Prognostic significance of loss of heterozygosity on chromosome 9p21–22 in human esophageal cancer

Background Deletions involving chromosome 9p21, on which the tumor suppressor genep16/MTS1 is located, have been noted in esophageal cancer. We investigated the relationship between the deletion of chromosome 9p21–22 and the clinical features of esophageal cancer. Methods We examined the loss of heterozygosity (LOH) on chromosome 9p21–22 in 56 esophageal cancers using polymerase chain reaction (PCR) analysis and 2 microsatellite markers (RPS6 and IFNA). Results In 18 out of 50 informative cases (36%), LOH had occurred at 1 or 2 loci on chromosome 9p21–22. We found no relationship between LOH on chromosome 9p21–22 and patient sex, age tumor length, location, histologic differentiation, depth of tumor invasion, the extent of lymph node metastasis, histologic stage, or curability. Among 35 patients without an absolute noncurative resection, the mean survival of 11 patients with LOH on chromosome 9p21–22 was 19.3 months, compared with 42.3 months for 24 patients with a normal allele; thus, the survival rate of those with LOH was significantly lower than that of patients without LOH on chromosome 9p21–22 (log-rank test;P=0.03). Conclusion These data suggest that LOH on chromosome 9p21–22, on which the cell-cycle regulatorp16/MTS1 gene is located, may be related to cancer development, and probably can serve as a clinical marker for evaluating a patient's prognosis.     

Tumor lysis syndrome in widely metastatic small-cell lung cancer

Tumor lysis syndrome is a rare complication of nonhematologic malignancies that results from massive necrosis of neoplastic cells after chemotherapy. This syndrome consists of life-threatening metabolic derangements, including severe hyperphosphatemia, hyperkalemia, hyperuricemia, and hypocalcemia, and may result in renal failure and death if not recognized early and treated appropriately. We report a case of tumor lysis syndrome after induction chemotherapy in a patient with widely metastatic smallcell lung cancer. This case emphasizes the importance of awareness and early treatment of this syndrome.     

Macroscopic features at the deepest site of tumor penetration predicting liver metastases of colorectal cancer

Liver metastasis is the gravest prognostic factor in colorectal cancer. To identify a reliable indicator for liver metastasis, we evaluated macroscopic features and seven established histopathological findings at the cut section containing the deepest penetration using univariate and multivariate analyses in 417 colorectal cancers. Macroscopic features were divided into two types, streak type and non-streak type, according to the presence or absence of white streak(s) at the advancing margin of tumor invasion. Streak type was observed in 109 patients (26%). The frequency of liver metastasis in streak type tumors (56%) was significantly higher than that in non-streak type tumors (13%) (p < 0.001). The white streak corresponded histologically with cancer cells showing focal dedifferentiation with marked stromal and perivascular fibrosis extending towards the serosa or adventitia. In 343 curatively treated patients, univariate analysis showed that recurrent liver metastasis was significantly associated with macroscopic features, venous invasion, focal dedifferentiation and lymph node metastasis. Multivariate analysis disclosed that macroscopic features and lymph node metastasis were independent indicators of liver metastasis. These macroscopic features, corresponding histologically to stromal behavior against invading cancer cells, are a simple and useful indicator of liver metastasis of colorectal cancer.      

Steno-Occlusive Changes in the External Carotid System in Moyamoya Disease

To evaluate the steno-occlusive changes in the external carotid system in moyamoya disease, cerebral angiograms of 39 moyamoya patients were retrospectively reviewed. There were 26 females and 13 males, age ranged from 4 to 62 years with a mean of 26 years. Initial symptoms were ischaemia in 27 patients, haemorrhage in 9, and none in 3. Stenosis, occlusion, and dilatation in the external carotid system were analysed angiographically. No stenosis or occlusion of the superficial temporal artery, middle meningeal artery, or occipital artery was observed in either preoperative or postoperative follow-up angiograms in any patients. Steno-occlusive changes do not occur in the external carotid system, but are confined in the internal carotid system in moyamoya disease.     

Tissue oxygen pressure during prolonged ischemia of the liver

BACKGROUND: The potential role of hepatovenous back-perfusion in maintaining organ viability of the inflow-occluded liver has been reported with respect to aspects of tissue perfusion and energy metabolism. In the present study, the physiological differences between liver ischemia induced by portal triad clamping (PTC) and that induced by total hepatic vascular exclusion (THVE) were investigated in a porcine disease model, with special reference to changes in tissue oxygen pressure (PtO(2)) of the liver. MATERIALS AND METHODS: Twelve female pigs were used for induction of 60 min of normothermic liver ischemia. They were assigned to two groups: a PTC group (n = 6) and a THVE group (n = 6). PtO(2) was measured before, during, and after the ischemic period at two different points in the middle lobe: on the central side close to the hepatovenous confluence and on the peripheral side close to the gallbladder bed. RESULTS: Although central PtO(2) decreased during ischemia in both groups, PTC group values at 40 and 60 min of ischemia remained significantly higher than THVE group values (60 +/- 28 and 42 +/- 21 mmHg vs 11 +/- 5 and 13 +/- 3 mmHg, respectively; means +/- SD). Peripheral PtO(2) in the PTC group during ischemia was low in comparison to corresponding central PtO(2) values. CONCLUSION: Oxygen supply to the tissue via hepatovenous reflux may contribute to maintaining organ viability under prolonged inflow occlusion of the liver.     

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     

Biological basis of anxiety disorders and serotonergic anxiolytics]

Selective serotonin reuptake inhibitors (SSRIs) have wide indications for the treatment of anxiety disorders, including panic disorder, generalized anxiety disorder, posttraumatic stress disorder, obsessive-compulsive disorder and social anxiety disorder in addition to depression. Until recently, no animal model has been available for screening the anxiolytic effect of SSRIs and studying its mechanism of action. We have investigated the relationship between serotonin neurotransmission and anxiety using conditioned fear stress (CFS), an animal model of anxiety. CFS increased serotonin neurotransmission in the medial prefrontal cortex and amygdala. In behavioral pharmacological studies, SSRIs, serotonin1A agonists and monoamine oxidase inhibitors, which are assumed to facilitate serotonin neurotransmission, decreased conditioned freezing, an index of anxiety or fear, in CFS. In vivo microdialysis studies showed that serotonin neurotransmission in the medial prefrontal cortex increased after recovery from the freezing behavior. Microinjection of SSRI to the basolateral nucleus of the amygdala reduced conditioned freezing, indicating that the amygdala is one of target brain sites of anxiolytic action of SSRIs. Furthermore, CFS-induced c-Fos expression in the basolateral nucleus of the amygdala was reduced by SSRI pretreatment. Taken together, recent studies indicate that facilitation of brain serotonin neurotransmission decreases anxiety in agreement with the clinical evidence.