***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25 % of patients with lymph nodes free of tumor cells by histopathology ( pN0 ) reflects the presence of occult metastases . Guanylyl cyclase 2C ( GUCY2C ) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk . OBJECTIVE To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA , using the reverse transcriptase-polymerase chain reaction , with recurrence and survival in patients with colorectal cancer . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve study of 257 patients with pN0 colorectal cancer enrolled between March 2002 and June 2007 at 9 US and Canadian centers ( 7 academic medical centers and 2 community hospitals ) provided 2570 fresh lymph nodes measuring 5 mm or larger for histopathology and GUCY2C messenger RNA analysis .  Patients were followed up for a median of 24 months ( range , 2 - 63 months ) for disease recurrence or death . MAIN OUTCOME MEASURES Time to recurrence ( primary outcome ) and disease-free survival ( secondary outcome ) relative to expression of GUCY2C in lymph nodes . RESULTS Thirty-two patients ( 12.5 % ) had lymph nodes negative for GUCY2C ( pN0 [ mol- ] ) , and all but 2 remained free of disease during follow-up ( recurrence rate , 6.3 % ; 95 % confidence interval [ CI ] , 0.8%-20.8 % ) . Conversely , 225 patients ( 87.5 % ) had lymph nodes positive for GUCY2C ( pN0 [ mol+ ] ) , and 47 developed recurrent disease ( 20.9 % ; 95 % CI , 15.8%-26.8 % ) ( P = .006 ) . Multivariate analyses revealed that GUCY2C in lymph nodes was an independent marker of prognosis . Patients who were pN0 ( mol+ ) exhibited earlier time to recurrence ( adjusted hazard ratio , 4.66 ; 95 % CI , 1.11 - 19.57 ; P = .04 ) and reduced disease-free survival ( adjusted hazard ratio , 3.27 ; 95 % CI , 1.15 - 9.29 ; P = .03 ) . CONCLUSION Expression of GUCY2C in histologically negative lymph nodes appears to be independently associated with time to recurrence and disease-free survival in patients with pN0 colorectal cancer The increasing use of primary tumors as surrogate markers for prognosis and therapeutic decisions neglects evolutionary aspects of cancer progression . To address this problem , we studied the precursor cells of metastases directly for the identification of prognostic and therapeutic markers and prospect ively analyzed single disseminated cancer cells from lymph nodes and bone marrow of 107 consecutive esophageal cancer patients .  Whole-genome screening revealed that primary tumors and lymphatically and hematogenously disseminated cancer cells diverged for most genetic aberrations . However , we identified chromosome 17q12 - 21 , the region comprising HER2 , as the most frequent gain in disseminated tumor cells that were isolated from both ectopic sites . Survival analysis demonstrated that HER2 gain in a single disseminated tumor cell but not in primary tumors conferred high risk for early death Purpose Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features . The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients . Methods We analyzed a prospect ively maintained data base of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center . We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone , without postoperative chemotherapy .  Results With median follow-up of 53 months , 5-year disease-specific survival for this cohort was 91 percent . Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival : tumor Stage T4 ( hazard ratio ( HR ) , 2.7 ; 95 percent confidence interval ( CI ) , 1.1–6.2 ; P = 0.02 ) , preoperative carcinoembryonic antigen > 5 ng/ml ( HR , 2.1 ; 95 percent CI , 1.1–4.1 ; P = 0.02 ) , and presence of lymphovascular or perineural invasion ( HR , 2.1 ; 95 percent CI , 1–4.4 ; P = 0.04 ) . Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent ; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent ; and five-year disease-specific survival for patients with ≥2 poor prognostic features was 57 percent . Conclusions Patients with Stage II colon cancer generally have an excellent prognosis . However , the presence of multiple adverse prognostic factors identifies a high-risk subgroup . Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival . Those identified as high-risk patients can be considered for adjuvant chemotherapy and /or enrollment in investigational trials PURPOSE A traditional end point for colon adjuvant clinical trials is overall survival ( OS ) , with 5 years demonstrating adequate follow-up . A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice . METHODS Individual patient data were pooled from 18 r and omized phase III colon cancer adjuvant clinical trials . Trials included 43 arms , with a pooled sample size of 20,898 patients . The primary hypothesis was that disease-free survival ( DFS ) , with 3 years of follow-up , is an appropriate primary end point to replace OS with 5 years of follow-up . RESULTS The recurrence rates for years 1 through 5 were 12 % , 14 % , 8 % , 5 % , and 3 % , respectively . Median time from recurrence to death was 12 months . Eighty percent of recurrences were in the first 3 years ; 91 % of patients with recurrence by 3 years died before 5 years . Correlation between 3-year DFS and 5-year OS was 0.89 . Comparing control versus experimental arms within each trial , the correlation between hazard ratios for DFS and OS was 0.92 . Within-trial log-rank testing using both DFS and OS provided the same conclusion in 23 ( 92 % ) of 25 cases . Formal measures of surrogacy were satisfied . CONCLUSION In patients treated on phase III adjuvant colon clinical trials , DFS and OS are highly correlated , both within patients and across trials . These results suggest that DFS after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens , although marginally significant DFS improvements may not translate into significant OS benefits OBJECTIVE To determine epithelial cell dissemination in patients with localized colorectal cancer . DESIGN Prospect i ve observational study . SETTING Academic hospital . PARTICIPANTS Two hundred twenty-two patients operated on for colorectal cancer . MAIN OUTCOME MEASURES Epithelial cell dissemination was determined using immunohistochemistry or cytology in histologically negative lymph nodes , the peritoneal cavity , and bone marrow . Prognostic significance was determined in relation to 140 clinicopathological variables . Median follow-up was 61 months . RESULTS Of 140 patients who underwent curative surgery ;  25 ( 17.9 % ) died of cancer-related causes ; 10 ( 7.1 % ) , of other causes ; and 11 ( 7.8 % ) developed local recurrence . Tumor cells were present in the peritoneal cavity of 22 % of patients , but this finding had only borderline influence on disease-free survival ( P = .07 ) . Lymph node micrometastases correlated with T category but not with survival . The presence of epithelial cells in the bone marrow was detected in 64 % of patients but was not associated with tumor stage or survival . Multivariate analysis failed to identify occult tumor cell dissemination into any body compartment as an independent prognostic factor of disease-free survival . CONCLUSIONS Tumor cells disseminate into various body compartments in early stages of disease . In about two-thirds of patients , tumor cells are left in the body after so-called curative surgery . However , the presence of minimal residual disease has no independent prognostic significance in relation to established risk factors for tumor progression . Thus , other factors , such as the presence of a cellular metastatic phenotype and /or ineffective immunological response , must play an important role 
    Output:
    
Molecular detection of occult disease in regional lymph nodes is associated with an increased risk of disease recurrence and poor survival in patients with node-negative CRC