Tumor Invasion of Lymph Node Capsules in Patients with Dukes C Colorectal Adenocarcinoma

Purpose The objective of this study was to investigate the correlation between the microscopic findings of positive lymph nodes, especially focusing on capsular invasion, and the outcome after curative surgical resection of colorectal cancer. Methods We analyzed 480 positive lymph nodes from 155 consecutive patients with Stage III colorectal cancer to determine the frequency and significance of lymph node capsular invasion. Recurrence-free and cancer-specific survival rates were assessed in the patients with and without lymph node capsular invasion. Results Between April 1995 and December 2000, 406 consecutive patients with primary colorectal cancer underwent curative resection. Regional lymph node metastases were present in 155 cases (38.2 percent). During the median follow-up period of 4.8 years, 41 patients (26.5 percent) developed recurrent disease and 28 patients died of cancer. Lymph node capsular invasion was detected in one or more lymph nodes from 75 cases (48.3 percent). The five-year recurrence-free rate was 56.1 percent in this group, whereas in the 80 patients without lymph node capsular invasion the rate was 88 percent (P<0.01). Features that were associated with recurrent disease were greater number of positive lymph nodes, venous invasion in primary tumor, infiltrative growth pattern of intranodal tumor, and presence of lymph node capsular invasion. Multivariate analysis identified lymph node capsular invasion as the only significant prognostic factor for recurrence. In multivariate analysis with regard to survival, lymph node capsular invasion, venous invasion, and number of positive nodes remained as significant prognostic factors. Conclusions Lymph node capsular invasion, determined by routine hematoxylin-eosin staining, is a potent prognostic factor in Stage III colorectal cancer. Read in part at the meeting of The International Society of University Colon and Rectal Surgeons, Budapest, Hungary, June 9, 2004. Reprints are not available.     

Risk Factors for Occult Lymph Node Metastasis of Colorectal Cancer Invading the Submucosa and Indications for Endoscopic Mucosal Resection

Purpose Although risk factors for histologically overt lymph node metastasis in patients with early-stage colorectal cancer have been clarified, the risk factors for occult lymph node metastasis are not clear. This study was designed to clarify risk factors for lymph node metastasis, including occult metastasis, in patients with colorectal cancer invading the submucosa and to determine the criteria for endoscopic resection of early colorectal cancer. Methods The risk factors for lymph node metastasis, including occult metastasis, were analyzed in 86 cases of surgically resected colorectal cancer invading the submucosa. The lymph nodes were assessed by immunohistochemistry with cytokeratin antibody CAM5.2. Results The frequencies of overt and occult metastasis to the lymph nodes were 13 percent (11/86) and 13 percent (10/75), respectively. Multivariate analysis showed vascular invasion (P = 0.001) and tumor budding (P = 0.003) to be independent risk factors for lymph node metastasis, including occult metastasis. For tumors with submucosal invasion ≤1,000 μm, no lymph node metastasis was found. The frequencies of lymph node metastasis for tumors with submucosal invasion of 1,000 to 2,000 μm and >2,000 μm were 21 and 37 percent, respectively. In considering combinations of risk factors, there was no lymph node metastasis in tumors having neither vascular invasion nor tumor budding and submucosal invasion of ≤3,000 μm. Conclusions Vascular invasion, tumor budding, and the degree of submucosal invasion were significant risk factors for lymph node metastasis, including occult metastasis. These three factors can be used in combination to identify patients requiring additional surgery after endoscopic resection. Supported in part by a Grant-in-Aid for Scientific Research (no. 15390401) from the Japanese Ministry of Education, Science, and Culture. Presented at the Congress of Japan Surgery Society, Tokyo, Japan, March 29 to 31, 2006. Reprints are not available.     

