Does preoperative neoadjuvant chemotherapy impact short-term surgical outcomes in patients with locally advanced colon cancer?

BACKGROUND: Preoperative neoadjuvant chemotherapy (NAC) for colon cancer in advanced stages is associated with improved outcomes and tumor regression. The aim of our study was to identify outcomes in patients with colon cancer who received preoperative NAC. METHODS: A 4-year analysis of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) was performed. We included patients with locally advanced colon cancer (non-metastatic T3, T4 with or without nodal involvement) who underwent colon cancer resection. Patients were stratified into two groups (NAC and No-NAC). Our outcome measures were anastomotic leaks, hospital length of stay (LOS), 30-day complications, 30-day mortality, and 30-day readmissions. We performed a multi-variable logistic regression analysis. RESULTS: We analyzed 90,055 patients of which 7694 (NAC: 7.8 % (n = 599) and No-NAC: 92.2% (n = 7095)) met the inclusion criteria and included in the analysis. Mean age was 67 ± 13 years, 51% were males, and 72% were whites. Patients in the NAC group were more likely to be younger (60 ± 12 years vs. 68 ± 13 years, p < 0.01) and males (62% vs. 50%, p < 0.01) compared to No-NAC. On regression analysis, preoperative NAC was independently associated with higher odds of anastomotic leak (OR 1.35 [1.05-1.97], p = 0.03) and 30-day readmission (OR 1.54 [1.24-2.05], p < 0.01) in reference to No-NAC. However, no association was found between NAC and 30-day complications and 30-day mortality. CONCLUSIONS: Preoperative NAC might be associated with adverse outcomes of anastomotic leaks and 30-day readmissions, however does not appear to impact 30-day complications nor 30-day mortality.

A Protocol-Driven Reduction in Surgical Site Infections After Colon Surgery.

BACKGROUND: Surgical site infection (SSI) is an established quality indicator and predictor for adverse patient outcomes. Multiple strategies have been established to reduce SSI; however, optimum protocol remains unclear. The aim of the study was to assess the impact of established protocol on SSI after colon surgery. METHODS: We established a colon SSI bundle in 2017, which includes a chlorhexidine prescrub followed by chloraPrep, betadine wound wash, antibiotic infused irrigation, use of closure tray, and incision coverage with silver impregnated dressing. Retrospective analysis of a 2-y (2016-2017) prospectively collected before and after analysis of all patients undergoing elective colon surgery was performed. Patients were divided into two groups: preprotocol (PP: year 2016) and postprotocol (PoP: year 2017). Patients in the two groups were matched using propensity score matching for age, gender, comorbidities, Anesthesiology Severity Score, indication of procedure, and procedure type. Outcome measures were SSI, hospital length of stay, and readmission rate. RESULTS: A total of 328 patients were analyzed, and after propensity matching, 94 patients (PP:47 and PoP:47) were included. The mean age was 63.7 ± 16.4 y, 43.6% male, and 44.6% of procedures were performed laparoscopically. There was no difference in demographics, comorbidities, and procedure details between two groups. PoP patients had significantly lower superficial (odds ratio: 0.91 [0.74-0.98]; P = 0.045) and deep SSI (odds ratio:0.97 [0.65-0.99]; P = 0.048) than PP patients. PoP patient had shorter length of stay (P = 0.049) and trend toward lower readmission rate (P = 0.098) compared with PP patients and an 85% reduction in the Centers for Medicare and Medicaid Services standardized infection rate. CONCLUSIONS: Protocol-driven patient care improves patient outcomes. SSI bundle reduced SSI in patient undergoing colon surgery. Establishing national SSI bundles will help standardize care and help optimize patient outcomes.

Does it matter where you get your surgery for colorectal cancer?

BACKGROUND: The influence of hospital-related factors on outcomes following colorectal surgery is not well-established. The aim of our study was to evaluate the relationship between hospital factors on outcomes in surgically managed colorectal cancer patients. METHODS: We performed a 2-year (2014-2015) analysis of the NIS database. Adult (> 18 years) patients who underwent open or laparoscopic colorectal resection were identified using ICD-9 codes. Patients were stratified based on hospital: volume (low vs. high), teaching status, and location (urban vs. rural). Outcome measures were complications and mortality. Multivariate logistic regression was performed. RESULTS: A total of 153,453 patients with CRC were identified of which 35.3% underwent surgical management. Mean age was 69 ± 13 years, 51.6% were female, and 67% were white. Twenty-seven percent of the patients were managed at a high-volume center, 48% at intermediate-volume center while 25% at a low-volume center. Complications and mortality rates were lower in patients who were managed at high-volume centers and urban hospitals, while no difference was noticed based on teaching status. On regression analysis, patients managed at high-volume centers (OR 0.76 [0.56-0.89]) and urban hospitals (OR 0.83 [0.64-0.91]) have lower odds of complications; similarly, high-volume centers (OR 0.79 [0.65-0.90]) and urban facility (OR 0.87 [0.70-0.92]) were associated with lower odds of mortality. However, there was no association between teaching status and outcomes. CONCLUSION: Hospital factors significantly influence outcomes in patients with CRC managed surgically. High-volume centers and urban facilities have relatively better outcomes. Regionalization of care along with the appropriate availability of resources may improve outcomes in patients with CRC. LEVEL OF EVIDENCE: Level III, Retrospective Observational Study.

