Examining the functional space of gut microbiome-derived peptides.

The human gut microbiome contains thousands of small, novel peptides that could play a role in microbe-microbe and host-microbe interactions, contributing to human health and disease. Although these peptides have not yet been systematically characterized, computational tools can be used to elucidate the bioactivities they may have. This article proposes probing the functional space of gut microbiome-derived peptides (MDPs) using in silico approaches for three bioactivities: antimicrobial, anticancer, and nucleomodulins. Machine learning programs that support peptide and protein queries are provided for each bioactivity. Considering the biases of an activity-centric approach, activity-agnostic tools using structural and chemical similarity and target prediction are also described. Gut MDPs represent a vast functional space that can not only contribute to our understanding of microbiome interactions but potentially even serve as a source of life-changing therapeutics.

Correlation between Multiparametric MR Imaging and Molecular Genetics in Pontine Pediatric High-Grade Glioma.

BACKGROUND AND PURPOSE: Molecular profiling is a crucial feature in the "integrated diagnosis" of CNS tumors. We aimed to determine whether radiomics could distinguish molecular types of pontine pediatric high-grade gliomas that have similar/overlapping phenotypes on conventional anatomic MR images. MATERIALS AND METHODS: Baseline MR images from children with pontine pediatric high-grade gliomas were analyzed. Retrospective imaging studies included standard precontrast and postcontrast sequences and DTI. Imaging analyses included median, mean, mode, skewness, and kurtosis of the ADC histogram of the tumor volume based on T2 FLAIR and enhancement at baseline. Histone H3 mutations were identified through immunohistochemistry and/or Sanger or next-generation DNA sequencing. The log-rank test identified imaging factors prognostic of survival from the time of diagnosis. Wilcoxon rank-sum and Fisher exact tests compared imaging predictors among groups. RESULTS: Eighty-three patients had pretreatment MR imaging and evaluable tissue sampling. The median age was 6 years (range, 0.7-17 years); 50 tumors had a K27M mutation in H3-3A, and 11, in H3C2/3. Seven tumors had histone H3 K27 alteration, but the specific gene was unknown. Fifteen were H3 wild-type. Overall survival was significantly higher in H3C2/3- compared with H3-3A-mutant tumors (P = .003) and in wild-type tumors compared with any histone mutation (P = .001). Lower overall survival was observed in patients with enhancing tumors (P = .02) compared with those without enhancement. H3C2/3-mutant tumors showed higher mean, median, and mode ADC_total values (P < .001) and ADC_enhancement (P < .004), with lower ADC_total skewness and kurtosis (P < .003) relative to H3-3A-mutant tumors. CONCLUSIONS: ADC histogram parameters are correlated with histone H3 mutation status in pontine pediatric high-grade glioma.

VARIATION IN RADIATION DOSE RATES FROM RADIONUCLIDES DISCHARGED BY THE SPENT NUCLEAR FUEL REPROCESSING PLANT IN ROKKASHO UNDER DIFFERENT YEARLY WEATHER CONDITIONS.

The radiation dose rate from radionuclides released by the spent nuclear fuel reprocessing plant in Rokkasho, Japan, was assessed for a year specified in the safety review during which the weather conditions were not significantly different from those of the other 10 y. However, the actual year-by-year variation in annual radiation dose rate was not examined. A model system for evaluating the dose rate from the radionuclides released into the atmosphere was constructed. In this study, the radiation dose rate in the weather conditions of 24 weather bins was estimated for a standard year by the model. The annual maximum dose rate from 1959 to 2012 was estimated using a simplified method that integrated the dose rates of each weather bin in the standard year by estimating the annual frequency of the bin in the target year. We obtained ~1.3 as the maximum/minimum ratio of the annual maximum dose rate.

Randomized, Double-Blind, Placebo-Controlled Phase III Study of Paclitaxel ± Napabucasin in Pretreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma.

