Initial stability of cementless acetabular cups using robotic-assisted total hip arthroplasty compared with the conventional manual technique: An in vitro biomechanical study.

BACKGROUND: The aim of this study is to determine whether the initial stability of a cementless cup with the Mako system is superior to that of a conventional manual technique using bone models. METHODS: The bone models were prepared using a polyurethane foam block. Two hemispherical cementless cups (highly porous titanium cup [Trident II Tritanium, Stryker] and hydroxyapatite-coated titanium cup [Trident HA, Stryker]) were implanted using the Mako system. The torque of the cups was measured by rotational and lever-out torque testing and compared with that of a conventional manual technique. RESULTS: The two types of cups that were implanted using the Mako system demonstrated significantly higher mean rotational torque than that of the manual technique (p < 0.01, p = 0.01, respectively). CONCLUSIONS: This study provides the advantage of the initial stability of a cementless hemispherical cup implanted by the Mako system compared with that of the conventional manual technique.

Antimicrobial prophylaxis for 1 day versus 3 days in liver cancer surgery: a randomized controlled non-inferiority trial.

PURPOSES: This study compared the effectiveness of 1-day vs 3-days antibiotic regimen to prevent surgical site infection (SSI) in open liver resection. METHOD: We performed a randomized controlled non-inferiority trial in 480 patients at 39 hospitals across Japan (registered as UMIN000002852). Patients with hepatocellular carcinoma scheduled to undergo resection were randomly assigned to receive either a 1-day regimen for antimicrobial prophylaxis, or a 3-day regimen. The primary endpoint was the incidence of SSI. RESULTS: Among 480 randomized patients, 232 assigned to the 1-day regimen and 235 to the 3-day regimen were included in the full analysis set. Baseline characteristics of the two groups were well balanced. SSI was diagnosed in 22 patients (9.5%) in the 1-day group vs 23 patients (9.8%) in the 3-day group (difference, - 0.30; 90% CI - 4.80 to 4.19% [95% CI - 5.66% to 5.05%]; one-sided P = 0.001 for non-inferiority), meeting the non-inferiority hypothesis. In both groups, remote site infection (16 [6.9%] vs 22 [9.4%], P ˂ 0.001 for non-inferiority) and drain-related infection (5 [2.2%] vs 4 [1.7%], P ˂ 0.001 for non-inferiority) were comparable. CONCLUSION: To prevent SSI in liver cancer surgery, a 1-day regimen of flomoxef sodium is recommended for antimicrobial prophylaxis because of confirming the non-inferiority to longer usage.

A randomised-controlled trial of 1-year adjuvant chemotherapy with oral tegafur-uracil versus surgery alone in stage II colon cancer: SACURA trial.

BACKGROUND: Efficacy of adjuvant chemotherapy in patients with stage II colon cancer is still controversial. The SACURA trial is a randomised-controlled study evaluating the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer. METHODS: Patients were randomly assigned to the surgery-alone group or UFT group (UFT at 500-600 mg/day for 5 days, followed by 2-day rest, for 1 year). The primary end-point was disease-free survival (DFS). Target sample size was 2000, determined with one-sided alpha of 0.05, power of 0.9 and assumed hazard ratio (HR) 0.729. RESULTS: A total of 1982 patients (997 in the surgery-alone group and 985 in the UFT group) were analysed. Median follow-up was 69.5 months, median age was 66 years and for stage IIA/IIB/IIC, the distribution was 84%/13%/3%. The 5-year DFS rate was 78.4% in the surgery-alone group and 80.2% in the UFT group. The HR for DFS was 0.91 (95% confidence interval [CI], 0.75-1.10; p = 0.31); superiority of UFT was not demonstrated. Approximately 9% of patients experienced second cancers, which consist 40.7% of the DFS events. The 5-year relapse-free and overall survival rates of the surgery-alone and UFT group were 84.6% and 87.2% (HR, 0.82; 95% CI, 0.65-1.04) and 94.3% and 94.5% (HR, 0.93; 95% CI, 0.66-1.31), respectively. Subgroup analysis failed to disclose superiority in prognosis of adding UFT to the patients with risk factors for recurrence. CONCLUSIONS: Superiority of 1-year adjuvant UFT over surgery alone was not demonstrated in stage II colon cancer. Patients with risk factors for recurrence did not benefit from UFT. TRIAL REGISTRATION: ClinicalTrials. Gov. #NCT00392899.