Higher frequencies of numerical aberrations of chromosome 17 in primary gastric cancers are associated with lymph node metastasis

We investigated the correlation between the frequency of numerical aberrations of chromosome 17 and clinicopathological features of gastric cancer. The copy number of chromosome 17 was examined with fluorescence in-situ hybridization (FISH) in frozen specimens from 100 primary gastric cancers. Chromosomal numerical aberrations were diagnosed as chromosomal loss (single signal) or gain (triple or more signals), in each cell. The frequency of numerical aberrations of chromosome 17 correlated significantly with the depth of invasion (P < 0.01), lymph node metastasis (P < 0.0001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.01). Numerical aberrations of chromosome 17 were associated with lymph node metastasis in 32 early gastric cancers. Multiple regression analysis identified the depth of invasion and numerical aberrations of chromosome 17 as independent significant determinants of lymph node metastasis. Our findings suggest that alterations in chromosome 17 may be linked with tumor progression in primary gastric cancer. Our results also indicate that numerical aberrations of chromosome 17 detected by FISH provide important information about the malignant potential (in particular, lymph node metastasis) of primary gastric cancer. (Received Feb. 22, 1998; accepted July 24, 1998)     

Clinical significance of serum levels of CD44 variant exons 8–10 protein in colorectal cancer

We examined serum levels of a CD44 splice variant that contained variant exons 8–10 (CD44v8–10) as a tumor marker in colorectal cancer patients. We performed enzyme-linked immunosorbent assays in 81 sera obtained from 71 colorectal cancer patients and 10 healthy controls. Serum CD44v8–10 levels were significantly higher in the colorectal cancer patients than in the healthy controls (0.209 ± 0.098 versus 0.114 ± 0.019 OD; P < 0.01). There was a close correlation between immunohistochemical expression and serum CD44v8–10 levels. Surgical resection of the tumors resulted in a reduction of serum CD44v8–10 levels. There was no significant correlation between serum CD44v8–10 level and serosal invasion or histologic type. However, a significant correlation was observed between serum CD44v8–10 level and lymphatic or venous invasion. In addition, serum CD44v8–10 levels were significantly higher in carcinomas associated with lymph node or liver metastasis than in those without metastasis. These findings suggest the usefulness of serum CD44v8–10 level in the prediction of colorectal cancer metastasis. (Received July 25, 1997; accepted Nov. 28, 1997)     

Location of Early Colorectal Cancers at Fold-Top May Reduce the Risk of Lymph Node Metastasis

Purpose This study was designed to look for significant correlations between location of early colorectal cancer, distance from muscularis mucosae to muscularis propria, and the frequency of lymph node metastasis. Methods A total of 166 early colorectal cancers, including 67 surgically resected lesions, were evaluated. The cancers were divided into two groups: metastatic and nonmetastatic. Cancer lesions were further subtyped at the fold-top or fold-bottom. Macroscopic classifications and histology were performed. Absolute invasive depth and distance from muscularis mucosae to muscularis propria was measured. Multivariate analysis was used to assess relationships among the variables. Results The percentage of polypoid cancer lesions at fold-bottom was higher than at fold-top (74.5 vs. 51.8 percent), whereas flat-type cancer lesions at fold-bottom occurred less often than at fold-top (8.2 vs. 30.4 percent). Logistic regression showed that deep absolute invasive depth, lymphatic and vessel invasion, and cancer location (at fold-bottom) were the significant risk factors for early colorectal cancers leading to lymph-node metastasis. The distance from muscularis mucosae to muscularis propria with lymph-node metastasis (1,396.7 ± 728.4 μm) was shorter than without lymph-node metastasis (3,533.9 ± 2,507.8 μm; P < 0.01). Multivariate analysis showed that distance from muscularis mucosae to muscularis propria was a statistically significant factor for early colorectal cancers leading to lymph node metastasis (P = 0.0054). Conclusions We conclude that early colorectal cancers at the fold-top or with a long distance from muscularis mucosae to muscularis propria have less tendency to metastasize to lymph nodes. Clinically, these results provide evidence of a new indicator of endoscopic mucosal resection for early colorectal cancers at the fold-top.     

Predictive Histopathologic Factors for Lymph Node Metastasis in Patients With Nonpedunculated Submucosal Invasive Colorectal Carcinoma

