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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. [ABSTRACT FROM AUTHOR]

BACKGROUND: The relationship between patient prognosis and various tumor biological factors has been reported previously, and prognostic factors of tumor biology may improve predictions of prognosis after hepatectomy for hepatocellular carcinoma (HCC) and may contribute to a new staging classification. This study was designed to provide an immunohistochemical analysis of tumor biological factors in patients who underwent hepatectomy for HCC. METHODS: Factors analyzed included p53 overexpression, microvessel counts, proliferating cell nuclear antigen, and expression of nm23. We examined 81 HCCs from patients with chronic liver diseases. RESULTS: In patients who underwent chemoembolization before surgery, or those a who had confluent multinodular tumor, p53 expression tended to be higher than in patients without chemoembolization (33% vs 11%) or those with a simple nodular tumor (28% vs 10%), but the difference was not statistically significant ( P = 0.051 and P = 0.092, respectively). A lower tumor microvessel count and negative nm23 expression were significantly associated with poor disease-free survival by univariate analysis ( P < 0.01 and P < 0.05, respectively). A lower tumor microvessel count was found to be a significant prognostic factor for disease-free and overall survivals (risk ratios, 2.44 and 3.13, respectively; P << 0.05), in addition to tumor size, vascular invasion, and longterm ascites, by Cox's multivariate analysis. CONCLUSIONS: Tumor microvessel count appears to be a useful prognostic marker for predicting HCC recurrence and patient survival. [ABSTRACT FROM AUTHOR]

Abstract 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 Lea, Lex, sialyl Lex) 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, Lea, sialyl Lea, Lex and sialyl Lex. 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 Lex 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 Lex 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 Lex in a colorectal carcinoma partially determines whether the tumor will have polypoid or non-polypoid growth. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We examined the expression of vascular endothelial growth factor (VEGF) and microvessel counts expressed by CD34 staining in 39 patients with primary and 44 patients with metastatic liver tumors of metastatic colorectal carcinoma, and 29 patients with nonmetastatic colorectal carcinoma as control in order to determine their value in the evaluation of prognosis and recurrence after hepatectomy. Microvessel counts in primary colorectal carcinomas of the metastatic group were significantly higher than those in control (P<0.05). Neither factor correlated with any clinicopathological feature of primary or metastatic liver carcinomas. Higher microvessel counts in metastatic liver tumors tended to be associated with a shorter disease-free interval to second recurrence in the remaining liver (P = 0.069) and were significantly associated with poor prognosis after hepatectomy (P<0.05). We conclude that microvessel count is an important marker of liver metastasis and prognosis in patients with colorectal carcinoma treated with hepatectomy. [ABSTRACT FROM AUTHOR]

To investigate the characteristics of the numerical chromosome aberrations in liver metastasis of colorectal cancers, fluorescence in situ hybridization (FISH) for chromosomes 8, 18, 14/22, and 20 was performed in 18 specimens of primary regions and 18 of metastatic regions in liver metastasis of colorectal cancers compared with 15 of non-liver metastatic cancers. Among these numerical aberrations, the gain of chromosome 20, especially copy numbers exceeding three, was frequently observed in primary and metastatic cancers. Among these numerical aberrations, the gain of chromosome 20, especially copy numbers exceeding three, was frequently observed in primary and metastatic regions of liver metastasis groups compared with that of the non-liver metastasis group (P < 0.05). The incidences of gain of chromosome 20 in both regions of the liver metastasis group were higher than that of the non-liver metastasis group (P < 0.05). The gain of chromosome 20 is a frequent aberration in primary and metastatic regions in patients with liver metastatic colorectal cancers and may be available as a genetic marker for the diagnosis or prediction of liver metastasis. [ABSTRACT FROM AUTHOR]

