Differences in 20q13.2 copy number between colorectal cancers with and without liver metastasis.

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.

Clinical and pathological significance of numerical aberrations of chromosomes 11 and 17 in colorectal neoplasms.

Numerical chromosome aberrations by interphase cytogenetic analysis have been reported in a few samples of colorectal neoplasms. No studies have defined a distinct relationship between these aberrations and clinicopathological features. To investigate the chromosome aberrations as a marker of invasiveness or prognosis, we conducted an interphase cytogenetic study using fluorescence in situ hybridization and examined 142 colorectal neoplasms consisting of 15 adenomas and 127 cancers. The target chromosomes were chromosomes 11 and 17. We also evaluated the nuclear DNA content as detected by flow cytometry, analyzed the relationship between the frequency of aneusomy and clinicopathological features, and examined the survival rate in these patients. The loss of chromosome 11 was observed in 31% of adenomas, whereas in cancers DNA aneuploidy was observed in 63% of cases, a gain of chromosome 17 was observed in 63% of cases, and a gain of chromosome 11 was observed in 42% of cases. Numerical chromosome aberrations in diploid DNA were also observed. Increased depth of invasion (>/=T3) and advanced Dukes' stage (>/=B) of malignant tumors were associated with a higher frequency of a gain of chromosome 11 (P < 0.01 and P < 0.05, respectively). Increased depth of invasion (>/=T2) in cancers was associated with a higher frequency of a gain of chromosome 17 (P < 0.05). Multivariate analysis of postoperative survival showed that a loss or gain of chromosome 11 was independently associated with a poor prognosis (P < 0.05). Numerical chromosome aberrations appear prior to the alteration of nuclear DNA content as detected by flow cytometry and influence the progression of colorectal cancers. Aneusomy of chromosome 11 is associated with poor postoperative prognosis of primary colorectal cancers.

Chromosomal imbalances associated with acquired resistance to fluoropyrimidines in human colorectal cancer cells.

The chromosomal aberrations underlying the development of resistance to fluoropyrimidines have not yet been identified. To characterise the genomic changes that induce the development of resistance to fluoropyrimidines, we used comparative genomic hybridisation (CGH) to analyse and compare the parent DLD-1 human colorectal cancer cell line and two cell lines, DLD-1/5-FU and DLD-1/FdUrd, which were resistant to 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd), respectively. Both resistant cell lines showed a genetic aberration derived from the parental cell line DLD-1. Losses of 3p and 3q were also detected as additional genetic changes in the two resistant cell lines. Both resistant cell lines showed decreased orotate phosphoribosyltransferase (OPRT) activity, which is associated with the activity of the uridine monophosphate (UMP) synthase gene (3q13). These results suggested that the loss of 3q might be a genetic change responsible for the decreased OPRT activity and fluoropyrimidine cytotoxic response in cancer cells. Amplification of 18p11.2-p11.3 containing the thymidine synthase (TS) gene (18p11.32) was observed only in the DLD-1/FdUrd-resistant cell line, which overexpresses TS. These findings suggested that 18p amplification represents a genetic change associated with the overexpression of the TS protein. Our results indicate that chromosomal aberrations identified by CGH could explain, at least in part, acquired fluoropyrimidine resistance.

Difference in prognostic value between sialyl Lewis(a) and sialyl lewis(x) antigens in blood samples obtained from the drainage veins of the colorectal tumors.

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.

Increased expression of sialyl Le(x) antigen in non-polypoid growth type of colorectal carcinoma.

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.

The relationship between circulating sialyl Tn antigen and polypoid or nonpolypoid growth characteristics in colorectal cancer.

Recent studies delineated two different patterns of tumor growth in colorectal carcinoma characterized as polypoid and nonpolypoid (PG-type and NPG-type, respectively). We quantified serum sialyl Lewis (Le)a (CA19-9), sialyl Lex (SLX), sialyl Tn (STN), and carcinoembryonic antigen (CEA) in 269 colorectal cancer patients to establish whether their levels correlated with any biological or clinical differences between PG-type and NPG-type cancer. Patients were divided into high and low antigen groups (higher or lower than a selected diagnostic-based cut-off value) and compared. Statistical testing was by univariate and multivariate (logistic regression) analyses. Forty-seven (17.5%) patients with PG-type and 222 (82.5%) with NPG-type cancer were studied. In contrast to NPG-type, the characteristics of the PG-type cancers included a low rate of lymph node metastasis and a high serum STN level. In contrast to a low STN level, a high STN level was independently related to the presence of distant metastasis in patients with PG-type cancer, and also to the presence of distant metastasis and large-sized tumor in patients with NPG-type cancer. These data suggest that differences in STN levels in the serum of patients with PG-type or NPG-type colorectal carcinomas may be at least partly responsible for different tumor progression behavior.

