Local skin flap reconstruction for abdominal wound dehiscence after abdominal surgery with a stoma: report of two cases.

Abdominal wound dehiscence is a serious complication of laparotomy, and fascial dehiscence in a patient with a stoma is especially difficult to manage. We describe how we performed local skin flap reconstruction for abdominal wound dehiscence in two patients with stomas. One patient underwent sigmoidectomy with a colostomy for peritonitis caused by perforated diverticulitis of the sigmoid colon. Postoperative fascial dehiscence was repaired by rhomboid flap reconstruction. The other patient underwent total gastrectomy, cholecystectomy, and splenectomy. An ileostomy was performed for digestive tract perforation, which was complicated by abdominal dehiscence with necrosis of the fascia. This was repaired by rotation flap reconstruction. The abdominal walls in both patients were repaired successfully without tension.

Interferon-beta inhibits liver metastases from murine colon 26 carcinoma and its highly metastatic variant.

PURPOSE: The antitumor effects of Interferon-beta (IFN-beta) are due to its direct inhibition of cell proliferation, immunostimulatory activity, and the inhibition of angiogenesis. We investigated the mechanism of the effects of IFN-beta on a murine colon 26 cell line (CT 26) and its highly metastatic variant (L5). METHODS: We examined its inhibitory effects on cell proliferation in vitro and the development of liver metastases in vivo. RESULTS: The proliferation of CT 26 in vitro was inhibited by IFN-beta in a dose- and time-dependent manner. The number of metastases was reduced in mice inoculated with CT 26 (P<0.01) and L5 (P<0.01) on Day 14 after treatment with IFN-beta. The median survival rate of the mice inoculated with L5 administered IFN-beta every other day, or every day was higher than in the control group (P<0.05). A dorsal air sac assay demonstrated that IFN-beta inhibited angiogenesis in mice inoculated with CT 26, but the effects disappeared with aminoguanidine, an inducible nitric oxide synthase inhibitor. CONCLUSION: These results showed that IFN-beta directly inhibits the proliferation of CT 26. In addition, the in vivo experiments suggested that IFN-beta might effectively inhibit liver metastases.

[A phase I study of postoperative combination therapy with TS-1 and low dose cisplatin against stage IV gastric carcinoma].

A dose-escalation study was conducted for postoperative patients with stage IV gastric cancer to determine the recommended dose of daily intravenous cisplatin combined with a fixed dose of TS-1. TS-1 was administered orally twice daily for 2 weeks followed by a 1-week rest. The dose of TS-1 was based on the body surface area (BSA) as follows: 80 mg/day for BSA less than 1.25, 100 mg/day for BSA 1.25 to less than 1.50, and 120 mg/day for BSA 1.5 or more. Three dose levels of cisplatin (2, 4, 6 mg/m(2)) were studied, and two courses were performed. Cisplatin was infused on day 1-5 and 8-12 for 30 minutes. The National Cancer Institute common toxicity criteria (NCI-CTC Version 3) were used to evaluate the grade of toxicity. Three patients enrolled in each level. Dose escalation was performed when dose-limiting toxicities (DLT) were seen in 0/3, and 3 more cases of the same level were added when DLTs were seen 1-2/3. Maximum-tolerated dose (MTD) were determined when DLTs were seen in 3 cases. DLTs were not recorded during the administration of CDDP up to 4 mg/m(2). However, DLTs were seen 3/3 at level 3. From these results, cisplatin of 4 mg/m(2)was determined to be the recommended dose (RD) in this protocol for postoperative stage IV gastric carcinoma.

Infiltration of neutrophils is required for acquisition of metastatic phenotype of benign murine fibrosarcoma cells: implication of inflammation-associated carcinogenesis and tumor progression.

QR-32 tumor cells, a clone derived from a murine fibrosarcoma, are poorly tumorigenic and nonmetastatic when injected into syngeneic C57BL/6 mice. However, they are converted to highly malignant ones once they have grown in vivo after being co-implanted in a subcutaneous site with a foreign body, a gelatin sponge. Early phase of inflammation induced by the gelatin sponge participates in the conversion and histological analysis shows predominant infiltration of neutrophils. The objective of this study was to determine whether the depletion of the infiltrating neutrophils has any effect on the tumor progression. Intraperitoneal administration of a monoclonal anti-granulocyte antibody, RB6-8C5 (RB6), depleted neutrophils from both the peripheral blood circulation and the local inflamed site in mice with co-implantation of QR-32 tumor cells and gelatin sponge. The RB6 administration did not inhibit either tumor development or growth of QR-32 tumor cells. In contrast, tumor cell lines established from RB6-administered mice showed a significant decrease in metastatic incidence as compared with the tumor cell lines obtained from the mice with administration of control rat IgG or saline. Metastatic ability was significantly suppressed when RB6 had been administered in the early phase (from day -2 to day 6 after implantation); however, the administration in the middle (from day 6 to day 14) or late (from day 14 to day 22) phase did not affect the metastatic ability. We confirmed the phenomena by using integrin beta(2) knockout mice that had impaired neutrophil infiltration into inflamed sites. In the knockout mice, neutrophils hardly infiltrated into the gelatin sponge and the tumors showed dramatically suppressed metastatic phenotype as compared with those in wild-type mice or nude mice. Immunohistochemical analysis demonstrated that expressions of 8-hydroxy-2'-deoxyguanosine and nitrotyrosine were parallel to those in the presence of neutrophils. These results suggested that inflammation, especially when neutrophils infiltrate into tumor tissue, is primarily important for benign tumor cells to acquire metastatic phenotype.

Immunological evaluation of peptide vaccination for patients with gastric cancer based on pre-existing cellular response to peptide.

There is no standard treatment modality for advanced gastric cancer (GC) at the present time. To develop a new treatment modality, we investigated the immunological responses of advanced GC patients (n = 13, 9 non-scirrhous and 4 scirrhous types) vaccinated with peptides to a regimen under which pre-vaccination peripheral blood mononuclear cells (PBMCs) were screened for their reactivity in vitro to each of 14 peptides on HLA-A24 or 16 peptides on -A2 allele, then only the reactive peptides (maximum: 4) were administered in vivo. This regimen was generally well tolerated, although grade I levels of fever and local skin reactions were observed in several patients. Delayed-type hypersensitivity (DTH) to the vaccinated peptides was observed in 4 patients. Increased cellular and humoral immune responses to the vaccinated peptides were observed in post-vaccination PBMCs from 4 of 8 patients and in post-vaccination sera of 8 of 10 patients tested, respectively. Prolonged survival was observed in patients showing cellular and humoral immune responses to the vaccinated peptides in the post-vaccination samples, including all 4 patients with the scirrhous type. These results encourage further development of peptide-based immunotherapy for GC patients.