Trends in surgical outcomes for Ileal pouch-anal anastomosis construction using a large nationwide database.

AIM: Ulcerative colitis (UC) affects over 3 million (1.3%) US adults, approximately 20% of whom will require surgery. Since it was first described in 1978, restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the gold standard for patients requiring surgery, as well as for patients with familial adenomatous polyposis (FAP). In 1991 the laparoscopic approach to IPAA was introduced. The aim of this study was to evaluate the advances made in IPAA as minimally invasive surgery (MIS) has become more prevalent. METHOD: The American College of Surgeons NSQIP database from 2005 to 2019 was used. Laparoscopic (MIS) and open cases of IPAA construction for UC or FAP were used. These patients were subdivided into three time point cohorts: early (2005-2009), middle (2010-2014) and recent (2015-2019). Univariable and multivariable analyses were performed to evaluate morbidity, mortality and hospital length of stay. RESULTS: A total of 6184 patients were analysed, and 2555 underwent MIS while 3629 underwent open surgery. After multivariable analysis, the MIS approach was associated with a lower risk of morbidity compared with open procedures [relative risk (RR) = 0.86, p < 0.0001, 95% CI 0.78-0.94], both in the early and recent periods [early period = RR = 0.66 (p < 0.0001), recent period RR = 0.78 (p = 0.0029)]. Superficial surgical site infection (SSI) was consistently lower in the MIS cohort across all three time periods. After multivariable analysis, the overall RR of superficial SSI in the MIS cohort was 0.41 (p < 0.0001) [early period RR = 0.35 (p < 0.0001), middle period RR = 0.55 (p = 0.0007), recent period RR = 0.31 (p < 0.0001)]. The RR of deep space SSI was decreased overall (RR = 0.58, p = 0.013, 95% CI 0.62-0.93), with the most significant effect occurring during the early period (RR = 0.30, p = 0.0260, 95% CI 0.105-0.868). Sepsis related to any infective aetiology was also decreased in the MIS cohort (RR = 0.76, p = 0.0093, 95% CI 0.62-0.93), especially in the recent time period (RR = 0.63, p = 0.0344, 95% CI 0.41-0.97). Furthermore, hospital length of stay was decreased in the MIS cohort (-0.287 days, p = 0.0170), with a greater difference occurring in the more recent cohort (-0.375 days, p = 0.0418). CONCLUSION: With increasing utilization of minimally invasive techniques in IPAA creation there have been significant decreases in the rates of morbidity including decreasing rates of superficial and deep space SSI, as well as decreased hospital length of stay.

A mixed methods exploration of the emergence of goal orientation in medical students' individualized learning plans.

PURPOSE: Goal orientation (GO) describes an individual's approach to different achievement situations. Understanding the motivations and approach to achieving goals of medical students is vital with the increasing emphasis on self-directed learning. The purpose of this study was to identify themes in self-improvement reflections that relate to each GO dimension (learning, performance-prove, and performance-avoid). METHODS: A sequential explanatory mixed methods design was used. GO data was used to categorize students into groups aligning with the GO dimension identified in the previous stage of quantitative analysis. Individualized learning plans (ILPs) for each GO dimension group were coded inductively to identify emergent themes related to goal setting and achievement. RESULTS: The learning GO group was the largest of the three GOs. Five themes were identified from inductive analysis: importance of practice, identifying elements that helped, identifying structural barriers, opportunities for improvement, and acknowledging experience. While these themes occur across GO, patterns exist within their ILPs based on GO. CONCLUSIONS: We identified common themes for motivations of medical students, and these motivations might differ depending on their GO. Further exploration into the themes over the course of their training will provide additional insights on what factors may be involved in student motivations towards learning and achievement. Educators can use this information to individualize feedback and students can better understand their motivations towards achieving goals.

Are the current colonoscopy recommendations for interval surveillance in patients with polyps enough? Machine learning-augmented propensity score cohort analysis of 1840 patients.

