Yasumasa Kondoh

Oligomerized grape seed polyphenols attenuate inflammatory changes due to antioxidative properties in coculture of adipocytes and macrophages

Macrophage infiltration of white adipose tissue (WAT) is implicated in the metabolic complications of obesity. In addition, inflammatory changes through dysregulated expression of inflammation-related adipokines such as tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) in WAT are considered to be one of the causes of insulin resistance. Recently, enhanced oxidative stress in adipocytes has been reported to be implicated in dysregulated expression of inflammation-related adipokines. Polyphenols are well known as potent natural antioxidants in the diet. In the present study, we investigated the antioxidative effects of an oligomerized grape seed polyphenol (OGSP) on inflammatory changes in coculture of adipocytes and macrophages. Coculture of HW mouse white adipocytes and RAW264 mouse macrophages markedly increased the production of TNF-alpha, MCP-1 and plasminogen activator inhibitor-1 compared with control culture. Treatment of HW cells with OGSP significantly attenuated the dysregulated production of adipokines. Moreover, OGSP significantly suppressed coculture-induced production of reactive oxygen species (ROS). Although enhanced release of free fatty acids (FFAs) by coculture was not altered by OGSP, FFA-induced ROS production in HW cells was significantly attenuated by OGSP. Furthermore, OGSP significantly reduced increases in the transcriptional activity of nuclear factor-kappaB and activation of extracellular signal-regulated kinase by coculture. Thus, these results suggest that the antioxidative properties of OGSP attenuate inflammatory changes induced by the coculture of adipocytes and macrophages.

Laparoscopy-assisted combined resection for synchronous gastric and colorectal cancer: Report of three cases

In gastric cancer patients, the most common form of synchronous cancer is colorectal cancer. To reduce the invasiveness of the resection, a laparoscopy-assisted combined resection was performed in three patients with synchronous gastric and colorectal cancer. Although all gastric lesions were in the early stages, two colorectal lesions were advanced cases. In all cases, the laparoscopic gastric resection and reconstruction was performed first, followed by the colorectal resection. In the case of right-side colon cancer in addition to gastric cancer, it was relatively easy to perform the combined resection with lymph node dissection sharing the same ports used for the gastrectomy, although we needed an additional port. In one case, in which rectal cancer was present in addition to gastric cancer located in the upper portion of the stomach, a totally laparoscopic proximal gastrectomy was combined with a laparoscopy-assisted low anterior resection, leaving only a lower abdominal minilaparotomy wound. All patients quickly returned to normal activity without remarkable complications, with the exception of a wound infection in one patient. With a mean follow-up of 30.7 months, all patients survived without any sign of recurrence. This procedure represents a feasible option for minimally invasive treatment of synchronous gastric and colorectal cancer.

Glycosidically bound sialic acid levels as a predictive marker of postoperative adjuvant therapy in gastric cancer

SummaryA group of 293 gastric cancer patients were examined to see if the preoperative value of glycosidically bound sialic acid is a predictor of prognosis and effectiveness of postoperative adjuvant therapy. All patients had gastrectomies and were histologically confirmed to have primary adenocarcinoma of the stomach. Some patients then received either postoperative adjuvant chemotherapy or immunochemotherapy. Patients with sialic acid levels less than 74.5 mg/dl survived significantly longer than those with sialic acid levels of 74.5 mg/dl or of 85.3 mg/dl and over. No significant differences in survival were found among patients treated by gastrectomy alone, gastrectomy plus chemotherapy and gastrectomy plus immunochemotherapy. However, patients with abnormally elevated levels of sialic acid survived significantly longer when they were treated with immunochemotherapy after gastrectomy than those treated by gastrectomy alone or with chemotherapy after gastrectomy. By using Coxs multivariate regression model, pTNM stages, postoperative adjuvant therapy (chemotherapy and immunochemotherapy) and preoperative serum levels of sialic acid were examined as prognostic variables. Postoperative therapy was a significant prognostic variable in patients with abnormally elevated levels of sialic acid. The preoperative serum level of sialic acid is a promising predictive marker of the response to postoperative adjuvant immunochemotherapy.

