Curative Colorectal Resection Research Articles

Efficacy and safety of esketamine combined with propofol for curative endoscopic resection in colorectum: a prospective, randomized controlled trial

BackgroundCurative endoscopic resection is widely used to treat colonic polyps and early stage cancers. The anesthetic strategy commonly involves the use of propofol combined with a small dose of opioids for sedation. Adverse respiratory or cardiovascular events such as hypotension often occur when attempting to achieve the necessary level of sedation. Several studies have suggested its advantages owing to the anesthetic, analgesic, and sympathomimetic properties of esketamine. However, there are no reports on curative colorectal endoscopic resection. We designed this randomized controlled trial to assess the efficacy and safety of esketamine combined with propofol for sedation in patients undergoing curative colorectal endoscopic resection.MethodsA total of 166 patients who underwent curative colorectal endoscopic resection were randomly assigned to groups A (propofol + fentanyl) or E (propofol + esketamine). Ideal sedation was assessed using the MOAA/S scale and was achieved using TCI-propofol with different doses of fentanyl and esketamine. The propofol consumption and vasoactive drug dosages were recorded. Sedation-related times, adverse events, and satisfaction were recorded.ResultsOf the 160 patients, the total propofol consumption was significantly lower in group E (n = 81) (300 mg) than in group A (n = 79) (350 mg). Hypotension and bradycardia were significantly lower in Group E than in Group A. The groups showed no significant differences in other adverse events, induction time, recovery time, or patient or endoscopist satisfaction.ConclusionCompared to fentanyl, esketamine helps decrease propofol consumption and increases cardiovascular stability during curative colorectal endoscopic resection in American Society of Anesthesiologists Class I–III patients without affecting anesthesia, patient and endoscopist satisfaction, or other adverse events.Trial registrationThe study was retrospectively registered at the Chinese Clinical Trial Registry (www.chictr.org.cn; registration number: ChiCTR2300069014 on 03/03/2023).

Assessment of Spanish hospitals involved in the Quality Oncology Practice Initiative program.

305 Background: Measuring and tracking quality of care is highly relevant in today’s healthcare. The Quality Oncology Practice Initiative (QOPI) program is a referral for evaluating oncology practices worldwide. The ECO Foundation (Excellence and Quality in Oncology), a collaboration of oncology experts from the major Spanish hospitals involved in cancer treatment, reached an agreement with ASCO (American Society of Clinical Oncology) to include Spanish hospitals in its QOPI program. Methods: We analyzed the scores of the QOPI rounds from 14 Spanish hospitals, which submitted their charts from 2016 to 2021, and the measures obtained from 2018 to 2021, regarding the core/symptom, breast, colorectal (CRC) and NSCLC modules, in comparison with the QOPI aggregate measures. Results: Since 2016, 14 Spanish hospitals have participated in the QOPI program, achieving the certification 12 of them, and 3 are in process. Along the years, they have obtained a score over 85%, being 87,41% the worse in 2021, and 92,80% the best in 2020. We also analyzed the outstanding measures from 2018 onwards. The highest scores in Spanish hospitals were for information of infertility risks and chemotherapy intent prior to prescription, and documented plan for oral chemotherapy. However, measures regarding pain addressed, appropriate antiemetic therapy for high- and moderate-emetic-risk antineoplastic agents and action taken to address problems with emotional well-being by the second office visit, were among the lowest scored measures. When we focused in breast and NSCLC modules, Spanish hospitals didn´t show negative values, highlighting in the administration of Tamoxifen or AI within 1 year of diagnosis by patients with AJCC Stage IA (T1c) and IB - III ER or PR positive and in the status documentation for patients with initial AJCC Stage IV or distant metastatic NSCLC. In CRC module, Spanish hospitals showed lower scores in colonoscopy before or within 6 months of curative colorectal resection or completion of primary adjuvant chemotherapy. Conclusions: This study evaluates QOPI scores in Spain, showing that repeated participation enhances quality of care, although there is room for improvement. ECO Foundation will continue supporting Spanish practices to increase their participation aiming of improve oncology care in Spain.

