类癌及结肠癌、肺癌中神经内分泌细胞免疫组织化学研究

应用铬粒素 A、NSE、S-100蛋白及 Leu7单克隆抗体免疫组织化学方法,对24例结肠癌和肺癌、8例类癌、4例小细胞肺癌进行研究,结果表明除类癌外,结肠腺癌和肺癌中也存在神经内分泌细胞,阳性率为铬粒素 A 20.8%(5/24 3,NSE 33%(8/24),S-100蛋白33%(8/24),Len7 12.5%(3/24)。探讨了神经内分泌源性肿瘤与结肠癌、肺癌之间的关系和组织发生学。初步提出了类癌可能起源于壁内内分泌细胞,但须进一步研究和证实。     

Trends in the lung cancer incidence and mortality in the Slovak and Czech Republics in the contexts of an international comparison

Introduction

Lung cancer represents the most frequent cause of cancer-related deaths in the industrialized countries. The aim of this study was to analyze the lung cancer incidence and mortality and the possible reasons for any differences discovered in two neighboring Central European countries??the Slovak Republic.

Methods

We used linear regression model when analyzing incidence and mortality; the trends are presented with corresponding 95?% confidence intervals (CI) and p-value with null hypothesis being constant with time.

Results

Statistically significant increase of age-standardized incidence (0.707/100,000/year, 95?% CI 0.107?C1.307, p?=?0,025) and mortality (1.339/100,000/year, 95?% CI 1.050?C1.629, p?Conclusions According to the lung cancer incidence and mortality trends in both countries (in correlation with smoking prevalence) we consider the support of efforts to change the attitude towards smoking predominantly in women and younger generation to be the most accurate action to reduce these trends.     

Experience in the treatment of synchronous and metachronous carcinoma of the oesophagus and the head and neck

BACKGROUND AND OBJECTIVES: Treatment of multiple primary squamous cell carcinomas of the head and neck and oesophagus is controversial. The poor prognosis of these 2 types of carcinoma taken individually and their anatomic proximity complicate the therapeutic strategy and limit the treatment choices for each location. METHODS: From 1986 to 1998, 43 patients received curative treatment for multiple synchronous (n = 30) or metachronous (n = 13) primary neoplasms of the oesophagus and head and neck. For synchronous cancers, the therapeutic strategy consisted of first curing the head and neck cancer and then planning oesophagectomy according to the type of head and neck cancer therapy. RESULTS: Ten total oesopharyngolaryngectomies and 33 subtotal oesophagectomies were performed. The postoperative mortality rate was 9.3% (4/43). The rate of anastomotic leakage was 30% (13/43), and all such leaks were cervical. Pulmonary infection occurred in 19% of cases (8/43). A past history of cervical radiation therapy or cervicotomy did not appear to be a significant risk factor for anastomotic leakage or pulmonary complications. Oesophagectomy did not affect the functional results in the 31 patients whose larynx could be preserved. CONCLUSIONS: Oesophagectomy after head and neck cancer treatment is possible with a low mortality rate and acceptable morbidity.     

Bone marrow cells in the DNA-synthesis-phase in the myelodysplastic syndrome and lymphome

The bromodeoxyuridine (BRDU) labelling of bone marrow cells was studied in 46 subjects. The labelling in 14 patients, mostly untreated, with the myelodysplastic syndrome (MDS) and four lymphoma patients was significantly (p = 0.043) higher (11.38 ± SE 2.3 % S-phase cells) than that of marrow cells (7.18 ± SE 1.04%) from 14 apparently healthy normal controls and from nine patients with non hematologic disease. Six iron deficiency had numerically but not significantly increased values. Bone marrow samples from MDS-patients showing the highest numbers of cells in the DNA-synthesis phase had the lowest numbers of colonies and clusters in the CFU-C assay(p < 0.03). The data suggest that the DNA-synthesis period is longer in MDS than in controls.     

Facts and controversies in the use of trastuzumab in the adjuvant setting

The human epidermal growth factor receptor-2 (HER2) is overexpressed and/or amplified in up to 25% of breast cancer patients, and this feature is associated with an aggressive phenotype, high recurrence rate and reduced survival. Until recently, combination chemotherapy (with or without endocrine therapy) was the only effective adjuvant treatment for HER2-positive patients. Trastuzumab is a monoclonal antibody directed against the HER2 extracellular domain, and five recent adjuvant breast cancer trials have demonstrated an astonishing and highly reproducible benefit in halving the recurrence rate and reducing mortality in patients with this phenotype. Many questions related to trastuzumab use in the adjuvant setting still remain; these include the optimum timing and duration of treatment, trastuzumab use with taxanes and radiotherapy, its role in small node-negative tumors, the optimum chemotherapy regimens and cost-effectiveness. This Review outlines the five adjuvant trastuzumab studies and discusses the controversies and challenges that have emerged for both the clinician and healthcare authorities worldwide as a consequence of the results from these trials.     

Similar defects in DNA repair and replication in the pigmented xerodermoid and the xeroderma pigmentosum variants

The "pigmented xerodermoid" was previously defined on the basis of mild clinical symptoms that suggested it might be similar to but distinct from xeroderma pigmentosum (XP). XP and pigmented xerodermoid cell cultures were irradiated with ultraviolet light and unscheduled DNA synthesis, strand breakage during repair, chain growth during semiconservative DNA replication with or without caffeine, and the recovery of DNA replication were determined. It is concluded that a pigmented xerodermoid cell culture is indistinguishable from the XP variant and the former term is therefore redundant. The defect common to these cell types appears to be the loss of a gene product that permits normal cells to replicate DNA without interruption at damaged sites (u.v.-induced pyrimidine dimers). The consequence of this loss is that replication forks are blocked more frequently and at lower doses in XP variant cells. The correlation between this defect and high levels of actinic carcinogenesis in these patients points to an important role for perturbations in DNA replication in human carcinogenesis.     

Daunorubicin and daunorubicinol pharmacokinetics in plasma and tissues in the rat

Recent evidence suggests that 13-hydroxy metabolites of anthracyclines may contribute to cardiotoxicity. This study was designed to determine the pharmacokinetics of daunorubicin and the 13-hydroxy metabolite daunorubicinol in plasma and tissues, including the heart. Fisher 344 rats received 5 mg kg^–1 daunorubicin i.v. by bolus injection. Rats were killed at selected intervals for up to 1 week after daunorubicin administration for determination of concentrations of daunorubicin and daunorubicinol in the plasma, heart, liver, kidney, lung, and skeletal muscle. Peak concentrations of daunorubicin were higher than those of daunorubicinol in the plasma (133±7 versus 36±2 ng ml^–1;P<0.05), heart (15.2±1.4 versus 3.4±0.4 g g^–1;P<0.05), and other tissues. However, the apparent elimination half-life of daunorubicinol was longer than that of daunorubicin in most tissues, including the plasma (23.1 versus 14.5 h) and heart (38.5 versus 19.3 h). In addition, areas under the concentration/time curves (AUC) obtained for daunorubicinol exceeded those found for daunorubicin in almost all tissues, with the ratios being 1.9 in plasma and 1.7 in the heart. The ratio of daunorubicinol to daunorubicin concentrations increased dramatically with time from <1 at up to 1 h to 87 at 168 h in cardiac tissue. Thus, following daunorubicin injection, cumulative exposure (AUC) to daunorubicinol was greater than that to daunorubicin in the plasma and heart. If daunorubicinol has equivalent or greater potency than daunorubicin in causing impairment of myocardial function, it may make an important contribution to the pathogenesis of cardiotoxicity.