BACKGROUND: Colonoscopy remains the gold standard for screening and surveillance of colorectal neoplasms, and is associated with a lower risk of colorectal cancer (CRC)-related mortality. The current interval surveillance recommendations in patients with previous adenomas lack sufficient evidence. The prevalence of subsequent adenomas, and especially high-risk adenomas, during surveillance is not well known. METHODS: The primary outcome of this study was to determine the prevalence of polyps upon surveillance colonoscopy in patients who have a history of adenomas on initial average-risk-screening colonoscopy, but then have a normal initial surveillance (second) colonoscopy between 2003 and 2017. This is the first known retrospective cohort study of adenoma detection rate (ADR) with sub-group analysis of patients with serial surveillance colonoscopies by abnormal and high-risk surveillance findings separately by prior abnormal colonoscopies and correct surveillance strategies based on the recent March 2020 updated guidelines. After ADR calculation, machine learning-augmented propensity score adjusted multivariable regression with augmented inverse-probability weighting propensity (AIPW) score analysis was used to assess the relationship between guideline adherence, as well as abnormal and high-risk surveillance findings. RESULTS: A total of 1840 patients with pathologically confirmed adenomas or cancer on an initial average-risk-screening (first) colonoscopy met study criteria. 837 (45.5%) had confirmed adenomas on second colonoscopy, and 1003 (54.5%) had normal findings. Of 837 patients with polyps on both first and second colonoscopy, 423 (50.5%) had adenomas on third colonoscopy. Of the 1003 patients without polyps on second colonoscopy, 406 (40.5%) had confirmed adenomas on third colonoscopy. Guideline adherence was low at 9.18%, though was associated in propensity score adjusted multivariable regression with increased odds of an abnormal third (but not high-risk) colonoscopy, with comparable AIPW results. CONCLUSION: This 14-year study demonstrates the ADR to be > 40% on the third colonoscopy for patients with adenomas on initial screening colonoscopy, who then have a normal second colonoscopy. Through advanced machine learning and propensity score analysis, we showed that correct adherence is associated with higher odds of abnormal, but not high-risk abnormal 3rd colonoscopy, with evidence that high-risk surveillance findings are reduced by providers shortening the time between surveillance colonoscopies in contrast to the guidelines for those for whom there is presumed greater clinical suspicion of eventual cancer. Larger prospective trials are needed to guide optimal surveillance for these patients.

Stem Cell Marker Expression in Early Stage Colorectal Cancer is Associated with Recurrent Intestinal Neoplasia.

BACKGROUND: Colorectal cancer (CRC) ranks second in cancer deaths worldwide and presents multiple management challenges, one of which is identifying high risk stage II disease that may benefit from adjuvant therapy. Molecular biomarkers, such as ones that identify stem cell activity, could better stratify high-risk cohorts for additional treatment. METHODS: To identify possible biomarkers of high-risk disease in early-stage CRC, a discovery set (n = 66) of advanced-stage tumors were immunostained with antibodies to stemness proteins (CD166, CD44, CD26, and LGR5) and then digitally analyzed. Using a second validation cohort (n = 54) of primary CRC tumors, we analyzed protein and gene expression of CD166 across disease stages, and extended our analyses to CD166-associated genes (LGR5, ASCL2, BMI1, POSTN, and VIM) by qRT-PCR. RESULTS: Stage III and metastatic CRC tumors highly expressed stem cell-associated proteins, CD166, CD44, and LGR5. When evaluated across stages, CD166 protein expression was elevated in advanced-stage compared to early-stage tumors. Notably, a small subset of stage I and II cancers harbored elevated CD166 protein expression, which correlated with development of recurrent cancer or adenomatous polyps. Gene expression analyses of CD166-associated molecules revealed elevated ASCL2 in primary tumors from patients who recurred. CONCLUSIONS: We identified a protein signature prognostic of aggressive disease in early stage CRC. Stem cell-associated protein and gene expression identified a subset of early-stage tumors associated with cancer recurrence and/or subsequent adenoma formation. Signatures for stemness offer promising fingerprints for stratifying early-stage patients at high risk of recurrence.

MiR-486-5p Downregulation Marks an Early Event in Colorectal Carcinogenesis.