Expression of blood group antigens A, B and H in carcinoma tissue correlates with a poor prognosis for colorectal cancer patients.

The deletion of blood group ABH isoantigens on tumor tissues has been reported to be an adverse prognostic marker for patients with various solid tumors. In the present study, we evaluated the prognostic value of altered expression of ABH isoantigens in colorectal carcinomas. Using monoclonal antibodies, the expression of A, B, and H antigens was assessed by immunohistochemistry on paraffin-embedded carcinoma samples from 82 patients who had undergone surgery for colorectal cancer. ABH isoantigens were found to be deleted in 36 carcinomas (43.9%) and expressed in 46 (56.1%). Univariate and multivariate analysis using a logistic regression model revealed that N factor (lymph node metastasis) and blood group type were independently related to the expression of ABH isoantigens. In contrast to previous reports on other cancers, patients whose colorectal carcinomas express ABH isoantigens had a poorer prognosis than those whose carcinomas showed deletion of ABH isoantigens (P = 0.0008). The expression of ABH isoantigens was an independent prognostic variable, in addition to T (depth of tumor invasion), N, and M (distant metastasis) factors, as shown by means of Cox regression analysis. In conclusion, the expression of ABH isoantigens in carcinoma tissue is an important poor prognostic factor in patients with colorectal cancer. This variable needs to be considered in the design of future trials of therapy.

Expression of ABH/Lewis-related antigens as prognostic factors in patients with breast cancer.

PURPOSE: The prognostic value of altered blood group factor and Lewis-related carbohydrate antigen expression in breast cancers has not been fully determined. METHODS: To this end, breast carcinoma samples from 87 radical mastectomy patients with primary cancer were analyzed by immunohistochemistry for the ABH factors, Le(a), sialyl Le(a), Le(x), and sialyl Le(x). RESULTS: It was found that ABH, Le(a), sialyl Le(a), Le(x), and sialyl Le(x) antigens were expressed in 25 (21.8%), 26 (22.6%), 26 (22.6%), 36 (31.3%), and 37 specimens (32.2%), respectively. Tumors with lymph node metastasis expressed Le(x) or sialyl Le(x) antigens more frequently than those without lymph node metastasis ( P=0.0020 or P=0.039, respectively). The survival time of patient s after surgery was significantly shorter for those whose tumors expressed Le(x) or sialyl Le(x) than for those without Le(x)- or sialyl Le(x)-positive tumors ( P=0.0028 and P=0.0029, respectively). Cox's multiple regression analysis revealed that sialyl Le(x) expression was an independent prognostic factor for patient survival regardless of primary tumor (T factor) and lymph node (N factor) status (hazards ratio, 3.80). CONCLUSIONS: Thus, expression of sialyl Le(x) antigen in tumor cells is associated with poor prognosis in patients with breast cancer and must be considered in the design of future therapeutic trials.

DNA aneuploidy in a case of rectosigmoid adenocarcinoma complicated by ulcerative colitis.

A case of Borrmann type IV colorectal adenocarcinoma detected as a complication of long-standing ulcerative colitis is reported. Barium enema and colonoscopy disclosed a stenotic area associated with a tumoral mass and a flat elevated lesion in the rectosigmoid region and a submucosal tumor-like lesion in the rectum. Total colectomy was performed and histological studies demonstrated a moderately differentiated adenocarcinoma accompanied by high- and low-grade dysplasia. DNA ploidy pattern analysis showed aneuploidy in the adenocarcinoma and high-grade dysplasia, but diploidy in the normal and atrophic mucosa and in low-grade dysplasia. DNA aneuploid content was associated with the presence of colorectal carcinoma complicating ulcerative colitis, indicating that DNA content studies should be included in screening programs to detect early colorectal carcinoma following this disease, as a complementary study to histological assessment.

An immunohistochemical study of the distribution of blood group substances and related antigens in primary colorectal carcinomas and metastatic lymph node and liver lesions, using monoclonal antibodies against A, B, H type 2, Le(a), and Le(x) antigens.

