Search

Purpose: Although S-1 based chemotherapy for patients with advanced gastric cancer has generally been accepted in Japan, discontinuations of treatment have been reported due to grade 3 or more adverse events. The present randomized phase II study was conducted to test whether alternate-day administration of S-1 would be comparably efficient and reduce adverse events compared with conventional daily administration in the first-line chemotherapy for advanced gastric cancer. Methods: 132 patients with advanced gastric cancer were randomly assigned to 1:2 ratios to receive treatment with daily at a standard dose of 80 mg/m/day or alternate-day administration group received S-1 on 4 days a week. The primary end point was progression-free survival (PFS), and the secondary end points were safety, overall survival, time to treatment failure (TTF), disease control rate, and response rate. Results: The 6-month PFS rate of the alternate-day administration group was 20.9% and failed to show significant difference from the pre-specified threshold at 15% ( p = 0.117), whereas that of the daily administration group was 39.1% and significantly higher than the threshold ( p = 0.001). The hazard ratio of the alternate-day administration group compared with the daily administration group was 1.753 (95% confidence interval (CI) 1.15-2.68, p = 0.010). With regard to OS, the hazard ratio of the alternate-day administration group compared with the daily administration group was 1.487 (95% CI 0.97-2.29, p = 0.072). The median TTF were 4.2 and 2.8 months in the daily and alternate-day administration group, respectively ( p = 0.007). Conclusion: The alternate-day administration of S-1 was not recommended as the first-line therapy for patients with advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Background: We investigated the factors influencing esophageal variceal recurrence after endoscopic treatment on the basis of 25 variceal patients who were measured for esophageal variceal pressure, which had been reported to have a close relationship to variceal rupture. Method: Six patients (24.0%) showed variceal recurrence during follow-up periods of up to 60 months. Clinical, biochemical, endoscopic and portal hemodynamic parameters were analyzed by univariate analysis in order to determine variceal recurrence. Results: The cumulative risk of variceal recurrence was greater in patients with F3 varices (P = 0.027), and esophageal variceal pressure (EVP) ≥ 15 mmHg (P = 0.021). It was not significantly related to any clinical, biochemical parameter. Large portosystemic collaterals, which were not concerned with esophageal varices, were demonstrated in five patients who had never showed variceal recurrence; all of their EVP were under 15 mmHg. Conclusion: It is suggested that the form of varices and EVP, which may reflect a part of portal hemodynamics, are the most reliable factors for predicting variceal recurrence. [ABSTRACT FROM AUTHOR]

Lymph node metastasis is a frequent type of metastasis in patients with gastric cancer. The mechanisms responsible for this type of metastasis, however, are not clearly understood. We hypothesize that the immunosurveillance system between cancer cells and lymphocytes may be associated with the lymph node metastatic process. In this study, we examined the correlation between lymph node metastasis and intercellular adhesion molecule-1 (ICAM-1), which mediates the immunosurveillance system between tumor cells and cytotoxic lymphocytes, in gastric cancer. Methods. One hundred and forty-three specimens resected from patients with gastric cancer were investigated by staining with a monoclonal antibody against ICAM-1. We studied the correlation between the expression of ICAM-1 and various clinicopathologic factors, as well as infiltration of tumor-infiltrating lymphocytes (TILs). Results. ICAM-1 expression on gastric cancer cells was significantly decreased in patients with lymph node metastasis. The infiltration of TILs was associated with ICAM-1 expression level. The prognosis of patients with ICAM-1-negative tumors was poorer than the prognosis of those with ICAM-1-positive tumors. Conclusions. These findings suggest that ICAM-1 expression on cancer cells is closely associated with lymph node metastasis in gastric cancer, under the influence of the host immunosurveillance system. [ABSTRACT FROM AUTHOR]

Background. In breast cancer, the prognosis worsens with increasing lymph node involvement, and aggressive therapies may prolong survival in patients with advanced breast cancer. However, there are sub-populations of patients with advanced breast cancer with ten or more diseased nodes who have long survival. Implementing appropriate treatment depends on having a realistic and well-founded view of the prognosis. Methods. Sixty-nine patients (mean follow-up, 46 months) were enrolled. All patients underwent adjuvant therapy following radical mastectomy. Thirty-seven patients relapsed after curative surgery and 40 died of their cancer. Clinicopathologic factors, tumor estrogen receptor (ER) status, progesterone receptor status, and p53 protein expression were analyzed for prognostic significance. Results. Lower lymph node stage and positive ER status reflected longer relapse-free survival ( P = 0.001 and P = 0.0001, respectively). Lower tumor stage ( P = 0.039), lower lymph node stage ( P = 0.006), absence of distant metastasis ( P = 0.006), positive ER status ( P = 0.0002), and negative p53 status ( P = 0.02) reflected longer overall survival. ER status was the only independent significant prognostic factor for both relapse-free and overall survival. Conclusion. ER status, an indicator of response to endocrine therapy, was the most significant factor predicting prognosis in patients with breast cancer with ten or more positive lymph nodes. [ABSTRACT FROM AUTHOR]

We investigated tissue staining for Bcl-2 and Bax proteins, which regulate apoptosis, as indicators of chemotherapeutic effect in patients with gastric cancer. In 23 patients with gastric carcinoma biopsy specimens were obtained endoscopically prior to chemotherapy and stained immunohistochemically with anti-Bcl-2 and anti-Bax antibodies. Patients then were treated with continuous infusion of 5-FU and cisplatin. No correlation was seen between chemotherapeutic effect and Bcl-2 or Bax alone. However, among the Bax-positive cases, the patients with Bcl-2-positive tumors were significantly more chemoresistant (p = 0.036) and had worse prognoses (p = 0.008) than Bcl-2-negative cases. Therefore, immunohistochemical staining for Bcl-2 protein may predict chemotherapeutic efficacy or guide specific therapeutic choices in treating Bax-positive tumors. [ABSTRACT FROM AUTHOR]

Recently, it has been reported that p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis by regulating expression of vascular endothelial growth factor (VEGF), which is a well-characterized angiogenic inducer. In this study, we investigated these antigens’ expression together with microvessel density, and investigated their clinical importance. One hundred twenty specimens resected from patients with gastric carcinoma were investigated using immunohistochemical methods. p53 and VEGF expression was observed in 42 and 35% tumors, respectively. p53 and VEGF staining status was coincided in 72% tumors, and a significant correlation was found between p53 and VEGF status. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in p53-positive or VEGF-positive tumors. According to prognosis, patients with p53-positive tumors had significantly worse survival than those with p53-negative tumors. There was also a significant worse survival in the patients with VEGF-positive tumors than those with VEGF-negative tumors. Moreover, the 5-year survival rate was lowest in the patients with p53-positive and VEGF-positive tumors, while it was highest in the patients with p53-negative and VEGF-negative tumors. In conclusion, both p53 and VEGF significantly correlated with tumor vascularity and prognosis in patients with gastric carcinoma. [ABSTRACT FROM AUTHOR]

Recently, it has been reported that cyclin D[sub 1] plays a major role in oncogenesis in various cancers; however, there have been few studies on the association of cyclin D[sub 1] overexpression and prognosis of patients with malignant tumors. We evaluated the prognostic significance of cyclin D[sub 1] overexpression in colorectal adenocarcinoma. One hundred twenty-three specimens resected from patients with colorectal adenocarcinomas were investigated by staining with a monoclonal antibody against cyclin D[sub 1] . As a result, both overall survival and disease-free survival were significantly poorer in the patients with tumors strongly positive for cyclin D[sub 1] than in those with cyclin-D[sub 1] -negative or weakly positive tumors. The 5-year survival rate of the patients with tumors strongly positive for cyclin D[sub 1] was 53.3%, while the 5-year survival rates of patients with cyclin-D[sub 1] -negative and weakly positive tumors were 96.2 and 78.8%, respectively. Moreover, multivariate analysis indicated that cyclin D[sub 1] overexpression is an independent predictor of disease recurrence in our patients. In conclusion, cyclin D[sub 1] overexpression may be useful as a predictor of disease recurrence in colorectal adenocarcinoma. [ABSTRACT FROM AUTHOR]