Colon cancer in the young: contributing factors and short-term surgical outcomes.

BACKGROUND: The incidence in young patients has increased significantly over the last few decades. The aim of this study is to evaluate demographic and tumor characteristics of young patients and analyze the short-term surgical outcomes of patients undergoing surgery. METHODS: We performed a 2-year review (2015-2016) of the ACS-NSQIP and included all patients with CC who underwent surgical management. Patients were stratified into two groups: early-onset CC (< 50 years old) and late-onset CC (≥ 50 years old). Outcome measures were hospital length of stay, 30-day complications, mortality, and readmission. RESULTS: We included a total of 15,957 patients in the analysis. Mean age was 65 ± 13 years, and 52% were male. Overall 10% of the patients had early-onset CC. Patients with early-onset CC were more likely to be black (11% vs 7%, p = 0.04) and Hispanic (8% vs 4%, p = 0.02). Additionally, they presented with a more aggressive tumor and higher TNM staging. Patients with early onset CC had lower 30-day complications (18% vs 22%, p = 0.02), shorter hospital length of stay (6[3-8] vs 8[5-11], p = 0.03) and lower 30-day mortality (0.4% vs 1.8%, p = 0.04) compared to their counterparts. However, there was no difference between the two groups regarding 30-day readmission. On regression analysis, there was no difference between the two groups regarding study outcomes. CONCLUSIONS: Racial disparity does exist in the incidence of colon cancer in the young with higher incidence in blacks. Younger patients with CC tend to have better surgical outcomes on univariate analysis. On regression analysis, the surgical outcomes between the two groups are comparable.

Rectal cancer in the young: analysis of contributing factors and surgical outcomes.

BACKGROUND: Rectal cancer (RC) among young patients (≤50 years) is on the rise. The factors associated with development of RC are established however; factors leading to early RC remain unclear. The aim of this study was to assess factors associated with RC among young patients. METHODS: National estimates for patients with RC were abstracted from the National Inpatient Sample (NIS) database [2010-2012]. Patients were divided into two groups: young (≤50 years) and old (>50 years). Demographic, comorbidities, procedures performed, and hospital outcomes were collected. Regression analysis was performed to compare both groups. RESULTS: A total of 68,699 patients with RC were included. Incidence of RC among young patients increased significantly over the study period (2.4% vs. 3.4%; P=0.04). Majority of young patients with RC were white females. Bleeding was the most common presentation among young patients (P=0.03). Younger patients were more likely to have a family history of RC (P=0.01) and were more likely to undergo elective surgery (P=0.04) and laparoscopic surgery (P=0.02) compared to the older patients. Younger patients with RC were also more likely to use alcohol (P=0.03), be obese (P=0.02) compared to elder patients. There was no difference in the other co-morbidities between the two groups. After controlling for all factors in a regression model, younger patients had a lower complication rate (P=0.01), hospital LOS (P=0.02), and mortality rate (P=0.04). CONCLUSIONS: RC in younger patients appears as a different disease with different outcomes. There appears to be multifactorial and environmental factors contributing to this trend. Race and gender also play a role in the incidence of RC in the young. Identifying these risk factors will lead to a more robust intervention plan to help improve care among younger patients with RC.

SFRP4 expression correlates with epithelial mesenchymal transition-linked genes and poor overall survival in colon cancer patients.

