Neoadjuvant chemoradiation improves oncologic outcomes in low and mid clinical T3N0 rectal cancers.

BACKGROUND: Controversial data exists in the current literature in regard to the use of neoadjuvant chemoradiation (nCRT) in patients with clinical T3N0 (cT3N0) rectal cancers, specifically based on location and relation to peritoneal reflection. We aimed to analyze the impact of nCRT on oncologic outcomes among cT3N0 rectal cancers, depending on the tumor height from anal verge (AV). METHODS: A retrospective analysis of patients with cT3N0 rectal cancers was included from a query of a prospectively maintained rectal cancer database from 1980 to 2016. Patients were divided into 3 groups based on the tumor height: low (1-5 cm from AV), mid (6-10 cm from AV), and upper (11-15 cm from AV). Patients were stratified by use of nCRT. MAIN OUTCOMES: 5-year overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and local recurrence (LR) using Kaplan-Meier curves. RESULTS: Five hundred ninety-two patients were included. Overall, 364 (61.4%) patients received nCRT and 228 (38.6%) patients did not. There were 251 (43%) patients with low, 302 (51%) with mid, and 39 (7%) with upper rectal cancer. Patients with low and mid rectal cancers received nCRT more frequently than those with upper rectal cancers (68.5% and 61.2% vs 43.6%, p = 0.007). The 5-year OS was 78% and 63%, DFS-88% and 73%, LR-1% and 8% in nCRT followed by resection vs. surgery alone (p < 0.001). In regard to cancer location after nCRT compared with surgery alone, low and mid cancers had better OS, DFS, and CSS, compared with upper ones. CONCLUSION: nCRT prolongs survival among patients with rectal cancer below 10 cm from AV; however, it has no effect on 5-year oncologic survival of patients with upper rectal cancer located below peritoneal reflection.

Allergic sensitization and clinical outcomes in urban children with asthma, 2013-2016.

BACKGROUND: The aim of this study was to examine if food and/or aeroallergen sensitization was associated with worse asthma, pulmonary function tests (PFT), and laboratory markers. METHODS: At our institution, 386 children with asthma were divided into allergic and nonallergic groups based on allergen-specific immunoglobulin E (IgE) testing classes 1-6 versus 0. Asthma severity and/or control, IgE level, eosinophil counts and/or percentages, forced vital capacity (FVC), forced expiratory volume in the first second of expiration (FEV1), and FEV1/FVC, were compared by using bivariate, regression, and subgroup analyses for children who were highly allergic (≥4 allergens). RESULTS: A total of 291 subjects with asthma were allergic, significantly older, and had higher mean IgE levels and eosinophil counts and percentages (all p < 0.001). A total of 203 subjects who were highly allergic had worse obstruction on PFTs. Increasing age predicted allergen sensitization after confounder adjustment, odds ratio (OR) 1.54 (95% confidence interval [CI], 1.18-2.02). Similarly, PFT obstruction was associated with multiple allergen sensitization (OR 0.97 [95% CI, 0.93-1.02]). CONCLUSION: Increasing age predicted allergic sensitization and multiple allergen sensitization. Worse obstruction on PFT also predicted multiple allergen sensitization. Continued surveillance of aeroallergen sensitization and PFT results may be beneficial in asthma management, particularly in older urban children.

Recurrence and survival rates of inflammatory bowel disease-associated colorectal cancer following postoperative chemotherapy: a comparative study.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC, suggesting differences in tumor behavior and response to treatment. We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD. METHODS: Search of the Cleveland Clinic's CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010. Twenty-one patients were excluded due to incomplete clinical data. Propensity score-matching based on age, surgery intent, CRC site, tumor grade, American Joint Committee on Cancer (AJCC) stage and T stage was used to match IBD and non-IBD patients (1:4). Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival, respectively. RESULTS: Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC. Among IBD patients, 29 (66%) had ulcerative colitis, 14 (32%) had Crohn's disease, and one (2%) had indeterminate colitis. Mean IBD diagnosis age was 28.1 ± 14.5 years, and mean IBD duration at time of CRC treatment was 21.5 ± 12.6 years. Ten (23%) IBD patients had tumor recurrence compared with 34 (19%) non-IBD patients (P = .074). There was no significant difference in disease-free survival (hazard ratio [HR] = 0.60; 95% CI: 0.35-1.05; P = 0.074) or overall survival (HR = 0.87; 95% CI: 0.54-1.4; P = 0.58) between IBD and non-IBD patients. CONCLUSION: Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD. Prospective studies are needed to confirm these findings and guide therapeutic decisions.