In a previous study, we obtained a novel monoclonal antibody (F1α-75) directed against a synthetic mucin antigen termed F1α, and demonstrated that this antigen was expressed in a high percentage (80.2%; 89/111) of gastric carcinomas. In the present study, we compared the expression of F1α with that of sialyl-Tn antigen, a mucin antigen similar to F1α, in 54 human early gastric carcinomas, intestinal metaplasia and adenomatous polyps of the stomach to determine how differences in the expression of these antigens correlated with gastric carcinogenesis. The rate of expression of F1α in early gastric carcinoma tissues, 81.5%, was higher than that of sialyl-Tn antigen, 57.4%. No correlation was found between the rate of expression and histological type, depth of cancerous invasion or lymph node metastasis. Sialyl-Tn antigen was extensively expressed in 77.5% of specimens of complete intestinal metaplasia and in 78.6% of those of incomplete intestinal metaplasia; however, the expression of F1α in those specimens was rare and sporadic, with rates of only 25.0 and 27.7%, respectively. In adenomatous polyps, the rate of expression of F1α is 6.25% and that of sialyl-Tn antigen is 43.8%. Our findings indicate that F1α is a more specific antigen for gastric cancer than sialyl-Tn antigen, and that F1α is an antigen associated with carcinogenesis of the stomach. [ABSTRACT FROM AUTHOR]

An investigation carried out on 100 cases of primary breast cancer, both clinicopathologically and immunohistologically, revealed estrogen receptor (ER)-positive cases to be found significantly more often in early stage cancer than advanced stage cancer. On the other hand, ER negative cases were found to have a greater incidence of high-grade lymph node metastasis and were seen significantly more frequently in large tumors. Span-1, CA19-9, and SLEX antigens were detected in 33 per cent, 38 per cent, and 64 per cent of the total cases, respectively and the ratio of ER negative cases was significantly higher in each antigen positive group. Irrespective of the presence or absence of lymph node metastasis, ER negative cases were found significantly more often in antigen-positive groups than in their counterparts and tumor size tended to be greater in the antigen-positive cases. The results of this study thus indicated that the disease progression in breast cancer appears to be correlated with ER status and carbohydrate antigen expression. [ABSTRACT FROM AUTHOR]

One hundred and twenty-one patients with gastric cancer of Borrman IV (type 4) were classified into two types according to the macroscopic appearance of their tumors, namely, those tumors with giant folds (type G, n=84) and those without giant folds (type P, n=37). A large percentage of the cases in both type groups had advanced stage carcinoma. Type G was found to be predominant in young women and the incidence of high-grade lymph node metastasis was higher in type G than in type P. Histochemically, it was shown that the tumor interstitium of type G contained obviously many more acid mucopolysaccharides (AMPS) than the localized Borrman II (type 2) gastric cancer, which was used as a control. The results of enzymatic digestion tests suggested that the amounts of hyaluronic acid, chondroitin sulfate, and sialic acid were greater in type G than in type P or the localized type, the differences involved being marked between type G and the localized type. [ABSTRACT FROM AUTHOR]

