Ramzi Amri

Impact of Screening Colonoscopy on Outcomes in Colon Cancer Surgery

IMPORTANCE Screening colonoscopy seemingly decreases colorectal cancer rates in the United States. In addition to removing benign lesions and preventing progression to malignancy, screening colonoscopy theoretically identifies asymptomatic patients with early-stage disease, potentially leading to higher survival rates. OBJECTIVES To assess the effect of screening colonoscopy on outcomes of colon cancer surgery by reviewing differences in staging, disease-free interval, risk of recurrence, and survival and to identify whether diagnosis through screening improves long-term outcomes independent of staging. DESIGN Retrospective review of prospectively maintained, institutional review board-approved database. SETTING Tertiary care center with high patient volume. PATIENTS All patients who underwent colon cancer surgery at Massachusetts General Hospital from January 1, 2004, through December 31, 2011. INTERVENTION Colon cancer surgery. MAIN OUTCOMES AND MEASURES Postoperative staging, death, and recurrence, measured as incidence and time to event. RESULTS A total of 1071 patients were included, with 217 diagnosed through screening. Patients not diagnosed through screening were at risk for a more invasive tumor (≥T3: relative risk [RR] = 1.96; P < .001), nodal disease (RR = 1.92; P < .001), and metastatic disease on presentation (RR = 3.37; P < .001). In follow-up, these patients had higher death rates (RR = 3.02; P < .001) and recurrence rates (RR = 2.19; P = .004) as well as shorter survival (P < .001) and disease-free intervals (P < .001). Cox and logistic regression controlling for staging and baseline characteristics revealed that death rate (P = .02) and survival duration (P = .01) were better stage for stage with diagnosis through screening. Death and metastasis rates also remained significantly lower in tumors without nodal or metastatic spread (all P < .001). CONCLUSIONS AND RELEVANCE Patients with colon cancer identified on screening colonoscopy not only have lower-stage disease on presentation but also have better outcomes independent of their staging. Compliance to screening colonoscopy guidelines can play an important role in prolonging longevity, improving quality of life, and reducing health care costs through early detection of colon cancer.

Obesity, outcomes and quality of care: body mass index increases the risk of wound-related complications in colon cancer surgery

BACKGROUND Obese patients may face higher complication rates during surgical treatment of colon cancer. The aim of this study was to measure this effect at a high-volume tertiary care center. METHODS All patients with colon cancer treated surgically at a single center from 2004 through 2011 were reviewed. Multivariate regression assessed relationships of complications and stay outcomes with body mass index (BMI) controlling for age, gender, comorbidity score, surgical approach, and history of smoking. RESULTS In 1,048 included patients, BMI was a predictor of several complications in both laparoscopic and open procedures. For every increase of BMI by one World Health Organization category, the odds ratios were 1.61 (P < .001) for wound infection and 1.54 (P < .001) for slow healing. Additionally, right colectomies had an odds ratio of 3.23 (P = .017) for wound dehiscence. No further associations with BMI were found. CONCLUSIONS BMI was incrementally associated with wound-related complications, illustrating how the proliferation of obesity relates to a growing risk for surgical complications. As the surgical community strives to improve the quality of care, patient-controllable factors will play an increasingly important role in cost containment and quality improvement.

Preoperative carcinoembryonic antigen as an outcome predictor in colon cancer

Several reports have shown that certain pre‐operative CEA intervals can be predictive of long‐term outcomes and have subsequently implied that preoperative CEA may be useful to assess the risk of recurrence or death as a continuous number for individual cases. This analysis assesses if this hypothesis is valid after correction for confounders.

The conundrum of the young colon cancer patient.

BACKGROUND Colonoscopy has had a major impact on the incidence and survival of colon cancer for patients who are screened, usually beginning at the age of 50. Meanwhile, the incidence rate of colon cancer is actually increasing in the patients younger than 50 while no routine screening is implemented for this age group. METHODS All patients surgically treated for colon cancer (2004-2011) without preexisting high-risk characteristics (hereditary nonpolyposis colorectal cancer, inflammatory bowel disease) were included (n = 1,015). Age-related disparities in baseline disease and outcomes were reviewed. RESULTS Patients younger than 50 years of age (n = 108; 10.6%) had the greatest baseline rates of metastatic (20.4% vs 8.0%; P < .001), node-positive disease (54.6% vs 39.4%; P = .002), and greater rates of extramural vascular invasion (38.9 vs 29.4%; P = .043). Cancer-related mortality also was greatest in this group (28.7 vs 18.4%; P = .011). Multivariable Cox regression shows that patients younger than 50 are still at significantly greater risk of mortality after adjustment for effects of age, baseline AJCC staging, smoking, and comorbidity (hazard ratio: 1.57, 95% confidence interval 1.01-2.45; P = .049). DISCUSSION Patients younger than 50 present with the most advanced and aggressive disease, giving them the worst stage-independent prognosis of all age groups. Potential causes include age-related differences in tumor biology and underdetection by current screening efforts. This raises the question of how to address the conundrum of the young colon cancer patient, who often is the proverbial needle in a haystack of young patients, with nonspecific gastrointestinal symptoms but who would benefit considerably from early detection.