PURPOSE Risk factors for lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma remain to be characterized. This study examines the relationship between lymph node metastasis and clinicopathologic factors in nonpedunculated submucosal invasive colorectal carcinoma.METHODS The study cohort comprised 155 patients who had undergone surgical treatment for nonpedunculated submucosal invasive colorectal carcinoma. The clinicopathologic factors investigated included gender, age, tumor location, macroscopic type, tumor size, histologic type and grade, intramucosal growth pattern, lymphatic invasion, venous invasion, degree of focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and the depth and width of submucosal invasion.RESULTS Lymph node metastases were found in 19 patients (12.3 percent). Univariate analysis showed that lymphatic invasion, focal dedifferentiation at the submucosal invasive front, status of the remaining muscularis mucosa, and depth of submucosal invasion all had a significant influence on lymph node metastasis. Multivariate analysis showed lymphatic invasion (P = 0.014) and high-grade focal dedifferentiation at the submucosal invasive front (P = 0.049) to be independent factors predicting lymph node metastasis. No lymph node metastasis was found in tumors with a depth of submucosal invasion of <1.3 mm.CONCLUSIONS Lymphatic invasion and high-grade focal dedifferentiation at the submucosal invasive front are important predictors of lymph node metastasis in patients with nonpedunculated submucosal invasive colorectal carcinoma. Depth of submucosal invasion can be used as an identifying marker for patients who do not require subsequent surgery after endoscopic resection.Supported in part by a grant-in-aid for cancer research from the Ministry of Health and Welfare of Japan.     

Expression of urokinase-type plasminogen activator receptor and plasminogen activator inhibitor-1 in gastric cancer

In gastric cancer, the urokinase-type plasminogen activator (uPA) system plays important roles in invasion and metastasis, processes which entail proteolysis and adhesion. Both the urokinasetype plasminogen activator receptor (uPAR) and the plasminogen activator inhibitor-1 (PAI-1) are thought to be important factors in this system. To clarify the relationship between these two factors and gastric cancer invasiveness, we evaluated the expression of uPAR and PAI-1 in 91 cases of gastric cancer by immunohistochemistry and in situ hybridization. Urokinase-type plasminogen activator receptor-mRNA, PAI-1-mRNA, uPAR and PAI-1 protein were diffusely distributed in the cytoplasm of the cancer cells and concentrated at invasive foci. Urokinase-type plasminogen activator receptor protein expression correlated with lymphatic, venous invasion (P<.01) and lymph node metastasis (P<0.05); uPAR-mRNA expression correlated with lymphatic, venous invasion and lymph node metastasis (P<0.05). Plasminogen activator inhibitor-1 protein expression correlated with lymphatic, venous invasion, lymph node metastasis and depth of invasion (P<0.01); PAI-1-mRNA expression was linked to lymphatic, venous invasion (P<0.01), lymph node metastasis and depth of invasion (P<0.05). This suggests that the proteolytic activity of uPAR and the cellular motility of PAI-1 in gastric cancer cells may determine penetration of lymphatic and blood vessels, whereby lymph node metastasis may be promoted and that the promotion of cellular motility by PAI-1 may influence the depth of cancer invasion.     

Lymphatic Vessel Density at the Site of Deepest Penetration as a Predictor of Lymph Node Metastasis in Submucosal Colorectal Cancer

Purpose Lymph node metastasis is an important factor that influences curability after endoscopic treatment of submucosal colorectal cancer. This study was designed to determine the usefulness of identification of lymphatic vessels by immunohistochemistry in predicting lymph node metastasis of submucosal colorectal cancer. Methods Lymphatic involvement was assessed by hematoxylin and eosin staining and podoplanin immunostaining on samples resected from 268 patients with submucosal colorectal cancer. Lymphatic vessel density was estimated by two investigators by average count of three fields (×200) in the area of greatest number of podoplanin-positive capillaries at the site of deepest submucosal penetration. Relations with other clinicopathologic parameters also were investigated. Results Lesions with high lymphatic vessel density (≥9 vessels per field) showed a significantly greater incidence of lymph node metastasis than did those with low lymphatic vessel density (<9 vessels per field; 23.3 vs. 8.4 percent). By multivariate analysis, lymphatic vessel density was determined to be an independent risk factor for lymph node metastasis of submucosal colorectal cancer (P = 0.0044). Lymphatic vessel density also correlated with tumor budding and the degree of inflammation at the invasive front. Conclusions Identification of lymphatic vessels by podoplanin immunostaining provides objective and accurate evaluation of lymphatic involvement. Lymphatic vessel density at the site of deepest penetration is a useful predictor of lymph node metastasis of submucosal colorectal cancer. Supported by a grant from the Japanese Society of Gastroenterological Endoscopy, Chugoku Branch. Presented at the meeting of The Japanese Society of Gastroenterology, Kokura, Fukuoka, Japan, April 20 to 22, 2006. Reprints are not available.     