A three-tier classification system based on the depth of submucosal invasion and budding/sprouting can improve the treatment strategy for T1 colorectal cancer: a retrospective multicenter study.

More than 85% of patients with T1 colorectal cancer have no lymph node metastasis and can be cured by endoscopic resection. To avoid unnecessary surgery after complete endoscopic resection, accurate histologic methods for evaluating resected specimens are needed to discriminate those at high risk for lymph node metastasis. A retrospective multi-institutional, cross-sectional study of 806 T1 colorectal cancer patients was conducted. A budding/sprouting score was incorporated for predicting lymph node metastasis in addition to other parameters, including the depth of submucosal invasion, histologic grade, and lymphovascular invasion. Lymph node metastasis was detected in 97 patients. Independent predictors of lymph node metastasis by multivariate analysis were depth of submucosal invasion ≥1000 µm (odds ratio (95% confidence interval)=5.56 (2.14-19.10)) and high-grade budding/sprouting (3.14 (1.91-5.21)). Among lesions with a depth of submucosal invasion ≥1000 µm, lymph node metastasis was detected in 59 (29%) of 207 patients with high-grade budding/sprouting, and in 34 (9%) of 396 with low-grade budding/sprouting. Lymph node metastasis was detected in only 4 (2%) of 203 lesions with a depth of submucosal invasion <1000 µm. Of these four tumors, three invaded lymphatic and/or venous vessels. Thus, the risk for lymph node metastasis can be classified into three groups: high risk with a depth of submucosal invasion ≥1000 µm and high-grade budding/sprouting, intermediate-risk with a depth of submucosal invasion ≥1000 µm and low-grade budding/sprouting, and low-risk with a depth of submucosal invasion <1000 µm. These findings revealed that a depth of submucosal invasion ≥1000 µm and high-grade budding/sprouting are powerful predictive parameters for lymph node metastasis in T1 colorectal cancer. This three-tier risk classification system will facilitate the decision for additional major surgery for T1 colorectal cancer patients after successful endoscopic treatment.

Multicenter study evaluating the clinical performance of the OSNA assay for the molecular detection of lymph node metastases in gastric cancer patients.

BACKGROUND: The accurate diagnosis of lymph node (LN) metastasis is important for making treatment decisions for gastric cancer patients. This multicenter study evaluated the clinical performance of the one-step nucleic acid amplification (OSNA) assay (Sysmex Corp.), an automated system that detects cytokeratin 19 (CK19) mRNA, in detecting LN metastases in gastric cancer patients. METHODS: LNs retrieved from patients who had undergone gastric cancer surgery at one of the four Japanese hospitals involved in this study were divided into blocks at 2-mm intervals. Alternate blocks were examined with the OSNA assay and the remaining blocks were assessed histologically. RESULTS: A total of 394 LNs from 61 patients were examined. The concordance rate between the OSNA assay and the histological examination was 0.942 (95 % CI, 0.914-0.963). Sensitivity and specificity of the OSNA assay compared to the histological examination were 0.833 (95 % CI, 0.707-0.921) and 0.959 (95 % CI, 0.932-0.977), respectively. Discordant results were observed in 23 LNs (5.8 %), and these were mainly the result of tissue allocation bias and/or low CK19 protein expression. CONCLUSION: The OSNA assay can detect lymph node metastases in gastric cancer patients as accurately as the histological examination of blocks sectioned at 2-mm intervals. The OSNA assay is a useful tool for the intraoperative diagnosis of LN metastasis in gastric cancer patients.

The rs6983267 SNP is associated with MYC transcription efficiency, which promotes progression and worsens prognosis of colorectal cancer.

