Search

There are currently no universally accepted indications and criteria for additional surgical resection of the colorectum after endoscopic resection of the submucosal invasive cancer. The purpose of the present study is to establish accurate indications and criteria for additional surgical resection of the colorectum, based on the prediction of lymph node metastasis, after endoscopic resection of the submucosal invasive cancer. We investigated 140 submucosal invasive colorectal cancers and analyzed the pathologic factors of lymph node metastasis. The tumors were evaluated for pathologic factors in the invasive area of the submucosal carcinoma and were compared between the cases with lymph node metastasis and those without lymph node metastasis. Lymph node metastasis was observed in 13 cases (9%). Univariate logistic regression analysis showed that the depth of invasion, cribriform-type structural atypia, absence of lymphoid infiltration, lymphatic permeation, and venous permeation were statistically significant as risk factors for lymph node metastasis. Multivariate logistic regression analysis showed that the important risk factors included, in decreasing order, lymphatic permeation, absence of lymphoid infiltration, cribriform-type structural atypia, venous permeation, and depth of invasion. Submucosal invasion of 2 mm or more, and/or, depth of lymphatic permeation of 2 mm or more are risk factors for lymph node metastasis. The pathologic criteria based on our results for additional colectomy enables greater accuracy selection of patients who will undergo further surgical treatment after endoscopic resection.

Summary. Hepatitis C virus (HCV) infection is the most common cause of chronic hepatitis, which frequently progresses to hepatocellular carcinoma. The pathogenesis of its persistent infection and tumour progression has not been fully characterized yet. The RCK gene was previously cloned at the breakpoint of the t(11;14)(q23;q32) chromosome translocation observed in human B-cell lymphoma cell line RC-K8. The RCK protein, rck/p54, which is a 54-kDa cytoplasmic protein belonging to the DEAD box/RNA helicase family, is considered to facilitate the translation of mRNA(s) of genes for cell proliferation and malignant transformation not only in B-cell lymphomas having the t(11;14) translocation but also in other solid tumours. The aim of this work was to examine the involvement of rck/p54 in carcinogenesis of hepatocellular carcinoma from HCV-related chronic hepatitis. We examined the expression of rck/p54 in 29 cases of HCV-related chronic hepatitis and eight cases of hepatocellular carcinoma by immunohistochemistry and Western blot analysis. Twenty-six of 29 cases with HCV-related chronic hepatitis and all cases with hepatocellular carcinoma tested overexpressed rck/p54 protein. The expression of rck/p54 was lowered by treatment with IFN-α in two cases who showed the decrease in HCV RNA levels. These findings suggest that rck/p54 protein is possibly involved in the replication of HCV genomes in hepatocytes and in tumourigenesis of hepatocellular carcinomas.

SUMMARY Cytokines such as IL-1, tumour necrosis factor-alpha (TNF-α), IL-6 and IL-8 are increased in inflamed colonic mucosa after administration of mouse DSS. Nuclear factor κB (NF-κB) is a transcription factor which regulates the expression of these cytokine genes. The effect of intracolonically administered NF-κB (p65) antisense phosphorothioate oligonucleotide was examined in mouse DSS-induced colitis using drinking water containing 5% DSS. When antisense oligonucleotide was given on day 0, the disease activity index (DAI) representing clinical symptoms improved and the histological score decreased; furthermore, IL-1, IL-6, and TNF-α concentrations in rectal mucosa were lower compared with the control group. Clinical and histological improvement was also observed when antisense oligonucleotide was begun on day 2 but not on day 7. In addition, the distribution of antisense oligonucleotides was investigated by confocal laser microscopy. In colonic mucosa, oligonucleotides were predominantly localized to cells in the lamina propria, but also in the epithelium. Western blot analysis using homogenized rectal mucosa showed the decreased expression of NF-κB p65 in the antisense oligonucleotide-treated group, although it was increased in the colitis group. These results suggest that intracolonic administration of NF-κB antisense oligonucleotide may be effective in ulcerative colitis.

To investigate the development and progression of colorectal carcinoma, submucosal invasive carcinoma (SMC) with residual intramucosal neoplasm was studied histopathologically. Intramucosal neoplasm was confirmed by immunohistochemical staining against anti-alpha-smooth muscle actin antibody. Submucosal invasive carcinoma was classified into polypoid growth-type carcinoma (PGC) and non-polypoid growth-type carcinoma (NPGC), depending on the presence of intramucosal tumor proliferation. Tumors were > 15 mm in size in 78.2% of the PGC lesions studied, but the degree of submucosal invasion was minimal (invasion of the upper 500 microm of the submucosal layer) in 52.9% of the PGC lesions. Conversely, 64.4% of NPGC lesions were 15 mm in size and the degree of submucosal invasion was moderate or severe (involving the middle and deeper layer of the submucosa) for 72.9% of NPGC. In other words, lesions of NPGC were significantly smaller in size but showed deeper infiltration than PGC lesions. Furthermore, PGC was derived from intramucosal polypoid carcinoma (including carcinoma with adenoma) and was morphologically identical to polyp cancer as reported previously. However, NPGC was derived from the flat and/or depressed type of intramucosal carcinoma classified not as polyp type, but as the superficial type. Typical NPGC was, therefore, also of the superficial type. In addition, approximately 25% of PGC lesions were identified as having an adenoma-carcinoma sequence. There was no coexistence with adenoma in the NPGC lesions, suggesting de novo development. When the degree of histologic atypia in the two types of intramucosal carcinoma was compared, 74.7% of PGC lesions showed low-grade carcinoma, regardless of tumor size, while 62.7% of NPGC lesions showed high-grade carcinoma in the intramucosal lesion. Approximately 25% of carcinomas with low-grade atypia were positive for p53 (as were the high-grade lesions), but it was not expressed in the adenoma. Therefore, tumor development and the degree of invasion differed significantly between the two types of carcinoma.