TH3.1 Implementation of a home finger-prick CEA test for follow-up of colorectal cancer - a pilot study of patient perspectives

Abstract Aim NICE guidance advocates 6 monthly CEA blood testing following curative colorectal resection. This usually takes place through face to face appointments with a phlebotomist, with associated monetary and resource cost to local services, as well as impacting on patient lives. This project piloted use of self-taken finger-prick blood tests in this patient population, to assess feasibility, patient perspectives and preferences. Methods During colorectal outpatient clinics, patients undergoing face to face CEA surveillance in primary care were offered postal finger-prick assessment. Recruitment stopped once 50 patients had been recruited. Recruited patients were sent finger-prick blood testing kits with pre-paid return packaging. Follow-up questionnaires were undertaken to assess patient perspectives and future preferences. Results 67.6% (50/74) of eligible patients agreed to participate. 76.0% (38/50) of patients successfully completed finger-prick CEA assessment. 46.8% (22/47) of patients felt they would prefer finger-prick rather than phlebotomy for future CEA testing, whilst 19.1% (9/47) had no preference. 38.3% (18/47) patients felt finger-prick testing was worse than their previous experience. No significant differences in preference existed between patients aged <65 and 65+. Qualitative data showed difficulties with pain, discomfort and sample collection. Patients felt that finger-prick samples were convenient and easier to fit in with their lives. Conclusions Whilst some patients prefer finger-prick CEA assessment, there are significant numbers for whom it is challenging, unnecessary or less preferable. Finger-prick CEA testing may represent a future strategy for reducing burden of follow-up blood tests on resources, but this would currently be acceptable only to limited patient groups.

Social deprivation aggravates post-operative morbidity in carcinologic colorectal surgery: Results of the COINCIDE multicenter study.

Evaluate the impact of social deprivation on morbidity and mortality in surgery for colorectal cancer. The COINCIDE prospective cohort included nearly 2,000 consecutive patients operated on for colorectal cancer at the Assistance Publique-Hospitals of Paris (AP-HP) from 2008 to 2010. The data on these patients were crossed with the PMSI administrative database. The European Social Deprivation Index (EDI) was calculated for each patient and classified into five quintiles (quintiles 4 and 5 being the most disadvantaged patients). Thirty-day post-operative morbidity was determined according to the Dindo-Clavien classification, with a Had®Hoc re-analysis of each file. Statistical analysis was performed using the proprietary Q-finder® algorithm. One thousand two hundred and fifty nine curative colorectal resections were analyzed. Mortality was 2.7% and severe morbidity (Dindo-Clavien≥3) occurred in 16.4%. Mortality was not statistically significantly increased among the most disadvantaged who made up almost two thirds of the population (64.2%). Patients in quintiles 4 and 5 had a statistically significant increase in severe morbidity. The relative risk remained 1.5 even after adjustment for the known risk factors found in the analysis: age>70 years, ASA score, urgency, and laparotomy. The EDI represents an independent risk factor for severe morbidity after carcinologic colorectal resection. This study suggests that the determinants of health are multidimensional and do not depend solely on the quality and performance of the care system. The inclusion of this index in our surgical databases is therefore necessary, as is its use in health policy for the distribution of resources.

The relationship between sarcopenia and survival at 1\xa0year in patients having elective colorectal cancer surgery

BackgroundColorectal cancer remains a common cause of cancer death in the UK, with surgery being the mainstay of treatment. An objective measurement of the suitability of each patient for surgery, and their risk–benefit calculation, would be of great utility. We postulate that sarcopenia (low muscle mass) could fulfil this role as a prognostic indicator. The aim of this study was to determine the relationship between sarcopenia and long-term outcomes in patients undergoing elective bowel resection for colorectal cancer.MethodsOne hundred and sixty-three consecutive patients who had elective curative colorectal resection for cancer were eligible for inclusion in the study. Psoas muscle mass was assessed on preoperative computed tomography scan at the level of the L3 vertebra and standardised for patient height (total psoas index, TPI). Sarcopenia (low muscle mass) was defined as < 524 mm2/m2 in males and 385 mm2/m2 in females. In addition to clinical–pathological parameters, postoperative complications were recorded and patients were followed up for mortality for 1 year after surgery.ResultsSarcopenia was present in 19.6% of the study participants and was significantly related to body mass index (p = 0.007), 30-day mortality (p = 0.042) and 1-year mortality (p = 0.046). In univariate analysis, American Society of Anesthesiologists grade (p = 0.016), tumour stage (p = 0.018) and sarcopenia (p = 0.043) were found to be significant independent predictors of 1-year mortality.ConclusionsThis study has found sarcopenia to be prevalent in patients with colorectal cancer having elective surgery. Independent of age, sarcopenia was associated with poorer 30-day mortality and survival at 1 year. Measurement of muscle mass preoperatively could be used to stratify a patient’s risk, allowing targeted strategies such as prehabilitation, to be implemented to modify sarcopenia and improve long-term outcomes for patients.

