The relationship between the expressions of the cell adhesion molecule CD44H, CD44v3, and CD44v6 and metastases in gastric cancer

Expression of CD44 variants in some tissues appears to relate to tumor progression, and particularly to the metastatic potential of some cancers. The aim of this study was to clarify the relation between the expression of CD44 splice variants and tumor metastasis by using CD44v-specific gastric cancer monoclonal antibodies. A total of 110 patients with primary gastric cancer were studied. Histological samples of 70 of the 110 (63.6%) were stained with three monoclonal antibodies directed against the CD44H and CD44 variants (CD44v3, CD44v6) in gastric cancer. The incidence of lymph node metastasis was higher in the CD44H strongerexpression group than in the weaker expression group. No significant correlation could be found between CD44H, CD44V3, or CD44v6 expression and liver metastasis or histological types (differentiated vs.undifferentiated) . Lymph node metastasis correlated with CH44H rather than CD44v3 or CD44v6. These results suggested that CD44H might be a useful marker for lymph node metastasis in resected gas-tric cancer. The 5-year survival rate was 57.3% in the group positively ex-pressing CD44 and 52.4% in the group with negative expression of CD44. Concerning prognosis, we found here that the expression of CD44 is not sig-nificantly associated with increased mortality. Further study of the expression of specific isoforms may help elucidate in more detail the mechanisms of these findings

Clinical Indication of Laparoscopic Surgery for Colorectal Cancer: The Optimal Extent of Lymph Node Dissection based on Depth of Colorectal Cancer and Technical Feasibility of Laparoscopic Colorectal Surgery.

Recently, laparoscopic colorectal surgery has been considered to be appropriate for colorectal cancer, and the feasibility of many laparoscopic techniques has been established; however, the indication for curative colorec-tal cancers is controversial. In this study, before laparoscopic procedure was performed on patients with colorectal cancers, 641 patients who had under-gone open laparotomy for colorectal cancer during the past 16 years were ev-aluated for the distribution of metastatic lymph nodes classified by depth of invasion. The results obtained were as follows: The rate of all lymph node metastasis of patients with pTis was 0%. The rate of intermediate lymph node (n2) metastasis of patients with pT1 and pT2 tumor was low (3.4% and 4.1% respectively) , however, in patients with pT3 and pT4 tumors, this rate was much higher (15.9% and 15.8% respectively) . Therefore, with re-gard to lymph nodes dissection for colorectal cancer it might be concluded that the intermediate lymph nodes metastases in patients with pT1 and pT2 tumors (less than 5%) were negligible. However, in patients with pT3 and pT4 tumors, for the purpose of performing a complete harvest of intermedi-ate lymph nodes, D3-dissection (including principal lymph node dissection) is required. it is questionable whether or not performance of the laparoscopic procedure for cancer achieves the same extent of lymph node dissection as compared with open laparotomy. Dissection was restricted to intermediate grade lymph node including the paracolic lymph nodes (D2) . Accordingly, patients with pT3 and pT4 tumor should be excluded from indication for laparoscopic procedure. Between October 1997 and November 1998, laparoscopic colorectal resec-actions were performed on a limited number of the above mentioned patients with Tis, Ti and T2 tumor. The grade of lymph node dissection was deter-mined by the results of a preoperative assessment of the depth of cancer in-vasion. With the exception of one patient, whose preoperative assessment for depth of cancer invasion was a limitation at the muscularis propria, but whose histological outcome had been pT3 tumor, all the other patients were able to undergo laparoscopic colorectal resection. The final histological results were as follows: 3 patients with pTis tumor, 6 pTl tumor, and 3 pT2 tumor. One of the pT3 patients alone was converted from a laparoscopic pro-cedure to open laparotomy because of the intraoperative proof of intermediate lymph node metastases, and subsequently this patient underwent principal lymph node dissection (D3-dissection) . With regard to the histological metas-tasis of harvested lymph nodes, no patients was found to have regional lymph node metastasis except for one patient only who had a pT3 tumor. Thus the histological findings were similar to those for conventional open laparotomy. In this study, it was concluded that by laparoscopic procedure a safe and complete dissection of intermediate lymph nodes including the paracolic lymph nodes (nl and n2) could be achieved. On the other hand, the true incidence of port site recurrence, and also its mechanism remain unknown to date. However, it is considered that the incidence of port site recurrence in patients with serosal invasion (T4 tumor) is higher than in those without (i.e., patients with pTis, pTl, pT2 and pT3 tumor) . We are also convinced that a number of patients with pTis, pTl and pT2 undergoing laparoscopic procedure were able to gain curative colorectal resection in terms of port site non-recurrence, and strongly believe that the application of laparoscopic col-orectal surgery for cancer might be acceptable

Tumorigenicity, Motility and Liver Metastasis of Human Gastric Carcinoma Lines with High Metastatic Potential in the Liver of Nude Mice

To analyze the human gastric carcinoma metastasis to the liver, a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ521 were expanded in vitro and subsequently injected into the spleens of nude mice. By repeating these proce-dures five times, we were able to obtain a cell line, designated AZ-H5c, with high metastatic potential in nude mice. It was observed that animals had liver metastasis in 10 of 12 (83%) cases injected with AZ-H5c, whereas only 14% with parental AZ521. The growth activity in vivo of AZ-H5c cells is much more rapid than that of AZ521 cells, but its growth activity in vitro is slower. The mortile activity in vitro of AZ-H5c is stronger than that of AZ521. These results suggest that our model can provide a new approach to basic and clinical studies of cancer metastasis

Gastric T-cell lymphoma associated with hemophagocytic syndrome

BACKGROUND: Lymphoma-associated hemophagocytic syndrome (LAHS) occurs in mostly extra nodal non-Hodgkin's lymphoma. LAHS arising from gastrointestinal lymphoma has never been reported. Here we report a case of gastric T-cell lymphoma-associated hemophagocytic syndrome. CASE PRESENTATION: A 51-year-old woman presented with pain, redness of breasts, fever and hematemesis. Hematological examination revealed anemia. Gastroscopy revealed small bleeding ulcers in the stomach and the computed tomography scan showed liver tumor. She underwent total gastrectomy for gastrointestinal bleeding and the histopathology revealed gastric T-cell lymphoma. She continued to bleed from the anastomosis and died on the 8th postoperative day. Autopsy revealed it to be a LAHS. CONCLUSIONS: If Hemophagocytic syndrome (HPS) occurs in lymphoma of the gastrointestinal tract, bleeding from the primary lesion might be uncontrollable. Early diagnosis and appropriate treatment are needed for long-term survival

Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer

Survivin is a member of the inhibitor of apoptosis protein (IAP) family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL) recognized by CD8+ cytotoxic T lymphocytes (CTLs). We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2), general malaise (grade 1), and fever (grade 1). No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9) decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer