Heterogeneous prognoses of patients with tumors invaded within muscularis propria according to tumor depth in the layers of the muscularis propria

Background  The muscularis propria of the stomach is histologically divided into three layers; namely, the innermost oblique, the inner circular, and the outer longitudinal layers. In patients with gastric cancer the depth of tumor invasion has been reported to correlate with lymph node metastasis and prognosis. However, it is unclear whether the depth of tumor invasion in the muscularis propria has an effect on lymph node metastasis and prognosis. Methods  Fifty-nine gastric cancer patients with muscularis propria invasion were analyzed retrospectively. These patients were divided into two groups, the inner group, with invasion up to the inner circular layer; and the outer group, with invasion beyond the inner circular layer. The relationships between tumor invasion and clinicopathological factors and survival were evaluated. Results  Of the 59 patients, 34 were classified as the inner group, and 25 were classified as the outer group. The inner group had a significantly lower probability of lymph node metastasis (P = 0.0053) and a significantly better overall cancer-specific survival (P = 0.017) than the outer group. Conclusion  Gastric cancers with muscularis propria invasion had heterogeneous prognoses according to the tumor depth in the muscularis propria layers.     

Tertiapin, a selective IKACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation.

It is well known that vagal nerve tone plays a crucial role in atrial fibrillation (AF). Acetylcholine-activated potassium current (IKACh) mediates much of the cardiac response to vagal nerve stimulation (VNS), but the contribution of IKACh to AF remains unknown. We investigated the role of the IKACh channel in canine AF models using tertiapin, a selective IKACh blocker. Tertiapin (4-41 nmol kg(-1), i.v.) terminated AF in the canine VNS-induced and aconitine-induced AF models. The muscarinic M-receptor antagonist AF-DX-116 terminated AF in these models, but the adenosine receptor antagonist DPCPX had no effect. Thus it is likely that IKACh activation via the M-receptor has a crucial role in both models. Tertiapin (12 nmol kg(-1), i.v.) preferentially prolonged the atrial effective refractory period (ERP) but not the ventricular ERP under the VNS condition. This peptide (4-41 nmol kg(-1), i.v.) did not affect PQ, QRS and corrected QT intervals in isoflurane-anaesthetised dogs. These results suggest that a selective IKACh blocker is effective in canine AF models without affecting ventricular repolarisation, and might be useful for the treatment of patients with AF.     

Resection versus palliation: treatment of stage III and IVA carcinomas of the pancreas employing intraoperative radiation

Abstract Whether advanced pancreatic carcinomas should be surgically removed has been a basic issue because performing an extended resection is futile if it has only a minimum impact on survival. The purpose of this study was to compare the results of pancreatic resection with those of a bypass operation for patients with stage III or IVA pancreatic carcinomas while applying intraoperative radiation therapy (IORT). The therapeutic outcomes of 132 patients who had received IORT for stage III or IVA carcinoma were analyzed retrospectively. The patients were divided into two groups: Group 1 included 68 patients with locally unresectable tumors who underwent a bypass operation; group 2 included 64 patients with resectable tumors who underwent pancreatic resection. Postoperative external beam radiation therapy (EBRT) was also delivered to 90 patients. Multivariate analysis indicated that strong independent predictors of increased survival were EBRT for group 1 (p < 0.0001) and R0 resection for group 2 (p = 0.017). Twenty patients who had been subjected to R0 resection showed the best survival, with a 3-year survival rate of 45%. The survival of group 1 patients receiving EBRT (n = 47) nearly equaled that of group 2 patients undergoing R1 or R2 resection (n = 44) (p = 0.72); but group 1 patients with tumors ≤ 6 cm (n = 31) had a better survival rate than group 2 patients with tumors > 3 cm (n = 28) (p = 0.03). We concluded that postoperative EBRT is essential for improving the survival outcome, even after administering IORT. Patients with stage III lesions undergoing an R0 resection and receiving IORT demonstrated an excellent 3-year survival. A bypass operation plus IORT in combination with EBRT is preferred over IORT used as an adjuvant to R1 or R2 resection. Electronic Publication     

A signal detection approach to the combined effects of work stressors on alcohol consumption

OBJECTIVE: To test the relationship between work stress and alcohol consumption and the efficacy of signal detection analysis in a work stress-alcohol consumption study. METHOD: The study was part of a Work Site Health Project, which included a stress reduction program, at a manufacturing company in Osaka, Japan. The study design was a cross-sectional survey. The participants were Japanese male whitecollar workers (N = 457; 30 to 50 years old) in the head administrative office of a large manufacturing company. Measurements consisted of demographic variables of the workers (age, marital status, manner of living and Type A personality), work stress measures, working hours and alcohol consumption. RESULTS: Of eight independent variables, six significant predictors of heavy alcohol consumption were identified in the first signal detection analysis. Of these six variables, job demand and skill discretion were work-stress-related measures. In the second multiple regression analysis, skill discretion and job demand were significant predictors of alcohol consumption among the workers in two of the seven subgroups categorized by the first signal detection analysis. CONCLUSIONS: It was revealed that work stress did relate to alcohol consumption. However, the effect of the work stress upon alcohol consumption was limited to specific types of workers with multiple specific attributes. It was also inferred that the signal detection approach is an effective approach to the work stress alcohol consumption relationship.     

Evaluation of the non-effective cases of irresectable multiple liver metastasis of colorectal cancer receiving hepatic arterial infusion chemotherapy

PURPOSE: Hepatic arterial infusion (HAI) chemotherapy is one of the suitable therapies for irresectable multiple liver metastasis from colorectal cancer, but in nearly half of such cases the therapy does not prove effective. Our goal is to clarify the characteristics of non-effective cases. METHODS: 84 cases with irresectable multiple liver metastasis from colorectal cancer were investigated clinicopathologically, and were divided into two groups; non-effective cases (N = 38) and effective cases (N = 46). All cases received continuous arterial infusion chemotherapy using 5-FU according to the following regimen; 5-FU (500 mg/day) was infused in the hepatic artery over 7 or 10 days for induction, and the infusion was maintained (250 mg/day) to the hepatic artery for 7 days every other week after the induction therapy. We evaluated the efficacy of HAI chemotherapy by Computed Tomography. RESULTS: There were statistically significant differences among these two groups in histological types. Rates of the histological type of non-effective cases were well (31.6%), mod (57.9%), por (7.9%), and muc (2.6%), respectively. Those of the effective cases were well (63.0%), mod (34.8%), por (0%), and muc (2.2%), respectively. In non-effective cases, 16 out of 38 cases (42.1%) had extra-hepatic metastasis. On the other hand, only 3 out of 46 cases (6.5%) had such metastasis in effective cases. CONCLUSION: There were non-well type cancers and extra-hepatic metastasis in a large number of non-effective cases. We thought that those cases were basically high-grade malignancies, so these were the limits of HAI chemotherapy for irresectable multiple liver metastasis of colorectal cancers.     

A signal detection approach to patient-doctor communication and doctor-shopping behaviour among Japanese patients

OBJECTIVES: As one of the factors related to doctor-shopping behaviour (i.e. consulting multiple doctors with regard to the same illness episode), very little has been revealed about the role of doctor explanation. We examined therefore the association between doctor explanation and doctor-shopping behaviour. METHODS: The subjects were internist-patient pairs in Japan. Signal detection analysis (SDA) was used for the data analysis. RESULTS: Of the 303 patients, 84 patients engaged in doctor shopping (27.7%). The following results were obtained: (1) of the 19 relevant variables, the 'level of doctor explanation: treatment' was the most significant predictor of doctor-shopping behaviour (P < 0.01), and (2) with regard to their subjective evaluations of the sufficiency of their explanations about treatment or testing, the evaluations of the doctors, rather than those of the patient, were significant predictors of doctor-shopping behaviour. CONCLUSIONS: These results imply the following: (1) a patient's inability to understand a doctor's explanation about treatment, which results from a large gap between the perceptions of the patient and those of the doctor, is the most significant predictor of doctor-shopping behaviour, and (2) in the context of favourable patient-doctor interactions, when doctors feel their explanations are insufficient, they may be able to prevent doctor-shopping behaviour by providing relatively thorough explanations about treatment.     

Effect of Conclevan on endurance capacity in mice

The purpose of this study was to clarify the anti-fatigue effect of Conclevan, which is mainly composed of liver hydrolysate, via a forced swimming test using mice. Conclevan was administered to mice for 6 weeks, and a forced swimming test was conducted to measure swimming time. After six weeks, the blood ammonia and glutamine concentrations were measured. In the Conclevan administration group, swimming time increased significantly compared to the swimming control group. In the swimming control group, an increase in blood ammonia and a decrease in blood glutamine were observed, relative to the non-swimming control group. In the Conclevan administration group, the increased blood ammonia and decreased blood glutamine induced by swimming were significantly reduced, compared to the swimming control group. The mRNA expression levels of the hepatic enzymes of the urea cycle (carbamoyl-phosphate synthetase, argininosuccinate synthetase, and arginase) and glutamine synthesis (glutamate dehydrogenase and glutamine synthetase) were significantly increased in the Conclevan administration group, compared to the swimming control group. The results of this study demonstrated the anti-fatigue effects of Conclevan. This product may inhibit an increase in the fatigue-inducing ammonia concentration in the blood by increasing the expression of hepatic enzymes, which convert ammonia to urea, leading to increased swimming time. In addition, Conclevan may prolong swimming time by increasing the hepatic synthesis of glutamine, which is an important amino acid for supplying energy in muscles.     

Consumption of a high-fat diet during pregnancy decreases the activity of cytochrome P450 3a in the livers of offspring

Recent studies have reported that a high-fat diet during pregnancy exerts various effects on the foetus and newborn. The purpose of this study was to clarify the effects of a high-fat diet during pregnancy on the activity of hepatic cytochrome P450 (Cyp) 3a in offspring in mice. The protein expression level and activity of Cyp3a in the livers of 6-week-old mice born to mothers that were given a high-fat diet during pregnancy (HF group) decreased significantly compared with the Control group. Triazolam, which is a substrate of Cyp3a, was intraperitoneally administered to the mice in the HF group. Compared with the Control group, an increase in the area under the plasma concentration-time curve and a decrease in total clearance were observed in the HF group. The hepatic constitutive androstane receptor (CAR) mRNA expression level in the HF group was significantly lower than that in the Control group. An increase in phosphorylation of extracellular signal-regulated kinase (ERK) was also observed in the HF group. The results of this study revealed that a high-fat diet during pregnancy causes an increase in ERK phosphorylation and a decrease in the expression level of CAR in the livers of offspring, which leads to decreased Cyp3a expression and activity. The results suggest that individual differences in pharmacokinetics may not only be expressed by genetic predisposition but also by a mother's living environment during pregnancy.