BACKGROUND: MicroRNAs are dysregulated in colorectal cancer and subsets correlated with advanced tumor stage and metastasis. Data are lacking on microRNA dysregulation from early to late-stage disease. OBJECTIVE: The purpose of this study was to identify a microRNA signature associated with the primary tumor and metastatic site in stage IV disease and to examine whether the signature is evident in earlier stages. DESIGN: A microRNA profile was generated and then explored in normal colon tissue (n = 5), early stage (stage I and II; n = 10), and late-stage (stage III and IV; n = 14) colorectal primary tumors via polymerase chain reaction to delineate molecular events that may promote colorectal carcinogenesis. SETTING: Genome-wide microRNA expression profiling was performed. PATIENTS: A total of 14 patient-matched stage IV primary colorectal cancer tumors and corresponding liver metastases were included. MAIN OUTCOME MEASURES: MicroRNA array technology was used to identify microRNA expression-predictive metastatic potential in the primary tumor. RESULTS: A distinct 9-member signature group of microRNAs was concurrent in stage IV primary colorectal cancer and their corresponding liver metastases, when compared with surrounding unaffected colon and liver tissue (microRNA-18b, microRNA-93, microRNA-182, microRNA-183, microRNA21, microRNA-486-5p, microRNA-500a, microRNA-552, and microRNA-941). Of the microRNA panel, only microRNA486-5p was differentially expressed in early stage colorectal cancer samples compared with normal tissue (p = 0.001) and additionally differentially expressed between late-stage colorectal cancer samples and normal tissue (p < 0.01). LIMITATIONS: Our microRNA profile was generated in a small subset of patients and will require validation in more samples. CONCLUSIONS: We identified a distinct microRNA signature in primary colon and matched metastatic disease. On additional investigation, 1 microRNA was differentially expressed in both early and late-stage cancer patient samples, and it may herald an early event in colorectal carcinogenesis. This study warrants additional investigation with a larger patient cohort to better understand the effect of microRNAs in carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A723.

Treatment and Survival of Small-bowel Adenocarcinoma in the United States: A Comparison With Colon Cancer.

BACKGROUND: Small-bowel adenocarcinoma is rare and fatal. Because of data paucity, there is a tendency to extrapolate treatment from colon cancer, particularly in the adjuvant stetting. OBJECTIVE: The purpose of this study was to evaluate the current surgical and adjuvant treatments of small-bowel adenocarcinoma and compare with colon cancer. DESIGN: This was a retrospective cohort study. SETTINGS: The linked Surveillance, Epidemiology, and End Results and Medicare database was used at a tertiary referral hospital. PATIENTS: Patients with small-bowel adenocarcinoma and colon cancer identified from 1992 to 2010, using International Classification of Diseases for Oncology, 3 Revision, site, behavior, and histology codes were included. MAIN OUTCOME MEASURES: Overall survival and cancer-specific survival were estimated using the Kaplan-Meier method and competing risk analysis. RESULTS: A total of 2123 patients with small-bowel adenocarcinoma and 248,862 patients with colon cancer were identified. Five-year overall survival rates for patients with small-bowel adenocarcinoma and colon cancer were 34.9% and 51.5% (p < 0.0001). A total of 1550 patients with small-bowel adenocarcinoma (73.0%) underwent surgery, compared with 177,017 patients with colon cancer (71.1%). The proportion of patients who received chemotherapy was similar, at 21.3% for small bowel and 20.0% for colon. In contrast to colon cancer, chemotherapy did not improve overall or cancer-specific survival for patients with small-bowel adenocarcinoma, regardless of stage. Predictors of poor survival for small-bowel adenocarcinoma on multivariate analysis included advanced age, black race, advanced stage, poor tumor differentiation, high comorbidity index, and distal location. Chemotherapy did not confer additional survival benefit compared with surgery alone (HR, 1.04 (95% CI, 0.90-1.22)). LIMITATIONS: This was a retrospective review. The reliance on Medicare data limited granularity and may have affected the generalizability of the results. CONCLUSIONS: The prognosis for small-bowel adenocarcinoma is worse than that for colon cancer, and only surgery improves survival. In contrast to colon cancer, a survival benefit from current chemotherapy regimens for small-bowel adenocarcinoma is not seen, suggesting that it may be overused and needs more rigorous study.

Psychiatric Illness is a Disparity in the Surgical Management of Rectal Cancer.