Dual expression of MYC and BCL2 proteins predicts worse outcomes in diffuse large B-cell lymphoma.

Recent studies suggested that MYC and BCL2 protein co-expression is an independent indicator of poor prognosis in diffuse large B-cell lymphoma. However, the immunohistochemistry protocols for dual-expression staining and the scoring cut-offs vary by study. Sixty-nine cases of diffuse large B-cell lymphoma were evaluated for MYC and BCL2 protein expression using various cut-offs that have been recommended in prior studies. Independent of the International Prognostic Index risk group, cases with dual protein expression of BCL2 and MYC using ≥50%/40% cut-offs and ≥70%/40% had significantly shorter overall survival than cases without. It was verified in this patient population that the use of BCL2 and MYC immunohistochemistry, performed with available in vitro diagnostic-cleared antibodies, provides rapid prognostic information in patients with de novo diffuse large B-cell lymphoma. This study has practical implications for diagnostic laboratories and serves as a guide for implementation in the setting of future clinical trials.

Crohn's disease-like reaction predicts favorable prognosis in colitis-associated colorectal cancer.

BACKGROUND: Idiopathic inflammatory bowel disease is associated with an increased risk of developing colorectal cancer. Colitis-associated colorectal cancer (CAC) has unique histomorphology features; however, whether histomorphology is predictive of survival in CAC, independent of overall clinical tumor stage, remains unknown. The aim of this study is to determine if clinicodemographics and tumor histomorphologic features are prognostic in patients with CAC. METHODS: A cohort of CAC patients were identified from the Pathology Database at Cleveland Clinic; slides were reviewed and other relevant data were collected by retrospective review of medical records. RESULTS: Univariate analysis demonstrated that poor differentiation, N stage (N1/N2 versus N0), M stage (M1 versus M0), Tumor, Node, Metastasis (TNM) stage (III/IV versus I/II), positive margin, and Crohn's-like reaction were significantly associated with both overall survival (OS) and progression-free survival (PFS) in CAC. Additionally, the presence of >2 tumor-infiltrating lymphocytes/high-power field was found to be significantly associated with longer PFS. Multivariate analysis confirmed that high TNM stage (III/IV versus I/II) was associated with shorter OS and PFS (hazard ratio 2.7, 95% confidence interval [CI]: 1.1-6.7, P = 0.04; 4.84 [95% CI: 2.0-11.5], P < 0.001, respectively), and positive margin status was associated with shorter OS (hazard ratio 4.0 [95% CI: 1.0-15.7], P = 0.05), whereas the presence of Crohn's-like reaction was associated with longer OS and PFS (hazard ratio 0.3 [95% CI: 0.12-0.79], P = 0.02; 0.25 [95% CI: 0.11-0.58], P = 0.001, respectively). CONCLUSIONS: In CAC, high tumor clinical stage and positive margin predict worse survival but Crohn's disease-like reaction is associated with longer OS and PFS.

Intraoperative colonoscopy does not worsen the outcomes of laparoscopic colorectal surgery: a case-matched study.