The rebleeding rate after endoscopic injection sclerotherapy was studied in 237 patients with esophageal varices, and the optimal outcome of treatment was determined. Two new categories, RC(2-) and F0, were added to the classification scheme of endoscopic findings of varices in Japan. RC(2-) represents a state in which no veins, not even small vessels, are observed by endoscopy after endoscopic injection sclerotherapy, and F0 represents a state in which no localized venous dilations in the esophagus exist. The criteria for defining the other categories were not altered, and the R-C sign was expressed as RC(2-), RC(-), or RC(+); the degree of dilation was classified as F0 to F3. By combining the R-C sign and the F number, endoscopic findings were classified 1 to 4 weeks after endoscopic injection sclerotherapy into groups designated RC(2-)F0, RC(-)F0, RC(-)F1, and RC(+)F1-RC(+)F2. The four groups were observed to determine the incidence of esophageal stricture and rebleeding. In the RC(2-)F0 group, the incidence of stricture was high, but the rebleeding rate was low. In the RC(-)F0 group, both the incidence of stricture and rebleeding rate were low. We conclude that the optimal outcome of endoscopic injection sclerotherapy is RC(-)F0.

The applicability of a new immunological fecal occult blood test in which hemoglobin (Hb) and transferrin (Tf) are simultaneously assayed was evaluated. The mean absorbance and standard deviation (510/630 nm) obtained by this test was 0.840 +/- 0.805 in 51 fecal samples from patients with colon cancer, 0.248 +/- 0.305 in 95 samples from patients with colon polyps, and 0.104 +/- 0.053 in 110 samples from control patients; these values differed significantly (P less than 0.005). Hb and Tf concentrations were separately determined in the same fecal samples, and qualitative evaluation was performed with a cutoff value of 5.1 micrograms/g feces for Hb and 0.4 micrograms/g feces for Tf. Hb or Tf was positive in 41 of the 51 samples in the colon cancer group, 33 of the 95 in the colon polyp group, and 3 of the 110 in the control group. Qualitative analysis of the values obtained by the combination assay of Hb and Tf with a cutoff value of 0.200 revealed positive rates of 41/51 in the colon cancer group, 33/95 in the colon polyp group, and 4/110 in the control group. These results suggest the usefulness of a combination assay of Hb and Tf as a fecal occult blood test.

A 68 year-old woman was admitted to our hospital with a high fever. Ultrasonography revealed the presence of two protruded mass lesions in the fundus of the gallbladder. Endoscopic retrograde choledochopancreatography (ERCP) indicated an anomalous union of the pancreaticobiliary ductal system (AUPD), with an anomalous junction heated at the site 30 mm proximal to the ampulla of Vater. ERCP also showed the presence of three flat elevated lesions at the fundus of the gallbladder. Amylase activity in the bile obtained from the common bile duct during ERCP was high. From these findings, gallbladder carcinoma associated with AUPD was suspected. Cholecystectomy, choledochectomy followed by hepaticojejunostomy were performed on this patient. A microscopic study of the resected gallbladder demonstrated adenocarcinoma with epithelia like intestinal metaplasia in those elevated lesions surrounded by mucosa associated with atypical hyperplasia without intestinal metaplasia. The authors believe that intestinal metaplasia is the main change accompanied by the cancer, but atypical hyperplasia was an important pre-cancerous lesion in this case.

Extracellular matrix and soluble plasma proteins generate peptides that regulate biological activities such as cell growth, differentiation and migration. Bradykinin, a peptide released from kininogen by kallikreins, stimulates vasodilatation and endothelial cell proliferation. Various classes of substances can potentiate these biological actions of bradykinin. Among them, the best studied are bradykinin potentiating peptides (BPPs) derived from snake venom, which can also strongly inhibit angiotensin I-converting enzyme (ACE) activity. We identified and synthesized sequences resembling BPPs in the vicinity of potential proteolytic cleavage sites in the collagen XVIII molecule, close to endostatin. These peptides were screened as inhibitors of human recombinant wild-type ACE containing two intact functional domains; two full-length ACE mutants containing only a functional C- or N-domain catalytic site; and human testicular ACE, a natural form of the enzyme that only contains the C-domain. The BPP-like peptides inhibited ACE in the micromolar range and interacted preferentially with the C-domain. The proteolytic activity involved in the release of BPP-like peptides was studied in human serum and human umbilical-vein endothelial cells. The presence of enzymes able to release these peptides in blood led us to speculate on a physiological mechanism for the control of ACE activities.

The RCK gene is a target of the t(11;14)(q23;q32) chromosomal translocation observed in human B-cell lymphoma, and the overexpression of its protein (rck/p54) by the translocation was shown to cause malignant transformation. The rck/p54 protein belongs to the DEAD box protein/RNA helicase family, which has a variety of functions such as translation initiation, pre-mRNA splicing and ribosome assembly. The expression of rck p54 in colorectal adenocarcinoma cells was examined by immunohistochemistry and Western blot analysis. The rck/p54 protein was found to be overexpressed in tumour tissues resected from 13 (50%) out of 26 cases of colorectal adenocarcinomas and two out of two (100%) cases of colonic severe dysplastic adenomas. In view of activities of rck/p54 determined in other tissue types, we suggest that rck/p54 may contribute to the cell proliferation and carcinogenesis at the translational level in the development of colorectal tumours. © 1999 Cancer Research Campaign