Impact of Synchronous Versus Metachronous Onset of Colorectal Peritoneal Metastases on Survival Outcomes After Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Multicenter, Retrospective, Observational Study

BackgroundCareful selection of patients with colorectal peritoneal metastases (PM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. It remains unknown whether the time of onset of colorectal PM (synchronous vs metachronous) influences surgical morbidity and survival outcomes after CRS with HIPEC.MethodsPatients with histologically proven colorectal PM who underwent CRS with HIPEC between February 2006 and December 2017 in two Dutch tertiary referral hospitals were retrospectively included from a prospectively maintained database. The onset of colorectal PM was classified as synchronous (PM diagnosed at the initiational presentation with colorectal cancer) or metachronous (PM diagnosed after initial curative colorectal resection). Major postoperative complications (Clavien–Dindo grade ≥ 3), overall survival (OS), and disease-free survival (DFS) were compared between patients with synchronous colorectal PM and those with metachronous colorectal PM using Kaplan–Meier analyses, proportional hazard analyses, and a multivariate Cox regression analysis.ResultsThe study enrolled 433 patients, of whom 231 (53%) had synchronous colorectal PM and 202 (47%) had metachronous colorectal PM. The major postoperative complication rate and median OS were similar between the patients with synchronous colorectal PM and those with metachronous colorectal PM (26.8% vs 29.7%; p = 0.693 and 34 vs 33 months, respectively; p = 0.819). The median DFS was significantly decreased for the patients with metachronous colorectal PM and those with synchronous colorectal PM (11 vs 15 months; adjusted hazard ratio, 1.63; 95% confidence interval, 1.18–2.26).ConclusionsMetachronous onset of colorectal PM is associated with early recurrence after CRS with HIPEC compared with synchronous colorectal PM, without a difference in OS or major postoperative complications. Time to onset of colorectal PM should be taken into consideration to optimize patient selection for this major procedure.

The Impact of Blood Transfusion on Recurrence and Mortality Following Colorectal Cancer Resection: A Propensity Score Analysis of 4,030 Patients

Whether blood transfusion exacerbates cancer outcomes after surgery in humans remains inconclusive. We utilized a large cohort to investigate the effect of perioperative blood transfusion on cancer prognosis following colorectal cancer (CRC) resection. Patients with stage I through III CRC undergoing tumour resection at a tertiary medical center between 2005 and 2014 were identified and evaluated through August 2016. Propensity score matching was used to cancel out imbalances in patient characteristics. Postoperative disease-free survival (DFS) and overall survival (OS) were analysed using Cox regression model. A total of 4,030 and 972 patients were analysed before and after propensity score matching. Cox regression analyses demonstrated blood transfusion associated with shorter DFS and OS before and after matching (hazard ratio: 1.41, 95% CI: 1.2–1.66 for DFS; 1.97, 95% CI: 1.6–2.43 for OS). Larger transfusion volume was linked to higher overall mortality (≤4 units vs. nil, HR = 1.58; >4 units vs. nil, HR = 2.32) but not more cancer recurrence. Preoperative anemia was not associated with decreased survival after adjusting covariates. Perioperative blood transfusion was associated with worse cancer prognosis after curative colorectal resection, independently of anemia status. Strategies aimed at minimizing transfusion requirements should be further developed.

PWE-336 Outcomes of colorectal cancer resections in patients with multiple co-morbidities and advanced tumours