BACKGROUND: Psychiatric disorders are common in the US and represent a major health disparity but little is known about their impact on surgical management and outcomes in cancer. OBJECTIVE: The aim of this study was to determine whether rectal cancer patients with psychiatric diagnoses have fewer sphincter-preserving procedures and higher postoperative complications. METHODS: Overall, 23,914 patients from the Nationwide Inpatient Sample (NIS) who underwent surgery for rectal cancer from 2004 to 2011 were identified. Patients with comorbid common psychiatric diagnoses were identified by International Classification of Diseases, Ninth Revision (ICD-9) codes. Main outcomes were measured by operation performed, length of stay (LOS), postoperative complications, and discharge disposition. RESULTS: Twenty percent of patients had a psychiatric diagnosis, with substance use being the most common psychiatric disorder (63 %). Patients with psychiatric diagnoses were more likely to be younger, White, have lower income, and have Medicaid insurance (p < 0.001) than those without. In a logistic regression model, patients with any psychiatric diagnosis were less likely to have sphincter-sparing surgery, controlling for patient sociodemographics, Charlson score, hospital procedure volume, and year (odds ratio 0.77; 95 % CI 0.72-0.83). LOS and postoperative complications were similar among the cohorts. Patients with psychiatric disorders were more likely to have home health care at discharge (p < 0.001). CONCLUSIONS: Fewer sphincter-sparing procedures were performed on rectal cancer patients with psychiatric diagnoses. However, no significant differences in postoperative complications were observed.

Disparities in postoperative outcomes among diverse patient groups with inflammatory bowel disease.

Background: Inflammatory bowel disease (IBD) represents a significant burden in the United States. We aim to evaluate disparities in postoperative outcomes among diverse patients undergoing surgery for IBD. Methods: The National Inpatient Sample (NIS) (2016-2018) was used to calculate national estimates for a number of postoperative complications in patients with IBD. Statistical analyses were performed using SAS survey procedures when calculating the national estimates. Results: A majority of the 107,375 patients (weighted) undergoing surgery for IBD were White (81.7%), rather than Black (10.1%) or Hispanic (8.2%). Black patients had higher rates of postoperative infections compared to White or Hispanic patients (4.2% vs. 3.1% vs. 2.7%, P=0.0137). There was a significant difference in morbidity and mortality, with higher rates in Black patients (20.1% vs. 17.1% vs. 17.9%, P=0.0029). Black patients experienced longer average hospital stays compared to White or Hispanic patients (12.6 vs. 9.6 vs. 11.2 days, P<0.001), despite suffering fewer comorbidities (Modified Charlson Index 1.9 vs. 2.3 vs. 2.0, P<0.001). Conclusions: This study demonstrated racial disparities in postoperative outcomes, with Black patients experiencing significantly higher rates of postoperative infections, overall morbidity and mortality, and length of stay, despite suffering from fewer comorbidities. This suggests an opportunity to improve equity of care for all patients with IBD by further examining social determinants of health that have not been traditionally studied.

Virtual Ileostomy as an Option for Complicated Colorectal Resections.

When surgery requires a colorectal anastomosis, a diverting ostomy may be created to decrease the clinical impact of anastomotic failure. Unfortunately, diverting ileostomies are also associated with significant morbidity. Recent literature suggests that diverting ostomies are not necessary for the majority of patients undergoing colorectal anastomosis and that creation of a virtual ileostomy (VI) may spare patients the complications that accompany diverting ileostomy creation. We present 4 patients with complex medical histories who underwent colorectal resections with primary anastomoses and VI creation. None of these patients suffered anastomotic leak or required conversion of VI to defunctioning ileostomy and there were no major complications associated with VI creation. Our results, although limited by sample size, support the creation of a virtual ileostomy as a safe and effective alternative to diverting ileostomy creation at the time of colorectal anastomosis.

Endoplasmic Reticulum Stress in Subepithelial Myofibroblasts Increases the TGF-ß1 Activity That Regulates Fibrosis in Crohn's Disease.