Lymphatic vessel invasion detected by monoclonal antibody D2-40 as a predictor of lymph node metastasis in T1 colorectal cancer

Objective  When selecting patients who are at high risk for lymph node metastasis, the detection of lymphatic vessel invasion (LVI) is important. We investigated LVI detected by D2-40 staining as a predictor of lymph node metastasis in T1 colorectal cancer. Materials and methods  Clinicopathological factors including LVI were investigated in 136 patients who underwent colectomy with lymph node dissection for T1 colorectal cancer. We used immunostaining with monoclonal antibody D2-40 to detect LVI. Results  Lymph node metastases were found in 18 patients (13.2%), and LVI were detected in 45 (33%); lymph node metastasis was more frequently observed in LVI-positive groups (13/45 vs 5/91, p < 0.001). Both univariate and multivariate analyses revealed that LVI detected by D2-40 and a poorly differentiated histology at the invasion front were independent risk factors of lymph node metastasis. Conclusion  LVI detected by D2-40 is important for the prediction of lymph node metastasis.     

Treatment strategy for rectal carcinoids: A clinicopathological analysis of 229 cases at a single cancer institution

Background and Aim: A treatment strategy for tumors with only venous invasion and characteristics of small rectal carcinoids with metastasis have not been clearly documented. The present study aims to determine the risk factors for lymph node metastasis and to elucidate characteristics of small tumors with metastasis. Methods: We investigated a total of 229 patients with rectal carcinoids. The relationship between each clinicopathological variable and the presence of lymph node metastasis was evaluated. Results: Tumor size (larger than 10 mm), presence of central depression, depth of tumor invasion, lymphatic invasion, and venous invasion were significantly associated with the incidence of lymph node metastasis (P < 0.001). Multivariate analysis revealed that tumor size (odds ratio: 63.3, P < 0.001) and venous invasion (odds ratio: 40.9, P < 0.001) were independently predictive of lymph node metastasis. In 204 patients with small (no larger than 10 mm) tumors, 10 patients had lymph node metastasis. All 10 tumors had low proliferation values indicated by mitosis and Ki‐67 index. Multivariate analysis for the 204 patients revealed that only venous invasion was independently associated with metastasis (odds ratio: 40.1, P < 0.001). Five‐year disease free survival rates of the total patients with metastasis and without metastasis were 81.1% and 95.5%, respectively (P < 0.001, log‐rank test). Conclusions: Venous invasion as well as tumor size and lymphatic invasion indicates high malignant potential to metastasize to lymph node and would provide useful information in considering the addition of radical surgery. Postoperative pathological examinations of specimens obtained by local resection are very important to avoid underestimation.     

Cyclooxygenase-2 Expression as a New Marker for Patients with Colorectal Cancer

PURPOSE: Epidemiologic studies indicate that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies demonstrate increased expression of cyclooxygenase-2 in human colorectal cancer tissues. However, the role of cyclooxygenase-2 expression in colorectal cancer has not yet been fully established. The aim of this study was to clarify the clinicopathologic significance of cyclooxygenase-2 expression in human colorectal cancer. METHODS: A total of 232 surgically resected colorectal cancer specimens were analyzed immunohistochemically with the use of a murine anti-human cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was then compared with clinicopathologic background and survival outcome. RESULTS: Cyclooxygenase-2 was expressed in the cytoplasm of the cancer cells but not in normal epithelium. Cyclooxygenase-2 expression was noted in 71.6 percent (166/232) of the cancer patients and correlated significantly with histologic type (P = 0.033), depth of invasion (P = 0.016), pathologic stage (P = 0.020), and metachronous liver metastasis (P = 0.001). Multivariate analysis for factors associated with metachronous liver metastasis showed that cyclooxygenase-2 expression was one of the independent risk factors, second only to lymph node metastasis. Patients with cyclooxygenase-2 expression showed a significantly poorer outcome compared with those without cyclooxygenase-2 expression (P = 0.002). CONCLUSION: Cyclooxygenase-2 expression in the primary lesion may be a useful marker for evaluating prognosis and liver metastasis in patients with colorectal cancer.     