Using indirect immunoperoxidase staining, we examined the distribution of blood group substances and related antigens, including Le(a), A, B, H type 2, and Le(x), in 87 carcinomas and 42 normal mucosal specimens of colon and rectum, as well as in metastatic lesions of 32 lymph nodes and 9 liver specimens. The compatible expression rate of A/B/H type 2 antigens was 33.3% (3/9) in proximal normal colon, but only 6.1% (2/33) in distal normal colon. Compatible expression was observed in 14 of 25 carcinomas in the proximal colon (56.0%), but these antigens in distal colon cancers reappeared with a high positive rate, 62.9% (39/62). The rate of H type 2 accumulation with the deletion of A and/or B antigens was 6.9% (6/87). Incompatible expression was not observed in colorectal cancer. Le(a) and Le(x) antigens were expressed in normal mucosa and primary carcinoma throughout the colon. Le(a) and Le(x) in primary carcinoma that showed A/B deletion with/without H type 2 accumulation was expressed more than in carcinoma with A/B/H type 2 compatible expression (88.2% vs 71.7% for Le(a); 94.1% vs 88.7% for Le(x), respectively). In 16 of 32 patients (50.0%), A/B/H type 2 antigen expression in metastatic lesions had disappeared or was decreased compared with that in primary carcinoma, followed by metastasis to regional lymph nodes. These results suggested that: (a) A/B/H type 2 blood group substances in the distal colon behave as tumor-associated antigens in colorectal carcinoma. (b) Most frequently, A/B/H type 2 antigens expressed in primary carcinoma were weakened or had disappeared in metastatic lymph nodes. Further investigation of the biological function of carbohydrate chains, such as those of blood group substances and related antigens on cancer cell surfaces may lead to a solution of the problem of the metastatic behavior of tumor cells.

Aneusomy of chromosome 18 is associated with the development of colorectal carcinoma.

Specific loss of heterozygosity of chromosome 18 has been observed frequently in advanced colorectal carcinoma and is closely associated with its development. We investigated the prevalence of numerical aberrations of chromosome 18 in 44 specimens of colorectal carcinomas, using fluorescence in situ hybridization. We also examined the relationship between aneusomy of chromosome 18 and the clinicopathological features of these tumors. Aneusomy of the specimens (monosomy and polysomy) was determined when the same aneusomic population was detected in more than 15% of the nuclei. The frequency of monosomy and polysomy of chromosome 18 in colorectal carcinomas was 43% (19/44) and 29% (12/44), respectively. The prevalence of monosomy and polysomy 18 was significantly higher in cancers with invasion exceeding category T2 compared with T1 (P < 0.01), and with tumor size exceeding 20 mm in diameter compared with tumors less than 20 mm (P < 0.05). However, the prevalence of aneusomy 18 was not associated with other clinico-pathological features. The mean survival period and the 5-year survival rate after operation in patients with aneusomy 18 was not different from findings for those with disomy 18. Our results indicate that aneusomy of chromosome 18 is associated with the development of colorectal carcinoma; however, it is not a useful indicator of postoperative prognosis.

An immunohistochemical employer monoclonal antibodies against Le(a), sialyl Le(a), Le(x), and sialyl Le(x) antigens in primary colorectal, carcinomas and lymph node and hepatic lesions.

The immunohistochemical expression of sialylated and non-sialylated forms of both Le(x) and Le(a) were studied in 87 carcinomas and 42 normal mucosal specimens of colon and rectum, as well as in 32 metastatic lymph nodes and 9 hepatic lesions, using an indirect immunoperoxidase staining. Their antigens were expressed in normal mucosa with the following frequencies: Le(a), 95.2% (40/42); sialyl Le(a), 88.1% (37/42); Le(x), 95.2% (40/42); and sialyl Le(x), 17.0% (7/42), whereas in carcinomas, the respective rate of frequency were: 78.2% (68/87); 78.2% (68/87); 90.8% (79/87); and 93.1% (81/87). Sialyl Le(x) antigen showed the highest tumor specificity compared to other antigens. In three normal mucosal specimens and four carcinomas with Le(a-b-) phenotype, the expression of type 1 antigens (Le(a) and sialyl Le(a)) was not consistent, whereas type 2 antigens (Le(x) and sialyl Le(x)) were consistently observed in carcinomas. The staining of type 1 antigens and Le(x) was decreased in metastatic lesions compared with primary carcinomas, whereas sialyl Le(x) antigen had the same positive-staining rate in both. Metastatic carcinoma expressed the sialylated form more predominantly than the non-sialylated form in type 2 antigens whereas the opposite result was observed in type 1 antigens. These results suggested that: (a) sialyl Le(x), defined by monoclonal antibody CSLEX1, may be useful as a tumor-associated antigen in colorectal carcinoma, and (b) the alteration of Lewis-related carbohydrate antigens in cancer cell membranes, including sialylation and/or aberrant glycosylation, may be related to metastatic behavior.