Purpose: Acute diffuse peritonitis (ADP) is an important surgical complication associated with high morbidity and mortality; however, the risk factors associated with a poor outcome have remained controversial. This study aimed in collecting integrated data using a web-based national database system to build a risk model for mortality after surgery for ADP., Methods: We included cases registered in the National Clinical Database in Japan. After data cleanup, 8,482 surgical cases of ADP from 1,285 hospitals treated between January 1 and December 31, 2011 were analyzed., Results: The raw 30-day and surgical mortality rates were 9.0 and 14.1 %, respectively. The odds ratios (>2.0) for 30-day mortality were as follows: American Society of Anesthesiologists (ASA) class 3, 2.69; ASA class 4, 4.28; ASA class 5, 8.65; previous percutaneous coronary intervention (PCI), 2.05; previous surgery for peripheral vascular disease (PVD), 2.45 and disseminated cancer, 2.16. The odds ratios (>2.0) for surgical mortality were as follows: ASA class 3, 2.27; ASA class 4, 4.67; ASA class 5, 6.54, and disseminated cancer, 2.09. The C-indices of 30-day and surgical mortality were 0.851 and 0.852, respectively., Conclusion: This is the first report of risk stratification after surgery for ADP using a nationwide surgical database. This system could be useful to predict the outcome of surgery for ADP and for evaluations and benchmark performance studies.

Objective: To construct a risk model for total gastrectomy outcomes using a nationwide Internet-based database., Background: Total gastrectomy is a very common procedure in Japan. This procedure is among the most invasive gastrointestinal procedures and is known to carry substantial surgical risks., Methods: The National Clinical Database was used to retrieve records on more than 1,200,000 surgical cases from 3500 hospitals in 2011. After data cleanup, 20,011 records from 1623 hospitals were analyzed for procedures performed between January 1, 2011, and December 31, 2011., Results: The average patient age was 68.9 years; 73.7% were male. The overall morbidity was 26.2%, with a 30-day mortality rate of 0.9%, in-hospital mortality rate of 2.2%, and overall operative mortality rate of 2.3%. The odds ratios for 30-day mortality were as follows: ASA (American Society of Anesthesiologists) grade 4 or 5, 9.4; preoperative dialysis requirement, 3.9; and platelet count less than 50,000 per microliter, 3.1. The odds ratios for operative mortality were as follows: ASA grade 4 or 5, 5.2; disseminated cancer, 3.5; and alkaline phosphatase level of more than 600 IU/L, 3.1. The C-index of 30-day mortality and operative mortality was 0.811 (95% confidence interval [CI], 0.744-0.879) and 0.824 (95% CI, 0.781-0.866), respectively., Conclusions: We have performed the first reported risk stratification study for total gastrectomy, using a nationwide Internet-based database. The total gastrectomy outcomes in the nationwide population were satisfactory. The risk models that we have created will help improve the quality of surgical practice.

Background: The health-care system, homogenous ethnicity, and operative strategy for lower rectal cancer surgery in Japan are to some extent unique compared to those in Western countries. The National Clinical Database is a newly established nationwide, large-scale surgical database in Japan., Objective: To illuminate Japanese national standards of clinical care and provide a basis for efforts to optimize patient care, we used this database to construct a risk model for a common procedure in colorectal surgery-low anterior resection for lower rectal cancer., Design: Data from the National Clinical Database on patients who underwent low anterior resection during 2011 were analyzed. Multiple logistic regression analyses were performed to generate predictive models of 30-day mortality and operative mortality. Receiver-operator characteristic curves were generated, and the concordance index was used to assess the model's discriminatory ability., Results: During the study period, data from 16,695 patients who had undergone low anterior resection were collected. The mean age was 66.2 years and 64.5% were male; 1.1% required an emergency procedure. Raw 30-day mortality was 0.4% and operative mortality was 0.9%. The postoperative incidence of anastomotic leakage was 10.2%. The risk model showed the following variables to be independent risk factors for both 30-day and operative mortality: BMI greater than 30 kg/m, previous peripheral vascular disease, preoperative transfusions, and disseminated cancer. The concordance indices were 0.77 for operative mortality and 0.75 for 30-day mortality., Limitations: The National Clinical Database is newly established and data entry depends on each hospital., Conclusions: This is the first report of risk stratification on low anterior resection, as representative of rectal surgery, with the use of the large-scale national surgical database that we have recently established in Japan. The resulting risk models for 30-day and operative mortality from rectal surgery may provide important insights into the delivery of health care for patients undergoing GI surgery worldwide.

