Submucosal electrocoagulation for prolapsed hemorrhoids:a new operative approach to hemorrhoidal varices.

The results of submucosal electrocoagulation (SEC), a new radical operation for prolapsed hemorrhoids, in 403 patients with third- or fourth-degree hemorrhoids are reported. After resecting the anal skin tags that coexisted with prolapsed hemorrhoids, the hemorrhoidal varices could be resected and electrically coagulated through the wound without cutting the anal canal epithelium by using a fine needle-type electric knife. The results of this series indicated that SEC could dramatically reduce the incidence of the postoperative complications that sometimes occur after conventional hemorrhoidectomy, such as severe anal pain, massive anal bleeding and anal stenosis. Moreover, SEC could ensure that operated patients make an early return to social activities and have a satisfactory quality of life. Relapse of prolapsed hemorrhoids after SEC was rare.

A synergistic antitumor effect of interleukin-2 addition with CD80 immunogene therapy for peritoneal metastasis of gastric carcinoma.

The co-stimulatory molecule CD80 is a ligand of CD28, which plays a key role in the induction of cell-mediated immune responses. Many tumors, including gastric cancer, decrease the expression of CD80, which results in the failure of immune recognition. We evaluated the effect of interleukin-2 addition combined with CD80 infection on the peritoneal metastasis in gastric cancer. CD80 infection combined with interleukin-2 addition significantly increased the activated cytotoxicity of mononuclear cells compared to CD80 gene infection and compared to the lacZ control group. In vivo, the survival of animals with intraperitoneal tumor was longest in those given CD80 infection with interleukin-2 addition (median survival, 46 days), followed by those given interleukin-2 (39 days), those given CD80 infection (37 days), and those given lacZ (29 days). These results suggest that interleukin-2 addition might contribute to improving the observed outcome of CD80 immunogene therapy in peritoneal metastasis of gastric carcinoma.

Up regulation of ICAM-1 gene expression inhibits tumour growth and liver metastasis in colorectal carcinoma.

We have previously reported that decreased intercellular adhesion molecule-1 (ICAM-1) expression in cancer cells is associated with liver metastasis of colorectal cancer. In this study, we have investigated the effect of ICAM-1 gene transfection into the human colorectal cancer cell line LM-H3 on cell adhesiveness and cytotoxicity of peripheral blood mononuclear cells (PBMC) to cancer cells. Furthermore, we have investigated the effects of this gene transfer on subcutaneous tumour and liver metastases of LM-H3 in nude mice. More PBMC adhered to ICAM-1 transfected LM-H3 cells, LM-H3/ICAM-1, than to non-transfected LM-H3 cells and control LM-H3/Vector. Lysis of LM-H3/ICAM-1 cells by PBMC was significantly increased compared with LM-H3/Vector. Liver metastases with LM-H3/ICAM-1 cells were fewer in number and smaller than metastases with LM-H3/Vector. Intra-tumoural injection of ICAM-1 adenoviral vector significantly inhibited the growth of subcutaneous LM-H3 tumour. In conclusion ICAM-1 gene transfection using adenovirus vector might be an effective therapy for liver metastasis of colorectal carcinoma.

Intraductal papillary-mucinous adenoma developed in the ventral pancreas in a patient with pancreas divisum.

A 34-year-old man was admitted to our hospital with the chief complaints of back pain and epigastralgia. The physical examinations on admission disclosed no abdominal tumor. The serum concentration of total bilirubin was 1.4 mg/dl. The serum elastase-1 level was elevated to 526 ng/dl. Computed tomography showed a cystic lesion, 1 cm in diameter, in the head of the pancreas, without dilatation of the main pancreatic duct. Endoscopic retrograde cholangiopancreatography via the papilla of Vater and the accessory papilla revealed an enlarged ventral pancreatic duct and pancreas divisum. The preoperative diagnosis was mucin-producing pancreatic tumor in the ventral pancreas of a patient with pancreas divisum. A pylorus-preserving pancreatoduodenectomy was performed. The gross findings of the cut surface of the resected specimen disclosed mural nodules in the dilated duct of the ventral pancreas. A histological examination of the mural nodules in the ventral pancreas revealed mucin and intraductal papillary adenoma. Benign tumors associated with pancreas divisum are rare; to the best of our knowledge, only three cases have been reported. Although in these three patients the tumor developed in the dorsal pancreas, the tumor developed in the ventral pancreas in our patient.

Usefulness of inhibiting the lymph node metastasis in human gastric carcinoma by B7-1 gene transfection.