BACKGROUND: Intraoperative colonoscopy is sometimes needed as an adjunct to colorectal surgery. When it is performed with laparoscopic surgery, there is the potential for prolonged bowel distension, obstructed surgical exposure, and increased morbidity. This study aimed to evaluate the overall safety and outcomes of laparoscopic colorectal procedures in which intraoperative colonoscopy was performed. METHODS: The study group consisted of patients who underwent intraoperative colonoscopy during laparoscopic intestinal resection at our institution between 1995 and 2011. They were individually matched for a number of factors including age, gender, diagnosis, American Society of Anesthesiologists (ASA) physical status score, and type of surgical procedure with a cohort of patients who underwent laparoscopic intestinal resection with no intraoperative colonoscopy during the same period. Early postoperative outcomes and time to flatus and first bowel movement were compared. RESULTS: For the study, 30 patients (18 females) and 30 matched control subjects were identified. The study and control groups did not differ in terms of operating time (132 vs 151 min; p = 0.5), estimated blood loss (216 vs 212 ml; p = 0.9), conversion to open surgery (n = 1 vs 5; p = 0.2), time to first flatus (3 vs 4 days; p = 0.4), time to first bowel movement (4 vs 4 days; p = 0.4), reoperation (n = 0 vs 1; p = 1), length of hospital stay (6 vs 9 days; p = 0.3), overall morbidity (n = 10 vs 14; p = 0.4), or readmission (n = 0 vs 1; p = 1). The complications that developed during or after surgery were similar in the two groups. No colonoscopy-related complications or deaths occurred. CONCLUSIONS: Intraoperative colonoscopy does not complicate the application and outcomes of laparoscopic intestinal resection. Surgeons should perform an intraoperative colonoscopy when it is indicated during laparoscopic surgery.

Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients.

BACKGROUND: Ileal pouch anal anastomosis (IPAA) is the treatment of choice for chronic, medically refractory mucosal ulcerative colitis, indeterminate colitis, familial adenomatous polyposis (FAP), and a select group of patients with Crohn's disease. AIM: : We report outcomes, complications, and quality of life (QOL) in a cohort of 3707 patients treated at our institution from January 1984 to March 2010. METHODS: Data were collected from a prospectively maintained database and chart review of 3707 consecutive primary IPAA cases. Patient demographics, postoperative complications, functional outcomes, and QOL data were available. Follow-up consisted of clinical examination with assessment of pouch function and QOL. RESULTS: A total of 3707 patients underwent primary pouch and 328 underwent redo pouch surgery. Postoperative histopathological diagnoses were mucosal ulcerative colitis (n = 2953, 79.7%), indeterminate colitis (n = 63, 1.7%), FAP (n = 223, 6%), Crohn's disease (n = 150, 4%), cancer/dysplasia (n = 97, 2.6%), and others (n = 221, 6.0%). Early perioperative complications were encountered in 33.5% of patients with a mortality rate of 0.1%. Excluding pouchitis, late complications were experienced by 29.1% of patients. Of those patients who had IPAA at our institution, pouch failure occurred in 197 patients (5.3%). During a median follow-up of 84 months, 119 patients (3.2%) required excision of the pouch, 32 (0.8%) had a nonfunctioning pouch, and 46 patients (1.2%) had redo IPAA. Functional outcomes and QOL were good or excellent in 95% of patients and similar in each histopathological subgroup. CONCLUSIONS: IPAA is an excellent option for patients with MUC, IC, FAP, and select patients with Crohn's disease.

BRAF mutations in colorectal cancer are associated with distinct clinical characteristics and worse prognosis.