Focus on the Conditions of Resection and Reconstruction in Gastric Cancer

To assess the roles of the extent of gastric resection and duodenal food passage reconstruction in gastric cancer, we examined a consecutive series of 1,061 patients who underwent total or partial (proximal and distal) gastrectomies with or without duodenal food passage reconstruction between August of 1974 and January of 2002, and received gastrectomies with D2–3 lymph node dissection. Patients who underwent distal or proximal gastrectomy were found to have significantly better survival rates than those who underwent total gastrectomy in stages 1A (10-year survival: 86.6 and 78.9 vs. 61.6%), 2 (56.5 and 65.6 vs. 34.4%), 3A (45.9 and 33.3 vs. 15.2%), and 4 (5-year survival rates: 23.7 and 50.0 vs. 7.1%). Additionally, patients with duodenal food passage reconstruction or double tract reconstruction also showed significantly better survival rates than those without duodenal food reconstruction in stages 1A (10-year survival: 86.4 and 82.5 vs. 61.7%), 1B (69.9 and 90.6 vs. 54.1%), 2 (60.5 and 63.3 vs. 16.5%), and 3A (39.9 and 47.4 vs. 23.1%). In multivariate analysis, the independent prognostic factors were age at operation, depth of tumor, duodenal food passage reconstruction, and lymph node metastasis. Our results indicate that both the extent of gastric resection and duodenal food passage reconstruction were important factors in the outcome of gastric cancer patients, and that surgeons should perform minimal gastric resection with preservation of the duodenal food passage when the gastric stump is tumor-free.

Immunotherapy and combined assay of serum levels of carcinoembryonic antigen and acute-phase reactants.

Abstract Our previous studies have revealed that gastric and esophageal cancer patients with abnormal sialic acid levels had a better response than those with normal levels if they received polysaccharide K (PSK), a nonspecific immunomodulator. Serum levels of carcinoembryonic antigen (CEA) and acute-phase reactants (APR) such as immunosuppressive acidic protein, acid-soluble glycoproteins, α1-antichymotrypsin, and sialic acid were analyzed in 872 gastric cancer patients who had undergone resection from March 1979 to September 1993 at the Department of Surgery of Tokai University. The patients were categorized into four groups according to the preoperative serum levels: group A had normal levels of both CEA and APR, group B had abnormal CEA and normal APR levels, group C had a normal CEA level and normal levels of one or more APR, and group D had abnormal levels of both CEA and of one or more APR. Patients in group D who received PSK showed significantly better survival than those without PSK (29.3% versus 6.9%; log-rank test, P = 0.0015; Breslow test, P = 0.0042). CEA-positive patients receiving PSK therapy exhibited a significantly better survival rate than those without PSK (38.1% versus 18.6%; log-rank test, P = 0.0136; Breslow test, P = 0.0125). Cox’s regression analysis showed that PSK therapy was significantly related to survival in group D, but not in the other groups. We conclude that the combined assay of tumor-associated factors (such as CEA) and various nonspecific reactants to the presence of cancer (such as immunosuppressive acidic protein, α1-antichymotrypsin, acid-soluble glycoproteins and sialic acid) provides a good set of preoperative indicators on which to base the selection of treatment for individual gastric cancer patients.

Endoscopy‐assisted anastomosis: a modified technique for laparoscopic side‐to‐side esophagojejunostomy following a total gastrectomy

Introduction: Esophagojejunostomy with a circular stapling device is sometimes difficult to perform in a laparoscopic setting. On the other hand, a side‐to‐side anastomosis with a linear stapling device is technically challenging.