PURPOSE: To compare napabucasin (generator of reactive oxygen species) plus paclitaxel with paclitaxel only in patients with second-line advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. EXPERIMENTAL DESIGN: In the double-blind, phase III BRIGHTER study (NCT02178956), patients were randomized (1:1) to napabucasin (480 mg orally twice daily) plus paclitaxel (80 mg/m2 i.v. weekly for 3 of 4 weeks) or placebo plus paclitaxel. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. RESULTS: Overall, 714 patients were randomized (napabucasin plus paclitaxel, n = 357; placebo plus paclitaxel, n = 357). 72.1% were male, 74.6% had gastric adenocarcinoma, and 46.2% had peritoneal metastases. The study was unblinded following an interim analysis at 380 deaths. The final efficacy analysis was performed on 565 deaths (median follow-up, 6.8 months). No significant differences were observed between napabucasin plus paclitaxel and placebo plus paclitaxel for OS (6.93 vs. 7.36 months), PFS (3.55 vs. 3.68 months), ORR (16% vs. 18%), or DCR (55% vs. 58%). Grade ≥3 adverse events occurred in 69.5% and 59.7% of patients administered napabucasin plus paclitaxel and placebo plus paclitaxel, respectively, with grade ≥3 diarrhea reported in 16.2% and 1.4%, respectively. CONCLUSIONS: Adding napabucasin to paclitaxel did not improve survival in patients with pretreated advanced gastric or GEJ adenocarcinoma. Consistent with previous reports, the safety profile of napabucasin was driven by manageable gastrointestinal events; grade ≥3 diarrhea occurred at a higher frequency with napabucasin plus paclitaxel versus placebo plus paclitaxel.

Synthetic Biology Medicine and Bacteria-Based Cancer Therapeutics.

Spontaneous tumor regression following bacterial infection has been observed for hundreds of years. These observations along with anecdotal medical findings in 1890s led to the development of Coley's "toxins," consisting of killed Streptococcus pyogenes and Serratia marcescens bacteria, as the first cancer immunotherapy. The use of this approach, however, was not widely accepted at the time especially after the introduction of radiation therapy as a treatment for cancer in the early 1900s. Over the last 30-40 years there has been renewed interest in the use of bacteria to treat human solid tumors. This is based on the observation that various nonpathogenic anaerobic bacteria can infiltrate and replicate within solid tumors when given intravenously. Bacteria tested as potential anticancer agents include the Gram-positive obligate anaerobes Bifidobacterium and Clostridium, as well as the gram-negative facultative anaerobe Salmonella. Recent advances in synthetic biology and clinical success in cancer immunotherapy provide renewed momentum for developing bacteria-based cancer immunotherapy for cancer treatment and should allow greater potential for the development of novel therapeutic approaches for this devastating disease.

Pediatric Case of Li-Fraumeni Syndrome in Honduras.

Li-Fraumeni syndrome is an inherited, autosomal dominant disease. It is categorized as a rare disease caused by mutations of the TP53 gene, which causes increased susceptibility of the patients and their children to many types of cancer. Choroid plexus tumor is rare, which occurs in 0.3 cases per 1,000,000 people, of which 40% turn out to be carcinomas. We present a 12-year-old boy with a history of worsening headaches of more than one month, gait disturbance, projectile vomiting, and right hemiparesis. An intraventricular tumor was identified in the occipital of the left lateral ventricle, which turned out to be a TP53-mutant choroidal plexus carcinoma.

Minimally invasive right colectomy with transrectal natural orifice extraction: could this be the next step forward?

BACKGROUND: The transvaginal natural orifice specimen extraction (NOSE) approach for right-side colon surgery has been proven to exhibit favorable short-term outcomes. However, thus far, no study has reported the advantages of transrectal NOSE for right-side colon surgery. The aim of this study was to compare the technical feasibility, safety, and short-term outcomes of minimally invasive right hemicolectomy using the transrectal NOSE method and those of conventional mini-laparotomy specimen extraction. METHODS: A study was conducted on consecutive patients who had minimally invasive right hemicolectomy either for malignancy or benign disease at Chang Gung Memorial Hospital, Linkou, Taiwan, between January 2017 and December 2018. The patients were divided into two groups: conventional surgery with specimen extraction using mini-laparotomy and NOSE surgery. Surgical outcomes, including complications, postoperative short-term recovery, and pain intensity, were analyzed. RESULTS: We enrolled 297 patients (151 males, mean age 64.9 ± 12.8 years) who had minimally invasive right hemicolectomy. Of these 297 patients, 272 patients had conventional surgery with specimen extraction through mini-laparotomy and 25 patients had NOSE surgery (23 transrectal, 2 transvaginal). The diagnosis of colon disease did not differ significantly between the conventional and NOSE groups. Postoperative morbidity and mortality rates were comparable. The postoperative hospital stay was significantly (p = 0.004) shorter in the NOSE group (median 5 days, range 3-17 days) than in the conventional group (median 7 days, range 3-45 days). Postoperative pain was significantly (p = 0.026 on postoperative day 1 and p = 0.002 on postoperative day 2) greater in the conventional group than in the NOSE group. CONCLUSIONS: NOSE was associated with acceptable short-term surgical outcomes that were comparable to those of conventional surgery. NOSE results in less postoperative wound pain and a shorter hospital stay than conventional surgery. Larger studies are needed.