This study was undertaken in order to histochemically investigate the mucoid substances (acid mucopolysaccharide and sialic acid) in experimental and human pancreatic carcinoma. The degree of alcian blue staining in the ductal and interstitial portions of the pancreas increased, especially in hamster tubular adenocarcinoma which had been induced by N-nitrobis (2-hydroxypropyl) amine. The pancreatic carcinoma of the rats, induced by di-methyl benz (α) anthracene, was usually poorly differentiated carcinoma, in which alcian blue and toluidine blue staining was high in the interstitial portion when compared with that of the hamster pancreatic carcinoma, which was usually well differentiated. The rates of enzyme digestion of acid mucopolysaccharide and sialic acid showed more prominently in the rat pancreatic carcinoma than in the hamster pancreatic carcinoma. Mucoid substances in the ductal portion of human pancreatic carcinoma revealed properties similar to those of hamster pancreatic carcinoma whereas those in the interstitial portion were similar to those of rat pancreatic carcinoma. These results suggested that mucoid substances, especially acid mucopolysaccharide, both in experimental and human pancreatic carcinomas, may play an important role in tumor growth. [ABSTRACT FROM AUTHOR]

We examined the effect of adhesion polypeptides on the adhesion and invasiveness of gastric cancer cell lines. We previously reported the establishment of an extensively peritoneal-seeding cell line, OCUM-2MD3, from a poorly seeding human scirrhous gastric carcinoma cell line, OCUM-2M. Both 2β1 and α3β1 integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM-2M cells, and the ability of OCUM-2MD3 cells to bind to the extracellular matrix (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion polypeptides, YIGSR and RGD, and two RGD derivatives significantly inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well differentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal dissemination given YIGSR sequenc e intraperitoneally was obviously longer than that of untreated mice. The survival of mice treated with RGD was also improved, and this effect was increased using the RGD derivatives, poly(CEMA-RGDS) and CM-chitin RGDS. These polypeptides appear to block the binding of integrins, which are expressed on OCUM-2MD3 cells, to the submesothelial ECM, and consequently inhibit peritoneal implantation. The peritoneal injection of adhe-sion polypeptides may be a new therapy against the dissemination of scirrhous gastric cancer, and may be useful for the prevention of dissemination in high-risk patients. © Rapid Science Ltd. [ABSTRACT FROM AUTHOR]

The actual mechanisms responsible for lymph node metastasis in gastric cancer are still unclear. To investigate the mechanisms of lymph node metastasis in gastric cancer, we established a lymph node metastatic model for human scirrhous gastric carcinoma. Lymph node metastasis had frequently developed after orthotopic implantation of OCUM-2M LN derived from a scirrhous gastric cancer cell line, OCUM-2M, which had low capacity for lymph node metastasis. We elucidated the different characteristics including binding ability, migratory capacity and immunoresponses induced by the cell surface molecules of these two cell lines. The binding ability to Matrigel and migratory capacity of OCUM-2M LN cells were significantly greater than those of OCUM-2M cells. On flow cytometric analysis, both OCUM-2M and OCUM-2M LN cells strongly expressed HLA-I (99.5 and 97.1%) and LFA-3 (76.6 and 99.2%) in level of expression between the two cell lines, but neither cell line expressed HLA-II (0.0 and 0 .0%), B7-1 (0.0 and 0.0%) or B7-2 (0.4 and 0.3%). ICAM-1 expression in OCUM-2M LN cells was weaker (0.7%) than that in OCUM-2M cells (36.8%). Strong adhesiveness and cytotoxicity of mononuclear lymphocytes for OCUM-2M cells were observed in adhesion and cytotoxic assays, both of which were significantly decreased by the addition of anti-ICAM-1 antibodies. On the other hand, the adhesiveness and cytotoxicity of OCUM-2M LN cells were significantly less than those of OCUM-2M cells, and were not affected by the addition of anti-ICAM-1 antibodies. These findings suggest that decreased ICAM-1 expression in a new gastric cancer cell line with a high rate of lymph node metasta-sis may in turn decrease immune responses mediated through LFA-1-dependent effector cell adhesion, and that this escape from the immunosurveillance system may be one of the factors inducing lymph node metas-tasis. In conclusion, we established a gastric cancer cell line, OCUM-2M LN, with a high rate of lymph node metasta sis. An in vivo lymph node-metastatic model with this cell line should be useful for analysing the mech-anism and therapeutic approach of lymph node metastasis. © Rapid Science Ltd. [ABSTRACT FROM AUTHOR]