MIXED INTESTINAL‐ AND DIFFUSE‐TYPE HISTOLOGY IS A RISK FACTOR FOR LYMPH NODE METASTASIS OF SUBMUCOSAL INVASIVE GASTRIC CANCER

Background: Endoscopic submucosal dissection is expected to increase the number of node‐negative submucosal invasive gastric cancers, particularly differentiated‐type adenocarcinomas that can be treated conservatively. Methods: Two hundred and seven consecutive surgically treated cases of differentiated‐type early gastric cancer with submucosal invasion were analyzed clinicopathologically. Comparison was made between patients with node‐positive (n = 33) and node‐negative cancer (n = 174). Whole sections of surgical specimens were reviewed and reclassified as pure intestinal type or mixed type. The intramucosal and submucosal components were also described histologically, and the depth of invasion from the muscularis mucosae as well as the width of submucosal invasion was measured. Results: Twenty‐four of 33 (73%) node‐positive cases were of the mixed type, whereas 71 of 174 (41%) node‐negative cases were of the mixed type (P < 0.01). As for the intramucosal histology, the ratio of mixed‐type was also higher in the node‐positive group (58% vs 34%; P < 0.05). Other factors associated with lymph node metastasis were larger tumor size (P = 0.003), deeper submucosal invasion (P < 0.001) and wider submucosal extension (P = 0.004), and lymphatic permeation (P < 0.001). Multivariate analysis demonstrated that lymphatic permeation (P = 0.001, OR 4.76), and mixed‐type histology (OR 2.56) were independent risk factors. Conclusions: Histological heterogeneity is a risk factor for metastasis of submucosal invasive gastric cancer to lymph nodes. Heterogeneity of mucosal components is also a significant risk factor and thus a good predictor of lymph node metastasis, potentially useful in distinguishing patients ineligible for conservative therapy.     

Direct Tumor Invasion in Colon Cancer: Correlation with Tumor Spread and Survival

Purpose  This study examined the correlation between depth of local invasion in colon cancer and tumor spread and patient survival. Methods  A cohort of 796 patients with a complete set of TNM staging information following an elective resection for colon cancer was selected. The rates of lymph node and distant metastasis, tumor differentiation, and extramural venous invasion for different tumor (T) categories were compared. The effects of initial tumor (T) category on overall patient survival were studied. Results  The depth of local tumor invasion correlated strongly with nodal involvement (P = 0.0001), rates of extramural venous invasion (P = 0.0002), poor differentiation (P = 0.0001), and distant metastasis (P = 0.0001). Fifty-seven percent of the patients remained lymph node-negative and distant metastasis-negative irrespective of their depth of tumor invasion had no impact on overall survival (P = 0.49). For patients with lymph node or distant metastasis (43 percent), depth of tumor invasion had significant impact on overall survival (P = 0.001). Thirteen percent of T3N1, 33 percent of T3N2, 40 percent of T4N1, and 68.percent of T4N2 cases had distant metastasis at presentation. Conclusion  Two types of colon cancer were observed: locally active and tendency to metastasize. For the latter, overall mortality and the risk of metastasis increased with depth of tumor invasion. Reprints are not available.     

Flow cytometric examination of p53 protein in primary tumors and metastases to the liver and lymph nodes of colorectal cancer

PURPOSE AND METHODS: To confirm prognostic significance of overexpression of p53 in cases of colorectal cancer, expression of p53 protein was examined by flow cytometry in 113 cases of colorectal cancer and its metastasis to the liver and lymph nodes. RESULTS: Overexpression of p53 was found in 44 (39 percent) of the 113 primary tumors. There were no significant correlations among the level of p53 protein in the primary tumor, clinicopathologic features, and prognosis of colorectal cancer. Overexpression of p53 protein was detected in 72 percent (18/25) of liver metastases and in 40 percent (10/25) of lymph node métastases. Frequency of samples that were positive for p53 was significantly higher for liver metastases than for primary tumors and lymph node metastases (P<0.01). By comparing overexpression of p53 in primary tumors with that in corresponding secondary tumors, a decrease of more than 5 percent in the fluorescence index, compared with primary tumor, was not found in liver metastasis but was found in 20 percent of lymph node metastases. Incidence of cases with lower level expression of p53, compared with primary tumor, was significantly higher in lymph node metastases (32 percent) than in liver metastases (8 percent;P<0.05). CONCLUSIONS: From these results, it seems possible that overexpression of p53 may not be a good prognostic indicator of colorectal cancer and may be influenced by environments of the tumor.Presented at the meeting of the Japanese Gastroenterological Surgery, Fukui City, Japan, July 20 and 21, 1995.     