Neuroimaging Findings in Children with Constitutional Mismatch Repair Deficiency Syndrome.

BACKGROUND AND PURPOSE: Constitutional mismatch repair deficiency is a hereditary childhood cancer predisposition syndrome characterized by brain tumors and colorectal and hematologic malignancies. Our objective was to describe the neuroimaging findings in patients with constitutional mismatch repair deficiency. MATERIALS AND METHODS: This retrospective study included 14 children with genetically confirmed constitutional mismatch repair deficiency who were referred to 2 tertiary pediatric oncology centers. RESULTS: Fourteen patients from 11 different families had diagnosed constitutional mismatch repair deficiency. The mean age at presentation was 9.3 years (range, 5-14 years). The most common clinical presentation was brain malignancy, diagnosed in 13 of the 14 patients. The most common brain tumors were glioblastoma (n = 7 patients), anaplastic astrocytoma (n = 3 patients), and diffuse astrocytoma (n = 3 patients). Nonspecific subcortical white matter T2 hyperintensities were noted in 10 patients (71%). Subcortical hyperintensities transformed into overt brain tumors on follow-up imaging in 3 patients. Additional non-neoplastic brain MR imaging findings included developmental venous anomalies in 12 patients (85%) and nontherapy-induced cavernous hemangiomas in 3 patients (21%). CONCLUSIONS: On brain MR imaging, these patients have both highly characteristic intra-axial tumors (typically multifocal high-grade gliomas) and nonspecific findings, some of which might represent early stages of neoplastic transformation. The incidence of developmental venous anomalies is high in these patients for unclear reasons. Awareness of these imaging findings, especially in combination, is important to raise the suspicion of constitutional mismatch repair deficiency in routine diagnostic imaging evaluation or surveillance imaging studies of asymptomatic carriers because early identification of the phenotypic "gestalt" might improve outcomes.

Functional and metabolic imaging in transthoracic biopsies guided by computed tomography.

OBJECTIVES: CT-guided biopsy of indeterminate lung lesions sometimes provides insufficient histological results due to tumor necrosis. Functional and metabolic methods such as DWI-MR and PET-CT may help by directing sample collection to a lesion area of greater biological representativeness. The objective is to evaluate the histopathological results based on findings on ADC and SUV levels in lung lesions suspected for primary cancer. METHODS: Tissue samples were evaluated after undergoing biopsies guided by either DWI-MR or PET-CT findings. In each patient, sample collection from two lesion areas was guided by local ADC and SUV. Values were used to define areas of low vs. high suspicion for cancer. RESULTS: Patients who underwent DWI-MR had median lesion size of 78.0 mm. Areas of higher suspicion (HSA) had a median ADC of 1.1 × 10-3 mm2/s, while areas of lower suspicion (LSA) had median ADC of 1.8 × 10-3 mm2/s (p = 0.0001). All HSA samples and 71.43% of LSA samples were positive for cancer (p = 0.0184). Patients who performed PET-CT had median lesion size of 61.0 mm. Median SUV was 7.1 for HSA and 3.9 for LSA (p = 0.0002). Positivity for cancer was observed in 76.9% of samples for both HSA and LSA (p = 0.0522). CONCLUSION: Use of DWI-MR and PET-CT showed that tumors are functional and metabolically heterogeneous and that this heterogeneity has implications for histopathological diagnosis. KEY POINTS: • Lung cancer is heterogeneous regarding functional and metabolic imaging. • Tumor heterogeneity may have implications in histopathological diagnosis. • Intralesional lower levels of ADC target highly suspected areas with a significant improvement in lung cancer diagnosis.

Synchronous colorectal carcinoma: predisposing factors and characteristics.