BACKGROUND: Colorectal cancer is a heterogeneous disease with multiple underlying genetic mutations causing different clinical phenotypes. Mutation in the BRAF oncogene is a key step in malignant transformation within the methylator pathway to colorectal cancer. However, there is a paucity of information about BRAF mutant colorectal tumors. OBJECTIVE: This study defines the clinical characteristics and oncologic outcome associated with colorectal cancer BRAF mutations. DESIGN: Colorectal adenocarcinomas from a single-institution frozen-tumor biobank were studied. Genomic DNA was isolated and analyzed for mutations in the BRAF oncogene by polymerase chain reaction amplification followed by direct sequencing. A sample was classified as mutant if any of the tested loci were mutated. Patient and tumor characteristics were recorded including patient age, sex, tumor location, tumor differentiation, and microsatellite instability. MAIN OUTCOME MEASURES: Statistical associations with BRAF mutant tumors were determined by the Fisher exact probability test, χ test, or Wilcoxon analysis. Kaplan-Meier estimates and multivariate Cox regression analysis were performed for overall survival. RESULTS: Four hundred seventy-five colorectal adenocarcinomas were included in the study population; 56 samples harbored a BRAF mutation (12%). There were significant differences between BRAF wild-type and mutant tumors in age (66 vs 75 years, p = 0.004), female sex (44% vs 71%, p < 0.001), proximal tumor location (44% vs 95%, p < 0.001), and frequency of microsatellite instability (16% vs 76%, p < 0.001). There was no difference in cancer stage between BRAF mutant and wild-type populations. Survival data were analyzed for 322 patients with stage I to III disease, and patients with a BRAF mutation had decreased overall survival than those without a mutation (p = 0.018). With the use of Cox regression analysis, BRAF mutation conferred a worse overall survival (HR 1.79, CI 1.05-3.05, p = 0.03) independent of microsatellite instability status. CONCLUSIONS: BRAF mutations in colorectal cancers are associated with distinct clinical characteristics and worse prognosis.

Presence of concomitant inflammatory bowel disease is associated with an increased risk of postcholecystectomy complications.

BACKGROUND: Surgery in patients with inflammatory bowel disease (IBD) is often associated with complications. The aim of our study was to evaluate whether concomitant IBD was associated with an increased risk of postcholecystectomy complications. METHODS: The study group consisted of 82 consecutive IBD patients who underwent cholecystectomy from January 2001 to October 2010. The control group included 296 cholecystectomy patients without IBD who were randomly selected from the cholecystectomy database. Variables were analyzed by univariate and multivariate analyses. RESULTS: There were no significant differences in age, gender, body mass index, presence of gallstones/common bile duct stones, indication for cholecystectomy, and postoperative mortality between the study and control groups. More patients in the study group had postoperative complications than in the control group (17.1% vs. 6.8%, P = 0.005). On multivariate analysis, the presence of concomitant IBD was independently associated with an increased risk for postoperative complications (odds ratio [OR] = 4.64; 95% confidence interval [CI], 1.63-13.20, P = 0.004) after adjusting for age, the presence of cirrhosis, diabetes, body mass index, the use of corticosteroids, immunomodulators, total parental nutrition, or biologics, the presence of primary sclerosing cholangitis (PSC), acute or chronic cholecystitis, cholelithiasis, or prior abdominal surgeries, and indication for surgery (elective vs. emergent). CONCLUSIONS: IBD patients undergoing cholecystectomy have a significantly increased risk of postoperative complications. Although further studies are warranted to clarify the reason for these differences, caution should be taken to determine the need and timing of cholecystectomy in IBD patients.

A novel data-driven prognostic model for staging of colorectal cancer.

BACKGROUND: The aim of this study was to develop a novel prognostic model that captures complex interplay among clinical and histologic factors to predict survival of patients with colorectal cancer after a radical potentially curative resection. STUDY DESIGN: Survival data of 2,505 colon cancer and 2,430 rectal cancer patients undergoing radical colorectal resection between 1969 and 2007 were analyzed by random forest technology. The effect of TNM and non-TNM factors such as histologic grade, lymph node ratio (number positive/number resected), type of operation, neoadjuvant and adjuvant treatment, American Society of Anesthesiologists (ASA) class, and age in staging and prognosis were evaluated. A forest of 1,000 random survival trees was grown using log-rank splitting. Competing risk-adjusted random survival forest methods were used to maximize survival prediction and produce importance measures of the predictor variables. RESULTS: Competing risk-adjusted 5-year survival after resection of colon and rectal cancer was dominated by pT stage (ie, tumor infiltration depth) and lymph node ratio. Increased lymph node ratio was associated with worse survival within the same pT stage for both colon and rectal cancer patients. Whereas survival for colon cancer was affected by ASA grade, the type of resection and neoadjuvant therapy had a strong effect on rectal cancer survival. A similar pattern in predicted survival rates was observed for patients with fewer than 12 lymph nodes examined. Our model suggests that lymph node ratio remains a significant predictor of survival in this group. CONCLUSIONS: A novel data-driven methodology predicts the survival times of patients with colorectal cancer and identifies patterns of cancer characteristics. The methods lead to stage groupings that could redefine the composition of TNM in a simple and orderly way. The higher predictive power of lymph node ratio as compared with traditional pN lymph node stage has specific implications and may address the important question of accuracy of staging in patients when fewer than 12 nodes are identified in the resection specimen.