Introduction Comorbid patients with advanced tumours constitute a rapidly growing segment of patients undergoing colorectal cancer resection, but their outcomes remain understudied and under-reported. Our aims were to analyse outcomes of high risk patients with advanced tumours undergoing curative colorectal resections compared with a similar cohort 2 decades younger. Method Data from a prospectively collected database of consecutive patients undergoing colorectal resection between 2011 and 2013 were analysed. Primary endpoints were 30-day mortality and morbidity. The secondary endpoint was long-term survival. Results We identified 308 patients undergoing elective resections. Overall 30 and 60 day mortality was 2.3% and 4.5% respectively independent of tumour grade and age/ASA grade. In those with pT3–4 tumours, this was comparable (2.2% and 5.4%). In those who were ASA 3–4 this rose to 6.5% and 10.8%. We studied 66 consecutive patients with ASA grade 3–4 andpT3–4 cancers, including 22 over 80 years of age. This cohort demonstrates 6% mortality at 30 days and 10.4% at 90 days with a 25.4% complication rate. Amongst those 80 and above with ASA 3–4 and pT3–4 cancers, 30 and 90 day mortality was 13.6% and 18.2% respectively, with a 31.8% complication rate. Conclusion Advanced tumour grade does not impact on 30 and 90-day survival following elective surgical resection. However ASA grade is the most significant factor affecting perioperative mortality. Octogenarians are more likely to have poor performance status, with limited physiological reserve. In these patients with advanced tumours and ASA3–4, there is a considerable increase in the perioperative risk. Resources should therefore be in place for postoperative high dependency care for this high-risk group. Disclosure of interest None Declared.

Stage Migration in Curative Colorectal Cancer Resections

Introduction The NHS Bowel Cancer Screening Programme (BCSP) introduced in 2006 aimed at detecting pre-malignant colorectal disease in patients aged &gt;60 years. We assessed the impact of screening on Dukes Stage presentation in patients undergoing curative colorectal resections. Method All patients undergoing curative resection between January 2008 and January 2012 were assessed. Demographics, age of diagnosis and histological Duke's Stage were analysed. Results 467 patients were identified. Median age was 69, male to female preponderance of 1.67:1. The total number of curative resections ranged from 111-123 (mean 117). A significant decrease in Dukes A cancers from 32.2% in 2008 to 15.5.% in 2012. (p=0.0024 chi-square) was observed. Dukes B cancers increased from 26.3% to 38% (p=0.05 Chi-square). An increase in Dukes C cancers by 4.9% was demonstrated, however this did not attain statistical significance (p=0.516 chi-square). Conclusions Dukes A disease has decreased but with a steady rise in Dukes B and C cancers in our cohort. The total number of annual curative resections remains unchanged. Stage migration to more advanced disease in curative resections may be attributable to more aggressive endoscopic treatment of premalignant adenomatous disease. Evaluation in larger cohorts is needed, which may necessitate screening in younger patients.

274. The postcode lottery: Effects on colorectal cancer stage and long term survival

Introduction: Colorectal cancer outcomes vary in the U.K between centres, with patients from deprived backgrounds presenting at an advanced stage, having poor long term survival. Our aim was to analyse the outcome of patients undergoing curative colorectal (CRC) resections based on their socioeconomic status (SES). Methods: Data from a prospectively constructed database between years 2006-2010 was analyzed. Primary endpoints were 30-day mortality and presentation stage with secondary endpoints being long term survival. Socioeconomic status was determined from postcode using UK geodemographic database providers. Results: A total of 662 patients undergoing curative CRC resections were identified. Colonic resections accounted for 57.5% (n1⁄4380) compared to 42.5% (n1⁄4282) of rectal resections. Dukes C stage cancers comprised of 47.1% of patients (n1⁄4312).Thirty-day mortality was 3.8% with an overall median survival of 75 months for all patients. On the basis of SES, patients were divided into 3 groups: high (10.2%), middle (32.8%) and low (57%). No significant survival benefit was seen between patients from different SES (p1⁄40.78, Mantel-cox). When stage at presentation was compared, patients from a high SES (23.1%) were more likely to present at an earlier stage compared to those from low SES (14.4%) (p1⁄40.03 Chisquare Test). Overall 30-day mortality was 4.1% (n1⁄427/662), being significantly lower in patients from a higher SES compared to those from a lower SES (n1⁄42/27 vs. n1⁄417/27). Conclusions: Patients from a low SES tend to present at a more advanced disease stage, having a significantly higher 30-day mortality compared to patients from a high SES. In our study, the overall survival was not affected by socioecomonic status contrary to what is stated in the literature. No conflict of interest.

Impact of the perioperative neutrophil-to-lymphocyte ratio on the long-term survival following an elective resection of colorectal carcinoma.

