A prediction of hospital mortality after surgical treatment for esophageal cancer

A series of 100 patients with thoracic esophageal cancer who underwent subtotal esophagectomy through a right thoractomy between 1985 and 1989, were statistically analyzed to assess the risk factors predicting hospital mortality from complications. Hospital mortality was termed as “complication death”, and the analyzed factors were age, pulmonary function [% vital capacity (%VC) or % forced expiratory volume_1.0 (%FEV_1.0)], cardiac function [ECG and Master test], renal function [creatinine clearance (C_CR)], hepatic function [15′ indocyanine green test (R₁₅·ICG)], diabetes mellitus [75 g oral glucose tolerance test (75OGTT)], depth of tumor invasion [T-factor], and the type of operative procedure [operation]. Each patient was scored according to risk severity on a scale from 0–3, with the higher numbers representing higher risk. Patients not succumbing to complication death had less than 8 points in the total score, while those who suffered a complication death had 8 or more points. Through stepwise logistic regression analysis, we produced a prediction formula. In cases where eight or more points are scored by the semi-quantitative analysis, or 0 or more, by the prediction formula, the operative procedure should be changed to a less radical one for improved prognosis. The introduction of this semi-quantitative analysis for postoperative risk reduced the incidence of complication death from 6% to 3%, and of hospital mortality from 13% to 3%.     

Plant innate immunity - direct and indirect recognition of general and specific pathogen-associated molecules

Plants have the capacity to recognise and reject pathogens at various stages of their attempted colonisation of the plant. Non-specific rejection often arises as a consequence of the potential pathogen's attempt to breach the first lines of plant defence. Pathogens able to penetrate beyond this barrier of non-host resistance may seek a subtle and persuasive relationship with the plant. For some, this may be limited to molecular signals released outside the plant cell wall, but for others it includes penetration of the cell wall and the delivery of signal molecules to the plant cytosol. Direct or indirect recognition of these signals triggers host-specific resistance. Our understanding of host-specific resistance and its possible links to non-host-specific resistance has advanced significantly as more is discovered about the nature and function of the molecules underpinning both kinds of resistance.     

Experimental gene therapy using p21Waf1 gene for esophageal squamous cell carcinoma by gene gun technology

In our previous study, the proliferation rate of esophageal squamous cell carcinoma cell lines, which poorly expressed p21Waf1, was found to be regulated by p21Waf1 gene transfection using adenovirus vector. In the present study, in order to examine the effect of p21Waf1 gene therapy in esophageal cancer, we used gene gun technology, which proved to be a powerful method to introduce the p21Waf1 gene into esophageal cancer cells. p21Waf1 transfection to KE3 and YES2 cells (weakly expressed p21Waf1 protein cells) showed a high expression of p21Waf1 protein after applying this gene gun technique. In KE3 and YES2 cells, statistical significant growth inhibition was observed after p21Waf1 transfection compared with LacZ transfection (KE3, p=0.0009; YES2, p<0.0001). In in vivo transfection experiments, on day 14, the estimated volume of KE3 tumors subjected to p21Waf1 gene transfection was 95% in comparison with the pretreatment volume on day 0, while the volume of KE3 tumors subjected to LacZ gene therapy increased to 268%. On day 14, the estimated volume of YES2 tumors subjected to either p21Waf1 or LacZ gene therapy increased to 474 and 686%, respectively. In KE3 and YES2 cells, significant growth inhibition was observed after combination therapy using p21Waf1 transfection and anticancer drug 5-fluorouracil (5Fu) compared with 5Fu alone (KE3, p<0.0001; YES2, p<0.0001). In conclusion, p21Waf1 gene therapy using the gene gun technique significantly inhibited the low basal p21Waf1 expressed esophageal cancer cell growth in vitro and in vivo. Furthermore, p21Waf1 transfection strongly enhanced the effect of 5Fu suggesting that p21Waf1 may prove beneficial in chemotherapy combined with gene therapy using gene gun technology in patients with esophageal cancer who have a low level of p21Waf1 expressed tumor.     

Loss of heterozygosity in ductal lavage for breast tumor and the contralateral breast

Detection of breast cancer at an early stage is the key to successful treatment and outcome. In tumors confined to the breast at diagnosis, stage is the most important prognostic factor. If detected early, breast cancer is eminently curable. We measured loss of heterozygosity (LOH) using 9 microsatellite markers in epithelial cells obtained by ductal lavage (DL) from 59 women before breast surgery (excisional biopsies, duct resections, and mastectomies). In addition, we analyzed LOH obtained by DL in the contralateral breast of breast cancer patients. As a result, histological examination revealed 46 malignancies and 13 benign lesions. Sensitivity, specificity, and diagnostic accuracy were 100.0, 15.4, and 82.3% for LOH. LOH frequency in DL of breast cancer was significantly greater than that in DL of benign tumors. In terms of the contralateral breast of breast cancer patients, DL showed that one subject (3.4%) was malignant, and LOH frequency was similar to breast carcinoma. In conclusion, breast tissues that appear non-neoplastic pathologically often harbor genetic changes that can be important in understanding the breast environment within which the cancer develops.     