Prevalence and clinical implications of positive serum anti-microsomal antibodies in symptomatic patients with ileal pouches.

BACKGROUND AND AIM: Autoimmune disorders (AID) have been shown to be associated with chronic antibiotic-refractory pouchitis (CARP). The role of anti-microsomal antibodies in ileal pouch disorders has not been investigated. The aims of the study were to investigate the prevalence of positive anti-microsomal antibody in symptomatic patients with ileal pouches and to investigate its clinical implications. METHODS: A total of 118 consecutive symptomatic patients with ileal pouches were included between January and October 2010. Anti-microsomal antibodies were measured at the time of presentation. Demographic, clinical, and laboratory characteristics were compared between patients with positive and negative anti-microsomal antibody. RESULTS: There were 14 patients (11.9%) with positive serum anti-microsomal antibody. The mean age of patients in the antibody positive and negative groups were 41.8 ± 14.4 and 42.0 ± 14.0 years, respectively (p = 0.189). All 14 patients in the antibody positive group (100%) had some form of AID, as compared to 20 patients (19.2%) in the antibody negative group (p < 0.001). Four (28.6%) patients in the antibody positive group had at least one AID in addition to Hashimoto's thyroiditis in contrast to four (3.8%) in the antibody negative group (p = 0.003). In addition, five (35.7%) patients had associated primary sclerosing cholangitis (PSC) in the antibody positive group compared to nine (8.7%) in the antibody negative group (p = 0.012). Eleven patients (78.6%) in the antibody positive group required steroids for treatment of pouch related symptoms in contrast to 26/104 (25%) patients in the antibody negative group (p = 0.002). CONCLUSIONS: Anti-microsomal antibodies were common in pouch patients presenting with symptoms. Patients with positive anti-microsomal antibodies were much more likely to have concurrent AID and PSC. These patients were more likely to require therapy with steroids.

Classification of large microarray datasets using fast random forest construction.

Random forest is an ensemble classification algorithm. It performs well when most predictive variables are noisy and can be used when the number of variables is much larger than the number of observations. The use of bootstrap samples and restricted subsets of attributes makes it more powerful than simple ensembles of trees. The main advantage of a random forest classifier is its explanatory power: it measures variable importance or impact of each factor on a predicted class label. These characteristics make the algorithm ideal for microarray data. It was shown to build models with high accuracy when tested on high-dimensional microarray datasets. Current implementations of random forest in the machine learning and statistics community, however, limit its usability for mining over large datasets, as they require that the entire dataset remains permanently in memory. We propose a new framework, an optimized implementation of a random forest classifier, which addresses specific properties of microarray data, takes computational complexity of a decision tree algorithm into consideration, and shows excellent computing performance while preserving predictive accuracy. The implementation is based on reducing overlapping computations and eliminating dependency on the size of main memory. The implementation's excellent computational performance makes the algorithm useful for interactive data analyses and data mining.

Risk of colorectal adenoma and carcinoma after colectomy for colorectal cancer in patients meeting Amsterdam criteria.

