Gastric resection in the aged (> or = 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 dominance 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 > or = 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.     

Metabolism of the alpha,beta-unsaturated ketones, chalcone and trans-4-phenyl-3-buten-2-one, by rat liver microsomes and estrogenic activity of the metabolites.

When chalcone and trans-4-phenyl-3-buten-2-one (PBO) were incubated with liver microsomes of untreated rats in the presence of NADPH, 4-hydroxychalcone and trans-4-(4-hydroxyphenyl)-3-buten-2-one (4-OH-PBO), respectively, were formed as major metabolites. Two minor metabolites of chalcone, 4'-hydroxychalcone and 2-hydroxychalcone, were also observed. The oxidase activity affording 4-hydroxychalcone was inhibited by SKF 525-A, disulfiram, ketoconazole, and alpha-naphthoflavone. The oxidase activities leading to 4-hydroxychalcone and 4'-hydroxychalcone were enhanced in liver microsomes of 3-methylcholanthrene- and phenobarbital-treated rats, respectively. The activity generating 2-hydroxychalcone was enhanced in liver microsomes of 3-methylcholanthrene- and dexamethasone-treated rats. The oxidation of PBO to 4-OH-PBO was inhibited by SKF 525-A, ketoconazole, disulfiram, and sulfaphenazole. This activity was enhanced in liver microsomes of 3-methylcholanthrene-, acetone- and phenobarbital-treated rats. 4-Hydroxylation, 4'-hydroxylation, and 2-hydroxylation of chalcone were catalyzed by rat recombinant cytochrome P450 1A1, 1A2, and 2C6; by 1A1 and 2C6; and by 1A1 and 3A1, respectively. PBO was oxidized by cytochrome P450 1A1, 1A2, 2C6, and 2E1. Chalcone and PBO were negative in an estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7. However, 4-hydroxychalcone, 2-hydroxychalcone, 4'-hydroxychalcone, and 4-OH-PBO exhibited estrogenic activity.     

A case of recurrent cholangitis after bile duct injury during laparoscopic cholecystectomy: Value of scintigraphy with Tc-99m GSA and hepatobiliary scintigraphy for indication of lobectomy

A 39-year-old woman with acute cholecystitis and gallstones underwent laparoscopic cholecystectomy. She suffered from recurrent episodes of cholangitis due to injury of the major bile ducts during laparoscopic cholecystectomy. Hepatobiliary scintigraphy with Tc-99m Sn-N-pyridoxyl-5-methyltryptophan was performed. Although normal bile excretion was found from the left hepatic duct to the percutaneous transhepatic biliary drainage (PTBD) tube, excretion from the right hepatic lobe was prolonged. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin demonstrated atrophy of the right hepatic lobe and enlargement of the left hepatic lobe. Cholangiography via the PTBD tube revealed complete obstruction of the left hepatico-jejunal anastomosis and could not enhance the right intrahepatic bile duct. A right hepatic lobectomy was performed because of the atrophy, glissonitis and the absence of an appropriate bile duct for reconstruction. Postoperatively she was active and exhibited no evidence of recurrent cholangitis.     

Induction of apoptosis and cell cycle arrest by imexon in human pancreatic cancer cell lines

Imexon is an aziridine-containing small molecule currently in Phase I clinical trials. This agent has been shown to bind to thiols and increase intracellular oxidants, inducing apoptosis in hematologic cancer cells. Pancreatic cancers are known to be sensitive to oxidation, suggesting this disease may be an appropriate target for this agent. The current report examines the activity of imexon in pancreatic cells. Imexon induced concentration-dependent and time-dependent apoptosis in a panel of six human pancreatic carcinoma cell (PCC) lines. The mean IC₅₀ (SD) for growth inhibition by the SRB assay was 200 (101) µM for a 48 h exposure with a range of 64–358 µM. Cell killing was schedule-dependent, favoring exposure times ≥48 h. Imexon-treated MiaPaCa-2 cells underwent non-lethal growth arrest following exposure to concentrations ≤200 µM for 48 h. When concentrations were increased to 300 µM for ≥48 h, the MiaPaCa-2 cells arrested in G₂ phase and activated caspases 3, 8, and 9 were detected. After a 72 h exposure to the IC₈₀ concentration of imexon, cells exhibited a loss of mitochondrial membrane potential detected by CMXRos staining. However, there was no loss of reduced cellular thiols unless very high concentrations of ≥400 µM were used. In contrast, reactive oxygen species (ROS) were elevated in a dose-dependent fashion, starting at very low imexon concentrations. Imexon also significantly inhibited MiaPaCa-2 tumor growth in SCID mice at 100 mg/kg/d for 9 d. The tumor growth inhibition (% T/C) was 27% of control, and the tumor growth delay was 21 d, indicating an active agent by NCI standards. The levels of imexon that are cytotoxic in human PCC’s are achievable based on the preliminary results of the ongoing Phase I trial. Imexon appears to be active against PCCs in vitro and has an entirely novel mechanism of action involving G₂ arrest, accumulation of ROS, and the induction of apoptosis.     