Effects of nonsteroidal antiandrogen agents on experimental esophageal carcinoma in rats

BackgroundThis study evaluated the antitumor effects of nonsteroidal antiandrogen agents, flutamide and bicalutamide, on the incidence of experimental esophageal carcinoma in rats.MethodsMale 7-week-old Sprague-Dawley rats were used. N-amyl-N-methylnitrosamine (AMN) was dissolved in tap water as a 0.003% solution and was given freely to 164 rats for the first 10 weeks. Of these, 85 rats were castrated at age 6 weeks. For the second 10 weeks, 68 of 129 rats were given flutamide in experiment 1, and 15 of 35 rats were given bicalutamide in experiment 2. All rats were killed at age 27 weeks and pathological examination was done.ResultsIn intact rats given AMN alone, the incidence of squamous cell carcinoma (SCC) was 82.7% in experiment 1 and 77.7% in 2. In castrated rats given AMN alone, the incidence of SCC was 62.5% in experiment 1 and 45.4% in 2. There was no significant difference between the incidence of SCC given AMN alone in experiments 1 and 2 for castrated and intact rats, respectively. The incidence of SCC in intact rats given flutamide was 61.7%, and that of those given bicalutamide was 71.4%. The incidence of SCC in castrated rats given flutamide was 47.0%, and that in those given bicalutamide was 25%. The incidence of SCC in castrated rats given flutamide or bicalutamide was significantly lower than that in intact rats given AMN alone (P < 0.005, P < 0.05, respectively).ConclusionsWe conclude that the observed antitumor effects of nonsteroidal antiandrogen agents on experimental esophageal carcinoma give credence to the possibility achieving antiandrogen therapy of esophageal squamous cell carcinoma.

Gastric Acid Secretion and Serum Gastrin Levels in Gastric Cancer

We investigated the association between gastric acid secretion, serum gastrin levels, and the differentiation of tumor cells in gastric cancer.Gastric acid output after stimulation by tetragastrin, and serum gastrin levels after stimulation by a test meal were, examined in 128 primary gastric cancer patients, in whom the tumor had invaded the mucosa. After tumors were histologically confirmed as adenocarcinomas, the patients underwent gastrectomy. Gastric ulcer patients showed decreases in both integrated gastrin response (T-IGR) after a test meal, and in gastric acid secretion related to their age. On the other hand, early gastric cancer patients showed decrease in acid secretion but an increase in T-IGR.

Immunosuppressive Acidic Protein and Postoperative Immunotherapy in Gastric Cancer

One hundred ninety-five gastric cancer patients who underwent total gastrectomy were examined for serum immunosuppressive acidic protein (IAP). Multivariate analysis utilizing Cox’s model was performed with seven variables including as age, sex, pTNM stage, postoperative adjuvant therapy, preoperative serum levels of IAP and histopathological grading. Postoperative chemotherapy with or without PSK was a significant prognostic factor in patients with abnormal levels of IAP. These results indicate that if patients with abnormal levels of IAP who had immunosuppressive status, they showed good results with postoperative immunotherapy, probably in combination with splenectomy.

HLA antigens and lymph node metastasis in gastric cancer can HLA antigens be indicators of local resection of tumor with preservation of regional lymph node

239例の胃癌切除例の術前にHLA抗原とPPD皮膚皮内反応, 急性相反応物質, NK細胞, リンパ球サブセットを測定し, リンパ節転移と対比検討したところ, HLAB40, Bw61, Cw3抗原はリンパ節転移抑制抗原, A9 (24) 抗原はリンパ節促進抗原であると考えられた. 深達度m-sm症例では, HLA抗原を測定することによってリンパ節転移の状態が106例中89例 (84.0%) 同定可能であった. リンパ節転移陰性症例のPPD皮膚皮内反応, 急性相反応物質, NK細胞, リンパ球サブセットの検討から, B40抗原陽性例では急性相反応物質が低値, OKT4が高値, OKT8が低値, Leu7が低値をA9 (24) では急性相反応物質が高値, OKT4/8が低値, Leu7, Leu11が高値を示した. 以上より, 胃癌の病態, 特にリンパ節転移に関与する遺伝的因子が主要組織適合性複合体遺伝子に強いかかわりをもつ可能性が考えられた. 術前のHLA抗原測定によりリンパ節転移が予測され, 胃癌の縮小手術が可能と思われる.