OBJECTIVE: To report the risk of metachronous colorectal neoplasia after colectomy for cancer in Hereditary Nonpolyposis Colorectal Cancer (HNPCC) syndrome. SUMMARY BACKGROUND DATA: Patients meeting Amsterdam criteria for diagnosis of HNPCC have a lifetime colorectal cancer risk approaching 80%, and a metachronous cancer rate of approximately 25%. Therefore, when colon cancer is diagnosed, total rather than segmental colectomy is advocated. However, information about adenoma and carcinoma risk after index surgery is still underreported. METHODS: A hereditary colorectal cancer database was reviewed for patients meeting Amsterdam criteria who underwent colectomy for cancer. Patient demographics, surgical management, and results of follow-up were recorded. Metachronous colorectal adenoma and carcinoma development were the primary end points. RESULTS: A total of 296 patients (253 with segmental colectomy and 43 with total colectomy/ileorectal anastomosis) were analyzed. Of the 253 segmental colectomy patients, 221 (88%) had postoperative endoscopic surveillance with median follow-up of 104 months. In 74 patients (33%), 256 adenomas were detected, including 140 high-risk adenomas in 48 patients (22%). Fifty-five patients (25%) developed a second colorectal cancer at a median of 69 months after index surgery. Stages of the metachronous cancers were I-16, II-18, III-12, and IV-2. By comparison, 4 of 38 patients (11%) who underwent total colectomy developed subsequent high-risk adenomas and 3 (8%) developed metachronous cancer. CONCLUSIONS: Amsterdam patients undergoing partial colectomy have a high rate of metachronous high-risk adenomas and carcinomas. Total colectomy for the index cancer is the procedure of choice. For either surgical option, yearly endoscopic surveillance is essential to remove premalignant adenomas.

Polishing the crystal ball: knowing genotype improves ability to predict desmoid disease in patients with familial adenomatous polyposis.

INTRODUCTION: Desmoid disease occurs in one third of patients with familial adenomatous polyposis. Patients may be protected by changing surgical strategy. We designed a formula to predict desmoid risk and tested the value of adding genotype to the formula. METHODS: A desmoid risk factor was calculated by summing points awarded for gender (male = 1, female = 3), extracolonic manifestations (nil = 1, one = 2, >one = 3), and family history of desmoids (negative = 1, one relative = 2, more than one relative = 3). Performance of the score with and without genotype (5' 1309 = 1, 1309-1900 = 2, 3' 1900 = 3) was analyzed. RESULTS: There were 839 patients (138 desmoids) without genotype and 154 (30 desmoids) with genotype. The mean desmoid risk factor score of patients without desmoids (no genotype) was 4.7 (+/-1.4 SD) and for patients with desmoid the desmoid risk factor was 6.0 (+/-1.7, P < 0.001). Corresponding data for patients with genotype was 6.1 +/- 1.3 (no desmoids) and 8.4 +/- 1.8 with desmoids (P < 0.001). Of patients without genotype, 648 patients were at low risk and 9.9% had desmoid disease, 178 patients were at medium risk and 34% had desmoids, and 10 patients were at high risk and all had desmoids. Of those with genotype information, 83 patients were at low risk and 5% had desmoids, 52 patients were at medium risk and 21% had desmoids, and 18 patients were at high risk and 83% had desmoids. CONCLUSION: The desmoid risk factor identifies patients with various levels of risk for developing desmoid disease, and can be used to plan surgical strategies designed to minimize desmoid risk.

Divergent oncogenic changes influence survival differences between colon and rectal adenocarcinomas.