The significance of abdominal para‐aortic lymph node metastasis in patients with lower thoracic esophageal cancer

Para‐aortic lymph node (PALN) recurrence is often seen in patients with lower thoracic esophageal cancer treated by esophagectomy with extended lymph node dissection. However, the clinicopathological characteristics of patients with PALN metastasis and the significance of PALN dissection are unknown. A total of 283 patients with lower thoracic esophageal cancer underwent esophagectomy with lymphadenectomy at our hospital between April 1984 and March 2007. Among these 283 patients, 60 patients were enrolled in this retrospective study according to following criteria: (i) clinical T2 to T4 tumor, (ii) no clinical PALN metastasis, and (iii) received PALN dissection. PALN dissection was indicated by a tumor depth of at least T2 and no severe complications. The clinicopathological data, recurrence pattern, and overall survival were compared between patients with PALN and without PALN metastasis. The mean length of surgery was 587 min and the mean blood loss was 1383 mL. The morbidity was 33.3% and mortality was 5% in this series. Sixteen patients (26.7%) had PALN metastasis; these showed significantly more lymph node metastases (15.8 ± 13.2 vs. 3.0 ± 3.2, P < 0.0001) and significantly worse survival rates (53.3% vs. 79.9% at 1 year, 6.7% vs. 62.0% at 3 years, P < 0.0001) than patients without PALN metastasis. The incidence of lymph node recurrence (P < 0.0001) and hematogenous recurrence (P= 0.0487) was also higher in patients with PALN metastasis than in patients without PALN metastasis. Among the 16 patients with PALN metastasis, a univariate analysis revealed total number of metastatic nodes < 8 (P= 0.0325) to be a significant prognostic factor. A multivariate logistic regression analysis of the regional lymph nodes identified the invasion of the lower mediastinal nodes (hazard ratio = 6.120) and retroperitoneal nodes (hazard ratio = 15.167) to be significantly correlated with PALN metastasis. PALN metastasis is suggested to be related to the systemic spread of lymphatic metastasis even in lower thoracic esophageal cancer. PALN dissection for pathological PALN(+) patients should not be performed. It remains to be determined in future prospective studies whether patients without pathological PALN metastasis, but showing PALN micrometastasis, could achieve improved survival with PALN dissection.     

Level of serum gastrin as a predictor of liver metastasis from colorectal cancer

There have been no reports on the relationship between serum gastrin level and liver metastasis in human colorectal cancer. One hundred forty patients who underwent surgery for colorectal cancer (T2 or more) were enrolled in this study. Fasting serum gastrin level was determined prior to the surgery. Incidence of liver metastasis was significantly (P<0.01) higher in patients with a serum gastrin level of 150 pg/ml (37 percent; 14/38) than in those with a serum gastrin level of <150 pg/ml (12 percent; 12/102). As for the tumors with venous invasion, liver metastasis was detected in 11 of 55 patients (20 percent) with a serum gastrin level of <150 pg/ml; however, it was detected in 11 of 19 patients (58 percent) with a serum gastrin level of 150 pg/ml (P<0.01). These results suggest that serum gastrin serves as a useful predictor of liver metastasis from colorectal cancer and that the predictability of liver metastasis can be improved when both serum gastrin level and venous invasion are considered.     

Relationship between indoleamine 2,3-dioxygenase activity and lymphatic invasion propensity of colorectal carcinoma

AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion(LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan(Trp) and kynurenine(Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologicallyand were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups(both p 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp(r = 0.450, p 0.01). Urinary biopterin was significantly higher in cancer cases(p 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients(p 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group(44.56% ± 6.11%) than negative colorectal cancer patients(24.04% ± 6.90%),(p 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis(p 0.01 and p 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients.CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.     

