Impact of RAS and BRAF mutations on carcinoembryonic antigen production and pattern of colorectal metastases

AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen(CEA) production.METHODS: In this retrospective study, we investigated the impact of RAS and BRAF mutational status on pattern of metastatic disease and CEA production. Only patients presenting with a newly diagnosed metastatic colorectal cancer(CRC) were included. Patients' characteristics, primary tumor location, site of metastatic disease and CEA at presentation were compared between those with and without RAS and BRAF mutations.RESULTS: Among 174 patients, mutations in KRAS, NRAS and BRAF were detected in 47%, 3% and 6% respectively. RAS mutations(KRAS and NRAS) were more likely to be found in African American patients(87% vs 13%; P value = 0.0158). RAS mutations were associated with a higher likelihood of a normal CEA(< 5 ng/mL) at presentation. BRAF mutations were more likely to occur in females. We were not able to confirm any association between mutational status and site of metastatic disease at initial diagnosis.CONCLUSION: No association was found between RAS and BRAF mutations and sites of metastatic disease at the time of initial diagnosis in our cohort. Patients with RAS mutations were more likely to present with CEA levels < 5 ng/mL. These findings may have clinical implications on surveillance strategies for RAS mutant patients with earlier stages of CRC.

Impact of medical and surgical intervention on survival in patients with cholangiocarcinoma

AIM:To examine surgical and medical outcomes for patients with cholangiocarcinoma using a populationbased cancer registry.METHODS:Using the California Cancer Registry's Cancer Surveillance Program,patients with intrahepatic cholangiocarcinoma treated in Los Angeles County from 1988 to 2006 were identified and evaluated for clinical and pathologic factors and therapies received(surgery,radiation,and chemotherapy).The surgical cohort was further categorized into three treatment groups:patients who received adjuvant chemotherapy,adjuvant chemoradiation,or underwent surgery alone(no chemotherapy or radiation administered).Survival was assessed by Kaplan-Meier method;and Cox proportional hazard modeling was used in multivariate analysis.RESULTS:Of 825 patients,60.2% received no treatment.Of the remaining 328 patients,18.5% chemotherapy only,7.4% chemoradiation,and 13.8% underwent surgery.More male patients underwent surgical resection(P = 0.004).Surgical patients were younger than the patients receiving chemotherapy or chemoradiation(P < 0.001).Of the surgical cohort(n = 114),60.5% underwent surgery alone while 39.5% underwent surgery plus adjuvant therapy(chemotherapy n = 20;chemoradiation,n = 21)(P < 0.001).Median survival for all patients in the study was 6.6 mo.Median survival was highest for patients who underwent surgery(23 mo),whereas both chemotherapy(9 mo) and chemoradiation(8 mo) alone were each less effective(P < 0.001).By multivariate analysis,extent of disease,receipt of surgery,and administration of chemotherapy(with/without surgery) were independent predictors of overall survival.CONCLUSION:This study demonstrates that surgery is a critical treatment modality.Multimodality treatment has yet to be standardized,but play a role in optimal therapy for cholangiocarcinoma.

Accuracy of computed tomography in nodal staging of colon cancer patients

AIM: To predict node-positive disease in colon cancer using computed tomography(CT).METHODS: American Joint Committee on Cancer stage Ⅰ-Ⅲ colon cancer patients who underwent curavtiveintent colectomy between 2007-2010 were identified at a single comprehensive cancer center. All patients had preoperative CT scans with original radiology reports from referring institutions. CT images underwent blinded secondary review by a surgeon and a dedicated abdominal radiologist at our institution to identify pericolonic lymph nodes(LNs). Comparison of outside CT reports to our independent imaging review was performed in order to highlight differences in detection in actual clinical practice. CT reviews were compared with final pathology. Results of the outside radiologist review, secondary radiologist review, and surgeon review were compared with the final pathologic exam to determine sensitivity, specificity, positive and negative predictive values, false positive and negative rates, and accuracy of each review. Exclusion criteria included evidenceof metastatic disease on CT, rectal or appendiceal involvement, or absence of accompanying imaging from referring institutions.RESULTS: From 2007 to 2010, 64 stageⅠ-Ⅲ colon cancer patients met the eligibility criteria of our study. The mean age of the cohort was 68 years, and 26(41%) patients were male and 38(59%) patients were female. On final pathology, 26 of 64(40.6%) patients had nodepositive(LN+) disease and 38 of 64(59.4%) patients had node-negative(LN-) disease. Outside radiologic review demonstrated sensitivity of 54%(14 of 26 patients) and specificity of 66%(25 of 38 patients) in predicting LN+ disease, whereas secondary radiologist review demonstrated 88%(23 of 26) sensitivity and 58%(22 of 38) specificity. On surgeon review, sensitivity was 69%(18 of 26) with 66% specificity(25 of 38). Secondary radiology review demonstrated the highest accuracy(70%) and the lowest false negative rate(12%), compared to the surgeon review at 67% accuracy and 31% false negative rate and the outside radiology review at 61% accuracy and 46% false negative rate.CONCLUSION: CT LN staging of colon cancer has moderate accuracy, with administration of NCT based on CT potentially resulting in overtreatment. Active search for LN+ may improve sensitivity at the cost of specificity.

Positron emission tomography as predictor of rectal cancer response during or following neoadjuvant chemoradiation

Positron emission tomography (PET) shows great promise as a tool to evaluate the effectiveness of rectal cancer neoadjuvant therapy as it has demonstrated high predictive value in several studies. Creating a standardized method of using PET has the potential to reduce ineffective treatments. However, relevant studies have been heterogenous in approach, making any unified standard difficult to establish. PET related parameters used to assess treatment response include magnitude and change of standard uptake value, total lesion glycolysis, and visual response. Finding the best evaluation interval and parameters to use for interpreting PET results in the neoadjuvant treatment of rectal cancer needs additional study.