Yoshikazu Noguchi

Early gastric carcinoma with special reference to macroscopic classification

During a period beginning in 1946 and ending in October of 1978, 1000 cases of solitary early gastric carcinoma were operated on at the Cancer Institute Hospital, Tokyo, Japan. The clinical characteristics and the macroscopic and chronological changes were studied in these cases. Early gastric carcinoma comprised one third of all resected gastric carcinoma. If early gastric carcinoma was divided into two groups, the depressed and the elevated, the former was more common. By location, the depressed type lesions were more frequently seen in the middle third of the stomach and the elevated type lesions in the lower third. By age, distribution of the elevated type lesions showed a peak with a mode at the age of 60 to 69 years and of the depressed type, a plateau with a mode at the age of 50 to 59 years. The relative incidence of the elevated type of gastric carcinoma to the depressed type was one to four. In depth of invasion, the mucosa and the submucosa were equally involved. Lymph node metastases were encountered in 12.7% of early gastric carcinoma cases. The incidence of positive nodes in mucosal carcinoma was 3.4% and that of submucosal lesions was 21.7%. Of the elevated type carcinoma, 20.9% of the cases had positive nodes. The 5‐year survival rate of the patients with surgery for cure was 93.8% in contrast to 56.5% of those with palliative resection.

Is gastric carcinoma different between Japan and the United States

Analyses of surgical results for gastric carcinoma often lead to the conclusion that gastric carcinoma occurring in Japan is different from that diagnosed in the U.S.

Plasma concentrations of VEGF and bFGF in patients with gastric carcinoma

We examined plasma levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 54 patients with gastric carcinoma. Postoperative survival was significantly poorer in patients with plasma VEGF levels more than 10.0 pg/ml at the time of surgery. By an univariate analysis of the factors affecting survival, serosal invasion, lymph node metastasis, peritoneal dissemination, lymphatic vessel invasion, curability, and VEGF proteins were significant. By a multivariate analysis only VEGF levels and curability remained significant. Patients with recurrent disease, including liver metastasis, had significantly higher plasma VEGF concentrations than those with resectable primary tumors. VEGF, not bFGF, may serve as an independent prognosticator and a sensitive indicator for liver recurrence in patients with gastric carcinoma.

Are cytokines possible mediators of cancer cachexia

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.

Suppression of facilitative glucose transporter 1 mRNA can suppress tumor growth

We attempted to suppress glucose transporter 1 (GLUT1) expression by transfecting MKN45 cells with cDNA for antisense GLUT1. Glucose transport was significantly decreased in cells with antisense GLUT1 compared with wild-type cells or cells with vector alone. Suppression of GLUT1 mRNA resulted in a decreased number of cells in the S phase. This was accompanied by overexpression of p21 protein. Tumorigenicity in the nude mice injected with antisense GLUT1 expressing cells was significantly slower than in those with wild-type MKN45 cells. These results suggest that antisense GLUT1 mRNA inhibits tumor growth through a G(1) arrest and that expression of antisense GLUT1 mRNA via gene therapy can be used as a tool in the treatment of cancer.

Is D2 lymph node dissection necessary for early gastric cancer

BackgroundThe objective of this study was to clarify a survival benefit of D2 lymphadenectomy in patients with early gastric carcinoma (GC).MethodsA retrospective study was conducted to examine the incidence of metastasis to level 2 lymph nodes, the causes of postoperative death, and the mode of recurrence in 1041 patients who head early GC and underwent D2 lymphadenectomy with curative intent.ResultsPostoperative mortality occurred in 129 (12,4%) of 1041 patients, 6 patients (.6%) died of surgical complications 108 (10.2%) died of diseases other than cancer, and 16 (1.5%) died of recurrence. Hematogenous metastasis was the major mode of recurrence (56.3% of recurrences). The incidence of metastasis to level 2 nodes was 2.5% (26 of 1041 patients, 18 of whom were alive). Thus, the estimated survival benefit of radical lymphadenectomy for patients with early GC was calculated to be 1.7% (18 of 1041 patients).ConclusionsD2 lymphadenectomy in patients with early GC had little survival benefit because (1) metastasis to level 2 nodes was rare, (2) most causes of death were not related to the tumor, and (3) more than half the recurrences were hematogenous. Use of radical lymphadenectomy for early GC should be limited.The objective of this study was to clarify a survival benefit of D2 lymphadenectomy in patients with early gastric carcinoma (GC). A retrospective study was conducted to examine the incidence of metastasis to level 2 lymph nodes, the causes of postoperative death, and the mode of recurrence in 1041 patients who head early GC and underwent D2 lymphadenectomy with curative intent. Postoperative mortality occurred in 129 (12,4%) of 1041 patients, 6 patients (.6%) died of surgical complications 108 (10.2%) died of diseases other than cancer, and 16 (1.5%) died of recurrence. Hematogenous metastasis was the major mode of recurrence (56.3% of recurrences). The incidence of metastasis to level 2 nodes was 2.5% (26 of 1041 patients, 18 of whom were alive). Thus, the estimated survival benefit of radical lymphadenectomy for patients with early GC was calculated to be 1.7% (18 of 1041 patients). D2 lymphadenectomy in patients with early GC had little survival benefit because (1) metastasis to level 2 nodes was rare, (2) most causes of death were not related to the tumor, and (3) more than half the recurrences were hematogenous. Use of radical lymphadenectomy for early GC should be limited.