A latissimus dorsi muscle flap used for repair of the esophagus after enucleation of a giant leiomyoma —A case report

A giant leiomyoma of the esophagus, 11.5×5.0 cm in size, which occupied half of the esophageal circumference, was surgically enucleated. A small epithelial defect caused by the enucleation of the tumor was directly closed, and a large muscular defect was covered with a latissimus dorsi muscle flap, introduced into the thoracic cavity through the space where the second rib had been resected. Postoperatively, a leakage at the epithelial suture line was noted, however, it was localized by the muscle flap coverage and spontaneously healed two weeks postoperatively. During the follow-up period of 1.5 years, no diverticle formation or stenosis occurred, and the patient had no complaints. The present clinical experience indicates that this procedure may be a useful method of grafting after excision of giant leiomyoma of the esophagus.     

Postischemic alterations of spontaneous activities in rat hippocampal CA1 neurons

Changes of spontaneous impulse discharges in rat hippocampal neurons during and after transient forebrain ischemia were investigated electrophysiologically. Spontaneous impulse frequencies of CA1 neurons before ischemia were varied from 0.4 to 20.0 impulses/s and its average was5.8 ± 1.2 (means±S.E., n = 36). These spontaneous discharges were completely suppressed during forebrain ischemia exept for the transient hyperactivity observed just after the beginning of ischemia. Recovery of spontaneous discharges of CA1 neurons from suppression induced by 5 min ischemia started at 5 min, and neuronal activities were restored to pre-ischemic levels approximately 30 min after reperfusion. On the other hand, spontaneous impulse frequencies at all time points recorded after 20 min ischemia were less than 40% of the pre-ischemic levels. These continuous suppression of spontaneous activity after 20 min ischemia may suggest that neuronal function is impaired during and/or in the early stages of reperfusion, and functional disorders precede morphological degeneration.     

Successful treatment with cyclosporin A of myelodysplastic syndrome with erythroid hypoplasia associated with t(6;8)(q15;q22)

We report a t(6;8)(q15;q22) in a patient with myelodysplastic syndrome (MDS) with erythroid hypoplasia. The patient was successfully treated with an immunosuppressive treatment with cyclosporin A, while the translocation was repeatedly detected as the sole anomaly with the percentages of positive cells ranging from 5% to 70%. To our knowledge, the t(6;8) has never been described in MDS.     

Preliminary evaluation of chemotherapy with docetaxel, 5-FU, CDDP for recurrent esophageal cancer--a pilot study

A pilot study has been conducted since January 2002 to investigate whether chemotherapy with docetaxel, 5-FU, CDDP could be an effective regimen for recurrent esophageal cancer. Ten patients with recurrent esophageal cancer were treated with the combination of docetaxel 60 mg/m2 (day 1), CDDP 10 mg/body (days 1-5) and 5-FU 500 mg/body (days 1-5) at intervals of 2-3 weeks. All patients had undergone surgery, had a recurrent tumor and had already been treated with chemo-radiotherapy or chemotherapy with CDDP + 5-FU. Response evaluation in 10 patients with measurable disease: partial response 4 patients, stable disease 2 patients and progressive disease 4 patients. The main NCI-CT grade 3/4 toxicity was leukopenia (8/10). Mild to moderate nausea (> or = grade 2) occurred in 3/10 patients.     

Expression profiles of non-small cell lung cancers on cDNA microarrays: identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs

To investigate genes involved in pulmonary carcinogenesis and those related to sensitivity of nonsmall cell lung cancers (NSCLCs) to therapeutic drugs, we performed cDNA microarray analysis of 37 NSCLCs after laser-capture microdissection of cancer cells from primary tumors. A clustering algorithm applied to the expression data easily distinguished two major histological types of non-small cell lung cancer, adenocarcinoma and squamous cell carcinoma. Subsequent analysis of the 18 adenocarcinomas identified 40 genes whose expression levels could separate cases with lymph-node metastasis from those without metastasis. In addition, we compared the expression data with measurements of the sensitivity of surgically dissected NSCLC specimens to six anti-cancer drugs (docetaxel, paclitaxel, irinotecan, cisplatin, gemcitabine, and vinorelbine), as measured by the CD-DST (collagen gel droplet embedded culture-drug sensitivity test) method. We found significant associations between expression levels of dozens of genes and chemosensitivity of NSCLCs. Our results provide valuable information for eventually identifying predictive markers and novel therapeutic target molecules for this type of cancer.