The present study was designed to evaluate the prognostic value of the perioperative neutrophil-to-lymphocyte ratio (NLR) for the long-term survival in patients with colorectal cancer. This was a retrospective study of 524 patients with histologically proven stage II or III colorectal cancer who underwent curative colorectal resection. We classified patients into a low NLR group or high NLR group base on their NLR values at three time points (before surgery (Pre), on the first postoperative day (POD1), and on the third or fourth postoperative day (POD3)) and evaluated the survival according to the group. The cancer-specific survival was significantly longer in the groups with a low NLR on POD3. The disease-free survival was significantly longer in the group with a low NLR on Pre. We subsequently allocated a score of 1 to patients with a high NLR at each point and reclassified patients into those with a low perioperative NLR group (score of 0 or 1) and high perioperative NLR group (score of 2 or 3). Both the cancer-specific survival and disease-free survival rates were significantly different between the two perioperative NLR groups. Both univariate and multivariate analyses demonstrated that being in the high perioperative NLR group was an independent risk factor for both the cancer-specific survival and disease-free survival. Not only the preoperative but also the postoperative NTR is thus considered to be a predictor of the long-time survival in patients with colorectal cancer.

Implementation of QOPI at Illinois CancerCare, P.C. (ILCC).

174 Background: ASCO’s Quality Oncology Practice Initiative (QOPI) is a practice based quality improvement program based on retrospective chart reviews. Data collection is performed twice a year. If scores meet a specified level, a practice may apply for certification. In order to achieve certification, a physician practice must meet minimum threshold scores in five areas including: Core, Symptom/Toxicity, Care at End of Life, Breast Cancer, Colon/Rectal Cancer and Non-Small Cell Lung Cancer. A QOPI on-site review is conducted after application. Once the application has been approved, the on-site review includes an audit of chemotherapy preparation and administration, patient education, treatment planning and the review of applicable policies. If acceptable, a 3 year certification is awarded to the practice. Methods: ILCC began QOPI participation in Fall 2011. For the first round, the scores were lower than the required minimum threshold certification score level requirements. The certification areas with lower than desirable scores included: Pain Score Assessed, Emotional Well Being Assessed and Colonoscopy within specified time frame. To improve scores, a committee was formed to identify improvements. Improvements included revising physician templates to include new areas and language. Physicians were also given the appropriate verbiage for assessing a patient’s Emotional Well Being, and employees also were engaged in our improvement efforts by addressing areas that needed to be asked in the first and second visits only. Results: All selected measures show improvement from Fall of 2011 to Spring of 2013. Pain addressed appropriately increased 59% (26% to 80%); patient emotional well being assessed increased 32% (19% to 51%), colonoscopy before or within 6 months of curative colorectal resection improved 35% (50%-86%). Our total certification score went from 72.05% to 87.99%, a 15% improvement. We applied for certification and became a QOPI certified practice in fall of 2012. Conclusions: QOPI is an effective program for evidence based quality improvement within oncology practices.

Outcome of colorectal cancer resection in octogenarians

Octogenarians constitute a rapidly growing segment of patients undergoing colorectal cancer resection, but their outcomes remain understudied and under-reported. Our aims were to analyse outcomes of octogenarian patients undergoing curative colorectal resections compared with a similar cohort 2 decades younger. Data from a prospectively collected database of consecutive patients undergoing colorectal resection between 2004 and 2006 were analysed. Primary endpoints were 30-day mortality and morbidity. The secondary endpoint was long-term survival. Eighty-one consecutive patients aged >80 years and 61 patients aged 60 - 70 years undergoing elective and emergency resections were identified. In the octogenarian group, 75.3% of resections were elective compared with 78.0% in the younger cohort (p=0.9), with pelvic procedures accounting for 34.6% and 44.3%, respectively (p=0.34). The elderly had a significantly higher median CR-Possum (performance status) score than the younger cohort (18.0 v. 14.0; p=0.001). Permanent stoma rates were similar (22% for octogenarians v. 27% for younger patients; p=0.8), as was pathological stage (p=0.24). There was 1 death within 30 days after resection in each group. Median survival in the octogenarian cohort was 73 months compared with 74 months in the younger cohort, and 5-year survival rates were 53.1% and 66.0%, respectively (p=0.2, Mantel-Cox). CR-Possum score did not affect overall survival (p=0.711, Mantel-Cox), but a higher score correlated with more postoperative complications in both groups. Octogenarians have poor performance status, but can undergo resection with acceptable mortality and morbidity. Overall survival in the two age groups studied was similar, with poor performance status being associated with higher postoperative complications but no long-term difference in survival.