Importance of cytogenetic markers for multiple primary carcinomas in colorectal cancer: chromosome 17 and p53 locus translocation.

The incidence of non-familial multiple primary cancer in colorectal cancer patients has increased in recent years in Japan. To clarify the characteristic genetic aberrations in such multiple cancers, we examined structural chromosomal aberrations by fluorescence in situ hybridization, using chromosome 17-specific and p53 cosmid DNA probes. We established short-term cultures of 78 surgical specimens and were able to obtain observable metaphase spreads in 23 single colorectal cancer specimens and in 6 colorectal cancer specimens from patients with double primary cancers. The frequency of chromosome 17 and/or p53 locus translocation was significantly greater in tumors with double cancer than in single colorectal cancers (P < 0.05 and P < 0.01, respectively). These aberrations in double cancers frequently appeared even at an early Dukes' stage (A and B) of colorectal carcinoma. Our results suggest that translocation of chromosome 17 and the p53 locus may be specific genetic events probably associated with carcinogenesis of multiple primary cancers in colorectal cancer.

Quantitative analysis of numerical chromosome aberrations in various morphological types of colorectal carcinomas.

Quantitative analysis by fluorescence in situ hybridization (FISH) on thin paraffin-embedded tissue sections, using specific probes for chromosomes 11, 17, and 18 was employed in various morphological types of early and advanced colorectal cancer to clarify tumor cytogenetics. The chromosome index (CI) was calculated as a quantitative measure of the chromosome copy number. Compared with the CI of normal epithelium, the CI of chromosome 11 in villous components of adenomas or polypoid early cancers was decreased, while the CI in flat type or advanced colorectal cancers, conversely, was increased (P < 0.05). The CI of chromosome 17 in villous components of adenomas and all cancers was higher than that of normal epithelium (P < 0.05), but the differences were not significant. In protruding advanced cancers, the CI of chromosome 18 was significantly decreased (P < 0.01) compared to the CI of normal epithelium. There was no significant chromosomal heterogeneity between the superficial and the deepest layer in each cancer. In mucosa adjacent to sessile and flat type cancers, the CI of chromosome 17 was significantly higher than the CI in normal epithelium or adenomas (P < 0.05). These results suggest that numerical chromosome aberrations are associated with the histological type of adenoma and the morphological diversity of cancer in the colorectum, and that chromosome 17 abnormality occurs in mucosa adjacent to sessile and flat cancers.

Carcinoma of the splenic flexure: multivariate analysis of predictive factors for clinicopathological characteristics and outcome after surgery.

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.

Relationship between morphological diversity and AgNORs or cathepsin B expression in colorectal cancers.

The biological characteristics associated with the morphological diversity of colorectal cancers were investigated to elucidate the causes of this diversity. We examined the proliferative and infiltrating activity of tumor cells, indicated by the mean number of Ag nucleolar organizer region associated proteins (NORs) per nucleus (MNA) and the immunohistochemical response to cathepsin B(CB), in various morphological types of early and advanced colorectal cancers. We examined 73 colorectal cancers obtained by endoscopic and surgical resection. MNA values for sessile and flat-elevated cancers were greater than the values for pedunculate, subpedunculate, and flat-or-depressed early cancers (sessile, P < 0.05). In advanced cancers invading the muscularis propria, protruding cancers showed significantly higher MNA values than small ulcerative cancers (P < 0.01). CB expression increased significantly with the progression of colorectal cancers (P < 0.01), but was not related to morphological diversity in early and advanced cancers. In both sessile and flat cancers, CB expression was higher in moderately differentiated than in well differentiated adenocarcinomas. These results indicate that, in colorectal cancers, protruding early cancers without stalks and protruding advanced cancers have higher proliferative activity than pedunculate or flat early cancers and small ulcerative advanced cancers, respectively, and that CB expression is not associated with morphological diversity, but with depth of invasion and histological differentiation.

Chromosome instability evaluated by fluorescence in situ hybridization in hereditary non-polyposis colorectal cancer.