BACKGROUND: Endoplasmic reticulum (ER) stress is an essential response of epithelial and immune cells to inflammation in Crohn's disease. The presence and mechanisms that might regulate the ER stress response in subepithelial myofibroblasts (SEMFs) and its role in the development of fibrosis in patients with Crohn's disease have not been examined. METHODS: Subepithelial myofibroblasts were isolated from the affected ileum and normal ileum of patients with each Montreal phenotype of Crohn's disease and from normal ileum in non-Crohn's subjects. Binding of GRP78 to latent TGF-ß1 and its subcellular trafficking was examined using proximity ligation-hybridization assay (PLA). The effects of XBP1 and ATF6 on TGF-ß1 expression were measured using DNA-ChIP and luciferase reporter assay. Endoplasmic reticulum stress components, TGF-ß1, and collagen levels were analyzed in SEMF transfected with siRNA-mediated knockdown of DNMT1 and GRP78 or with DNMT1 inhibitor 5-Azacytidine or with overexpression of miR-199a-5p. RESULTS: In SEMF of strictured ileum from patients with B2 Crohn's disease, expression of ER stress sensors increased significantly. Tunicamycin elicited time-dependent increase in GRP78 protein levels, direct interaction with latent TGF-ß1, and activated TGF-ß1 signaling. The TGFB1 DNA-binding activity of ATF-6α and XBP1 were significantly increased and elicited increased TGFB1 transcription in SEMF-isolated from affected ileum. The levels of ER stress components, TGF-ß1, and collagen expression in SEMF were significantly decreased following knockdown of DNMT1 or GRP78 by 5-Azacytidine treatment or overexpression of miR-199a-5p. CONCLUSIONS: Endoplasmic reticulum stress is present in SEMF of patients susceptible to fibrostenotic Crohn's disease and can contribute to development of fibrosis. Targeting ER stress may represent a novel therapeutic target to prevent fibrosis in patients with fibrostenotic Crohn's disease.

HIV positivity and anal cancer outcomes: A single-center experience.

BACKGROUND: Anal cancer remains common among human immunodeficiency virus (HIV) patients. Chemoradiation has had mixed results. We evaluated outcome differences by HIV status. METHODS: We retrospectively analyzed 14 HIV+ and 72 HIV- anal cancer patients (2000 to 2013). Outcomes included chemoradiation tolerance, recurrence, and survival. RESULTS: HIV+ patients were more often male (100% vs 38%, P < .001) but diagnosed at similar stages (P = .49). They were less likely to receive traditional chemotherapy (36% vs 86%, P < .001). Recurrence (P = .55) and survival time (P = .48) were similar across groups. HIV+ patients had similar colostomy-free survival (P = .053). Receipt of 5-fluorouracil/mitomycin C (MMC) chemotherapy predicted recurrence-free and overall survival (Hazard ratios .278, .32). HIV status did not worsen recurrence (P = .71) or survival (P = .57). CONCLUSIONS: HIV+ patients received more non-MMC-based chemoradiation but had equivalent colostomy-free, recurrence, and overall survival. Use of 5-fluorouracil/MMC chemotherapy increased after 2008.

Trends in the surgical management of diverticulitis.

Sigmoid diverticulitis is an increasingly common Western disease associated with a high morbidity and cost of treatment. Improvement in the understanding of the disease process, along with advances in the diagnosis and medical management has led to recent changes in treatment recommendations. The natural history of diverticulitis is more benign than previously thought, and current trends favor more conservative, less invasive management. Despite current recommendations of more restrictive indications for surgery, practice trends indicate an increase in elective operations being performed for the treatment of diverticulitis. Due to diversity in disease presentation, in many cases, optimal surgical treatment of acute diverticulitis remains unclear with regard to patient selection, timing, and technical approach in both elective and urgent settings. As a result, data is limited to mostly retrospective and non-randomized studies. This review addresses the current treatment recommendations for surgical management of diverticulitis, highlighting technical aspects and patterns of care.

Recent developments in the surgical management of perianal fistula for Crohn's disease.

Perianal manifestations of Crohn's disease (CD) are common and, of them, fistulas are the most common. Perianal fistulas can be extremely debilitating for patients and are often very challenging for clinicians to treat. CD perianal fistulas usually require multidisciplinary and multimodality treatment, including both medical and surgical approaches. The majority of patients require multiple surgical interventions. CD patients with perianal fistulas have a high rate of primary non-healing, surgical morbidity, and high recurrence rates. This has led to constant efforts to improve surgical management of this disease process.