIVO:Evaluar la tasa de anastomosis bolsa ileal-anal después de la colectomía total para la colitis ulcerosa en una población nacional e identificar los factores asociados con la anastomosis bolsa ileal-anal.DISEÑO:Se trata de un estudio de cohortes retrospectivo.LUGAR:Este estudio se realizó en los Estados Unidos.PACIENTES:Los pacientes que tenían ≥18 años de edad que se sometieron a colectomía total entre 2009 y 2019 para un diagnóstico de colitis ulcerosa fueron identificados dentro de una base de datos comercial. Esta base de datos excluyó a los pacientes con seguro público, incluidos todos los pacientes >65 años con Medicare.MEDIDAS DE RESULTADO PRINCIPALES:El resultado primario fue la anastomosis ileal bolsa-anal. Se utilizó una regresión logística multivariable para evaluar la asociación entre las covariables y la probabilidad de someterse a una anastomosis ileal.RESULTADOS:En total, se incluyeron 2.816 pacientes, de los cuales 1.414 (50,2%) se sometieron a anastomosis ileo-anal, 928 (33,0%) no se sometieron a ninguna otra intervención quirúrgica y 474 (16,8%) se sometieron a proctectomía con ileostomía terminal. La edad más joven, las comorbilidades más bajas, el caso electivo, y el abordaje laparoscópico en la colectomía inicial se asociaron significativamente con la anastomosis ileal bolsa-anal, pero no el estatus socioeconómico.LIMITACIONES:Este estudio retrospectivo incluyó sólo pacientes con seguro comercial.CONCLUSIONES:Un 50,2% de los pacientes se someten a anastomosis ileo-anal y la edad más joven, las comorbilidades más bajas y los casos electivos se asocian con una mayor tasa de colocación de anastomosis ileo-anal. Esto subraya la importancia de asegurar el seguimiento con cirujanos colorrectales para ofrecer la opción de cirugía reparadora, especialmente en pacientes sometidos a colectomías urgentes o emergentes. (Traducción-Dr. Yolanda Colorado ).
Abstract BACKGROUND As part of the Crohn’s & Colitis Foundation’s IBD Plexus, a novel prospective, longitudinal multicenter surgical inception cohort was implemented. In this first report from the first 100 patients enrolled, we aimed to assess patient reported outcomes before and after IBD surgery. We hypothesized surgery is associated with improved patient reported outcomes. METHODS Beginning in Aug. 2022 patients were prospectively enrolled into a multicenter IRB-approved observational longitudinal cohort at 6 centers with 17 enrolling surgeons. Inclusion criteria: adults undergoing major abdominopelvic surgery for a known diagnosis of IBD. Baseline demographics, intra-operative details, 30-day outcomes, and patient reported outcomes were recorded at baseline and 30-days postoperatively. Overall health status was assess using the PROMIS General Health measures, symptom specific measures: PROMIS Pain Interference, Fatigue, and Sleep scales, and disease-specific measures: the Crohn’s & Ulcerative Colitis Questionnaire items. Figures represent frequency (proportion), median (range). P-values represent Wilcoxon rank-sum test or chi-squared test or Fisher’s exact test. RESULTS A total of 103 patients were enrolled to date; median age 43 (20 – 74), 49% female, diagnoses: Crohns (64%), ulcerative colitis (35%), and IBDu (1%). A total of 69 (67%) patients completed surveys, and 58 (56%) patients completed the post-operative survey. In terms of overall health status within 7 days, improved overall median pain scores (3 vs. 2, p=0.04), overall health (p=0.04), physical health (p=0.03), and less fatigue (p=0.05) were observed after surgery compared to baseline (Table 1), while overall quality of life, mental health, social measures, and emotional problems were similar. Patients reported more difficulties with activities of daily living after surgery (p=0.01). In terms of symptoms within 7 days, less fatigue (p<0.05), but no difference in pain interference or sleep disturbance was observed after surgery (p>0.05). In terms of disease-specific outcomes within 2 weeks, fewer days feeling unwell (5 vs. 3, p=0.02), bloated (5 vs 2, p=0.04), or needing to rush to the toilet (5 vs 1, p=0.007), and no difference in feeling tired, upset, abdominal pain, or nocturnal bowel movements was observed after surgery. CONCLUSIONS In a prospective longitudinal cohort, surgery was associated with improved pain and physical health scores, with fewer days feeling unwell, fatigued, bloating, and fecal urgency. On the other hand, mental, social, and emotional health did not change 30-days after surgery. Our data suggest patients are still recovering 30-days after surgery, and longer follow-up may reveal further improvements. Targeted psychosocial interventions and support at home early in the acute post-operative period may improve the quality of recovery after surgery for patients with IBD. Table 1 Table 2
Surgical skills vary drastically among practicing surgeons. This variation in skill has been demonstrated to translate directly into patient outcomes, highlighting the importance of skill development. Despite this, directed efforts to improve surgical skills and performance among practicing surgeons remain limited. The development of surgical coaching programs offers an exciting opportunity for surgeon performance improvement and lifelong development. In this article, we will discuss the promise of surgical coaching programs, some of the challenges met when developing a program, and future avenues and opportunities for growth within the field.