Cell motility is an important factor in the process of invasion and metastasis of tumor. In this study, the relationship between cell motility and experimental metastatic potential was examined using two human pancreatic cancer cell lines, SW1990 and PANC-1. Serum-free conditioned medium from the highly metastatic cell line SW1990 was found to contain a factor that stimulated the migration of and induced a fibroblast-like morphological change in the weakly metastatic cell line PANC-1. Preincubation of PANC-1 cells with SW1990 conditioned medium (SW-C.M.) induced liver metastasis following splenic injection of PANC-1 cells in nude mice, although no liver metastasis was observed without pretreatment of SW-C.M. This factor, temporarily termed PDMF (pancreatic cancer-derived motility factor) is a heparin non-binding protein having a molecular weight of 40 kDa calculated by gel-filtration HPLC which acts not only chemotactically but also chemokinetically, and also acts mainly in a paracrine fashion. However, this factor had no effect on the proliferation of PANC-1 cells; it therefore appears to be a so-called motility factor. Only TGF-b1 and IL-6 were recognized in the SW-C.M. among cytokines thought to stimulate cell motility. These cytokines stimulated the motility of PANC-1 cells, but differed from PDMF in the neutralizing test with antibody against these cytokines. Results of characterization and preliminary purification suggest that this factor may be a novel motility factor. The above findings suggest that this motility factor may play an important role in the invasion and metastasis of pancreatic cancer, and complete purification of it will be useful in elucidating the mechanism of progression of cancer and designing a strategy for inhibition of invasion and metastasis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Human colon cancer is associated with antigenic and structural changes in mucin-type carbohydrate chains (-glycans). To elucidate the control of the biosynthesis of these -glycans in colon cancer, we have studied glycosyltransferase and sulphotransferase activities involved in the assembly of elongated -glycan structures. We analysed homogenates prepared from cancer tissue, adjacent normal and distal normal tissue from 20 patients. Several transferase activities showed pronounced changes in cancer tissue. The changes correlate with previous findings of a loss of -glycans in cancer mucins, but did not always correlate with levels of Tn, sialyl-Tn, T and Le antigens in homogenates or with the differentiation status and Duke's stages of the cancer tissue or the patient's blood type, sex and age. UDP-GlcNAc: Gal NAc-R β3--acetylglucosaminyltransferase (where GlcNAc is -acetyl-D-glucosamine and GalNAc is -acetyl-D-galactosamine) synthesizing -glycan core 3, GlcNAcβ1-3GalNAc-, CMP-sialic acid: GalNAc-peptide α6-sialyltransferase synthesizing the sialyl-Tn antigen and sulphotransferase activities towards -glycan core 1, Galβ1-3GalNAc-, were found to be decreased in cancer. UDP-GlcNAc: Galβ1-3GalNAc β6--acetylglucosaminyltransferase was also decreased in cancer concomitant with a loss of the ability to synthesize the I antigen and core 4, GlcNAcβ1-6(GlcNAcβ1-3) GalNAc-. CMP-sialic acid: Galβ1-3GalNAc-R α3-sialyltransferase and GDP-fucose: Galβ-R α2-fucosyltransferase, synthesizing the blood group H determinant, were found to be 4- and 3- to 8-fold increased, respectively, in cancer compared to normal tissue. The data suggest that the biosynthesis of antigens and mucin-bound -glycan structures in colon cancer is subject to complex control mechanisms. [ABSTRACT FROM PUBLISHER]

= 0.013). Tissue from 3 of the responders and 7 of the nonresponders that stained for bcl-2 were positive prior to chemotherapy; however, there was no association between bcl-2 staining and chemotherapeutic effect. In conclusion, immunohistochemical identification of p53 in pretreatment tissue may represent a useful predictor for chemotherapeutic outcome in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

