Papers - NANASHIMA Atsushi
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Nakagoe T., Sawai T., Tsuji T., Jibiki M., Nanashima A., Yamaguchi H., Yasutake T., Kurosaki N., Ayabe H., Arisawa K.
Cancer Detection and Prevention 25 ( 3 ) 299 - 308 2001.6
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cancer Detection and Prevention
In this study, we examined the preoperative serum levels of sialyl Lewisa, sialyl LewisX, sialyl Tn, and carcinoembryonic antigen in 243 colorectal cancer patients in order to clarify the role of these antigens as prognostic factors after curative surgery. The patients were divided into two groups: low and high antigen groups (lower and higher than a selected diagnostic-based cut-off value). Patients with high serum levels of sialyl Lewisa and carcinoembryonic antigen had shorter disease-free intervals than those with low serum levels of the respective antigen, although sialyl Lewisx and sialyl Tn showed no significant differences. Multivariate analysis revealed that three independent prognostic variables, including depth of tumor invasion, lymph node metastasis, and serum sialyl Lewisa level, did prove to have value in predicting disease-free interval. In conclusion, among the four antigens examined in this study, the preoperative serum level of sialyl Lewisa is the only independent prognostic variable for recurrence after curative resection of colorectal cancer.
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Nakagoe T., Sawai T., Tsuji T., Jibiki M., Ohbatake M., Nanashima A., Yamaguchi H., Kurosaki N., Yasutake T., Ayabe H., Arisawa K.
Journal of Experimental and Clinical Cancer Research 20 ( 1 ) 85 - 90 2001.5
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Experimental and Clinical Cancer Research
Two types of colorectal cancer with distinct morphologies have been described in recent studies: polypoid growth type (PG-type) and non-polypoid growth type (NPG-type). We hypothesize that the morphologic differences may correspond to additional biological distinctions. Ratios of sialyl Lewis a (CA19-9), sialyl Lewis x (SLX), or carcinoembryonic antigen (CEA) in the venous blood drainage from the tumor to that of the respective antigen in the peripheral venous blood (d/p ratio) was examined in order to ascertain whether or not the ratio is correlated with either the PG-type or NPG-type colorectal tumor growth pattern. Blood samples from 118 patients with colorectal cancer were obtained from a peripheral vein and from the tumor drainage vein during surgical excision of the tumor. Statistical tests were conducted by univariate and multivariate (logistic regression) analyses. Among the cancers examined there were 17 PG-type (14.4%) and 101 NPG-type (85.6%). NPG-type cancers had a higher frequency of moderately differentiated adenocarcinoma cells and T3/T4 tumors than PG-type cancers (P < 0.0001 and P < 0.0001, respectively). NPG-type cancers had a more advanced stage than PG-type cancers (P=0.0007). The d/p ratio of SLX in NPG-type cancers was significantly higher than that in PG-type cancers (P=0.028). Multivariate logistic regression analysis showed that three variables, namely histologic type, T factor, and d/p ratio of SLX, were independently related to tumor growth patterns. In conclusion, NPG-type cancers are characterized by a high SLX d/p ratio, which may be at least partly responsible for a different tumor progression pattern compared to other cancer types.
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Nakagoe T., Sawai T., Tsuji T., Jibiki M., Nanashima A., Yamaguchi H., Kurosaki N., Yasutake T., Ayabe H.