AIM: Whether some diseases are related to the occurrence of synchronous colorectal carcinoma (sCRC) is unknown. Investigating the risk factors and presentation of sCRC could aid in the treatment of patients with colorectal cancer (CRC). The prognosis of sCRC compared with that of solitary CRC remains unclear. METHODS: A total of 17 093 CRC patients were recruited between 1st January 1995 and 31th December 2016. The risk factors of sCRC development were assessed using univariate and multivariate logistic regression. The effect of sCRC on survival was analysed using the multivariate Cox regression model. RESULTS: The prevalence of sCRC was 5.6% in this study. The independent risk factors of sCRC development were advanced age (P < 0.001), male sex (P < 0.001), hereditary cancer (P < 0.001), hypertension (P < 0.001) and liver cirrhosis (P = 0.024). Compared with solitary CRC, a higher number of patients with sCRC presented with an abnormal carcinoembryonic antigen (CEA) level (P = 0.011), anaemia (P < 0.001) and hypoalbuminemia (P < 0.001). Multivariate analysis revealed that sCRC was a significant factor for poor survival in patients at TNM Stage I [hazard ratio (HR) = 1.86; P < 0.001], Stage II (HR = 1.65; P < 0.001) and Stage III (HR = 1.40; P < 0.001). CONCLUSIONS: In addition to hypertension and liver cirrhosis, other risk factors for sCRC were identified in this study. The prognosis of patients with sCRC was significantly worse than that of those with solitary CRC through TNM Stages I to III. Anaemia, abnormal CEA and hypoalbuminemia were more commonly seen in patients with sCRC.

Surface Molecular Markers of Cancer Stem Cells: Computation Analysis of Full-Text Scientific Articles.

The data on cancer stem cell surface molecular markers of 27 most common cancer diseases were analyzed using natural language processing and data mining techniques. As a source, 8933 full-text open-access English-language scientific articles available on the Internet were used. Text mining was based on searching for three entities within one sentence, namely a tumor name, a phrase "cancer stem cells" or its synonym, and a name of differentiation cluster molecule. As a result, a list of surface molecular markers was formed that included markers most frequently mentioned in the context of certain tumor diseases and used in studies of human and animal tumor cells. Based on similarity of the associated markers, the tumors were divided into five groups.

Two controls of cell proliferation underlie cancer relapse.

Much progress has been made in understanding the basis of cancer. Current therapies can effectively shrink tumors. But they frequently relapse, metastasize to other locations, and are lethal. Effective therapies are very much needed for preventing this relapse. Creation of a eukaryotic organism commences with one original stem cell, a fertilized egg, which multiplies and differentiates. Mutations of normal stem cells can produce cancer stem cells (CSC). These cells may resist chemotherapy, proliferate, and produce new tumors. Human chorionic gonadotrophin (hCG) is composed of two proteins (alpha and beta) that bind to the cell membrane and activate a number of intracellular pathways. hCG has been shown to activate the proliferation of cancer stem cells. Cyclin dependent regulation of the adult cells is created in normal differentiation and replaces the hCG regulation of stem cells. To selectively kill the cancer stem cells conventional cancer therapies could be followed with a therapy based on inactivating human chronic gonadotrophin (HCG). For example chemically modified prostaglandins like RU486 prevent binding of the unmodified steroid to hCG and inactivate hCG.

JOURNAL CLUB: Preparative Fasting for Contrast-Enhanced CT in a Cancer Center: A New Approach.

OBJECTIVE: Most diagnostic imaging centers ask patients to fast for 4-6 hours before contrast-enhanced CT. Previous studies have shown that prolonged fasting can be harmful. In addition, manufacturers of contrast agents claim that there is no special preparation needed before examination. The aim of this study was to evaluate the effects of preparative fasting on contrast-enhanced CT at a cancer center. SUBJECTS AND METHODS: Outpatients (n = 3206) were prospectively evaluated and randomly assigned to two groups: the 1619 patients in group 1 fasted for at least 4 hours before the examination, whereas the 1587 patients in group 2 received a light meal. Adverse symptoms observed before and after contrast agent administration were compared between groups. RESULTS: Adverse symptoms occurring after IV contrast agent administration were reported by 45 patients (1.5%) in group 1 and 30 patients (0.9%) in group 2. The most common symptoms were nausea (n = 32), weakness (n = 12), and vomiting (n = 5). The frequency of symptoms did not differ statistically significantly between groups (p > 0.05). CONCLUSION: In this sample of patients with cancer undergoing contrast-enhanced CT, very few adverse symptoms were reported regardless of preparative fasting. These results support the idea that preparation for contrast-enhanced CT can be simplified, decreasing the discomfort and inconvenience experienced by patients.

A complete, homozygous CRX deletion causing nullizygosity is a new genetic mechanism for Leber congenital amaurosis.