Objective: This study aimed to create a risk model of mortality associated with esophagectomy using a Japanese nationwide database., Methods: A total of 5354 patients who underwent esophagectomy in 713 hospitals in 2011 were evaluated. Variables and definitions were virtually identical to those adopted by the American College of Surgeons National Surgical Quality Improvement Program., Results: The mean patient age was 65.9 years, and 84.3% patients were male. The overall morbidity rate was 41.9%. Thirty-day and operative mortality rates after esophagectomy were 1.2% and 3.4%, respectively. Overall morbidity was significantly higher in the minimally invasive esophagectomy group than in the open esophagectomy group (44.3% vs 40.8%, P = 0.016). The odds ratios for 30-day mortality in patients who required preoperative assistance in activities of daily living (ADL), those with a history of smoking within 1 year before surgery, and those with weight loss more than 10% within 6 months before surgery were 4.2, 2.6, and 2.4, respectively. The odds ratios for operative mortality in patients who required preoperative assistance in ADL, those with metastasis/relapse, male patients, and those with chronic obstructive pulmonary disease were 4.7, 4.5, 2.3, and 2.1, respectively., Conclusions: This study was the first, as per our knowledge, to perform risk stratification for esophagectomy using a Japanese nationwide database. The 30-day and operative mortality rates were relatively lower than those in previous reports. The risk models developed in this study may contribute toward improvements in quality control of procedures and creation of a novel scoring system.

A 72-year-old woman with diabetes mellitus was admitted with fever and general fatigue. Blood biochemistry showed elevated hepatic and biliary enzyme levels, abdominal computed tomography showed multiple liver abscesses with portal and superior mesenteric vein thrombosis, and total colonoscopy revealed a submucosal bacterial abscess in the ascending colon. The abscesses were determined to be associated with Enterococcus faecalis infection. The patient was treated conservatively with antibiotics (meropenem) and anticoagulants (warfarin), which led to a gradual amelioration of symptoms and resolution of thrombosis.

Background: Right hemicolectomy is a very common procedure throughout the world, although this procedure is known to carry substantial surgical risks. The present study aimed to develop a risk model for right hemicolectomy outcomes based on a nationwide internet-based database., Methods: The National Clinical Database (NCD) collected records on over 1,200,000 surgical cases from 3,500 Japanese hospitals in 2011. After data cleanup, we analyzed 19,070 records regarding right hemicolectomy performed between January 2011 and December 2011., Results: The 30-day and operative mortality rates were 1.1 and 2.3 %, respectively. The 30-day mortality rates of patients after elective and emergency surgery were 0.7 and 6.0 %, respectively (P < 0.001). The odds ratios of preoperative risk factors for 30-day mortality were: platelet <50,000/μl, 5.6; ASA grade 4 or 5, 4.0; acute renal failure, 3.2; total bilirubin over 3 mg/dl, 3.1; and AST over 35 U/l, 3.1. The odds ratios for operative mortality were: previous peripheral vascular disease, 3.1; cancer with multiple metastases, 3.1; and ASA grade 4 or 5, 2.9. Sixteen and 26 factors were selected for risk models of 30-day and operative mortality, respectively. The c-index of both models was 0.903 [95 % confidence interval (CI) 0.877-0.928; P < 0.001] and 0.891 (95 % CI 0.873-0.908; P < 0.001), respectively., Conclusion: We performed the first reported risk stratification study for right hemicolectomy based on a nationwide internet-based database. The outcomes of right hemicolectomy in the nationwide population were satisfactory. The risk models developed in this study will help to improve the quality of surgical practice.