BACKGROUND: The oncogenic single nucleotide polymorphism rs6983267, located on 8q24.21, may affect copy number aberrations and/or expression profiles in colorectal cancer (CRC). We investigated the role of this single nucleotide polymorphism in the clinical outcome of CRC. METHODS: Array comparative genomic hybridization (aCGH) and oligomicroarrays were performed on cancer cells from 157 primary CRC tissues. Expression profiles were analyzed by means of extraction expression module (EEM) analyses. Mutations in TP53, KRAS, and BRAF and microsatellite instability were also examined in 107 of the 157 cases. RESULTS: aCGH analysis revealed two clusters; more frequent genomic copy number alteration (CNA) was observed in the 89 cases in cluster B than in the 18 cases in cluster A. The average CNA was higher in samples containing the major allele (GT/TT) of rs6983267 than in those containing the minor allele (GG). Additionally, MYC expression was the highest in samples containing the GG allele (n = 18), followed by the GT and TT alleles (n = 41 and 48, respectively). EEM analysis revealed dominant up-regulation of MYC in samples containing the minor allele. Moreover, the presence of the minor allele in a MYC-positive, CNA-negative context predicted a poorer prognosis than the presence of the major allele in a MYC-negative, CNA-positive context in CRC. CONCLUSIONS: The presence of the minor allele of rs6983267 at 8q24.21 worsened the prognosis of CRC through up-regulation of MYC transcription. Furthermore, progression of CRC may require global CNA in the presence of the major allele and with lack of MYC transcription.

Study protocol of the SACURA trial: a randomized phase III trial of efficacy and safety of UFT as adjuvant chemotherapy for stage II colon cancer.

BACKGROUND: Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy, but the usefulness of adjuvant chemotherapy for stage II colon cancer remains controversial. The major Western guidelines recommend adjuvant chemotherapy for "high-risk stage II" cancer, but this is not clearly defined and the efficacy has not been confirmed. METHODS/DESIGN: SACURA trial is a multicenter randomized phase III study which aims to evaluate the superiority of 1-year adjuvant treatment with UFT to observation without any adjuvant treatment after surgery for stage II colon cancer in a large population, and to identify "high-risk factors of recurrence/death" in stage II colon cancer and predictors of efficacy and adverse events of the chemotherapy. Patients aged between 20 and 80 years with curatively resected stage II colon cancer are randomly assigned to a observation group or UFT adjuvant therapy group (UFT at 500-600 mg/day as tegafur in 2 divided doses after meals for 5 days, followed by 2-day rest. This 1-week treatment cycle is repeated for 1 year). The patients are followed up for 5 years until recurrence or death. Treatment delivery and adverse events are entered into a web-based case report form system every 3 months. The target sample size is 2,000 patients. The primary endpoint is disease-free survival, and the secondary endpoints are overall survival, recurrence-free survival, and incidence and severity of adverse events. In an additional translational study, the mRNA expression of 5-FU-related enzymes, microsatellite instability and chromosomal instability, and histopathological factors including tumor budding are assessed to evaluate correlation with recurrences, survivals and adverse events. DISCUSSION: A total of 2,024 patients were enrolled from October 2006 to July 2010. The results of this study will provide important information that help to improve the therapeutic strategy for stage II colon cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00392899.

Genomic copy number of a carcinogenic single nucleotide polymorphism at 8q24 in non-risk allele colorectal cancer associated with insulin growth factor 2 receptor expression.

BACKGROUND AND AIM: The incidence of both diabetes mellitus and hyperlipidemia is increasing and they are risk factors for colorectal cancer (CRC). On the other hand, the carcinogenic significance of the single nucleotide polymorphism (SNP), rs6983267 at 8q24, in CRC has been reported. The association between the SNP genotype and genes associated with diabetes or hyperlipidemia was investigated in cases of CRC. METHODS: In 107 cases of CRC diagnosed in eight institutes from 2003 to 2008, array-CGH and cDNA microarray was performed and the data analyzed from two groups subdivided according to SNP genotype. RESULTS: In the array-CGH data, we selected 38 genes related to diabetes or fat metabolism, and of these 10 had a correlation coefficient between the genome copy number at 8q24 locus and that of each gene. Of the 10 genes, insulin growth factor 2 receptor (IGF2R) was the only one with an expression level significantly associated with the 8q24 genotype. IGF2R expression was significantly lower in non-risk allele than in risk allele cases (P = 0.012). There was neither a diabetes- nor a fat metabolism-related gene that was significantly associated with CRC cases with the risk allele at 8q24. CONCLUSIONS: SNP at 8q24 makes diabetes a risk factor of CRC via IGF2R, especially in genetically non-risk allele cases. We speculate that the risk allele of 8q24 might be risky enough that diabetes is not necessary to worsen the risk for CRC.