Insulin resistance in patients with cancer: relationships with tumor site, tumor stage, body-weight loss, acute-phase response, and energy expenditure.

We examined peripheral insulin sensitivity in 32 patients with cancer (17 with stomach cancer, 7 with colorectal cancer, and 8 with lung cancer) and 6 normal control subjects by the euglycemic hyperinsulinemic glucose clamp technique. The relationships between insulin resistance and tumor factors (type and stage), malnutrition, and inflammatory reaction were evaluated. Insulin sensitivity often was reduced in patients with cancer; however, the amount of glucose metabolized was not related to tumor site or stage. The decreased glucose uptake was negatively correlated with the acute-phase response but was not correlated with body-weight loss, serum albumin, or resting energy expenditure. Our results suggest that insulin resistance in cancer patients was not induced by malnutrition. Although the qualitative presence of tumor might be the major factor inducing insulin resistance, other factors such as inflammatory reactions might be involved in the development of insulin resistance.

Cyclooxygenase‐2 mRNA is up‐regulated in cirrhotic or chronic hepatitis liver adjacent to hepatocellular carcinoma

Background and Aim: Hepatocellular carcinoma (HCC) is unique in that its carcinogenesis is related to inflammatory changes and regenerative activities in the background liver. Although there are some data on cyclooxygenase (COX)‐2 expression in HCC by immunohistochemical studies, little is known about the possible role of COX‐2 in inducing hepatitis and/or carcinoma. To elucidate whether COX‐2 is involved in a part of these processes, we attempted to examine COX‐2 mRNA both in the adjacent non‐tumoral liver and in HCC.

An isolated dissecting aneurysm of the superior mesenteric artery : report of a case

We report herein the case of a 56-year-old man found to have an isolated dissecting aneurysm of the superior mesenteric artery (SMA) after he presented with a 3-day history of postprandial epigastralgia of sudden onset. An echogram showed marked dilatation of the SMA and a high level of peripheral echoes in a linear fashion within its lumen. A thin-section contrast enhanced computed tomography revealed a thin flap, separating two distinct well-enhanced lumina. Angiography confirmed the presence of a localized dissecting aneurysm of the SMA. The patient was treated conservatively and has since been followed up as an outpatient. Following the presentation of this case, the problems regarding the diagnosis and management of this rare disease are discussed based on a review of the literature.

Expression of nitric oxide synthase in gastric cancer

The expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in samples of normal gastric mucosa and gastric cancer were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and semi-quantitative Western blot. In normal gastric mucosa, eNOS protein was found in all samples examined (mean, 70.2 +/- 60.1), relative to a standard protein. In gastric cancer specimens, eNOS protein was also detected in all samples, but the quantity (86.5 +/- 76.6) was not different from that found in samples of normal mucosa. The quantity of eNOS in gastric cancer tissues was negatively correlated with serosal invasion. iNbS mRNA, detected in nine of 18 cases, was slightly related to massive lymph node metastasis (n1-3 vs. n4). Neither tumor necrosis factor alpha (TNF-alpha) mRNA nor interleukin-6 (IL-6) mRNA was related to the expression of iNOS mRNA. These results suggest that iNOS not eNOS plays a role in gastric cancer tumor extension, but iNOS mRNA appears not to be induced by either TNF-alpha or IL-6.