CRX is a transcription factor required for activating the expression of many photoreceptor-neuron genes. CRX may be mutated in three forms of human blindness; Leber congenital amaurosis (LCA), cone-rod degeneration (CRD) and retinitis pigmentosa (RP). The pathogenic mechanism in most cases is likely dominant negative, with gain of function. We report a novel, complete homozygous CRX deletion in LCA. We identified a Lebanese family with 3 affected LCA cases. The proband was sequenced by NGS. Quantitative PCR, array comparative genomic hybridization, and long range PCR were performed. Full eye examinations, OCT and photography were performed. We identified a homozygous 56,000 bp deletion of CRX, which co-segregates and is heterozygous in four parents, who report normal vision. The blind children with LCA manifest severe retinal degeneration, a phenotype typical for CRX and LCA. We hypothesized that a single copy of CRX (haplo-insufficiency) in the causes mild abnormal foveal development, but not LCA. Two parents had significant inner and outer foveal and photoreceptor abnormalities. This is the first reported case of a homozygous, complete CRX deletion. Nullizygosity of CRX thus causes LCA while haplo-insufficiency of CRX causes abnormal foveal development, but not LCA. Our data suggest a new disease mechanism for CRX.

Napabucasin versus placebo in refractory advanced colorectal cancer: a randomised phase 3 trial.

BACKGROUND: Napabucasin is a first-in-class cancer stemness inhibitor that targets STAT3, which is a poor prognostic factor in colorectal cancer. This study aimed to test napabucasin in advanced colorectal cancer. METHODS: This study was a double-blind randomised phase 3 trial done at 68 centres in Canada, Australia, New Zealand, and Japan. Patients with advanced colorectal cancer with a good Eastern Cooperative Oncology Group (ECOG) performance status (0-1) for whom all available standard therapies had failed were eligible for the study. Patients were randomly assigned (1:1) to receive placebo or napabucasin through a web-based system with a permuted block method, after stratification by ECOG performance status, KRAS status, previous VEGF inhibitor treatment, and time from diagnosis of metastatic disease. Napabucasin 480 mg or matching placebo was taken orally every 12 h. All patients received best supportive care. The primary endpoint was overall survival assessed in an intention-to-treat analysis. This is the final analysis of this trial, which is registered at ClinicalTrials.gov, number NCT01830621. FINDINGS: Accrual began on April 15, 2013, and was stopped for futility on May 23, 2014, at which point 282 patients had undergone randomisation (138 assigned to the napabucasin group and 144 to the placebo group). Overall survival did not differ significantly between groups: median overall survival was 4·4 months (95% CI 3·7-4·9) in the napabucasin group and 4·8 months (4·0-5·3) in the placebo group (adjusted hazard ratio [HR] 1·13, 95% CI 0·88-1·46, p=0·34). The safety population included 136 patients in the napabucasin group and 144 patients in the placebo group. More patients who received napabucasin had any grade of treatment-related diarrhoea (108 [79%] of 136 patients), nausea (69 [51%]), and anorexia (52 [38%]) than did patients who received placebo (28 [19%] of 144 patients, 35 [24%], and 23 [16%], respectively). The most common severe (grade 3 or worse) treatment-related adverse events were abdominal pain (five [4%] patients receiving napabucasin vs five [3%] receiving placebo), diarrhoea (21 [15%] vs one [1%]), fatigue (14 [10%] vs eight [6%]), and dehydration (six [4%] vs one [1%]). 251 (89%) patients had data on pSTAT3 expression, of whom 55 (22%) had pSTAT3-positive tumours (29 in the napabucasin group, 26 in the placebo group). In a prespecified biomarker analysis of pSTAT3-positive patients, overall survival was longer in the napabucasin group than in the placebo group (median 5·1 months [95% CI 4·0-7·5] vs 3·0 months [1·7-4·1]; HR 0·41, 0·23-0·73, p=0·0025). INTERPRETATION: Although there was no difference in overall survival between groups in the overall unselected population, STAT3 might be an important target for the treatment of colorectal cancer with elevated pSTAT3 expression. Nevertheless, these results require validation. FUNDING: Canadian Cancer Society Research Institute and Boston Biomedical.

Pre-operative serum albumin level substantially predicts post-operative morbidity and mortality among patients with colorectal cancer who undergo elective colectomy.