Optimal colorectal cancer staging criteria in TNM classification.

PURPOSE: Histologic components of the TNM classification system have been repeatedly revised since the fifth edition (TNM5). TNM classification revisions provide different criteria for categorizing tumor nodules without residual lymph node structure (ND). However, there are few systematic evaluations regarding the effectiveness of these revisions. PATIENTS AND METHODS: A multicenter pathologic review for ND in colorectal cancer (CRC) was performed. Tumor staging defined by TNM5, sixth edition (TNM6), and seventh edition (TNM7) were compared on the basis of Akaike information criterion (AIC) and Harrell's concordance index (c-index). Moreover, TNM7's prognostic value was compared between the original ND and modified criteria, which considered all regional NDs as lymph node metastasis (LNM) irrespective of the original structure. RESULTS: In 1,716 treated patients with CRC (1994 to 1998), tumor stages (I/II/III) exhibited better prognoses in TNM7 (AIC, 3055.1; c-index, 0.7215) than in TNM6 (AIC, 3063.7; c-index, 0.7149), but not better than in TNM5 (AIC, 3051.6; c-index, 0.7240). Comparing the original TNM7 and modified criteria, 4.2% of patients were classified in different N stages (N0/N1/N2a/N2b); both AIC and the c-index were superior in the modified criteria (AIC, 3029.40; c-index, 0.7271) compared with the original criteria (AIC, 3040.58; c-index, 0.7230). Modified criteria were also associated with improved prognostic power of tumor stages (I/IIA/IIB/IIC/IIIA/IIIB/IIIC). These results were similar in another cohort of 2,242 treated patients with CRC (1999 to 2003). CONCLUSION: The prognostic value of TNM7 is better than that of TNM6; however, improvement over TNM5 is insignificant. By considering all regional NDs as LNM irrespective of their morphology, TNM classification can be simplified and its prognostic value improved.

Multicenter study for optimal categorization of extramural tumor deposits for colorectal cancer staging.

OBJECTIVE: This study aimed to determine the optimal categorization of extramural tumor deposits lacking residual lymph node (LN) structure (EX) in colorectal cancer staging. BACKGROUND: The TNM classification system categorizes EX on the basis of their contour characteristics (the contour rule). METHODS: We conducted a multicenter, retrospective, pathological review of 1716 patients with stage I to III curatively resected colorectal cancer who were treated at 11 institutions (1994-1998). In addition, 2242 patients from 9 institutions (1999-2003) were enrolled as a second cohort for validating results. EX were classified as isolated foci confined to vascular or perineural spaces (ie, lymphatic, venous, or perineural invasion) or as tumor nodules (ND). N- and T-staging systems employing different categories for staging were compared in terms of their prognostic power. In addition, the diagnoses of extramural, discontinuously spreading lesions made by 11 observers from different institutions were assessed for interobserver agreement. RESULTS: EX were observed in 18.2% of patients in the first cohort. The method of categorization of EX in tumor staging has a stronger impact on N than T staging. The N-staging system in which all ND types were classified as N factor (the ND rule) could more effectively stratify the survival outcome than the contour rule (Akaike information criterion, 3040.8 vs 3059.5; the Harrell C-index, 0.7255 vs 0.7103). EX were observed in 16.9% of patients in the second cohort. Statistically, the ND rule was more informative than the contour rule for N staging. The Fleiss kappa coefficient for distinguishing LN metastases from EX (0.74) was lower than expected for complete agreement, and it decreased further to 0.51 when calculated for the judgment of ND with smooth contours. CONCLUSIONS: Classifying all ND types as N factors irrespective of contours can simplify the tumor staging system by enhancing diagnostic objectivity, resulting in improved prognostic accuracy.