We present herein the case of a 64-year-old man diagnosed as having a mucoepidermoid carcinoma of the pancreas. The tumor originated in the tail of the pancreas and invaded the spleen, left adrenal gland, left kidney, and transverse colon. Liver and peritoneal metastases were also noted. Despite surgical treatment and adjuvant chemotherapy, the disease progressed rapidly and the patient died of cachexia 4 months after his initial diagnosis. Mucoepidermoid carcinoma of the pancreas is a rare entity, and is believed to be a form of adenosquamous carcinoma known as adenoacanthoma. However, in this patient, no differentiated squamous cell component could be detected. In fact, the tumor was composed of mucin-producing cells, epidermoid cells, and intermediate cells. Immunohistochemical staining for the carcinoembryonic antigen, CA19-9, and SPan-1 demonstrated a production of cancerous mucin in the epidermoid cells, suggesting that mucoepidermoid carcinoma may arise from the squamoid metaplasia of an adenocarcinoma. [ABSTRACT FROM AUTHOR]

The cytokinetics of the human pancreatic adenocarcinoma cell line Capan-2 were analyzed by a bromodeoxyuridine (BrdUrd)/DNA analysis with flow cytometry (FCM). The reproducibility of data was shown to be superior to that achieved using a DNA analysis program with FCM. The perturbation of cytokinetics following irradiation was examined. Bivariate distribution was able to distinguish each cell phase cohort, even following as strong an irradiation as 10 Gy, a condition for which DNA analysis proved unusable. BrdUrd/DNA analysis showed the GM phase population after irradiation with 2 Gy to be significantly greater ( P<0.005) than that of the untreated cells. This difference was not detectable by the DNA analysis program due to the large standard deviation (SD) of the data. BrdUrd/DNA analysis has a sufficient quantitative accuracy that strongly perturbed cytokinetics in patients treated with various therapeutic agents, for example, with combined therapies, can thus be analyzed by this approach. [ABSTRACT FROM AUTHOR]

Copyright of World Journal of Surgery is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of World Journal of Surgery is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The remnant stomach after partial gastrectomy is considered to have a predilection for the development of primary gastric carcinoma. However, early gastric stump carcinomas are uncommon because the diagnosis of gastric stump carcinoma is more difficult than that of carcinoma in the intact stomach. Triple early gastric stump carcinomas, as in the present case, are exceedingly rare and may provide some clues for further investigation of carcinogenesis in the gastric stump. We studied about the histological appearance, genetic alterations (P-53 gene, c-erbB-2 gene and K-ras gene), and expression of tumor-associated antigens (carcinoembryonic antigen, carbohydrate antigen 19-9, and sialyl-Tn) in this rare case. The three carcinomas differed from each other histologically. With respect to genetic alterations, c-erbB-2 was amplified in one lesion, but no mutations of K-ras and P-53 gene were detected. The three carcinomas also differed from each other on the expression of tumor-associated antigens. In noncancerous mucosal epithelium at the anastomosis showing hyperplasia and cystic formation of glandular epithelial cells, no genetic alterations were detected, but sialyl-Tn and carbohydrate antigen 19-9 were expressed. These results suggest that there may be different processes of carcinogenesis of the three carcinomas even though they occurred under identical environmental conditions to those that have increased cancer risk. [ABSTRACT FROM AUTHOR]

Gastric mucosal blood flow plays an important role as a background factor in the pathogenesis of acute gastric mucosal lesion. In this study, endoscopic measurement of regional gastric mucosal blood flow was performed on 41 patients with esophageal varices due to liver cirrhosis to ascertain the possible relations of this parameter to liver function, portal pressure, and acute gastric mucosal lesion. The effect of sclerotherapy and of esophageal transection on gastric mucosal blood flow were also investigated. Regional gastric mucosal blood flow in either the antrum or the corpus was significantly decreased in these patients, compared with normal controls. There was also a significant difference in gastric mucosal blood flow between two subgroups of patients, one with gastric mucosal lesions and the other without these lesions. Sclerosing therapy for esophageal varices tended to affect this parameter. Gastric mucosal blood flow had no significant correlation with portal pressure. [ABSTRACT FROM AUTHOR]