Najjia N. Mahmoud

Aspirin prevents tumors in a murine model of familial adenomatous polyposis

BACKGROUND Both human and murine studies suggest that anti-inflammatory drugs prevent intestinal neoplasia. The purpose of this study was to investigate the role of aspirin as a chemopreventive agent for colorectal cancer. METHODS We administered aspirin to the Min/+ mouse, an animal with a germline mutation in Apc, a gene that is essential for normal epithelial cell growth and differentiation. Apc mutation increases cytoplasmic beta-catenin, a regulatory protein associated with the cytoskeleton. Min/+ mice develop multiple intestinal adenomas and exhibit altered cell growth in the preneoplastic intestinal epithelium. RESULTS Aspirin decreased the rate of tumor formation in Min/+ mice by 44%. Aspirin also normalized enterocyte growth by increasing apoptosis and proliferation in the preneoplastic intestinal mucosa. Finally, aspirin produced a decrease in intracellular beta-catenin levels, suggesting that modulation of this protein is associated with tumor prevention. CONCLUSIONS These data confirm a role for aspirin in suppression of Apc-associated intestinal carcinogenesis.

Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma

AbstractPURPOSE: An interval of six to eight weeks between completion of preoperative chemoradiation therapy and surgical resection of advanced rectal cancer has been described. Our purpose was to determine whether a longer time interval between completion of therapy and resection increases tumor downstaging and affects perioperative morbidity. METHODS: Forty patients with advanced adenocarcinoma of the rectum underwent preoperative chemoradiation on a prospective trial with irinotecan (50 mg/m2), 5-fluorouracil (225 mg/m2), and concomitant external-beam radiation (45–54 Gy) followed by complete surgical resection of the tumor with total mesorectal excision. The time interval between completion of chemoradiation and surgical resection ranged from 28 to 97 days. The patients were divided into two groups with 33 eligible patients: Group A (4-week to 8-week time interval; 28–56 days) and Group B (10-week to 14-week interval; 67–97 days). Tumor downstaging was compared between these two groups. The number of patients downstaged by at least one T stage, those downstaged by at least one N stage, those with pathologic complete responses, and those with only residual microscopic tumor foci were compared. Postoperative length of stay, estimated blood loss, perioperative morbidity, and sphincter-sparing procedures were also compared. Chi-squared tests and Student’s t-test were calculated. RESULTS: Group A had 19 patients, and Group B had 14 patients. Patient demographics were comparable. Mean age was 52 years, and 70 percent of patients were male. There were no deaths. There were no statistical differences in perioperative morbidity, with three anastomotic leaks in Group A. Tumors were downstaged in 58 percent of patients in Group A and 43 percent of those in Group B (P = 0.61). Nodal downstaging occurred in 78 percent of Group A and 67 percent of Group B (P = 0.9). The pathologic complete response rate was 21 percent in Group A and 14 percent in Group B (P = 0.97), and a residual microfocus of tumor was found in 33 percent of patients in Group A and 42 percent of those in Group B (P = 0.90). These differences were not statistically significant. CONCLUSIONS: Perioperative morbidity is not affected by longer intervals. A longer interval between completion of neoadjuvant chemoradiation and surgical resection may not increase the tumor response rate of advanced rectal cancer in this cohort.

Biologic Determinants of Tumor Recurrence in Stage II Colon Cancer: Validation Study of the 12-Gene Recurrence Score in Cancer and Leukemia Group B (CALGB) 9581

PURPOSE A greater understanding of the biology of tumor recurrence should improve adjuvant treatment decision making. We conducted a validation study of the 12-gene recurrence score (RS), a quantitative assay integrating stromal response and cell cycle gene expression, in tumor specimens from patients enrolled onto Cancer and Leukemia Group B (CALGB) 9581. PATIENTS AND METHODS CALGB 9581 randomly assigned 1,713 patients with stage II colon cancer to treatment with edrecolomab or observation and found no survival difference. The analysis reported here included all patients with available tissue and recurrence (n = 162) and a random (approximately 1:3) selection of nonrecurring patients. RS was assessed in 690 formalin-fixed paraffin-embedded tumor samples with quantitative reverse transcriptase polymerase chain reaction by using prespecified genes and a previously validated algorithm. Association of RS and recurrence was analyzed by weighted Cox proportional hazards regression. RESULTS Continuous RS was significantly associated with risk of recurrence (P = .013) as was mismatch repair (MMR) gene deficiency (P = .044). In multivariate analyses, RS was the strongest predictor of recurrence (P = .004), independent of T stage, MMR, number of nodes examined, grade, and lymphovascular invasion. In T3 MMR-intact (MMR-I) patients, prespecified low and high RS groups had average 5-year recurrence risks of 13% (95% CI, 10% to 16%) and 21% (95% CI, 16% to 26%), respectively. CONCLUSION The 12-gene RS predicts recurrence in stage II colon cancer in CALGB 9581. This is consistent with the importance of stromal response and cell cycle gene expression in colon tumor recurrence. RS appears to be most discerning for patients with T3 MMR-I tumors, although markers such as grade and lymphovascular invasion did not add value in this subset of patients.