Gender and ethnic disparities in colon cancer presentation and outcomes in a US universal health care setting.

Access to care is a pillar of U.S. healthcare reform and could potentially challenge existing ethnic and gender disparities in care. We present a snapshot of these disparities in surgical colon cancer patients in the largest public hospital in Massachusetts, a state leading in providing universal healthcare, to indicate potential changes that might result from universal care access.

Association of Radial Margin Positivity With Colon Cancer

IMPORTANCE In colon cancer, radial margin positivity (RMP) is defined as primary disease involvement at the cut edge of the mesentery or nonserosalized portions of the colon. Although extensively studied for rectal malignancies, RMP has unclear prognostic implications for tumors of the colon. OBJECTIVE To determine the effect of RMP on perioperative outcomes as well as survival and disease-free survival in colon cancer. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study including all patients with surgically treated colon cancer at a tertiary care center from January 1, 2004, through December 31, 2011. The cohort was retrospectively extracted from an institutional patient data repository and included in a data repository maintained prospectively starting June 1, 2011, to April 1, 2014. Participants included 984 patients with surgical colon cancer in the given period, excluding patients with intramucosal tumors (n = 47), palliative resections (n = 24), and patients where radial margin status was not assessable (n = 16). MAIN OUTCOMES AND MEASURES Surgical characteristics, postoperative staging, and long-term outcomes, including recurrence and disease-free survival. RESULTS Of the 984 included cases, 52 (5.3%) had an involved radial margin. Patients with RMP had much higher rates of multivisceral resection (40.4% vs 12.8%; relative risk, 3.16 [95% CI, 2.18-4.58]; P < .001) and conversion (50.0% vs 13.7%; relative risk, 3.78 [95% CI, 1.56-9.18]; P = .01). All patients with RMP had American Joint Committee on Cancer stage II cancer or higher, with higher rates of node positivity (86.5% vs 38.8%; relative risk, 2.23 [95% CI, 1.95-2.55]; P < .001), metastasis (34.6% vs 6.7%; relative risk, 5.20 [95% CI, 3.34-8.11]; P < .001), extramural vascular invasion (76.9% vs 28.4%; relative risk, 2.71 [95% CI, 2.26-3.24]; P < .001), and high-grade tumor (45.1% vs 18.2%; relative risk, 3.01 [95% CI, 2.44-3.88]; P < .001). In patients without baseline metastasis, metastatic disease in follow-up was considerably higher in patients with RMP (37.5% vs 12.5%; relative risk, 3.32 [95% CI, 2.79-3.95]; P < .001), especially peritoneal (18.8% vs 2.6%; relative risk, 7.24 [95% CI, 2.40-21.8]; P < .001) and liver (18.8% vs 6%; relative risk, 3.10 [95% CI, 1.08-8.92]; P = .04) metastasis. In multivariable Cox regression, the hazard ratio for survival adjusted for baseline staging, age, comorbidity, smoking, and neoadjuvant chemotherapy was higher (hazard ratio, 3.39; 95% CI, 2.41-4.77; P < .001) compared with metastasis adjusted for baseline staging, smoking, and neoadjuvant chemotherapy (hazard ratio, 2.03; 95% CI, 1.43-2.89; P < .001). The median follow-up duration for patients alive on April 1, 2014, was 51 months (interquartile range, 33-76 months). CONCLUSIONS AND RELEVANCE An involved radial margin leads to high rates of conversion and multivisceral resection. Although occurring infrequently, RMP is an important stage-independent outcome predictor strongly associated with recurrence, risk of death, and shorter survival. Preoperative assessment, especially imaging, could play a key role in the timely identification of potential patients with RMP to take adequate preparatory surgical and therapeutic measures.