Curative colorectal resections in patients aged 80 years and older: clinical characteristics, morbidity, mortality and risk factors

The management of colorectal cancer in the elderly presents unique challenges. The objective of this study was to determine outcomes following curative colorectal resection in patients aged 80 years and older. Study design is retrospective. Data were extracted from the university hospital database and medical records of patients aged 80 years and older operated between April 2004 and December 2009. Intervention was curative colorectal resection. Main outcome measures include postoperative morbidity, mortality and individual risk factors associated with them. Three hundred fifty-eight patients (43.8% males, age = 84 ± 3 years) were included; 72.6% received elective surgery. A significantly higher complication rate and 30 day, 1 year and 4 year mortality were present for emergency operations compared to elective (p < 0.001). One-year survival was 65.0% for elective resections and 55.1% for emergency. At 4 years of follow-up, survival was 49.2% for the elective vs. 27.6% for emergency. The American Society of Anesthesiologists (ASA) score is the only factor associated with the 30-day mortality at the multivariate analysis (p < 0.01), Dukes staging with overall mortality (p < 0.005), sex and mode of the operation with major complications (p < 0.05). A limitation of the study is that is retrospective. The highest mortality rates following colorectal surgery in the elderly are in the early postoperative period, especially for emergency operations and patients with significant comorbidities. However, the 1-year survival following elective curative resection for colorectal cancer approaches 65 %. ASA score and modality of the operation (elective vs. emergency) impacted on postoperative mortality and morbidity and could be used to select patients with more favourable outcomes.

Survival Benefit Associated With Surgical Oophorectomy in Patients With Colorectal Cancer Metastatic to the Ovary

The purpose of this study was to determine the outcome of patients with colorectal cancer metastatic to the ovary and the impact of surgical oophorectomy on the outcome. We conducted a retrospective evaluation of patients with metastatic colorectal cancer to the ovary. Of 3776 female patients with colorectal cancer seen at MD Anderson from 2001-2008, 110 (2.9%) were identified as having metastases to the ovary. The Kaplan-Meier method and log-rank test were used to examine the survival functions. Seventy-one patients (64.5%) had disease metastatic to the ovary at the time of initial presentation; in 39 patients (35.5%) the ovaries were a site of relapse after previous curative colorectal surgical resection. Patients who presented with ovarian relapse after previous colorectal surgery and who underwent oophorectomy had a median survival of 50 months compared with 12 months for those who did not (P < .0001). Patients with metastatic disease at the time of presentation who underwent oophorectomy had a median survival of 39.4 months vs. 18.2 months for those who did not. This retrospective analysis suggests that women with metastatic colorectal cancer metastatic to the ovary may derive a survival benefit from palliative oophorectomy.

Advanced Synchronous Adenoma but Not Simple Adenoma Predicts the Future Development of Metachronous Neoplasia in Patients With Resected Colorectal Cancer

Patients with resected colorectal cancer remain at a high risk for developing metachronous neoplasia in the remnant colorectum. The aim of this study was to identify baseline clinical and colonoscopic features predictive of metachronous neoplasia after curative resection of colorectal cancer. The baseline clinical and colonoscopic data and follow-up details of 503 patients who had colonoscopic surveillance after curative colorectal resection between January 2000 and October 2005 in a single tertiary institution were analyzed. Univariate and multivariate analyses were done to identify risk factors for metachronous adenoma. Metachronous adenomas were diagnosed in 176 patients (35.0%) and advanced adenomas in 39 (7.8%) during the follow-up period (35.7+/-20.9 mo). Among the clinical and colonoscopic factors at baseline, advanced age (> or = 60 y) (odds ratio (OR)=3.64; 95% confidence intervals (CI), 1.55-8.52), the presence of advanced synchronous adenoma (OR=4.38; 95% CI, 1.77-10.85), and longer total follow-up period (OR=1.03; 95% CI, 1.01-1.04) were independently correlated with developing advanced metachronous adenoma. Patients who had synchronous tubular adenoma without advanced features at baseline were not found to have an increased risk for future development of advanced metachronous adenoma compared with those in the synchronous adenoma-free group (OR=1.75; 95% CI, 0.69-4.43, P=0.650). Our data showed that patients with advanced synchronous adenoma at baseline were identified to have an increased risk of advanced metachronous neoplasia during a longer follow-up period but those with tubular adenoma without advanced features at baseline were not.