Journal of Gastroenterology 36 ( 3 ) 166 - 172 2001.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology
Preoperative serum levels of sialyl Lewis a (CA 19-9), sialyl Lewis x (SLX), and sialyl Tn (STN) antigens in colorectal cancer patients were examined to establish predictive factors for serum levels of these antigens compared with carcinoembryonic antigen (CEA). A total of 308 patients who underwent resection for a colorectal cancer were divided into low and high antigen groups (higher or lower than a selected diagnostic-based cutoff value). The cutoff values were 37 U/ml for CA19-9, 38 U/ml for SLX, 45 U/ml for STN, and 2.5 ng/ml for CEA. The American Joint Committee on Cancer Classification and Stage grouping was used to classify the tumors. Statistical tests were conducted using univariate and multivariate logistic regression analyses. For CA19-9, 81 patients (26.3%) were assigned to the high antigen group; for SLX, 39 (12.7%); for STN, 33 (10.7%); and for CEA, 133 (43.2%). Multivariate logistic regression analysis revealed that predictive factors associated with high antigen levels were female sex (odds ratio [OR], 1.78 vs male sex), T4 (OR, 3.26 vs T1/T2), and M1 (OR, 3.35 vs MO) for CA19-9; M1 (OR, 6.40 vs MO) for SLX; mucinous carcinoma (OR, 8.45 vs well differentiated adenocarcinoma) and M1 (OR, 8.24 vs MO) for STN; and mucinous carcinoma (OR, 7.21 vs well differentiated adenocarcinoma), T3/T4 (OR, 3.84/ 4.18, respectively, vs T1/T2), and M1 (OR, 6.39 vs MO) for CEA. In conclusion, high serum levels of CA19-9, SLX, and STN are strongly associated with distant metastasis. In addition, high serum levels of CA19-9 may be an independent predictor for female gender and T4, and high serum levels of STN may be an independent predictor for mucinous carcinoma.
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Surgical treatment and subsequent outcome of patients with carcinoma of the splenic flexure
Nakagoe T., Sawai T., Tsuji T., Jibiki M., Ohbatake M., Nanashima A., Yamaguchi H., Yasutake T., Kurosaki N., Ayabe H., Ishikawa H.
Surgery Today 31 ( 3 ) 204 - 209 2001.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Surgery Today
Extended resection, comprising extended right hemicolectomy, splenectomy, and distal pancreatectomy, has been advocated for carcinoma of the splenic flexure because the lymphatic drainage at this site is variable. The present study addresses the problems associated with selecting the most appropriate operative procedure to achieve cure of splenic flexure cancers. We conducted a retrospective review of 27 patients with splenic flexure cancer who underwent curative resection. Left partial colectomy was performed in 20 patients and partial resection of the transverse/descending colon was performed in 7 patients. The combined resection of adjacent organs due to tumor adherence was performed in three patients. The spleen and distal pancreas were the organs most frequently resected among a collective total of six adjacent organs. The median duration of follow-up was 60.9 months after resection for splenic flexure cancer. No patient developed local recurrence. There was no significant difference in 5-year survival between patients with splenic flexure cancers and those with colon cancers at other sites. In conclusion, splenic flexure cancer resected by left partial colectomy or partial resection of the transverse/descending colon without routine extended resection was not associated with a worse prognosis than colon cancers at other sites.
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Nakagoe T., Fukushima K., Nanashima A., Sawai T., Tsuji T., Jibiki M., Yamaguchi H., Yasutake T., Ayabe H., Matuo T., Tagawa Y.
Journal of Gastroenterology and Hepatology (Australia) 16 ( 2 ) 176 - 183 2001.2
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology and Hepatology (Australia)
Background and Aims: Colorectal tumors can be classified based on their growth pattern into the polypoid growth-type (PG-type) and non-polypoid growth-type (NPG-type). To ascertain whether there is any relationship between the expression of particular blood group-related antigens (A, B, H, Lewis (Le) a , sialyl Le a , Le x , sialyl Le x ) in a colorectal tumor, and a tumor having polypoid or non-polypoid growth, we examined 78 PG-type and NPG-type colorectal cancers. Methods: Fourteen PG-type and 64 NPG-type colorectal carcinomas were subjected to immunohistochemical analyses by using monoclonal antibodies against A, B, H, Le a , sialyl Le a , Le x and sialyl Le x . Results: The patients with NPG-type carcinomas had a significantly younger age of onset, significantly smaller maximal tumor diameter, significantly higher rate of lymph node metastasis and significantly worse prognosis than those with PG-type carcinomas. Among the 32 tumors of patients with blood type A or AB, isoantigen A was expressed in a significantly larger percentage of NPG-type carcinomas than PG-type carcinomas (95.8 vs 62.5%, respectively; P=0.014). Among all 78 tumors, sialyl Le x antigen was expressed in a significantly larger percentage of NPG-type than PG-type carcinomas (90.6 vs 64.3%, respectively; P=0.010). Multivariate analysis using the logistic regression model revealed that isoantigen A and sialyl Le x expression were independent predictive risk factors for the development of NPG-type colorectal carcinoma. Conclusions: These data suggest that the expression of isoantigen A and sialyl Le x in a colorectal carcinoma partially determines whether the tumor will have polypoid or non-polypoid growth. © 2001 Blackwell Science Asia Pty Ltd.
