Gastric resection in the aged (≥ 80 years) with gastric carcinoma: a multivariate analysis of prognostic factors

Background : The incidence of gastric neoplasm is increasing in the elderly population. Therefore, a rational method of treatment for gastric cancer in the elderly should be constituted to improve the survival. The purpose of the present study was to clarify whether the patient’s age is an independent prognostic factor and to determine clinicopathological characteristics in the elderly. Methods : Curative resection of gastric cancer was carried out on 601 patients who were 40 years or older. They were divided into the following two groups: younger patients (between 40 and 79 years old) and elderly patients (80 years or older). The clinicopathologic features of these patients were reviewed retrospectively and multivariate analysis was carried out. Results : The distinguishing features of gastric cancer in the elderly patients were intestinal and mixed types of cancer, distal third stomach dominancy in the tumour location, advanced stage of disease, and a low rate of extensive lymph node dissection (D3 or more). Regarding the recurrence site, the liver was the dominant site in the elderly group (25.3% in the younger group vs 54.5% in the elderly group). The 10‐year disease‐free survival rate of the elderly group was 53.2%, which was significantly worse than that (79.9%) of the younger patients (P = 0.0004). In multivariate analysis, an age of ≥ 80 years is an independent prognostic factor, as well as stage, depth of tumour invasion, lymph node metastasis, scirrhous carcinoma, and blood transfusion. Conclusions : Results indicate that gastric cancer in elderly patients has a poorer prognosis than that in younger patients.     

Impaired nitric oxide-independent dilation of renal afferent arterioles in spontaneously hypertensive rats.

Sustained hypertension alters vasomotor regulation in various vascular beds. We studied whether nitric oxide (NO)-dependent and NO-independent vasodilator mechanisms are altered in renal microvessels in hypertension. To directly visualize the renal microcirculation, the isolated perfused hydronephrotic rat kidney model was used. After pretreatment with indomethacin (100 micromol/l), afferent arterioles were constricted by norepinephrine (NE) or by increasing renal arterial pressure (i.e., myogenic constriction; from 80 to 180 mmHg). Acetylcholine (ACH) was then added, and the renal microvascular response was assessed by computer-assisted video image analysis. A similar protocol was conducted in the presence of nitro-L-arginine methylester (L-NAME; 100 micromol/l). During NE constriction, ACH caused dose-dependent and sustained vasodilation of the afferent arteriole, similar in magnitude in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the presence of L-NAME, ACH (0.01-1 micromol/l) elicited only transient dilation, and the degree of vasodilation was very low in SHR. During myogenic constriction, afferent arterioles from WKY and SHR kidneys responded to ACH with only transient vasodilation, which was unaffected by NO inhibition; the transient vasodilative responses elicited by ACH (0.1-1 micromol/l) were smaller in SHR than in WKY. In conclusion, ACH has both sustained and transient vasodilative effects on the afferent arteriole. Sustained vasodilation is attributed to NO generation, which is similar in WKY and SHR. In contrast, transient vasodilation, mediated by NO-independent vasodilator factors, is impaired in SHR. Deranged vasodilatory mechanisms in hypertension may disturb the renal microcirculation, which may result in renal injury.     

Antitumor activity and pharmacokinetics of a morpholino-anthracycline derivative (KRN8602) against human breast carcinoma xenografts serially transplanted into nude mice

The antitumor activity and pharmacokinetics of (7R, 8S, 10S)-10-((3-deamino- 3-(4-morpholino)-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-8- ethyl- 7,8,9,10-tetrahydro-1,6,7,8,11-pentahydroxy-5,12-naphthacenedione hydrochloride (KRN8602) were evaluated using five human breast carcinoma xenografts in nude mice. The maximum non-toxic dose of KRN8602 was 2 mg/kg by q4d x 3 intraperitoneal and peroral administration. KRN8602 showed significant antitumor activity against MX-1, which is less sensitive to adriamycin, with the chemotherapeutic indices of 13.0 for po administration and 9.5 for ip injection. Although KRN8602 also inhibited the growth of T-61 significantly, the antitumor activity of this agent against the other three breast carcinoma xenografts was limited. To elucidate this discrepancy, pharmacokinetic analysis and MTT assay were conducted using the KRN8602-sensitive MX-1 and KRN8602-insensitive R-27. While no differences were observed in the area under the curve and the peak concentration of KRN8602 for each tumor, a difference in the sensitivity of the tumor strains was obvious in MTT assay. The efficacy of this agent seemed to depend on the sensitivity of each type of tumor cell rather than the concentration of agent in tumor tissues. If it were possible to select patients with sensitive tumor cells to this agent by the MTT assay, the phase II trial might be completed within a short period by reducing the number of studied patients.     