The quantitative relationship between serum albumin level and surgical outcomes has not been clearly established. This study included 3732 patients with colon cancer who underwent a potentially curative colectomy. Post-operative mortality and morbidity were analysed according to the patients' demographic data, pre-operative comorbidities, and tumour-related factors. Age, asthma, renal impairment, and albumin level were significantly associated with post-operative morbidity and mortality in the multivariate analyses. Logistic regression analysis revealed linear relationships of post-operative morbidity and mortality with albumin level. The morbidity and mortality rates decreased by 7.3% and 15.6%, respectively, for each 0.1 g/dL increase in albumin level. This finding remained significant in the hypoalbuminaemia subgroup but not in the normoalbuminaemia subgroup. That is, the morbidity and mortality rates significantly decreased by 8.7% and 17.7%, respectively (both P < 0.001), in the former group and decreased by 2.7% (P = 0.112) and 11.6% (P = 0.092), respectively, in the latter group. This study demonstrated that serum albumin level linearly predicted the post-operative morbidity and mortality among the colorectal cancer patients. Pre-operative serum albumin level may therefore be used as a continuous rather than a categorical marker of disease severity, especially among patients with hypoalbuminaemia.

[Molecular markers of cancer stem cells verified in vivo]. / Molekuliarnye markery rakovykh stvolovykh kletok, verifitsirovannye in vivo.

This systematic review aims to analyze molecular markers of cancer stem cells. Only studies that confirmed tumor-initiating capacity of this population by in vivo assay in immunodeficient mice were included. Final sample of papers that fully correspond with initial aim consists of 97 original studies. The results of their analysis reveal that markers commonly used for cancer stem cells deriving were as follows: CD133, СD44, ALDH, CD34, CD24 and EpCAM. The review also contains description of molecular features of some cancer stem cell markers, modern approaches to cancer treatment by targeting this population and brief assessment of cancer stem cell theory development.

Plate augmentation for femoral nonunion: more than just a salvage tool?

OBJECTIVE: The aim of the current study was to determine whether plate augmentation was a successful treatment algorithm for selected femoral nonunions initially managed with intramedullary nailing. MATERIALS AND METHODS: A total of 30 femoral nonunion cases were managed using the plate augmentation strategy with 13 primary cases and 17 multi-operated femurs (avg 2.8 ineffective procedures). Adjunctive strategies included autologous bone grafting and/or BMP for atrophic/oligotrophic and bone defect cases. Deformity correction was performed when required. RESULTS: Osseous union occurred in 29 of 30 cases. One multi-operated case with bone defect and prior infection required repeat autologous grafting prior to union. CONCLUSION: Plate augmentation should be added to the armamentarium for management of selected femoral nonunion that have failed initial intramedullary nailing.

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer.

BACKGROUND: Quantification of Circulating Tumor Cells (CTCs) as a prognostic marker in metastatic colorectal cancer (mCRC) has already been validated and approved for routine use. However, more than quantification, qualification or characterization of CTCs is gaining importance, since the genetic characterization of CTCs may reflect, in a real time fashion, genetic profile of the disease. OBJECTIVE: To characterize KRAS mutations (codon 12 and 13) in CTCs from patients with mCRC and to compare with matched primary tumor. Additionally, correlate these mutations with clinical and pathological features of patients. METHODS: Blood samples were collected from 26 patients with mCRC from the AC Camargo Cancer Center (São Paulo-Brazil). CTCs were isolated by ISET technology (Isolation by Size of Epithelial Tumors; Rarecells Diagnostics, France) and mutations analyzes were performed by pyrosequencing (QIAGEN). RESULTS: KRAS mutation was detected in 7 of the 21 cases (33%) of samples from CTCs. In matched primary tumors, 9 of the 24 cases (37.5%) were found KRAS mutated. We observed that 5 of the 9 samples with KRAS mutation in their primary tumor had also KRAS mutation in CTCs, meaning a concordance of 71% of matched cases (P = 0.017). KRAS mutation neither on primary tumor nor in CTCs was associated with clinical-pathological parameters analyzed. CONCLUSION: Faced with a polyclonal disease like colorectal cancer, which is often treated with alternating and successive lines of chemotherapy, real time genetic characterization of CTCs, in a fast and feasible fashion, can provide important information to clinical management of metastatic patients. Although our cohort was limited, it was possible to show a high grade of concordance between primary tumor and CTCs, which suggests that CTCs can be used as surrogate of primary tumors in clinical practice, when the knowledge of mutation profile is necessary and the primary tumor is not available.