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Nakagoe T., Sawai T., Tsuji T., Jibiki M., Ohbatake M., Nanashima A., Yamaguchi H., Yasutake T., Ayabe H., Arisawa K.
Tumor Biology 22 ( 2 ) 115 - 122 2001.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Tumor Biology
The serum levels of sialyl Lewisa (CA19-9), sialyl Lewisx (SLX), sialyl Tn (STN) and carcinoembryonic antigen (CEA) in peripheral venous blood and tumor drainage venous blood of colorectal cancer patients were examined to determine their value as prognostic factors after surgery. Blood samples were obtained from the peripheral vein and from the tumor drainage vein from 124 colorectal cancer patients during surgical excision of the tumor. The patients were divided into high-antigen and low-antigen groups for each antigen in each location. Serum levels of SLX, STN and CEA in tumor drainage venous blood (d-SLX, d-STN and d-CEA, respectively) were significantly higher than in peripheral venous blood (p-SLX, p-STN and p-CEA, respectively). The survival time after surgery for patients with high d-SLX or d-CEA levels and low levels of the same antigen in peripheral venous blood was significantly shorter than the survival time for those patients with low levels of antigen at both sites (p = 0.0003 or p = 0.0406, respectively). Cox's regression analysis revealed that a high d-SLX or high d-CEA level was an independent prognostic variable for patient survival. In conclusion, determining d-SLX or d-CEA is more useful than p-SLX or p-CEA in predicting the outcome for colorectal cancer patients. Copyright © 2001 S. Karger AG, Basel.
DOI： 10.1159/000050605
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Nanashima A., Yamaguchi H., Fukuda T., Sakamoto I., Kuroda A., Sawai T., Nakagoe T., Ayabe H.
Journal of Gastroenterology and Hepatology (Australia) 16 ( 1 ) 87 - 92 2001
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology and Hepatology (Australia)
Background: To evaluate pancreatic exocrine function, we measured the changes in T 2 enhanced hydrograhic intensity on magnetic resonance (MR) images of the pancreas following an injection of secretin, which is representative of the changes in duodenal fluid volume. Methods: The subjects were 10 patients with normal pancreatic function (N > 70% detected by using a pancreatic function diagnostant test) and 12 patients with hypo-function, including those with mild hypo-function (MH, 50-70%, six patients) and severe hypo-function (SH < 50%, six patients). Results: In the N group, T 2 enhanced intensity of the pancreas increased to a maximum value (more than 10% compared with baseline) within 5 min of stimulation, then gradually decreased. No significant difference in the response was observed between the head and body of the pancreas. Changes in the MH group were similar to those of the N group. In contrast, significantly lower changes in T 2 enhanced intensity were observed in SH group, relative to both the N and MH group (P < 0.05). The amount of secretin-induced increase in duodenal fluid after 16 min was not significantly different among the three groups. Furthermore, an evaluation of the residual pancreatic tissue after a pancreatoduodenectomy was also feasible. Conclusions: Our results indicate that the MR-secretin test is useful for the evaluation of severe pancreatic exocrine dysfunction. The diagnostic test is simple, direct and non-invasive. © 2001 Blackwell Science Asia Pty Ltd.