Prognostic value of carcinoembryonic antigen distribution in tumor tissue of colorectal carcinoma

Carcinoembryonic antigen (CEA) can be detected in colorectal tumor tissue but its role in the survival of patients remains controversial. To characterize the expression of tissue CEA using immunohistochemical staining in colorectal tumors and to analyze the relationship between this finding and preoperative plasmatic level of CEA, morphologic features and survival of patients operated with curative intent for colorectal carcinoma. Forty-seven patients were included in the study: 18 (38.3%) males and 29 (61.7%) females, with a mean age of 67.8 +/- 9.7 years (37 to 84 years). Immediately before laparotomy, pre-operative serum levels of CEA were obtained where normal levels were considered < or =2.5 ng/mL for non-smokers, and < or =5.0 ng/mL for smokers. CEA immunohistochemical studies were carried out using anti-human CEA monoclonal mouse antibody. The expression of immunostaining for each neoplasia was classified according to the pattern of CEA tissular distribution into apical or cytoplasmic. The variables considered for the statistical analysis were plasmatic preoperative CEA level, location of the lesion within the large intestine, lesion diameter, lymph node involvement, Duke's classification, vein invasion, grade of cellular differentiation, survival and pattern of CEA tissular distribution. The statistical models utilized were Spearman's correlation and the Mann-Whitney, Kruskal-Wallis and Student t tests. Patients' survival was analyzed using the Kaplan-Meier method. The mean preoperative CEA value was 15.4 +/- 5.5 ng/mL (0.2 to 92.1 ng/mL). The neoplasm was located in the colon in 29 (61.7%) and in the rectum in 18 (38.3%) patients. Eight (17.0%) patients were classified as Duke's stage A, 22 (46.8%) as stage B and 17 (36.2%) as stage C. On immunohistochemical studies, the pattern of CEA tissular distribution was apical in 33 (70.2%) patients and cytoplasmic in 14 (29.8%) patients. Patients with apical patterns presented a mean sera CEA level of 15.5 +/- 6.5 ng/mL while those with cytoplasmic pattern attained a mean sera CEA level of 15.1 +/- 7.3 ng/mL, with no significant difference between these values (P = 0.35). Apical distribution of CEA occurred in 6 (12.8%) Duke A, 18 (38.2%) Duke B and 9 (12.2%) Duke C patients, while cytoplasmic CEA tissular distribution was observed in 2 (4.2%) Duke A, 3 (6.4%) Duke B and 9 (19.1%) Duke C patients. Patients with Duke B neoplasms presented significantly more apical CEA tissular distribution patterns (P = 0.049) than subjects with cytoplasmic CEA tissular patterns. The apical CEA tissular distribution pattern in neoplasms was significantly more frequent in neoplasms with no lymph node compromise compared to the cytoplasmic pattern (P = 0.50). However, no significant differences were seen between apical and cytoplasmic CEA tissular distribution patterns in terms of colon or rectal site (P = 0.21), lesion diameter across greatest axis (P = 0.19), vein invasion (P = 0.13) or degree of cellular differentiation (P = 0.19). Of the 47 patients operated, 33 (70.2%) survived for more than 5 years where mean survival was 31.1 +/- 5.6 months. Survival between patients with apical and cytoplasmic CEA tissular distribution showed no significant difference (P = 0.38). Although the apical distribution pattern of CEA was significantly more frequent in more advanced stages of Duke's classification, the CEA tissular distribution presented no relationship with serum CEA levels, morphological features of the neoplasm or survival of patients undergoing curative colorectal carcinoma resection.

Two Subtypes of Mucinous Adenocarcinoma of The Colorectum: Clinicopathological and Genetic Features

This work is aimed at comparing mucinous colorectal adenocarcinomas (MUC) and non-mucinous colorectal adenocarcinomas (non-MUC), and at verifying the existence of two different subgroups of MUC, in terms of clinicopathological features, chromosomal alterations, and outcome, in a geographical area where mucinous colorectal cancer resulted as being very frequent. One hundred and fifty-six unselected patients who underwent curative colorectal resection for sporadic colorectal cancer over a 4-year period were evaluated for histological classification as to MUC and non-MUC subtype, for microsatellite instability (MSI) using six microsatellite markers, and for the presence of p27, Fhit, and cyclooxygenase-2 (Cox-2). Molecular data, immunohistochemical results, recurrence frequency, and patient survival were analyzed statistically in relation to histological subtypes. MUC accounted for 38.5% of all colorectal carcinomas. Compared to non-MUCs, MUCs were more frequently located in the proximal colon (p < 0.001), and more frequently showed MSI phenotype (p < 0.001), altered protein expression of hMlh1 (p = 0.030), Fhit (p <0.001), and p27 (p < 0.001). Compared to MUC with microsatellite-stable (MSS) phenotype, MUC with MSI more frequently resulted as being located in the proximal colon (p = 0.013), and more frequently showed altered expression of hMlh1 (p < 0.001), hMsh2 (p = 0.008), Fhit (p < 0.001), and p27 (p = 0.015). Significantly better survival of patients with proximal MUC (p = 0,012), with MSI MUC (p = 0.017), and with MUC with altered p27 expression (p = 0.02). The results of the present study confirm that MUC represents distinct clinicopathological and genetic features as compared to non-mucinous tumors and support the hypothesis that MUC includes two subtypes with different genetic pathways and behavior.

