Mitsuru Toyono

Expression of acetylated and dimethylated histone H3 in colorectal cancer.

Aim: The expression of acetylated and dimethylated histone H3 in colorectal cancer was examined by immunohistochemistry and chromatin immunoprecipitation (ChIP)/Western blot (WB) assay. The correlation between the expression of histone H3 and clinicopathological findings was analyzed. Methods: Formalin-fixed and paraffin-embedded sections obtained from 80 operated cases of colorectal cancer were immunostained with anti-acetylated histone H3 (H3Ac) antibody and anti-dimethylated histone H3 lysine 4 (H3K4) antibody. Positive immunoreactivity was evaluated using the Allred scoring system. Furthermore, the expression was confirmed by ChIP/WB assay using formalin-fixed and paraffin-embedded sections. Results: There was good correlation between immunostaining and expression on ChIP/WB assay (p = 0.0005). There was a significant difference between the Allred score of H3K4 and the depth of tumor invasion (p = 0.0003) and the pathological stages (p = 0.0065). In overall survival classified by Allred scores of H3Ac (p = 0.0072) and H3K4 (p = 0.0187), the highest scores represented significantly worse prognoses than the other scores. Specifically, in stages II and III, the highest scores represented significantly worse prognoses than the other scores (p < 0.0001 and p = 0.0173, respectively). Conclusion: The expression of H3Ac and H3K4 may estimate patient prognosis.

Evaluation of salvage surgery for type 4 gastric cancer

Patients with type 4 gastric cancer and peritoneal metastasis respond better to chemotherapy than surgery. In particular, patients without gastric stenosis who can consume a meal usually experience better quality of life (QOL). However, some patients with unsuccessful chemotherapy are unable to consume a meal because of gastric stenosis and obstruction. These patients ultimately require salvage surgery to enable them to consume food normally. We evaluated the outcomes of salvage total gastrectomy after chemotherapy in four patients with gastric stenosis. We determined clinical outcomes of four patients who underwent total gastrectomy as salvage surgery. Outcomes were time from chemotherapy to death and QOL, which was assessed using the Support Team Assessment Schedule-Japanese version (STAS-J). Three of the patients received combination chemotherapy [tegafur, gimestat and otastat potassium (TS-1); cisplatin]. Two of these patients underwent salvage chemotherapy after 12 and 4 mo of chemotherapy. Following surgery, they could consume food adequately and their STAS-J scores improved, so their treatments were continued. The third patient underwent salvage surgery after 7 mo of chemotherapy. This patient was unable to consume food adequately after surgery and developed surgical complications. His clinical outcomes at 3 mo were very poor. The fourth patient received combination chemotherapy (TS-1 and irinotecan hydrochloride) for 6 mo and then underwent received salvage surgery. After surgery, he could consume food adequately and his STAS-J score improved, so his treatment was continued. After the surgery, he enjoyed his life for 16 mo. Of four patients who received salvage total gastrectomy after unsuccessful chemotherapy, the QOL improved in three patients, but not in the other patient. Salvage surgery improves QOL in most patients, but some patients develop surgical complications that prevent improvements in QOL. If salvage surgery is indicated, the surgeon and/or oncologist must provide the patient with a clear explanation of the purpose of surgery, as well as the possible risks and benefits to allow the patient to reach an informed decision on whether to consent to the procedure.