Risk Stratification for Surgical Site Infections in Colon Cancer

Importance Surgical site infections (SSIs) feature prominently in surgical quality improvement and pay-for-performance measures. Multiple approaches are used to prevent or reduce SSIs, prompted by the heavy toll they take on patients and health care budgets. Surgery for colon cancer is not an exception. Objective To identify a risk stratification score based on baseline and operative characteristics. Design, Setting, and Participants This retrospective cohort study included all patients treated surgically for colon cancer at Massachusetts General Hospital from 2004 through 2014 (n = 1481). Main Outcomes and Measures The incidence of SSI stratified over baseline and perioperative factors was compared and compounded in a risk score. Results Among the 1481 participants, 90 (6.1%) had SSI. Median (IQR) age was 66.9 (55.9-78.1) years. Surgical site infection rates were significantly higher among people who smoked (7.4% vs 4.8%; P = .04), people who abused alcohol (10.6% vs 5.7%; P = .04), people with type 2 diabetics (8.8% vs 5.5%; P = .046), and obese patients (11.7% vs 4.0%; P < .001). Surgical site infection rates were also higher among patients with an operation duration longer than 140 minutes (7.5% vs 5.0%; P = .05) and in nonlaparoscopic approaches (clinically significant only, 6.7% vs 4.1%; P = .07). These risk factors were also associated with an increase in SSI rates as a compounded score (P < .001). Patients with 1 or fewer risk factors (n = 427) had an SSI rate of 2.3%, equivalent to a relative risk of 0.4 (95% CI, 0.16-0.57; P < .001); patients with 2 risk factors (n = 445) had a 5.2% SSI rate (relative risk, 0.78; 95% CI, 0.49-1.22; P = .27); patients with 3 factors (n = 384) had a 7.8% SSI rate (relative risk, 1.38; 95% CI, 0.91-2.11; P = .13); and patients with 4 or more risk factors (n = 198) had a 13.6% SSI rate (relative risk, 2.71; 95% CI, 1.77-4.12; P < .001). Conclusions and Relevance This SSI risk assessment factor provides a simple tool using readily available characteristics to stratify patients by SSI risk and identify patients at risk during their postoperative admission. Thereby, it can be used to potentially focus frequent monitoring and more aggressive preventive efforts on high-risk patients.

Does active smoking induce hematogenous metastatic spread in colon cancer

BACKGROUND No consensus exists on the influence of active smoking on the baseline staging of colon cancer patients. METHODS A cohort of colon cancer patients treated surgically at Massachusetts General Hospital (2004 to 2011) was reviewed. RESULTS Of 1,071 patients, 563 reported ever smoking, among which 128 (12%) patients were current smokers. Ex-smokers and never smokers had similar rates of nodal (relative risk [RR] .9, P = .19) and metastatic disease (RR .96, P = .72), leading to comparable colon cancer-related mortality (RR 1.01, P = .95). Current smokers had similar rates of lymph node disease (RR 1.01, P = .88), but had significantly higher stage-adjusted odds of metastatic disease at presentation (odds ratio 2.57, 95% confidence interval 1.36 to 4.98, P = .005), in addition to higher stage-adjusted all-cause mortality (hazard ratio 1.44, P = .017). CONCLUSIONS Active smoking was a stage-independent risk factor for baseline hematogenous metastasis and mortality. As this link was not present in former smokers, a potential healthcare benefit may be achieved in terms of baseline colon cancer presentation and outcomes through smoking cessation.

Diverse repetitive element RNA expression defines epigenetic and immunologic features of colon cancer

There is tremendous excitement for the potential of epigenetic therapies in cancer, but the ability to predict and monitor response to these drugs remains elusive. This is in part due to the inability to differentiate the direct cytotoxic and the immunomodulatory effects of these drugs. The DNA-hypomethylating agent 5-azacitidine (AZA) has shown these distinct effects in colon cancer and appears to be linked to the derepression of repeat RNAs. LINE and HERV are two of the largest classes of repeats in the genome, and despite many commonalities, we found that there is heterogeneity in behavior among repeat subtypes. Specifically, the LINE-1 and HERV-H subtypes detected by RNA sequencing and RNA in situ hybridization in colon cancers had distinct expression patterns, which suggested that these repeats are correlated to transcriptional programs marking different biological states. We found that low LINE-1 expression correlates with global DNA hypermethylation, wild-type TP53 status, and responsiveness to AZA. HERV-H repeats were not concordant with LINE-1 expression but were found to be linked with differences in FOXP3+ Treg tumor infiltrates. Together, distinct repeat RNA expression patterns define new molecular classifications of colon cancer and provide biomarkers that better distinguish cytotoxic from immunomodulatory effects by epigenetic drugs.

The fate of unscreened women in colon cancer: impact on staging and prognosis

BACKGROUND Several nationwide reports show lower female participation in colon cancer screening. We therefore assessed for outcome differences in women of screening age presenting for surgical treatment of colon cancer patients. METHODS All patients over 50 years undergoing surgery for first-onset colon cancer at Massachusetts General Hospital (2004 to 2011) were included. Differences between (unscreened) women and the remaining population in presentation characteristics and subsequent morbidity and mortality were assessed. RESULTS We included 919 patients (49.1% female). Women were less often diagnosed through screening (26.4 vs 32.7%, P = .036). Unscreened women were at significantly higher risk (all P < .001) for having high-grade tumors (Relative risk [RR] = 1.61), lymph node metastasis (RR = 1.36), and distant metastasis (RR = 2.26) on pathology, leading to higher colon cancer-related mortality (RR = 1.72). CONCLUSION Unscreened women present with more advanced colon cancer and higher mortality, confirming that disparities in screening lead to ever-increasing disparities in outcomes.