Treatment of severe infections in hematologic malignancies with piperacillin sodium

Combination antibiotic therapies using piperacillin (PIPC) were evaluated in 60 episodes of severe infections in 38 neutropenic patients with hematologic malignancies. 1. The overall efficacy rate was 46.7%. Efficacy rates were 30% in patients with pneumonia, 60% in patients with sepsis and 50% in patients with suspected sepsis in which causative organisms were not identified. 2. Eradication rates were 44.4% for Gram-negative bacilli, 50% for Pseudomonas aeruginosa and 22.2% for Gram-positive cocci. 3. Efficacy rates were 33.3% in patients with initial count of neutrophil less than 100/microliters, 60% in patients with those 100 to 500/microliters and 66.7% in patients with those higher than 500/microliters. Initial neutrophil counts correlated well with efficacies of PIPC on severe infection in patients with hematologic malignancies. 4. Mild increases of transaminase were observed in 2 cases. From these results it is concluded that PIPC is one of the most important antibiotics in the treatment of severe infections in neutropenic patients with hematologic malignancies.     

A calculation of percutaneous drug absorption--II. Computation results

The numerical computation data of percutaneous drug absorption are reported in this article. When the concentration of a drug in the uppermost epidermis can be considered unchanged, more than 50, 75, 90, 95 and 99% of the amount saturated at quasi-steady-state are accumulated after the respective time intervals of 0.5, 1, 2, 3 and 4 times the lag-time. After the ointment removal, the drug flux from the skin becomes linear on a semilogarithmic scale and the elimination rate constant is not dependent on the initial condition.     

MIG-17/ADAMTS controls cell migration by recruiting nidogen to the basement membrane in C. elegans

Mutations in the a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family of secreted proteases cause diseases linked to ECM abnormalities. However, the mechanisms by which these enzymes modulate the ECM during development are mostly unexplored. The Caenorhabditis elegans MIG-17/ADAMTS protein is secreted from body wall muscle cells and localizes to the basement membrane (BM) of the developing gonad where it controls directional migration of gonadal leader cells. Here we show that specific amino acid changes in the ECM proteins fibulin-1C (FBL-1C) and type IV collagen (LET-2) result in bypass of the requirement for MIG-17 activity in gonadal leader cell migration in a nidogen (NID-1)-dependent and -independent manner, respectively. The MIG-17, FBL-1C and LET-2 activities are required for proper accumulation of NID-1 at the gonadal BM. However, mutant FBL-1C or LET-2 in the absence of MIG-17 promotes NID-1 localization. Furthermore, overexpression of NID-1 in mig-17 mutants substantially rescues leader cell migration defects. These results suggest that functional interactions among BM molecules are important for MIG-17 control of gonadal leader cell migration. We propose that FBL-1C and LET-2 act downstream of MIG-17-dependent proteolysis to recruit NID-1 and that LET-2 also activates a NID-1-independent pathway, thereby inducing the remodeling of the BM required for directional control of leader cell migration.     

Occurrence of breast cancer, renal cancer and multiple myeloma in a Nagasaki atomic bomb survivor

A 60-year-old female, who was exposed to the Nagasaki atomic bomb at 18 years old, had renal cancer and subsequently was found to have multiple myeloma (IgG kappa). She underwent the left mastectomy for breast cancer at 43 years old but was not given chemotherapy and radiotherapy. The karyotype of bone marrow cells was 46, XX. The estimated radiation dose was under 10 rads. While the effect of such a low-dose of radiation is considered to be almost negligible, there would be a possibility that in this case the risk of carcinogenesis was enhanced as her age advanced.     

Endoscopic treatment of early cancer of the large bowel

The indication for endoscopic polypectomy as treatment of early cancer of the large bowel was studied in 766 polypectomized specimens which had been obtained over a period of 11 years (1973 to 1983) at the Cancer Institute Hospital, Tokyo and the following results were obtained. There were 15 lesions with remaining cancer at the polypectomy site. Thirteen cases of them were invasive cancer with massive submucosal invasion which could not be removed completely by polypectomy. There were 3 recurrent cancers: one of them had remained in the mucosal membrane, but the other two had developed into advanced cancer. The polypectomized specimens of these advanced cancers were diagnosed as invasive cancer with marked mucus production. In both cases there was massive submucosal invasion. Strict follow-up with short intervals is required in order to detect local recurrent cancer if prompt operation cannot be done in those cases which show invasive cancer. Endoscopic polypectomy is not indicated for lesions measuring larger than 18 mm in the largest diameter because there often occurred deep ulcer (Ul-III and IV) which indicated that colonic wall was liable to perforation.