Increased risk for CRC in diabetic patients with the nonrisk allele of SNPs at 8q24.

BACKGROUND: Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated. METHODS: A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures. RESULTS: Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM. CONCLUSIONS: We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present.

Down-regulation of miR-125a-3p in human gastric cancer and its clinicopathological significance.

Recent reports have demonstrated that another strand of mature microRNA (miRNA), called microRNA* or 3p (5p) strand, which is generated from the same precursor miRNA (Pre-miR), has a crucial role in cellular function. We previously reported the tumor suppressive effect of miR-125a-5p in gastric cancer. The current study was designed to examine the function and clinical significance of miR-125a-3p, a partner strand of miR-125a-5p, in human gastric cancer. Quantitative RT-PCR was used to evaluate miR-125a-3p expression in 70 gastric cancer cases to determine the clinicopathologic significance of miR-125a-3p expression. In addition, the effect of miR-125a-3p on the proliferation of gastric cancer cells was investigated. Low expression levels of miR-125a-3p were associated with indicators of enhanced malignant potential such as tumor size (p=0.0002), tumor invasion (p=0.0149), lymph node metastasis (p=0.018), liver metastasis (p=0.016), peritoneal dissemination (p=0.03), advanced clinical stage (p=0.0037) and poor prognosis (p=0.0083). Multivariate analysis indicated that low miR-125a-3p expression was an independent prognostic factor for survival, while in vitro assays demonstrated that miR­125a-3p suppressed the proliferation of gastric cancer cells. MiR-125a-3p is a potent prognostic marker in gastric cancer. The clinical significance and tumor suppressive effect of miR­125a-3p, as well as previously reported miR-125a-5p, suggest that the functional role of another strand of the mature form miRNA cannot be ignored, at least in miR-125a biogenesis.

New criteria for histologic grading of colorectal cancer.

Conventional tumor grading systems based on the degree of tumor differentiation may not always be optimal because of difficulty in objective assessment and insufficient prognostic value for decision making in colorectal cancer (CRC) treatment. This study aimed to determine the importance of assessing the number of poorly differentiated clusters as the primary criterion for histologic grading of CRC. Five hundred consecutive patients with curatively resected stage II and III CRCs (2000 to 2005) were pathologically reviewed. Cancer clusters of ≥5 cancer cells and lacking a gland-like structure were counted under a ×20 objective lens in a field containing the highest number of clusters. Tumors with <5, 5 to 9, and ≥10 clusters were classified as grade (G)1, G2, and G3, respectively (n=156, 198, and 146 tumors, respectively). Five-year disease-free survival rates were 96%, 85%, and 59% for G1, G2, and G3, respectively (P<0.0001). Poorly differentiated clusters affected survival outcome independent of T and N stages and could help in more effective stratification of patients by survival outcome compared with tumor staging (Akaike information criterion, 1086.7 vs. 1117.0; Harrell concordance index, 0.73 vs. 0.67). The poorly differentiated cluster-based grading system showed a higher weighted κ coefficient for interobserver variability (5 observers) compared with conventional grading systems (mean, 0.66 vs. 0.52; range, 0.55 to 0.73 vs. 0.39 to 0.68). Our novel histologic grading system is expected to be less subjective and more informative for prognostic prediction compared with conventional tumor grading systems and TNM staging. It could be valuable in determining individualized postoperative CRC treatment.

Impact of race/ethnicity on prognosis in patients who underwent surgery for colon cancer: analysis for white, African, and East Asian Americans.