Altered Expression of a Li-Cadherin in Gastric Cancer and Intestinal Metaplasia

The aims of this study were to examine Li-cadherin expression in 74 gastric carcinoma tissues, 10 cases with normal gastric tissues, and 21 cases with intestinal metaplasia and to investigate the role of Li-cadherin in cell differentiation, cancer invasion, and metastasis. Expression of Li-cadherin was analyzed by immunohistochemistry and semiquantitative polymerase chain reactio and correlated with clinicopathological parameters. Immunohistochemistry showed that Li-cadherin was mainly present on the cell membrane and there was no staining for liver–intestine cadherin in normal tissues. The reduction of Li-cadherin mRNA expression was inversely correlated with the grade of differentiation (P < 0.05). Significant differences in the expression of liver–intestine cadherin were found in lymphatic metastasis of the tumors (P < 0.05), but the expression of liver–intestine cadherin was not associated with gender (P=0.748), serosal invasion (P=0.136), TNM stage (P=0.172), Helicobacter pylori infection (P=0.572), liver metastasis (P=0.374), or peritoneal metastasis (P=0.621). Multivariate analysis revealed that the expression of Li-cadherin is an important predictor of lymph node metastasis. We conclude that there is a significant correlation between Li-cadherin expression and the differentiation of gastric carcinoma, and Li-cadherin can be a good marker to detect gastric cancer at early stages. Increased Li-cadherin expression may contribute to gastric cancer invasion to lymph nodes.     

Curative Resection of T1 Colorectal Carcinoma: Risk of Lymph Node Metastasis and Long-Term Prognosis

PURPOSE The features of T1 colorectal adenocarcinoma and the risk determination of lymph node metastasis were reviewed. Prognostic factors were assessed to verify whether the risk of lymph node metastasis would influence the long-term prognosis.METHODS Patients undergoing curative resection of T1 colorectal adenocarcinoma at the Taipei Veterans General Hospital from December 1969 to August 2002 were retrospectively studied. Patients with synchronous colorectal cancer, distant metastasis, familiar adenomatous polyposis, or inflammatory bowel disease were excluded. The associations between lymph node metastasis and clinicopathologic variables were evaluated univariately using chi-squared test, Fisher’s exact test, or Student’s t -test, and multivariately using logistic regression. Univariate analysis by the log-rank test and multivariate analysis by Cox regression hazards model determined the factors influencing the overall survival.RESULTS A total of 159 patients were included. Sixteen patients (10.1 percent) had lymph node metastasis. The risk of lymph node metastasis included histologic grade (P = 0.005), lymphatic vessel invasion (P = 0.023), inflammation around cancer (P = 0.049), and budding at the invasive front of tumor (P = 0.022). Age (P = 0.001) and number of total sampling lymph nodes (P < 0.0001) were found to be the factors influencing the overall survival.CONCLUSIONS Variables that predict lymph node metastasis in surgically resected T1 colorectal carcinoma may not impact the long-term prognosis.Supported by a grant from the Research Foundation of Taipei Veterans General Hospital.     

Computed tomography and magnetic resonance imaging evaluation of lymph node metastasis in early colorectal cancer

AIM: To assess the role of computed tomography(CT) and magnetic resonance imaging(MRI) and establish imaging criteria of lymph node metastasis in early colorectal cancer.METHODS: One hundred and sixty patients with early colorectal cancer were evaluated for tumor location, clinical history of polypectomy, depth of tumor invasion, and lymph node metastasis. Two radiologists assessed preoperative CT and/or MRI for the primary tumor site detectability, the presence or absence of regional lymph node, and the size of the largest lymph node. Demographic, imaging, and pathologic findings were compared between the two groups of patients based on pathologic lymph node metastasis and optimal size criterion was obtained.RESULTS: The locations of tumor were ascending, transverse, descending, sigmoid colon, and rectum. One hundred and sixty early colorectal cancers were classified into 3 groups based on the pathological depth of tumor invasion; mucosa, submucosa, and depth unavailable. A total of 20(12.5%) cancers with submucosal invasion showed lymph node metastasis. Lymph nodes were detected on CT or MRI in 53 patients. The detection rate and size of lymph nodes were significantly higher(P = 0.000, P = 0.044, respectively) in patients with pathologic nodal metastasis than in patients without nodal metastasis. Receiver operating curve analysis showed that a cut-off value of 4.1 mm is optimal with a sensitivity of 78.6% and specificity of 75%.CONCLUSION: The short diameter size criterion of≥ 4.1 mm for metastatic lymph nodes was optimal for nodal staging in early colorectal cancer.