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Nakagoe T., Sawai T., Tsuji T., Jibiki M., Nanashima A., Yamaguchi H., Yasutake T., Ayabe H., Arisawa K., Ishikawa H.
European Journal of Surgical Oncology 27 ( 8 ) 731 - 739 2001
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：European Journal of Surgical Oncology
Aims: To clarify the prognostic value of preoperative serum levels of sialyl Tn antigen (STN) for survival of gastric cancer patients. Methods: Pre-operative serum levels of STN, sialyl Lewis a antigen (CA19-9) and carcinoembryonic antigen (CEA) were examined in 180 patients who underwent resection of gastric cancer. Patients were divided into high and low antigen groups on the basis of a selected diagnostic-based cut-off value. Correlation between high antigen serum levels, established clinicopathologic factors and prognosis was examined by univariate and multivariate analysis. Results: Twenty-eight patients (15.6%) were classified as high STN; 37 (20.6%) as high CA19-9; and 33 (18.3%) as high CEA. The survival time of the high STN, CA19-9 or CEA group was shorter than that of the respective low-antigen group (P < 0.0001, P=0.0008 or P=0.0002, respectively). Patients with stage III/IV tumours with high STN had a shorter survival time that those with low STN (P=0.0004). Cox's regression with multiple covariates showed that high serum STN is an independent factor predicting a worse outcome in gastric cancer patient s. Multiple logistic regression analysis revealed that high serum STN is an independent predictor for the development of liver metastasis. Conclusions: Pre-operative high serum levels of STN predict both liver metastasis and poor prognosis after resection for gastric cancer. © 2001 Harcourt Publishers Ltd.
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Nanashima A., Yamaguchi H., Shibasaki S., Sawai T., Yamaguchi E., Yasutake T., Tsuji T., Jibiki M., Nakagoe T., Ayabe H.
Journal of Gastroenterology and Hepatology (Australia) 16 ( 10 ) 1158 - 1163 2001
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology and Hepatology (Australia)
Background and Aim: The serum hyaluronic acid (HA) concentrations reflect the degree of hepatic fibrosis and sinusoidal endothelial cell damage. The HA concentrations were examined to evaluate liver damage during the perioperative period of hepatectomy. Methods: The HA level of serum samples from 79 patients who underwent a hepatectomy was measured, and the results were compared to conventional liver function tests, the degree of fibrosis, liver regeneration and complications. Results: Hyaluronic acid concentrations correlated with the severe fibrosis or histological activity index, and also correlated with liver function tests including transaminase level, platelet counts, prothrombin time activity, indocyanine green retention rate at 15 min (ICG R15), liver activity at 15 min by technetium-99m galactosyl human serum albumin scintigraphy (LHL 15), and portal pressure. The HA level postoperatively correlated with liver function, especially with total bilirubin. Hyaluronic acid levels at day 28 postoperatively correlated with ICG R15 and LHL 15. The hyaluronic acid level before surgery and at day 28 postoperatively correlated with the regeneration of remnant liver in major hepatectom y. The HA levels were significantly higher in patients with hepatic failure or prolonged ascites. Conclusion: Our results indicate that the measurement of the HA level is useful for monitoring liver damage or predicting complications associated with liver surgery. ©2001 Blackwell Science Asia Pty Ltd.
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Nanashima A., Yamaguchi H., Sawai T., Yamaguchi E., Kidogawa H., Matsuo S., Yasutake T., Tsuji T., Jibiki M., Nakagoe T., Ayabe H.
Digestive Diseases and Sciences 46 ( 8 ) 1623 - 1628 2001
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Digestive Diseases and Sciences
The present study was designed to provide a systemic analysis of prognosis in 62 patients who underwent hepatic resection for colorectal liver metastasis. The analyzed factors included microvessel counts stained by CD34 and expression of two adhesion molecules, E-cadherin and CD44 variant exon 6-(v6) in these tumors. No significant factors related to recurrence were identified and only negative expression of CD44v6 tended to correlate with recurrence (P = 0.075). A short disease-free period to recurrence was noted in patients with high CEA levels (>10 ng/ml) and H2/3 classification. A short surgical margin, H2/3 classification, high microvessel counts (>60/field, ×200), and negative expression of CD44v6 and E-cadherin tended to be associated with poor prognosis. A high microvessel count was the most significant prognostic factor by multivariate Cox proportional hazards regression model. Hepatic resection without tumor exposure and a careful follow-up in cases identified with poor prognostic factors are necessary.