PURPOSE: We retrospectively investigated the impact of race/ethnicity on prognosis in patients who underwent surgery for colon cancer. METHODS: Surveillance, Epidemiology, and End Results population-based data on 39,210 colon cancer patients without distant metastasis who underwent radical surgery were analyzed. Prognostic impact of race/ethnicity for non-Hispanic white, Hispanic white, African American, and East Asian (Japanese, Chinese, Korean) American patients, and confounding factors of age, sex, registry region, year of diagnosis, tumor, node, metastasis system stage, tumor grade, tumor site, and the number of lymph nodes examined were analyzed by the Cox proportional hazard model. The lymph node count was analyzed and adjusted means were calculated by a generalized multiple regression model with respect to race and other factors. RESULTS: Significant differences due to race/ethnicity were observed in crude hazard ratios with respect to overall and colon cancer-specific mortality, which persisted even after adjusting for confounding factors. Adjusted hazard ratios of colon cancer-specific mortality for non-Hispanic white, Hispanic white, African American, and East Asian American patients were 1 (reference), 1.01 (95% confidence interval 0.91-1.12), 1.40 (95% confidence interval 1.31-1.50), and 0.83 (95% confidence interval 0.74-0.94), respectively. There were significant differences in crude number of lymph nodes examined among races, which were no longer significant after adjusting for covariates. CONCLUSIONS: East Asian American patients had significantly better prognosis, while African American patients had worse prognosis than non-Hispanic white patients, despite the identical adjusted number of lymph nodes examined after surgery for colon cancer. This disparity in prognosis among races/ethnicities should be taken into consideration when deciding adjuvant chemotherapy for nonwhite patients.

[Chemoradiation combined with total mesorectal excision for patients with locally advanced rectal cancer].

Rectal cancer is characterized by a high rate of local recurrence. Although it is widely believed that local control results in improved patient outcome, its strategy is still controversial. In Japan, total mesorectal excision (TME) or tumor-specific mesorectal excision (TSME) with pelvic sidewall dissection is regarded as the standard procedure, while TME or TSME with preoperative chemoradiotherapy (CRT) is common in Western countries. Most clinical data have indicated that preoperative CRT is not associated with improved long-term survival but with a lower incidence of local recurrence. In addition, CRT is known to enhance the severity of impaired sphincter function. Currently, trials using CRT regimens with newly developed chemotherapy agents are ongoing to elucidate the effect on the control of distant metastasis. According to clinical reports, the prognosis of Japanese patients undergoing surgery alone is as favorable as that in patients undergoing surgery plus CRT in the West, which implies that CRT is not a necessary treatment but a selective option. The precise prediction of tumor response and advances in CRT regimens resulting in better survival may improve the treatment of rectal cancer in the future.

Pretreatment CD133 and cyclooxygenase-2 expression as the predictive markers of the pathological effect of chemoradiotherapy in rectal cancer patients.

BACKGROUND: CD133 confers chemoradioresistance properties to cells and has recently been used to identify cancer-initiating cells. OBJECTIVE: We investigated whether the overexpression of CD133 and cyclooxygenase-2 can be used as predictive markers of tumor response to preoperative chemoradiotherapy in patients with rectal cancer. SETTING: The study was conducted at the National Defense Medical College Hospital in Japan. PATIENTS: We recruited 96 patients who underwent a single regimen of preoperative short-term chemoradiotherapy (20 Gy in 5 fractions with 400 mg/day Tegafur/Uracil for 1 week) and radical resection. DESIGN: This was a retrospective study. We obtained pretreatment biopsy specimens of these patients and immunostained these specimens with antibodies for CD133, cyclooxygenase-2, p53, p27, p21, and epidermal growth factor receptor. The resected primary tumor was evaluated according to 2 different tumor regression grading systems that were based on the degrees of fibrosis and cytological alterations. RESULTS: Positivity for CD133 or cyclooxygenase-2 expression was associated with chemoradioresistance, which was determined by the degree of fibrosis, in both univariate (P = .02 and P = .0003) and multivariate (P = .03 and P = .001) analyses. Univariate and multivariate analyses of the degree of cytological alterations also revealed a significant association between chemoradioresistance and the expression of CD133 (P = .005 and P = .003) and cyclooxygenase-2 (P = .005 and P = .03), whereas other markers failed to associate. LIMITATIONS: The information on patients' outcome was not available. CONCLUSIONS: Our study revealed the independent predictive values of CD133 and cyclooxygenase-2 expressions in histological tumor regression after preoperative chemoradiotherapy.