Chen, Kevin MD; Stem, Jonathan MD; Guillem, Jose G MD, FACS; Gomez, Shawn M EngScD; Kapadia, Muneera Rehana MD, FACS Author Information
Background Ureteral injury (UI) is a rare but devastating complication during colorectal surgery. Ureteral stents may reduce UI but carry risks themselves. Risk predictors for UI could help target the use of stents, but previous efforts have relied on logistic regression (LR), shown moderate accuracy, and used intraoperative variables. We sought to use an emerging approach in predictive analytics, machine learning, to create a model for UI. Methods Patients who underwent colorectal surgery were identified in the National Surgical Quality Improvement Program (NSQIP) database. Patients were split into training, validation, and test sets. The primary outcome was UI. Three machine learning approaches were tested including random forest (RF), gradient boosting (XGB), and neural networks (NN), and compared with traditional LR. Model performance was assessed using area under the curve (AUROC). Results The data set included 262,923 patients, of whom 1519 (.578%) experienced UI. Of the modeling techniques, XGB performed the best, with an AUROC score of .774 (95% CI .742-.807) compared with .698 (95% CI .664-.733) for LR. Random forest and NN performed similarly with scores of .738 and .763, respectively. Type of procedure, work RVUs, indication for surgery, and mechanical bowel prep showed the strongest influence on model predictions. Conclusions Machine learning-based models significantly outperformed LR and previous models and showed high accuracy in predicting UI during colorectal surgery. With proper validation, they could be used to support decision making regarding the placement of ureteral stents preoperatively.
14 Background: Surgical margins following rectal cancer resection impact oncologic outcomes and may reflect adequacy of care. We examined the relationship between race, ethnicity, or region of care with margin positivity following rectal cancer resection. Methods: We queried the National Cancer Database (NCDB) for patients diagnosed with stage II-IV rectal cancer between 2004-2018 who underwent surgical resection and excluded patients with missing data for race/ethnicity and radiation therapy/surgery status, and/or who had local excision only. We performed a propensity-score analysis via inverse probability of treatment weighting (IPTW) of margin positivity rate as outcome and race/ethnicity and region as predictors of interest. We controlled for age, sex, Charlson-Deyo Score, pathologic stage, pathologic grade, time from diagnosis to surgical resection, surgery type, sequence of radiation and surgery, facility type, insurance type, level of education, distance between patient and facility, and region of the United States. Results: Our query yielded 73,269 patients. Median patient age was 63 (IQR: 54-72) years and 40% were female. 81%,8%, 6%, and 5% were non-Hispanic White, non-Hispanic Black, Hispanic, and non-Hispanic Other, respectively. After IPTW adjustment, non-Hispanic Black patients had 19% higher odds of margin positivity relative to non-Hispanic White patients (OR: 1.185, 95% CI: 1.094-1.284; p<.0001) Patients in the Northeast United States had a 10% lower odds of margin positivity compared to those in the South (OR: 0.900, 95% CI: 0.842-0.962; p=0.0019). Conclusions: Being non-Hispanic Black was significantly associated with a higher likelihood of positive margin following rectal cancer resection when compared to their non-Hispanic White counterparts. Patients in the South also experienced significantly higher rates of positive margin when compared to Northeast patients. Further investigation into potential interactions between racial and regional disparities and other contributors is warranted.[Table: see text]
Introduction: In pediatric ulcerative colitis (UC), surgery is often postponed until disease is life-threat-ening or refractory to immune suppression. In these settings, diverting ileostomy (DI) is theorized to have a protective effect on the new anastomosis. However, analyses have been performed only in single -institution series and the true impact of performing DI at the time of IPAA on postoperative outcomes is unclear. Methods: We performed a retrospective cohort study using claims data from the International Business Machines (IBM) MarketScan (R) database. Patients were sorted to the DI group if they carried a CPT code for ostomy closure within 6 months of index procedure. We examined demographics, preoperative risk factors, and performed regression analysis to compare 30-day postoperative outcomes between groups. Results: We identified 317 patients <= 18yo that underwent IPAA procedure and met inclusion criteria from 2000 to 2019. Of these, 238 patients were assigned to the IPAA + DI cohort and 79 patients were assigned to the IPAA cohort. Adverse outcomes were comparable between cohorts. Surgical site infection (SSI) rates between IPAA and IPAA + DI were 10.1 vs. 11.3% (p = 0.67). Rates of intra-abdominal drainage procedures were 3.8 vs. 2.1% (p = 0.39). The rates of 30-day readmissions were 16.5 vs. 19.3% (p = 0.39). Creation of a DI was not associated with higher odds of 30-day readmission (OR = 1.4, p = 0.31). Conclusion: Creating a DI necessitates an additional surgery for closure and is not associated with decreased adverse outcomes. There is still a role for multicenter studies to define which patient pop-ulations may benefit from diversion.Level of Evidence: Retrospective comparative study.Type of Study: Level III. (c) 2023 Elsevier Inc. All rights reserved.