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Treatment of surgical site infection with aqua oxidation water: Comparison with povidone iodine
Nanashima A., Yamaguchi H., Sawai T., Tsuji T., Shibasaki S., Matsuo S., Jibiki M., Yasutake T., Nakagoe T., Ayabe H.
Acta Medica Nagasakiensia 46 ( 1-2 ) 33 - 37 2001
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Acta Medica Nagasakiensia
Aqua oxidation water is a new disinfectant with a bactericidal activity based on high oxidation-reduction potential and acidity. We compared the effectiveness of aqua oxidation water and povidone iodine against the surgical Site infection (SSI). The bacteriological effect against several organisms and the efficacy of both disinfectants were almost similar. However, the duration of treatment with aqua oxidation water was shorter than that with the povidone iodine in healed wounds (p<0.05) and the number of patients treated with aqua oxidation water who reported pain was smaller than that with povidone iodine (p<0.05). Our results indicated that aqua oxidation water useful and effective for the treatment of incurable SSI.
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Prognostic value of circulating sialyl Tn antigen in colorectal cancer patients
Nakagoe T., Sawai T., Tsuji T., Jibiki M., Nanashima A., Yamaguchi H., Kurosaki N., Yasutake T., Ayabe H., Tagawa Y.
Anticancer Research 20 ( 5 C ) 3863 - 3869 2000.12
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Anticancer Research
To examine the prognostic value of assessing the concentration of circulating sialyl Tn antigen (STN) after surgery, we determined serum STN levels in peripheral venous blood (designated 'p-') in 308 colorectal cancer patients and what we have termed the 'd-p gradient' (obtained by subtracting the serum concentration in peripheral venous blood from that in the tumor's drainage venous blood) in 144 patients. The prognostic value of STN and carcinoembryonic antigen (CEA) was compared. Patients were divided into low or high p-antigen groups and low, intermediate, or high d-p gradient groups. Univariate and multivariate analyses revealed that high STN d-p gradient, high p-CEA, or high CEA d-p gradient were each independent variables for poor patient outcome after surgery, separate from stage. In conclusion, a high STN d-p gradient was a predictor of poor outcome after resection for colorectal cancer, while p-STN was not independent of stage.
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Nakagoe T., Sawai T., Tsuji T., Jibiki M., Ohbatake M., Nanashima A., Yamaguchi H., Kurosaki N., Yasutake T., Ayabe H., Tagawa Y.
Cancer Letters 159 ( 2 ) 159 - 168 2000.10
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cancer Letters
Subtraction values, (i.e. values obtained by subtracting the serum titer of sialyl Lewis a (CA19-9) and sialyl Lewis(x) (SLX) antigens in peripheral venous blood from the serum titer of the same antigen in the tumor's drainage venous blood) were determined in order to clarify whether or not such values for these specific antigens (d-CA19-9 and d-SLX) are prognostic factors after resection for colorectal cancer. The blood samples were obtained from 144 colorectal cancer patients during surgical excisions of the tumors. Univariate and multivariate analyses revealed that d-SLX level was an independent prognostic factor, separate from stage, while d-CA19-9 level did not have any additional prognostic value. In conclusion, a high d-SLX level is a predictor of poor outcome after surgery. (C) 2000 Elsevier Science Ireland Ltd.
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Nakagoe T., Nanashima A., Sawai T., Tuji T., Yamaguchi E., Jibiki M., Yamaguchi H., Yasutake T., Ayabe H., Matuo T., Tagawa Y.
