***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*** 
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    Input: Background Lymphovascular invasion ( LVI ) in colorectal cancer ( CRC ) is considered a strong stage-independent prognostic factor and influences decisions regarding adjuvant chemotherapy in patients with stage II tumors . However , the degree of interobserver agreement among pathologists for LVI in CRC is largely unknown . This study was undertaken to examine such interobserver variability , and we hypothesized that the use of immunohistochemical markers for vascular and lymphatic channels could improve interobserver agreement . Design Fifty cases of American Joint Committee on Cancer stage II moderately differentiated CRC from 1990 to 2005 from the pathology archives were selected ; mucinous , medullary , and other recognized special subtypes were excluded . Fifty hematoxylin and eosin ( H&E ) slides ( 1 from each case ) were circulated to 6 gastrointestinal pathologists , who independently assessed small and large vessel invasion . No diagnostic guidelines were given to the participating pathologists ; each was instructed to apply the criteria for LVI that he or she used in daily practice . Immunohistochemistry ( IHC ) for D2 - 40 and CD31 was performed on corresponding paraffin blocks . The IHC slides were r and omized , recirculated , and rescored for LVI . Results were analyzed by kappa ( κ ) statistics , which correct for agreement by chance , and for percentage agreement . Results The average κ values were determined for the H&E slides ( large and small vessel ) , CD31 ( small vessel ) , and D2 - 40 ( small vessel ) ( Fig. 1 ) . Agreement was fair for H&E small vessel invasion [ κ=0.28 ; 95 % confidence interval ( CI ) : 0.22 - 0.34 ] . The least agreement was seen in interpretation of H&E large vessel invasion ( κ=0.18 ; 95%CI : 0.11 - 0.26 ) . Agreement was not improved by use of immunohistochemical stains : CD31 ( large vessel , κ=0.42 , 95%CI : 0.20 - 0.63 , small vessel , κ=0.26 , 95%CI : 0.10 - 0.42 ) and D2 - 40 ( κ=0.32 , 95%CI : 0.21 - 0.42 ) . Conclusions Interobserver variability in diagnosis of LVI was substantial on H&E slides and did not improve upon use of IHC . Agreement in evaluation of large vessel invasion was only slightly higher than would be seen by chance alone . This study highlights the need for criteria in evaluation of LVI , as this assessment may impact patient prognosis and thus change the course of clinical treatment Background Lymph node status is the most important prognostic factor for colorectal cancer . The number of lymph nodes that should be histologically examined has been controversial . The aims of this study were to assess the impact of the number of lymph nodes examined on survival of patients with stage II colorectal cancer and to determine the optimal number of lymph nodes that should be examined . Methods The study included 664 patients who underwent resection for stage II colorectal cancer . The clinical and histopathologic data of the patients were prospect ively collected and analyzed . Results The median number of lymph nodes examined was 12 ( range : 1 to 58 ) . The 5-year disease free survival rate was significantly higher for patients with 12 or more lymph nodes examined compared to those with less than 12 lymph nodes examined . The significant difference in 5-year disease free survival persisted if the dividing number increased progressively from 12 to 23 . However , the difference in survival was most significant ( lowest p value and highest hazard ratio ) for the number 21 . The 5-year disease free survival of patients with 21 or more lymph nodes examined was 80 % whereas that of patients with less than 21 lymph nodes examined was 60 % ( p = 0.001 , hazard ratio 2.08 ) . Multivariate analysis showed that 21 or more lymph nodes examined was a factor that independently influenced survival . The 5-year disease free survival also increased progressively with the number of lymph node examined up to the number 21 . After the number 21 , the survival rate did not increase further . It was likely that 21 was the optimal number , at and above which the chance of lymph node metastasis was minimal . Conclusions The number of lymph nodes examined in colorectal cancer specimen significantly influences survival . It is recommended that at least 21 lymph nodes should be examined for accurate diagnosis of stage II colorectal cancer BACKGROUND The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence , for whom the indication for such treatment is unclear . METHODS After apparently curative resections of colon or rectal cancer , 3239 patients ( 2963 [ 91 % ] with stage II [ node negative ] disease , 2291 [ 71 % ] with colon cancer , median age 63 [ IQR 56 - 68 ] years ) enrolled between May , 1994 , and December , 2003 , from 150 centres in 19 countries were r and omly assigned to receive chemotherapy with fluorouracil and folinic acid ( n=1622 ) or to observation ( with chemotherapy considered on recurrence ; n=1617 ) . Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil ( 370 mg/m2 ) with high-dose ( 175 mg ) L-folinic acid or low-dose ( 25 mg ) L-folinic acid . Until 1997 , levamisole ( 12 courses of 450 mg over 3 days repeated every 2 weeks ) or placebo was added . After 1997 , patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only . The primary outcome was all-cause mortality . Analyses were done by intention to treat . This trial is registered with the International Clinical Trial Registry , number IS RCT N82375386 . FINDINGS At the time of analysis , 61 ( 3.8 % ) patients in the chemotherapy group and 50 ( 3.1 % ) in the observation group had missing follow-up . After a median follow-up of 5.5 ( range 0 - 10.6 ) years , there were 311 deaths in the chemotherapy group and 370 in the observation group ; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 ( 95 % CI 0.70 - 0.95 ; p=0.008 ) . There were 293 recurrences in the chemotherapy group and 359 in the observation group ; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 ( 0.67 - 0.91 ; p=0.001 ) . Treatment efficacy did not differ significantly by tumour site , stage , sex , age , or chemotherapy schedule . Eight ( 0.5 % ) patients in the chemotherapy group and four ( 0.25 % ) in the observation group died from non-colorectal cancer causes within 30 weeks of r and omisation ; only one of these deaths was deemed to be possibly chemotherapy related . INTERPRETATION Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer , although the absolute improvements are small : assuming 5-year mortality without chemotherapy is 20 % , the relative risk of death seen here translates into an absolute improvement in survival of 3.6 % ( 95 % CI 1.0 - 6.0 ) Background Colorectal carcinoma is the most common malignancy of the gastrointestinal tract . It remains controversial for adjuvant chemotherapy in patients with stage II colon cancer . This study was design ed to identify the risk factors of tumor recurrence in stage II colon cancer . Furthermore , the benefit of adjuvant chemotherapy for high-risk stage II colorectal cancer will be investigated . Material s and methods From May 1998 until August 2004 , 375 patients with stage II ( T3N0M0 , T4N0M0 ) colon cancer received curative operation in a single hospital . The clinical data were extracted from the prospect ively collected colorectal cancer data base . The disease-free survival curves were calculated with Kaplan – Meier ’s analysis , and the survival difference was determined by log-rank test . The p value less than 0.05 was considered to be significant . Results Of 375 stage II colon cancer , 66 patients received 5-FU-based adjuvant chemotherapy , either oral or intravenous ( IV ) form . Within the median of 48.5 months of follow-up , recurrence developed in 35 patients ( 9.3 % ) . T4 lesion ( p=0.024 ) , lymphovascular invasion ( p=0.022 ) , obstruction at presentation ( p=0.008 ) , and mucinous component more than 50 % ( p=0.032 ) were associated with significantly decreased disease-free survival .  High-risk patients ( n=102 ) , but not other patients with stage II colon cancer , benefited from adjuvant therapy ( 3-year disease-free survival : 96.4 % vs. 84.7 % , p=0.045 ; 5-year overall survival : 100 % vs. 86.4 % , p=0.015 ) . Conclusion Adjuvant therapy for high-risk stage II colon cancer may be beneficial , and we suggest adjuvant therapy should be considered in high-risk stage II colon cancer patients PURPOSE A greater underst and ing of the biology of tumor recurrence should improve adjuvant treatment decision making . We conducted a validation study of the 12-gene recurrence score  ( RS ) , a quantitative assay integrating stromal response and cell cycle gene expression , in tumor specimens from patients enrolled onto Cancer and Leukemia Group B ( CALGB ) 9581 . PATIENTS AND METHODS CALGB 9581 r and omly assigned 1,713 patients with stage II colon cancer to treatment with edrecolomab or observation  and found no survival difference . The analysis reported here included all patients with available tissue and recurrence ( n = 162 ) and a r and om ( approximately 1:3 ) selection of nonrecurring patients . RS was assessed in 690 formalin-fixed paraffin-embedded tumor sample s with quantitative reverse transcriptase polymerase chain reaction by using prespecified genes and a previously vali date d algorithm . Association of RS and recurrence was analyzed by weighted Cox proportional hazards regression . RESULTS Continuous RS was significantly associated with risk of recurrence ( P = .013 ) as was mismatch repair ( MMR ) gene deficiency ( P = .044 ) . In multivariate analyses , RS was the strongest predictor of recurrence ( P = .004 ) , independent of T stage , MMR , number of nodes examined , grade , and lymphovascular invasion . In T3 MMR-intact ( MMR-I ) patients , prespecified low and high RS groups had average 5-year recurrence risks of 13 % ( 95 % CI , 10 % to 16 % ) and 21 % ( 95 % CI , 16 % to 26 % ) , respectively . CONCLUSION The 12-gene RS predicts recurrence in stage II colon cancer in CALGB 9581 . This is consistent with the importance of stromal response and cell cycle gene expression in colon tumor recurrence . RS appears to be most discerning for patients with T3 MMR-I tumors , although markers such as grade and lymphovascular invasion did not add value in this subset of patients BACKGROUND A high-risk group of patients with stage II colon cancer has been identified by the results of studies in Western population s. The aim of this study was to investigate the prognostic factors of adjuvant chemotherapy in Turkish patients with stage II colon cancer . METHODS A total of 554 stage II colon cancer patients were retrospectively enrolled in the study . Three hundred fifty-three patients had received adjuvant chemotherapy ( 5-FU-LV , FOLFOX or FLOX ) and 201 had received no adjuvant chemotherapy . T4 tumor stage , lymphovascular invasion , perineural invasion , bowel obstruction and /or perforation , < 12 harvested lymph nodes , and poor differentiation were defined as high-risk factors . RESULTS The median age of the patients was 62 years ( range 26 - 88 ) . The median disease-free survival ( DFS ) was 58.1 months ( 95 % CI , 47.6 months to 68.5 months ) in the non-treatment group and has not been reached in the treatment group ( P < 0.01 ) . In univariate analysis , patient age > 60 years and T4 tumor stage were statistically significant factors that affected DFS as poor prognostic factors . Adjuvant chemotherapy reduced the risk of recurrence with statistical significance ( P < 0.01 ) . In multivariate analysis , patient age > 60 years and T4 tumor stage were independent risk factors affecting DFS . In addition , adjuvant chemotherapy was an independent favorable prognostic factor for DFS ( P < 0.01 ) . CONCLUSIONS Clinical and pathological risk factors in patients with stage II colon cancer may be different in the Turkish population compared to other population s. Further prospect 
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Further subgroup analysis revealed that the significance of the association between LVI and worse prognosis in CRC patients is not affected by below factors , including geographic setting , LVI positive rate , treatment , tumor site , and quality of the study .
The current meta- analysis suggests that LVI may be a poor prognostic factor for stage I/II CRC patients