BACKGROUND: Colon cancer is among the most commonly diagnosed cancers in the United States with an estimated 97220 new cases expected by the end of 2018. It affects 1.2 million people around the world and is responsible for about 0.6 million deaths every year. Despite decline in overall incidence and mortality over the past 30 years, there continues to be an alarming rise in early-onset colon cancer cases (< 50 years). Patients are often diagnosed at late stages of the disease and tend to have poor survival. We previously showed that the WNT "gatekeeper" gene, secreted frizzled-related protein 4 (SFRP4), is over-expressed in early-onset colon cancer. SFRP4 is speculated to play an essential role in cancer by inhibiting the epithelial mesenchymal transition (EMT). AIM: To investigate the correlation between SFRP4 expression and EMT-linked genes in colon cancer and how it affects patient survival. METHODS: SFRP4 expression relative to that of EMT-linked genes and survival analysis were performed using the University of California Santa Cruz Cancer Browser interface. RESULTS: SFRP4 was found to be co-expressed with the EMT-linked markers CDH2, FN1, VIM, TWIST1, TWIST2, SNAI1, SNAI2, ZEB1, ZEB2, POSTN, MMP2, MMP7, MMP9, and COL1A1. SFRP4 expression negatively correlated with the EMT-linked suppressors CLDN4, CLDN7, TJP3, MUC1, and CDH1. The expression of SFRP4 and the EMT-linked markers was higher in mesenchymal-like samples compared to epithelial-like samples which potentially implicates SFRP4-EMT mechanism in colon cancer. Additionally, patients overexpressing SFRP4 presented with poor overall survival (P = 0.0293). CONCLUSION: Considering the implication of SFRP4 in early-onset colon cancer, particularly in the context of EMT, tumor metastasis, and invasion, and the effect of increased expression on colon cancer patient survival, SFRP4 might be a potential biomarker for early-onset colon cancer that could be targeted for diagnosis and/or disease therapy.

Disparities in colon and rectal cancer queried individually between Hispanics and Whites.

BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer related deaths in the United States. Racial disparities between Hispanics and Whites exist for incidence of late-onset (LO) CRC. However, not much is known about potential disparities between colon cancer (CC) and rectal cancer (RC) incidence queried individually. METHODS: Using the SEER database data from 2000 to 2010, we obtained the national estimates of CC and RC for Hispanics and Whites. We analyzed trends in incidence, mortality, gender and stage of disease for early-onset (EO) (<50 years old) and LO (>50 years old) CC and RC. RESULTS: In Hispanics, the overall incidence of CC and RC increased by 47% and 52%, respectively; while in Whites, the overall incidence of CC and RC decreased by 13% and 2% respectively. Incidence of EO CC increased in both Hispanics and Whites by 83% and 17%, respectively, and incidence of EO RC also increased for both groups with a 76% increase in Hispanics and a 34% increase in Whites. For LO CC, the incidence increased by 37% in Hispanics while it decreased by 17% in Whites and for LO RC, the trend in incidence increased in Hispanics by 41%, but decreased in Whites by 11%. CONCLUSIONS: This study established that the incidence of CC and RC are different and there is racial disparity in incidence between Whites and Hispanics. This study, hopefully, will help in crafting public policy that might help in addressing this disparity.

Increasing Incidence of Colon Cancer in the Young: Assessing the Tumor Biology.

BACKGROUND: The overall incidence of colon cancer (CC) is decreasing, but with increasing early-onset colon cancer (EOCC < 50 years old). Our recent study revealed unique overexpression of cartilage oligomeric matrix protein (COMP) in EOCC and its association with aggressiveness. The aim of this study was to assess CC biology, especially in the young, by evaluating the role of COMP in CC carcinogenesis and cancer progression, detecting COMP in serum and its association with disease stage. STUDY DESIGN: Cancer and matching noninvolved tissue blocks from 12 sporadic EOCC and late-onset colon cancer (LOCC) patients of 4 disease stages were obtained from pathology archives. Ribonucleic acid expression profiling of 770 cancer-related genes using nCounter platform was performed. The COMP levels from 16 EOCC and LOCC serum samples were measured by ELISA. Carcinoembryonic antigen levels from these 16 samples were taken at the time of diagnosis. Transwell assay was performed to elucidate the role of COMP in motility and metastases. RESULTS: Expression profiling revealed increased COMP levels in higher disease stage. There was 7-fold higher COMP expression (p ≤ 0.05) in stage III compare to stage I and its coexpression with GAS1, VEGFC, MAP3K8, SFRP1, and PRKACA. Higher COMP expression was seen in stage II compared with stage I (p = 0.07) and its coexpression withTLR2, IL8, RIN1, IRAK3, and CACNA2D2, and COMP was detectable in serum and showed significantly higher levels in EOCC compared with LOCC. Similar correlation was seen with CEA levels, but the difference was not significant. Transwell assay revealed significantly increased motility of HT-29 cells after treatment with recombinant COMP. CONCLUSIONS: These findings suggest different tumor biology between EOCC and LOCC. Cartilage oligomeric matrix protein plays a significant role in CC carcinogenesis and has potential as biomarker for CC, especially aggressive EOCC.

Racial disparities in the incidence of colon cancer in patients with inflammatory bowel disease.