Expression of l1 cell adhesion molecule and morphologic features at the invasive front of colorectal cancer.

To obtain the correlation between morphologic features in the invasive fronts of colorectal cancer (CRC) and L1 cell adhesion molecule (L1CAM) expression, 275 CRCs were assessed with L1CAM immunostaining and 29 CRCs were examined for L1CAM messenger RNA (mRNA) expression. Based on immunostaining, the positive rate of L1CAM expression increased according to the grade of tumor budding (P = .0002) and solid cancer nests (SCNs; P = .0046). L1CAM mRNA levels at the invasive front of the tumor were higher than those at the center of the tumor (median, 3.7-fold). The gap of L1CAM mRNA level between the invasive front and the central area was 7.3-fold in tumors having SCN lesions, whereas it was 1.9-fold in tumors having non-SCN lesions (P = .0004). L1CAM expression was correlated with nodal involvement in protein and mRNA levels (P = .0007 and P = .036, respectively). Tumor regulation of L1CAM expression is associated with morphologic features at the invasive front in CRC.

Heterogeneity of metalloproteinase expression in colorectal cancer - relation of molecular findings to basic morphology.

AIM: To clarify the correlation between morphological features and the mRNA expression of a disintegrin and metalloproteinases (ADAMs) and matrix metalloproteinases (MMPs) in colorectal cancer. MATERIALS AND METHODS: In 29 colorectal tumors, cancer cells were isolated by laser microdissection, and the mRNA expression of metalloproteinases was compared between the tumor center and the invasive front. RESULTS: Regarding the central region as the standard, the mRNA levels of ADAM-12, MMP-1, -2, -7, and -9 at the invasive front were up-regulated. The degree of up-regulation was significantly higher in solid cancer nest (SCN)-positive tumors than in SCN-negative tumors for the mRNA levels of ADAM-12, MMP-2, -7, and - 9 (SCN-positive, median 5.1-, 3.9-, 9.9-, and 2.7-fold; SCN-negative 2.0-, 1.0-, 2.4-, and 0.8-fold; p<0.05, respectively). CONCLUSION: Up-regulation of the mRNA expression of particular metalloproteinases was significantly associated with the SCN at the leading edge of colorectal tumors.

Actual status of distribution and prognostic impact of extramural discontinuous cancer spread in colorectal cancer.

PURPOSE: To clarify the prognostic impact of tumor nodules without residual lymph node (LN) structure (ND) in colorectal cancer and to determine optimal categorization of ND in tumor staging. PATIENTS AND METHODS: A multicenter, retrospective pathologic review was performed for 1716 patients with stages I to III curatively resected colorectal cancer treated at 11 institutions between 1994 and 1998. An additional 2242 patients from nine institutions were enrolled between 1999 and 2003 as a second cohort to validate the results. RESULTS: LN metastasis (LNM) and ND were observed in 33.7% and 16.0% (smooth-contour nodule [S-ND], 8.2%; irregular-contour nodule [I-ND], 10.7%) of patients in the first cohort. S-ND and I-ND were similarly distributed in the regional area. There was no considerable difference in the impact on survival between S-ND (hazard ratio [HR], 2.7; 95% CI, 1.9 to 3.8) and I-ND (HR, 4.3; 95% CI, 3.3 to 5.8) or between LNM (HR, 4.5; 95% CI, 3.4 to 6.0) and ND (HR, 4.0; 95% CI, 3.1 to 5.3). LNM and ND were similarly associated with the mode of recurrence. Tumor nodules ≥ 5 mm growing with venous/perineural invasion (ND [v/pni+]), judged with 0.61 κ value among 11 observers, had an independent prognostic value for 5-year survival of 42%; similar results were observed in the second cohort. CONCLUSION: These results do not support the TNM system in which S-ND is treated differently from I-ND in tumor staging; LNM and ND should be considered together in the same category. The presence of ND (v/pni+) has a considerable adverse prognostic effect.