PURPOSE: Colorectal cancers develop through various mechanisms such as chromosomal instability, DNA mismatch repair deficiency (microsatellite instability), and epigenetic DNA promoter methylation (CpG island methylator phenotype). This study evaluated the disparity in neoplastic changes between colon and rectal cancers. METHODS: A clinic-based colorectal frozen tumor bank at a single institution was queried for colon and rectal adenocarcinomas. Tumor DNA was extracted and analyzed for microsatellite instability, methylation, and mutations in the oncogenes KRAS and BRAF. Patient demographics, tumor characteristics, and clinical outcomes were compared. RESULTS: The 268 patients with colon cancer and 89 with rectal cancer were similar in gender, tumor size, stage, and differentiation. Colon cancers had a higher incidence of microsatellite instability (27 percent) and methylator phenotype (28 percent) compared with rectal cancers (7 percent, 3 percent, respectively; P < 0.001). Although KRAS mutation rate was similar, colon cancers had a higher incidence of BRAF mutations (16.7 percent vs. 0 percent; P < 0.001). Microsatellite stable tumors had an increased risk of disease recurrence compared with microsatellite unstable tumors (odds ratio, 3.86). Despite overall differences in outcome between colon and rectal cancers, no significant difference in survival existed when similar molecular phenotypes were compared across anatomic sites. CONCLUSIONS: Although colon cancers are molecularly heterogeneous, rectal cancers arise mostly via a single neoplastic pathway. Genetic and molecular differences influence prognosis more than anatomic location and suggest that oncogenic pathways contribute to survival differences between colon and rectal cancers.

Development of a clinically feasible molecular assay to predict recurrence of stage II colon cancer.

The 5-year survival rate for patients with Stage II colon cancer is approximately 75%. However, there is no clinical test available to identify the 25% of patients at high risk of recurrence. We have previously identified a 23-gene signature that predicts individual risk for recurrence. The present study tested this gene signature in an independent group of 123 Stage II patients, and the 23-gene signature was highly informative in identifying patients with distant recurrence in both univariate (hazard ratio [HR] 2.51) and multivariate analyses (HR, 2.40). The composition of this representative patient group also allowed us to refine the 23-gene signature to a 7-gene signature that exhibited a similar prognostic power in both univariate (HR, 2.77) and multivariate analyses (HR, 2.87). Furthermore, we developed this prognostic signature into a clinically feasible test with real-time quantitative PCR using standard fixed paraffin-embedded tumor tissues. When a 110-patient cohort was evaluated with the PCR assay, the 7-gene signature, demonstrated to be a strong prognostic factor in both univariate (HR, 6.89) and multivariate analyses (HR, 14.2). These results clearly show the prognostic value of the predefined gene signature for Stage II colon cancer patients. The ability to identify colon cancer patients with an unfavorable outcome may help patients at high risk for recurrence to seek more aggressive therapy.

Adenoma detection rate: the real indicator of quality in colonoscopy.

PURPOSE: Completion rate is the most commonly used index of quality in colonoscopy, and yet a complete examination is not necessarily a good examination. The ability to detect and treat adenomas is an important component of endoscopic skill, because many colonoscopies are performed for this express purpose. Adenoma detection rate is rarely reported, although it seems to depend on the time taken for withdrawal. The literature suggests that adenomas should be detected in approximately 25 percent of men and 15 percent of women older than age 50 years. We have reviewed the adenoma detection rates of six colorectal surgeons to provide insight into the range of adenoma detection rates and the factors that influence them. METHODS: A prospective departmental colonoscopy database was queried. Colonoscopy completion rates, adenoma detection rates, and times of insertion and withdrawal were noted and stratified by the six staff colonoscopists. Adenoma detection rates were tabulated for the four common indications for colonoscopy. RESULTS: Each staff endoscopist performed >250 examinations per year and had performed >1,000 total examinations. Although completion rates are fairly uniform (mean, 96.5 (range, 94.8-97.9) percent), there is a wide range of ADR, especially when adenomas are common (polyp or cancer surveillance; range, 14.2-27.4 percent). With the exclusion of one outlier staff, regression of withdrawal time against adenoma detection rate produced an r(2) of 0.975 (P = 0.0016). CONCLUSIONS: Adenoma detection rate is independent of completion rate as a colonoscopy quality indicator. There is a wide range of adenoma detection rates among experienced colorectal surgeons. Colonoscopists need to be aware of their adenoma detection rate.

Clinical outcomes and cost analysis of a "fast track" postoperative care pathway for ileal pouch-anal anastomosis: a case control study.