An association between plasma levels of 8-isoprostane and alcohol drinking habits in Japanese volunteers]

Lipid peroxidation and oxidative stress may play a certain role in the pathogenesis of pressure-induced atherosclerosis, and alcohol related diseases. Recently, 8-isoprostane in biological fluids has been reported to be a reliable marker for lipid peroxidation and oxidative stress in vivo. In the present study, we developed an ELISA method for 8-isoprostane which has high sensitivity, intra- and inter-assay reproducibility and wide dynamic assay range. Using this method, we examined the effects of drinking and smoking habits on plasma levels of 8-isoprostane in healthy subjects. A total of 157 apparently healthy volunteers was assayed for plasma 8-isoprostane. Subjects were divided into three groups according to their alcohol consumption. Group I is non- or few-drinkers, Group II includes subjects who drink once or twice a week, and subjects of Group III intake 3 to 5 times a week or almost every day. In addition, the same population was divided into two groups, 96 non-smokers and 61 smokers. Plasma 8-isoprostane was extracted with ODS gel followed by NH2 Sep-Pak column. The 8-isoprostane fractions thus separated were assayed by a commercial ELISA kit (Cayman Chemical). The plasma 8-isoprostane was estimated to be 20.9 +/- 93 pg/ml in a total of 157 volunteers (83 male, 74 female). The plasma 8-isoprostane levels were elevated in the Group III (26.6 +/- 9.5 pg/ml) compared with Group I (20.3 +/- 6.1 pg/mL, p<0.0001) and Group II (20.9 +/- 5.7 pg/ml, p<0.001). Significant increase of the plasma 8-isoprostane was observed only in habitual drinkers of females, but not in those of males. On the other hand, no significant difference of the plasma 8-isoprostane levels were observed between non-smokers (21.5 +/- 7.3 pg/ml) and smokers (22.8 +/- 7.4 pg/ml, p>0.05). We suppose that plasma 8-isoprostane may increase in the habitual drinkers due to the oxidization stress induced by alcohol intake, and it may become a useful marker to estimate drinking habit     

Impact of screening survey of gastric cancer on clinicopathological features and survival: retrospective study at a single institution

BACKGROUND: Detection of gastric cancer in an early stage is important to improve the prognosis of patients with gastric cancer. This study compared the clinicopathologic characteristics and surgical results in patients with asymptomatic gastric cancer detected by a screening program with those of patients with symptomatic cancer. The efficacy of 2 screening methods (barium meal and endoscopy) was also compared. METHODS: The subjects included 196 patients with asymptomatic gastric cancer detected by screening (screening group) and 612 patients with symptomatic gastric cancer (nonscreening group) treated from 1979 to 1997. The screening group was subdivided into the barium meal study group (n = 150) and the endoscopic study group (n = 46). RESULTS: The incidences of early gastric cancer and 5-year survival rates between the screening and nonscreening groups were 77% versus 29% (P <.0001) and 81% versus 44% (P <.0001), respectively. The endoscopic study appeared to be able to detect smaller gastric cancer in an earlier stage compared with the barium meal study, although no statistical differences in survival rate were noted between these 2 screening methods. CONCLUSIONS: Screening plays an important role in detecting gastric cancer in an early stage and in potentially reducing death attributable to gastric cancer. Endoscopic screening is recommended as the best screening method.     

New‐onset fulminant type 1 diabetes after severe acute respiratory syndrome coronavirus 2 vaccination: A case report

Fulminant type 1 diabetes is characterized by a rapid progression of insulin deficiency triggered by viral infection. Here, we report a case of a 45‐year‐old Japanese woman with fulminant type 1 diabetes that developed 8 days after receiving messenger ribonucleic acid vaccine against severe acute respiratory syndrome coronavirus 2. She had been healthy and had no symptoms suggestive of viral infection before the vaccination. Laboratory tests showed exhaustion of insulin secretion and negative results for islet autoantibodies. Human leukocyte antigen genotype analysis showed the DRB1*04:05 and DQB1*04:01 alleles. This is the first case report of new‐onset fulminant type 1 diabetes after severe acute respiratory syndrome coronavirus 2 vaccination, and suggests that a severe acute respiratory syndrome coronavirus 2 vaccine might trigger the onset of fulminant type 1 diabetes in susceptible individuals. However, a causal relationship remains to be identified, and further studies are required to determine the incidence of such cases.     

刺人参甙Q和R的分离与结构鉴定

从刺人参叶中分离并鉴定了2种新甙,丝石竹皂甙元-3-O-β-D呲喃葡萄糖基-28-O-α-L-呲喃鼠李糖基(1→4)-β-D-呲喃葡萄糖基(1→6)-β-D-呲喃葡萄糖甙和3β-羟基羽扇豆-20(29)-烯-23-醛-28-酸-3-O-β-D-呲喃葡萄糖基-28-O-α-L-呲喃鼠李糖基(1→4)-β-D-呲喃葡萄糖基(1→6)-β-D-呲喃葡萄糖甙。     

Visualization of the photodegradation of a therapeutic drug by chemometric-assisted fluorescence spectroscopy

The fluorescence spectral fingerprint, also known as the excitation-emission matrix (EEM), is used to assess and visualize therapeutic drug photodegradation in combination with chemometrics. Examination of EEM-parallel factor analysis (PARAFAC) data showed that an individual component was easily separated from a mixture of photogenerated products of a heterocyclic pharmacophore, in this case, phenothiazine drugs (PTZs). Detailed investigations of both structure–EEM relationships and kinetics revealed that the components extracted from EEM–PARAFAC could be quantitatively attributed to such photogenerated products as phenothiazine sulfoxide and carbazole derivatives. EEM in combination with principal component analysis (PCA) could be used as a mapping tool to visualize information of the photodegradation process of PTZs. We also assessed the photostability of various types of PTZs containing side chains by using validated EEM–PARAFAC methodology.

Drug quality and assurance changes with time under the influence of a variety of environmental factors, such as light, temperature, and moisture.