People living with HIV (PLWH) are at an elevated risk for developing anal cancer. As screening is invasive, markers predicting those at highest risk for anal cancer could guide individualized screening. Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are surrogate inflammatory/immune markers known to correlate with cancer outcomes. This study aims to assess whether these markers correlate with anal cancer risk in PLWH. This is a retrospective single-institution cohort study of PLWH at a single academic medical center who were diagnosed with or screened for anal dysplasia between 2001 and 2019. Aforementioned markers collected within one year of diagnosis were recorded. Regression modeling was used to estimate odds of anal cancer. Receiver operating characteristic analysis was utilized to determine optimal cutoff for screening values. Five-hundred-fourteen patients were included. NLR and PNI were significantly associated with cancer risk on univariate (p = 0.03, p = 0.001) and multivariate analyses (p = 0.03, p = 0.01). NLR increased across all grades of dysplasia. PLR was not associated with cancer risk. A NLR of ≥ 1.64 can be utilized to capture 76% of cancer patients in our cohort. NLR values in patients living with HIV correlate with risk of anal cancer and increasing grades of dysplasia. A cutoff NLR of ≥ 1.64 can be used to help capture those at risk. NLR is a promising marker of risk of anal cancer and progression of anal dysplasia in patients with HIV infection and could be used to risk-stratify screening and surveillance intervals.
Readmission after colorectal surgery is common and often implies complications for patients and costs for hospitals. Previous works have created predictive models using logistic regression for this outcome but have shown limited accuracy. Machine learning has shown promise in improving predictions by identifying non-linear patterns in data. We sought to create a more accurate predictive model for readmission after colorectal surgery using machine learning. Patients who underwent colorectal surgery were identified in the National Quality Improvement Program (NSQIP) database including years 2012–2019 and split into training, validation, and test sets. The primary outcome was readmission within 30 days of surgery. Three types of machine learning models were created, including random forest (RF), gradient boosting (XGB), and neural network (NN). A logistic regression (LR) model was also created for comparison. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC). The dataset included 213,827 patients after application of exclusion criteria. A total of 23,083 (10.8%) of patients experienced readmission. NN obtained an AUROC of 0.751 (95% CI 0.743–0.759), compared with 0.684 (95% CI 0.676–0.693) for LR. RF and XGB performed similarly with AUROCs of 0.749 (95% CI 0.741–0.757) and 0.745 (95% CI 0.737–0.753) respectively. Ileus, index admission length of stay, organ-space surgical site infection present at time of surgery, and ostomy placement were identified as the most contributory variables. Machine learning approaches outperformed traditional statistical methods in the prediction of readmission after colorectal surgery. After external validation, this improved prediction model could be used to target interventions to reduce readmission rate.
Procedure-specific complications can have devastating consequences. Machine learning–based tools have the potential to outperform traditional statistical modeling in predicting their risk and guiding decision-making. We sought to develop and compare deep neural network (NN) models, a type of machine learning, to logistic regression (LR) for predicting anastomotic leak after colectomy, bile leak after hepatectomy, and pancreatic fistula after pancreaticoduodenectomy (PD). The colectomy, hepatectomy, and PD National Surgical Quality Improvement Program (NSQIP) databases were analyzed. Each dataset was split into training, validation, and testing sets in a 60/20/20 ratio, with fivefold cross-validation. Models were created using NN and LR for each outcome. Models were evaluated primarily with area under the receiver operating characteristic curve (AUROC). A total of 197,488 patients were included for colectomy, 25,403 for hepatectomy, and 23,333 for PD. For anastomotic leak, AUROC for NN was 0.676 (95% 0.666–0.687), compared with 0.633 (95% CI 0.620–0.647) for LR. For bile leak, AUROC for NN was 0.750 (95% CI 0.739–0.761), compared with 0.722 (95% CI 0.698–0.746) for LR. For pancreatic fistula, AUROC for NN was 0.746 (95% CI 0.733–0.760), compared with 0.713 (95% CI 0.703–0.723) for LR. Variables related to intra-operative information, such as surgical approach, biliary reconstruction, and pancreatic gland texture were highly important for model predictions. Machine learning showed a marginal advantage over traditional statistical techniques in predicting procedure-specific outcomes. However, models that included intra-operative information performed better than those that did not, suggesting that NSQIP procedure-targeted datasets may be strengthened by including relevant intra-operative information.