PURPOSE: Traditional length of hospital stay after ileal pouch-anal anastomosis is 8 to 15 days. Fast track rehabilitation programs reduce stay, but there are concerns that readmission and complication rates may be increased. This study evaluated a fast track pathway after ileoanal pouch surgery. METHODS: One hundred three consecutive patients underwent ileal pouch-anal anastomosis on two colorectal services using a fast track protocol with early ambulation, diet, and defined discharge criteria. Direct hospital costs and 30-day and long-term complication data were collected. Patients were matched to controls managed with traditional care pathways by other colorectal staff. RESULTS: Matching was established for 97 patients. Fast track patients had shorter hospital stay than controls (median 4 vs. 5 days; mean 5.0 vs. 5.9, P = 0.012). Readmission and recurrent operation rates were similar (24 vs. 20 percent, P = 0.49, and 9 vs. 10 percent, P = 0.8, fast track vs. control, respectively). Median direct costs per patient (US$) within 30 days were lower with fast track (5692 vs. 6672, P = 0.001), primarily because of reductions in postoperative management expenses. Complication rates, including pouch failure, bowel obstruction, pouchitis, and anastomotic stricture were comparable. Early discharge (< or = 5 days from surgery) occurred in 79 (77 percent) fast track patients. Failure with early discharge was associated with male gender, reoperations, and anastomotic complications. CONCLUSIONS: Fast track protocol after ileoanal pouch surgery reduces length of stay and hospital costs without increasing complication rates. Successful early discharge usually signals a benign postoperative course.

Surgical outcome in patients with primary sclerosing cholangitis undergoing ileal pouch-anal anastomosis: a case-control study.

BACKGROUND: The outcome of restorative proctocolectomy in the setting of chronic ulcerative colitis complicated by primary sclerosing cholangitis (PSC) is not clear. The purpose of this study was to determine the surgical outcome, risk of dysplasia/cancer, morbidity/mortality, long-term results, and functional and quality of life results in patients with inflammatory bowel disease (IBD) and PSC who underwent restorative proctocolectomy with ileal pouch-anal anastomosis and compare them in a case-matched study. METHODS: Patients with PSC-associated IBD undergoing restorative proctocolectomy between 1983 and 2002 were included in the study. This study group was matched for age, gender, diagnosis, duration of disease, anastomosis technique, and proximal diversion to a cohort of IBD patients with no associated PSC who underwent restorative proctocolectomy during the same period of time. Postoperative morbidity, incidence of neoplasia/cancer in the resected specimen, pouchitis, pouch failure, long-term mortality, and 5-year survival rates were compared between the groups. The functional and quality of life records were prospectively collected and compared between the groups. For each group, matched Kaplan-Meier survival analysis was also conducted comparing 5-year survival between the 2 cohorts, matching for diagnosis, duration of disease, age, gender, anastomosis type, and proximal diversion. RESULTS: Sixty-five patients with PSC and IBD underwent restorative proctocolectomy with ileal pouch-anal anastomosis during the study period. Two hundred sixty IBD patients with no associated PSC who matched with the outlined criteria comprised the control group. The follow-up period was 68 +/- 50 months for the PSC group and 102 +/- 62 months for the control group. A higher incidence of cancer (14% vs 5%, P = .02) and dysplasia in the resected specimen (40% vs 7%, P < .001), an associated increased risk of postoperative pelvic sepsis (14% vs 5%, P = .02), and higher long-term mortality (35% vs 4%, P < .001) were found in the PSC group compared with control group with no associated PSC. The majority, 13 of 23 (57%), of the deaths in the PSC group were a result of liver disease. Five-year survival for the PSC group was significantly poorer than the 5-year survival for the control group with no associated PSC. No significant differences were found in functional and quality of life results between the groups in the short- and long-term follow-up periods. CONCLUSIONS: PSC-associated IBD patients after restorative proctocolectomy have a higher risk of neoplasia/cancer in the resected specimen, postoperative pelvic sepsis, and higher long-term mortality. Functional and quality of life remains similar in IBD patients after restorative proctocolectomy with or without associated PSC in the follow-up. However, patients with IBD and PSC have a significantly poorer survival than patients with no associated PSC after restorative proctocolectomy.