Impact of Surgical Site Infections on Length of Stay and Costs in Selected Colorectal Procedures

BACKGROUND Length of stay (LOS) and inpatient costs for open-abdomen colorectal procedures have not been examined recently. The aim of this study was to determine LOS and costs for several colorectal procedures in the context of factors potentially associated with surgical site infection (SSI). METHODS We used a large U.S. hospital database to identify the variables associated with longer LOS and higher costs for colorectal procedures from January 1, 2005, through June 30, 2006. The study population consisted of all patients >18 years, identified via International Classification of Disease, Ninth Revision, procedural codes for elective colorectal surgery. Patient demographics, surgical procedure, and a modified Study of the Efficacy of Nosocomial Infection Control (SENIC) infection risk score were examined using logistic regression as predictors of LOS >or=1 week and cost >or=

National Cancer Institute designation predicts improved outcomes in colorectal cancer surgery.

15,000. Patients given cefotetan as surgical prophylaxis were compared with patients given cefazolin/metronidazole. Superficial and deep SSIs were considered; intra-abdominal infection was not. RESULTS The 25,825 patients were of average age 63 years, with 53% being female and 75% being Caucasian. The overall infection rate was 3.7%. The mean LOS was 7.25 days, and the mean +/- standard deviation total cost per patient

Metastasectomy for stage IV colorectal cancer.

13,746 +/-

Gender influences treatment and survival in colorectal cancer surgery.

13,330. Rates of infection, LOS, and mean hospital costs were all greater for patients with a high SENIC score and increasing disease acuity. Values for these outcome variables were highest for procedures involving stoma formation, followed by operations on the small bowel and large bowel. Variables independently predictive of longer LOS were SSI (odds ratio [OR] 11.74; 95% confidence interval [CI] 9.67, 14.26), age >or=65 years (OR 1.90; 95% CI 1.81, 2.01), and high SENIC score (OR 1.79; 95% CI 1.67, 1.92), whereas Caucasian race (OR 0.86; 95% CI 0.81, 0.91) was predictive of a shorter LOS. Cefazolin/metronidazole was not predictive of a shorter LOS compared with cefotetan (OR 1.06; 95% CI 0.96, 1.17) but was associated with significantly more hospitalizations with costs >or=

Effect of time interval between surgery and preoperative chemoradiotherapy with 5‐fluorouracil or 5‐fluorouracil and oxaliplatin on outcomes in rectal cancer

15,000 (OR 1.39; 95% CI 1.23, 1.56). CONCLUSIONS Length of stay and cost rise proportionally with SENIC score, disease acuity, and patient characteristics such as age. Surgical site infections are significantly and independently associated with LOS and cost and contribute to inpatient morbidity and expense. Cefotetan has limited availability, and substitutions are utilized increasingly. Although equally efficacious in elective colon procedures, cefotetan used as surgical prophylaxis was associated with lower hospitalization costs than cefazolin plus metronidazole.

Secular Trends in Small Bowel Obstruction and Adhesiolysis in the United States, 1988–2007

Background:Although National Cancer Institute (NCI) designation as a cancer center is based almost solely on research activities, it is often viewed, by patients and referring providers, as an indication of clinical excellence. Objective:To compare the short- and long-term outcomes of colon and rectal cancer surgery performed at NCI-designated centers to the outcomes after resection at non–NCI-designated hospitals. Methods:We performed a retrospective cohort study of Survival, Epidemiology, and End Results (SEER)-Medicare database patients undergoing segmental colectomy (n = 33,969) or proctectomy (n = 8591) for cancer from 1996–2003. Multivariate logistic regression, with and without propensity scores, and matched conditional regression were performed to evaluate the relationship between NCI status and postoperative mortality (in-hospital or 30-day death). The log-rank test, Kaplan-Meier curves, and Cox regression compared survival between hospital types. Results:We evaluated 33,969 colectomy and 8591 proctectomy patients. Postoperative mortality after colectomy was 6.7% at non-NCI and 3.2% at NCI centers. Mortality after proctectomy was 5.0% and 1.9%, respectively. These differences were significant when adjusted for patient and hospital characteristics. For both colon and rectal cancer patients, long-term mortality was significantly improved after resection at NCI centers (HR 0.84, P < 0.001; HR 0.85, P = 0.02, respectively). Conclusion:NCI designation is associated with lower risk of postoperative death and improved long-term survival. Possible factors responsible for these benefits include surgeon training, multidisciplinary care, and adherence to treatment guidelines. Studies are underway to elucidate the factors leading to improved patient outcomes.

A novel approach to assessing technical competence of colorectal surgery residents: The development and evaluation of the colorectal objective structured assessment of technical skill (COSATS)

Metastatic colorectal cancer traditionally has been considered incurable. Over the past 3 decades, however, resection of low-volume hepatic disease has been recognized as beneficial in some cases. More recently, resection of isolated pulmonary metastases has been shown to offer long-term survival in carefully selected patients. Resection of metastases to more unusual sites (ovary, brain, peritoneal cavity) is more controversial; nevertheless, retrospective data suggest that a few patients may be cured with resection of these tumors. In this article, we review the history and current status of metastasectomy in stage IV colorectal cancer.