INTRODUCTION: Lymph node metastasis is one of the crucial prognostic factors in gastric cancer. We have reported that ICAM-1 gene transfection was effective against lymph node metastases of gastric cancer. B7-1, one of the co-stimulatory factors, was reported to induce cytotoxic T lymphocytes when using melanoma and bladder cancer cell lines, as well as ICAM-1. In this study, we investigated the inhibitory effect of B7-1 on lymph node metastasis by B7-1 gene transfection into gastric cancer cells. MATERIALS AND METHODS: We transfected B7-1 genes into a gastric cancer cell line (OCUM-2MLN) and analyzed the effect of B7-1 transduction on lymph node metastasis, the in vitro adhesiveness and cytotoxicity assay of mononuclear lymphocytes to cancer cells and lymph node metastatic ability after orthotopic implantation of gastric cancer cells in vivo. RESULTS: We revealed that mononuclear lymphocytes showed significantly stronger adherence and cytotoxicity to B7-1 transfected cells (2MLN/B7) than its parent OCUM-2MLN cells. The tumor growth rate of 2MLN/B7 xenograft was significantly slower than OCUM-2MLN xenograft in nude mice. In orthotopic implantation experiments for nude mice, 2MLN/B7 cells in stomach developed significantly less lymph node metastasis than OCUM-2MLN cells. Histologic findings showed that leukocytes were intensively infiltrated in both the 2MLN/B7 tumors and its metastatic lesions, however, were scarcely observed in the lesions associated with 2MLN cells. CONCLUSION: B7-1 may play an important role in inhibiting lymph node metastasis by the mechanism of enhanced immunogenicity, and that B7-1 gene transduction might be effective against lymph node metastases of gastric cancer.

CD80 gene therapy for lymph node involvement by gastric carcinoma.

The co-stimulatory molecule, CD80 (B7-1), is a ligand of CD28 and plays a key role in the induction of cell-mediated immune responses. Many tumors, including gastric cancer, have decreased expression of CD80 which leads to a failure of immune recognition. Lymph node spread is a factor of poor prognosis in gastric cancer. In this study, we transfected the CD80 gene by an adenovirus vector into a human gastric cancer cell line, OCUM-2MLN, and analyzed the effect on lymph node disease in vitro and in vivo. After transfection of CD80 in vitro, the adhesive ability of cancer cells for peripheral blood mononuclear cells and their cytotoxicity showed significant regression (p<0.01). Intratumoral injection of AdCD80 caused significantly growth of subcutaneous tumors. In vivo lymph node spread was suppressed by injection of AdCD80 into gastric tumors. Histopathologic findings revealed CD80-positive cells around the tumor. These results suggest that CD80 gene transfer into cancer cells using an adenovirus vector might be a promising approach for in vivo cancer therapy.

ICAM-2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma.

PURPOSE: Human scirrhous gastric carcinoma develops peritoneal dissemination with high frequency, and the prognosis of patients with peritoneal metastasis is poor. There have been few reports of an immunogene therapy for peritoneal dissemination. Intercellular adhesion molecule (ICAM)-2 is a second ligand of leukocyte function-associated antigen-1, which functions as a costimulatory molecule for effector cells. In the present study, we examined whether ICAM-2 transfection using adenovirus vector is effective gene therapy for peritoneal metastasis of gastric cancer. EXPERIMENTAL DESIGN: We constructed an adenovirus vector, AdICAM-2, that encodes the full-length human ICAM-2 gene under control of the cytomegalovirus promoter. This vector expresses high levels of ICAM-2 on the human gastric cancer cell line OCUM-2MD3, which has high peritoneal metastatic ability in nude mice. We investigated the antitumor effects of gene transfer of ICAM-2 using the adenovirus vector AdICAM-2 in vitro and in vivo. RESULTS: ICAM-2 expressed on OCUM-2MD3 cells by AdICAM-2 demonstrated significantly high adhesiveness to and cytotoxicity against peripheral blood mononuclear cells in vitro compared with the control adenovirus vector AdlacZ. Intratumoral injection of AdICAM-2 significantly inhibited the growth of s.c. tumor. Mice with peritoneal metastasis survived for a significantly longer time after AdICAM-2 injection, compared with injection of AdlacZ. Histopathological findings revealed that many natural killer cells infiltrated the peritoneal metastatic lesions after AdICAM-2 injection. CONCLUSIONS: These findings suggest that transduction of ICAM-2 into cancer cells enhances the adhesion and activation of natural killer cells, resulting in a reduction of peritoneal metastasis. ICAM-2 transfection using adenovirus vector might be an effective form of gene therapy for peritoneal metastasis of gastric cancer.

Suppression of peritoneal metastasis in human gastric carcinoma by enhanced immunogenicity of B7-1 transfection.

B7-1, a co-stimulatory factor, has been reported to induce cytotoxic T lymphocytes (CTL). In the present study, we transfected B7-1 genes into a gastric cancer cell line (2MD3) and analyzed the effects of B7-1 transduction on peritoneal metastasis in vitro and in vivo. We revealed that mononuclear lymphocytes show significantly stronger adherence and cytotoxicity to B7-1 transfected cells (2MD3/B7) than to their parent 2MD3 cells. We also demonstrated that mice inoculated with 2MD3/B7 cells in the peritoneal cavity have a significantly better survival rate than those inoculated with 2MD3 cells (log-rank test, p<0.01). Histologic findings showed that leukocytes intensively infiltrate the 2MD3/B7 metastatic nodules, but can scarcely be observed in the nodules associated with 2MD3 cells. These findings indicate that the B7-1 may play an important role in suppressing peritoneal metastasis by the mechanism of enhanced immunogenicity, and that B7-1 gene transduction might be effective against peritoneal metastases of gastric cancer.