Oncology 59 ( 2 ) 131 - 138 2000.8
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Oncology
Colorectal tumors can be classified based on their growth pattern into the polypoid growth type (PG-type) and nonpolypoid growth type (NPG-type). We examined sialyl Tn antigen expression in advanced colorectal carcinomas that were classified as PG-type and NPG-type cancers in order to ascertain whether or not su ch expression correlates with other biologically and clinically important differences. A total of 94 advanced colorectal carcinomas were examined for sialyl Tn antigen expression, which was immunohistochemically detected by the monoclonal antibody TKH2. Univariate and multivariate analyses using logistic regression models were performed. Forty carcinomas (42.6%) were negative and 54 (57.5%) were positive for sialyl Tn antigen. Eighteen carcinomas (19.2%) were of PG type and 76 (80.8%) of NPG type. NPG- type cancers had a higher proportion of positive lymph node metastasis than PG-type cancers. Furthermore, sialyl Tn antigen was less often detected in NPG-type cancers (39 of 76; 51.3%) than in PG-type cancers (15 of 18; 83.3%; p = 0.0167). Multivariate analysis showed that two variables, lymph node metastasis and sialyl Tn antigen expression in carcinoma, were independently related to tumor growth patterns, that is NPG type and PG type. These data suggest that the difference in sialyl Tn antigen expression between two kinds of tumor growth patterns of advanced colorectal carcinomas, PG type and NPG type, may reflect different biological behaviors during tumor progression. Copyright (C) 2000 S. Karger AG, Basel.
DOI： 10.1159/000012150
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Nakagoe T., Sawai T., Tsuji T., Jibiki M., Nanashima A., Yamaguchi H., Yasutake T., Ayabe H., Ishikawa H.
Journal of Gastroenterology 35 ( 7 ) 528 - 535 2000.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Gastroenterology
The clinicopathological characteristics and outcome of splenic flexure cancer after surgery have yet to be fully elucidated. The aim of the current study was, therefore, to establish predictive factors related to splenic flexure cancer and outcome after surgery. We compared the clinicopathological characteristics and outcome of 34 patients with splenic flexure cancers (which represents 3.7% of the total number of colon cancers in our series) with those of 418 patients with right colon and 475 patients with left colon cancers by univariate and multivariate analyses, using logistic regression analysis and Cox's proportional hazards model. Splenic flexure cancers had a high risk of obstruction (26.5% of patients), and had a more advanced stage and lower cure rate than left colon cancers. Logistic regression analysis revealed that two independent factors, colonic obstruction and the presence of distant metastases, were related to the splenic flexure tumor site. Splenic flexure cancer patients had a poorer outcome than those with left colon cancer (P = 0.0361). However, there was no difference in survival between patients with splenic flexure, those with right colon cancer and those with left colon cancer who underwent curative surgery. Cox's regression analysis revealed that neither the site of splenic flexure nor colonic obstruction was an independent prognostic factor. In conclusion, splenic flexure cancer is characterized by a high risk of obstruction and the presence of distant metastases. However, after curative resection, splenic flexure cancer has a similar outcome to colon cancer at other sites. In addition, neither the splenic flexure site nor colonic obstruction had an independent influence on patient survival after surgery.
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Differences in 20q13.2 copy number between colorectal cancers with and without liver metastasis
Hidaka S., Yasutake T., Takeshita H., Kondo M., Tsuji T., Nanashima A., Sawai T., Yamaguchi H., Nakagoe T., Ayabe H., Tagawa Y.
Clinical Cancer Research 6 ( 7 ) 2712 - 2717 2000.7
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Clinical Cancer Research
Frequent gains of 20q have been identified recently in many neoplasias, including breast, bladder, ovarian, pancreatic, and colon cancers. A high level of 20q13.2 amplification is associated with poor prognosis in breast cancer. We investigated the copy number of the 20q13.2 region including the ZNF217 oncogene in 17 nonmetastatic colorectal cancers (CRCs), 18 primary CRC tumors with liver metastasis, and 18 metastatic lesions by two-color fluorescence in situ hybridization to evaluate the significance of an increased copy number of 20q13.2 in CRC, especially in those cases with liver metastasis. The frequency of increased relative copy number of the 20q13.2 region was higher in primary and liver metastatic lesions of CRC than in CRC lesions without liver metastasis. In particular, a high-level increase ( > 3.0- fold) in the relative copy number of 20q13.2 was observed in 2 of 18 (11%) primary CRC lesions with liver metastasis, 7 of 18 (39%) liver metastatic lesions, and in none of the cases of primary CRC without liver metastasis. The absolute and relative copy number of chromosome 20q13.2 was higher in CRCs with metastasis than in CRCs without metastasis. The percentage of cells with high-level 20q13.2 amplification was also higher in both lesions with metastasis per specimen than without metastasis. Our results suggest that the level of 20q13.2 amplification correlates with the metastatic potential and tumor progression of CRC. The results also suggest that 20q13.2 amplification with ZNF217 is associated with increased metastatic potential.
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Nakagoe T., Sawai T., Tsuji T., Jibiki M., Ohbatake M., Nanashima A., Yamaguchi H., Yasutake T., Ayabe H., Tagawa Y.
Annals of Surgical Oncology 7 ( 4 ) 289 - 295 2000.5
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Annals of Surgical Oncology
Background: To investigate colorectal cancer-related carbohydrate antigen release and distribution, we evaluated serum levels of sialyl Le a (CA19-9) and sialyl Le(x) antigen (SLX) in blood samples obtained from both a peripheral vein and a tumor's draining vein. Methods: Blood samples were obtained during surgery from 126 patients. Based on these samples, patients were placed into a high-antigen group, with a concentration above a selected cutoff value, or into a low-antigen group, with a tumor marker concentration below that same value. The blood samples obtained from peripheral veins were designated by the 'p' prefix, and samples from drainage veins were designated by the 'd.' Results: Serum d-SLX levels were significantly higher than p-SLX levels (P < .0001), although there was no difference between those of d-CA19- 9 and p-CA19-9. Only 1 (3.6%) of 28 patients in the high d-CA19-9 group had a low p-CA19-9. In contrast, 6 (33.3%) of 18 patients in the high d-SLX group had low p-SLX levels (P = .0103). Correlations between pathological variables and either p-CA19-9 levels or d-CA19-9 levels were similar. However, both distant metastasis and venous invasion d id prove to be independent variables related to d-SLX levels, as shown by logistic regression analysis. Conclusions: SLX may drain predominantly via the draining veins of colorectal tumors into portal circulation, whereas CA19-9 may drain via another route.
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Increased expression of sialyl Le(x) antigen in non-polypoid growth type of colorectal carcinoma
Nakagoe T., Fukushima K., Nanashima A., Sawai T., Tsuji T., Jibiki M., Yamaguchi H., Yasutake T., Ayabe H., Matuo T., Tagawa Y.
Cancer Letters 151 ( 2 ) 209 - 216 2000.4
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Cancer Letters
Colorectal carcinoma can be morphologically divided into two different categories, namely polypoid growth (PG-type) and non-polypoid growth (NPG-type). To ascertain whether the expression of sialyl Le(x) antigen correlates with biologically and clinically important differences, an immunohistochemical assay was performed in 30 PG-type and 119 NPG-type cancers. In contrast to PG-type, the characteristics of the NPG-type include (1) an increased expression of sialyl Le(x); (2) a high rate of lymph node metastasis; (3) a high proportion of moderately differentiated adenocarcinoma cells; (4) young age of onset. It is concluded that differences in sialyl Le(x) expression between the PG-type and NPG-type cancers may be at least partly responsible for different tumor progression behavior. Copyright (C) 2000 Else vier Science Ireland Ltd.
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Fujise N., Nanashima A., Taniguchi Y., Matsuo S., Hatano K., Matsumoto Y., Tagawa Y., Ayabe H.