Anastomotic Leakage is Associated with Poor Long-Term Outcome in Patients After Curative Colorectal Resection for Malignancy

The impact of anastomotic leakage on long-term outcomes after curative surgery for colorectal cancer has not been well documented. This study aimed to investigate the effect of anastomotic leakage on survival and tumor recurrence in patients who underwent curative resection for colorectal cancer. Prospectively collected data of the 1,580 patients (904 men) of a median age of 70 years (range: 24–94), who underwent potentially curative resection for colorectal cancer between 1996 and 2004, were reviewed. Cancer-specific survival and disease recurrence were analyzed using Kaplan Meier method, and variables were compared with log rank test. Cox regression model was used in multivariate analysis. The cancer was situated in the colon and the rectum in 933 and 647 patients, respectively. Anastomotic leakage occurred in 60 patients (clinical leakage: n = 48; radiological leak: n = 12). The leakage rate was significantly higher in patients with surgery for rectal cancer (6.3 vs 2.0%, p < 0.001). The 5-year cancer-specific survivals were 56.9% in those with leakage and 75.9% in those without leakage (p = 0.012). The 5-year systemic recurrence rates were 48.4 and 22.6% in patients with and without anastomotic leak, respectively (p = 0.001), whereas the 5-year local recurrence rates were 12.9 and 5.7%, respectively (p = 0.009). Anastomotic leakage remained an independent factor associated with a worse cancer-specific survival (p = 0.043, hazard ratio: 1.63, 95% CI: 1.02–2.60) and a higher systemic recurrence rate (hazard ratio: 1.94, 95% CI: 1.23–3.06, p = 0.004) on multivariate analysis. In rectal cancer, anastomotic leakage was an independent factor for a higher local recurrence rate (hazard ratio: 2.55, 95% CI: 1.07–6.06, p = 0.034). In conclusion, anastomotic leakage is associated with a poor survival and a higher tumor recurrence rate after curative resection of colorectal cancer. Efforts should be undertaken to avoid this complication to improve the long-term outcome.

Loss of p27 expression and microsatellite instability in sporadic colorectal cancer

The role of the loss of p27 protein expression in the oncogenesis of colorectal cancer is still in debate. In this study, we prospectively examined the immunohistochemical expression of p27 in 108 consecutive colorectal cancers, and we analysed the relationship with the results, the clinicopathological data, microsatellite instability (MSI) and other genetic alterations of tumours. Unselected patients (108) who underwent curative colorectal resection for sporadic colorectal cancer in a three-year period were evaluated for MSI using 6 microsatellite markers, and for the presence of p27, p53, Fhit, Mlh1 and Msh2 proteins by means of immunostaining. The relationships between these markers were analysed. p27 protein expression was examined for association with disease recurrences and survival. Lack of p27 expression was noted in 33 out of 108 (30.5%) colorectal cancer cases (P<0.05). This altered expression was significantly higher in proximal cancers (P<0.05), mucinous tumours (P<0.001), poorly differentiated histology (P<0.01), cancers with MSI (P<0.05), tumours with altered expression of Mlh1 (P<0.01), of Msh2 (P<0.05), and of Fhit (P<0.01). Overall survival was better in the patient group with altered level of phenotypic p27 expression, although the difference does not reach statistical significance (P=0.069). The analysis performed only for patients with tumour at stage II showed significantly better survival when the tumour exhibited altered p27 expression (P<0.02). The results of the present study support the hypothesis that altered expression of p27 may be part of the genetic pathway involving MSI, which is responsible for the development of some colorectal cancers.