BACKGROUND: Studies have explored the relationship between inflammatory bowel disease (IBD) [ulcerative colitis (UC) and Crohn's disease (CD)] and colon cancer (CC). Additionally, racial disparities in the incidence of CC is well known. However, the impact of racial disparity in IBD patients who develop CC remains unclear. The aim of this study is to address the knowledge gap in this particular group of patients. METHODS: A retrospective analysis was done using the National Inpatient Sample (NIS) database from 2011. We included patients with IBD over age ≥18 years with a diagnosis of CC. Patients were stratified by race, gender, age, presence of IBD and CC. Statistical analysis was performed to compare the groups. RESULTS: A total of 57,542 patients were included (CD: 36,357, UC: 21,001). Of all patients with and without IBD, advanced age, Black and Asian race conferred an increased risk of developing CC, whereas female gender, Hispanic and Native American race conferred a protective effect. In patients with IBD, advanced age conferred an increased risk for developing CC while female gender conferred a protective effect. In this subset of patients, black race conferred a protective effect. CONCLUSIONS: Racial disparity exists in the overall incidence of CC and among patients with IBD who develop CC. Interestingly, black race conferred a protective effect for patients with IBD, contrary to what is seen in the general population. These findings could be attributed to the environmental factors and genetic makeup between racial groups. Further studies are warranted to better understand these disparities.

Racial and gender disparities in the incidence of anal cancer: analysis of the Nationwide Inpatient Sample (NIS).

BACKGROUND: Racial and gender disparities have been shown in other gastrointestinal cancers. However, there is a paucity of data on racial and gender disparities in anal cancer (AC). The aim of this study was to assess racial and gender disparities among patients with AC. METHODS: We analyzed data from the National Inpatient Sample (NIS) 2011 database of patients diagnosed with AC with age ≥18. Demographic data including age, race and gender were assessed. Patients were stratified based on race and gender. Log binomial regression was used to generate risk ratios. RESULTS: A total of 6,013,105 patients were assessed and 1,956 (0.03%) patients had AC. Female patients were more at risk of developing AC [relative risk (RR): 1.14, P=0.02]. Whites and Blacks had the highest incidence followed by Asians/Pacific Islanders. Black males had increased risk of AC (RR: 1.43, P<0.01). Amongst Hispanics; both males (RR: 0.69, P=0.05) and females (RR: 0.46, P<0.0001) had decreased risk of developing AC. Finally, we saw that Asian females had a much lower risk of developing AC (RR: 0.33, P<0.01). CONCLUSIONS: Racial disparities and gender differences exist in the incidence of AC. Potential causes for this disparity are disparate access to healthcare, lack of education, and lack of awareness. Greater understanding of the racial disparity in AC can help identify at risk population and eventually lead to improved preventative measures to ultimately reduce the incidence of AC.

COMP Gene Coexpresses With EMT Genes and Is Associated With Poor Survival in Colon Cancer Patients.

BACKGROUND: About 1.2 million new cases of colon cancer (CC) and 0.6 million deaths are reported every year, establishing CC as an important contributor to worldwide cancer morbidity and mortality. Although the overall incidence and mortality of CC have declined over the past 3 decades, the number of early-onset colon cancer ([EOCC], patients <50 y old) continues to rise alarmingly. These young patients are often diagnosed at a more advanced stage and tend to have poor survival. Our recently published data showed that the cartilage oligomeric matrix protein (COMP) is overexpressed in early-onset colon cancer patients. COMP is also reported in several cancers to coexpress with epithelial-mesenchymal transition (EMT) transcription factors. Given the role of EMT in cancer metastasis and cell invasion, we assessed the correlation between COMP gene expression and EMT gene expression in CC, and COMP's relationship to patient survival. METHODS: mRNA expression of COMP was compared to that of EMT markers using the UCSC Cancer Genomics Browser. Survival analysis was performed using the UCSC Xena Browser for cancer genomics. RESULTS: Expression analysis revealed coexpression of COMP with the EMT markers CDH2, FN1, VIM, TWIST1, TWIST2, SNAI1, SNAI2, ZEB1, ZEB2, POSTN, MMP2, MMP9, and COL1A1. Samples that were more mesenchymal had higher expression levels of COMP and EMT markers, thus suggesting a potential role of COMP in EMT. Patients with increased COMP expression presented with poorer overall survival compared to patients with no change or reduced COMP expression (P = 0.02). CONCLUSIONS: These findings reveal COMP as a potential biomarker for CC especially in more aggressive CC and CC in young patients, with a likely role in EMT during tumor metastasis and invasion, and a contributing factor to patient survival.