Lung Cancer 27 ( 1 ) 19 - 26 2000.1
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Lung Cancer
The expression of Cathepsin B (CB) and matrix metalloproteinase-9 (MMP-9) in extirpated tissues of adenocarcinomas in non-small cell lung cancer from 90 cases was investigated immunohistologically, and the correlations between the extent of the expression and the clinicopathological features were assessed for investigaiting the process of tumor metastasis. It is important to reveal the mechanisms of destruction of the basal membrane and infiltration of tumor cells at the primary lesion. Sections were obtained from 10%-formalin-fixed and paraffin-embedded tissues. They were reacted with an anti-human CB polyclonal antibody or an anti-human MMP-9 polyclonal antibody. Of 90 patients, 58 (64.4%) and 39 (48.3) cases were found to be positive for CB and MMP-9 expression, respectively. A significantly higher extent of the CB expression was observed in the tissues of patients who showed postoperative recurrence of the tumor (P=0.013). Especially, a similar observation was obtained among early cases of T1N0 (P=0.023). In contrast, no such tendency was demonstrated in the expression profile of MMP-9. Furthermore, the enzyme expressions were compared among different types of metastases. Patients with higher extents of CB expression tended to show significantly higher rates of hematogenous and intrapulmonary metastases (P=0.023 and P=0.010, respectively). However, there was no significant correlation between MMP-9 expression and the prognostic factor of the patients. Therefore, we suggested that evaluation of CB expression in the tumor tissue might be useful as a postoperative prognostic factor of pulmonary adenocarcinoma. Especially, early cancer of T1N0 cases showing higher expression of CB may need postoperative adjuvant chemotherapy. Copyright (C) 2000 Elsevier Science Ireland Ltd.
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Nakagoe T., Fukushima K., Nanashima A., Sawai T., Tsuji T., Jibiki M., Yamaguchi H., Yasutake T., Ayabe H., Matuo T., Tagawa Y., Arisawa K.
Canadian Journal of Gastroenterology 14 ( 9 ) 753 - 760 2000
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Canadian Journal of Gastroenterology
Background: Altered expression of blood group-related carbohydrate antigens such as sialyl Lewis (Le)(x) antigen in tumours is associated with tumour progression behaviour and subsequent prognosis. However, the prognostic value of the expression of Le-related antigens in colorectal tumours remains unclear. Purpose: To clarify the prognostic value of Le a , sialyl Le a , Le(x) and sialyl Le(x) expression in colorectal carcinomas as prognostic factors after surgery. Patients and Methods: Colorectal carcinoma samples from 101 patients with primary colorectal carcinoma who underwent surgical resection were subject to immunohistochemica l analyses for Le a , sialyl Le a , Le(x) and sialyl Le(x) expression with the respective monoclonal antibodies. Results: Le a , sialyl Le a , Le(x) and sialyl Le(x) were expressed in 69 (68.3%), 73 (72.3%), 66 (65.4%) and 76 (75.3%) carcinomas, respectively. The patients with sialyl Le(x)-expressing tumours had more advanced cancer than those with nonsialyl Le(x)-expressing tumours (P=0.0029). The survival time after surgery of patients with Le(x)- or sialyl Le(x)-expressing tumours was significantly shorter than the survival time of those with non-Le(x)- or nonsialyl Le(x)-expressing tumours, respectively (P=0.023 and P=0.0001, respectively). Cox's regression analysis revealed that Le(x) and sialyl Le(x) expression, separate from stage and histological type, were prognostic variables for patient survival (hazard ratio [HR] for sialyl Le(x)-positive expression to sialyl Le(x)-negative expression 2.90; HR for Le(x)-positive expression to Le(x)-negative expression 12.76 in stage I/IV, 0.63 in stage II and 1.69 in stage III). Conclusions: Le(x) expression and sialyl Le(x) expression in colorectal carcinomas are each associated with poor prognosis. These variables should be considered in the design of future trials.
DOI： 10.1155/2000/149851