Numerical aberrations of chromosome 17 and nuclear DNA content were compared in patients with hereditary non-polyposis colorectal cancer (HNPCC) and those with sporadic colorectal cancer (SCRC). During a period of 22 years, 30 cases (3.2%) from 28 families satisfied the Japanese clinical criteria of HNPCC. Using freshly frozen tissue samples, we investigated chromosomal aberration with fluorescence in situ hybridization with alpha satellite DNA probe for chromosome 17. Flow cytometric quantification of nuclear DNA content showed DNA aneuploidy in 9 of 15 patients (60.0%) with HNPCC and in 160 of 234 patients (68.4%) with SCRC, there was no significant difference between HNPCC and SCRC. The mean proportion of nuclei with aneusomy 17 (numerical chromosome aberration index: NCAI) in 14 patients with HNPCC was significantly higher than that in 42 patients with SCRC (46.8 +/- 5.0% vs 39.0 +/- 10.3%, P < 0.01). NCAI increased in proportion with the progression of the disease in SCRC (26.1% in stage I, 33.3% in stage II, 38.8% in stage IIIa, 42.7% in stage IIIb, and 46.2% in stage IV, P < 0.01), whereas NCAI in HNPCC was high in all stages (43.5%-49.2%). The proportion of patients with multiple numerical aberration of chromosome 17 was significantly higher in HNPCC (9/14) than among SCRC (11/42). Our data suggest that chromosome 17 is present in an unstable condition in HNPCC.

Expression of multidrug resistance protein in metastatic colorectal carcinomas.

To clarify the relationship between multidrug resistance protein (MRP) and clinicopathologic features, the influence of adjuvant chemotherapy, and prognosis of patients who underwent resection of metastatic liver carcinomas originating from colorectal carcinomas, we examined the expression of MRP in tumor tissues by immunostaining. Specimens of 38 primary colorectal tumors and 44 metastatic liver tumors of colorectal origin were examined (metastatic group). We also examined 28 nonmetastatic colorectal carcinomas. The percentages of nonmetastatic tumors and of primary and metastatic tumors of the metastasis group that expressed MRP were similar. MRP expression in primary and metastatic tumors did not correlate with any clinicopathologic features. The use of adjuvant chemotherapy after operation for primary colorectal carcinomas was associated with increased MRP expression among metastatic liver tumors. Expression of MRP in the tumor did not influence the prognosis or survival rate after resection of primary or metastatic tumors. Our data suggest that MRP expression in metachronous liver metastases from colorectal carcinomas may be induced by administration of anticancer drugs but is not associated with clinicopathologic features of the tumor, liver metastasis, or prognosis.

Circulating sialyl Lewis(x), sialyl Lewis(a), and sialyl Tn antigens in colorectal cancer patients: multivariate analysis of predictive factors for serum antigen levels.

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 M0) for CA19-9; M1 (OR, 6.40 vs M0) for SLX; mucinous carcinoma (OR, 8.45 vs well differentiated adenocarcinoma) and M1 (OR, 8.24 vs M0) 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 M0) 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.

Long-term outcomes of radical surgery after gasless video endoscopic transanal excision of T1/T2 rectal cancers.

AIMS: We aim to clarify the long-term outcomes after an additional radical operation following gasless video endoscopic transanal rectal tumour excision (gasless VTEM) of 'high-risk' T1 and T2 rectal cancer. METHODS: Gasless VTEM involves modification of transanal endoscopic microsurgery (TEM) by incorporating a standard laparoscopic video camera without a CO(2) insufflation system. This study between 1993 and 2003 included six men and five women with a median age of 64 years (range, 36-79). Specimens resected by gasless VTEM revealed (1) high-risk T1 carcinomas with one of the following histological types: poorly differentiated, lymphovascular invasion, and massive invasion of the submucosa (submucosal invasion greater than 200-300 microm from the muscularis mucosa) and (2) T2 carcinomas. RESULTS: Eight patients had a high-risk T1 carcinoma and three patients had a T2 carcinoma. In two patients with a high-risk T1 carcinoma, a residual tumour was found in the specimen resected by the additional radical surgery. At a median follow-up of 86.5 months (range, 63.2-110.5), none of the patients developed tumour recurrence. Although one patient died with cancer at another organ site (hilar cholangiocarcinoma of the liver) 87 months after the additional radical surgery, the other 10 patients are alive and disease free. CONCLUSIONS: This study revealed favorable long-term outcomes after additional radical surgery following gasless VTEM in patients with high-risk T1 and T2 carcinomas.