Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication

Cyclin B1 is a key molecule for G2-M-phase transition during the cell cycle and is overexpressed in various tumor types. However, the expression status of cyclin B1 in lung cancer and its clinical significance remain unknown. We used immunohistochemistry studies to examine the expression of cyclin B1 in 77 non-small cell lung cancer specimens from patients with histological stage I disease. All of the patients underwent curative surgical treatment. The median length of follow-up care is 8.2 years. High-level cyclin B1 expression (a cyclin B1 labeling index > or =15%) was observed in 17 of the 77 (22%) tumors. Patients whose tumors expressed a high level of cyclin B1 had a significantly shorter survival time than patients whose tumors expressed a low level of cyclin B1 (P = 0.02, log-rank test). Interestingly, overexpression of cyclin B1 was more frequently observed in tumors with squamous cell histology than in tumors with other histological cell types (P = 0.01, Fisher's exact test). A subgroup analysis revealed that cyclin B1 overexpression seems to be an adverse prognostic factor only in patients with squamous cell carcinoma (SCC) of the lung (P = 0.02, log-rank test). Our data indicate that cyclin B1 may be dysregulated in non-small cell lung cancer, particularly in the SCC subtype, and that a high level of cyclin B1 expression may be a prognostic marker for patients with early-stage SCC of the lung.     

Results of treating cervical metastases of an unknown primary tumor. A report of 29 cases

A retrospective study was made of 29 patients with cervical metastasis of an unknown primary tumor. Sixteen patients received local treatment with surgery and radiotherapy (group A) and 13 patients were treated with induction chemotherapy, surgery and radiotherapy (group B). All patients responded. Local recurrence occurred in 21.4% of group A and 20% of group B. The frequency of distant metastases was similar (18.8% vs 15.4%). The mean survival time of 68 months in group A was longer than the 40 months of group B, and the a 2-year survival rate was 81% in group A and 67% in group B. The 5-year survival was better in group B (56% vs 40%). The primary tumor was identified twice as often in the patients who received only local treatment (group A 37.5% and group B 15.4%). Detection of the primary tumor was the only factor that significantly influenced patient survival.     

Assessing abnormal gene promoter methylation in paraffin-embedded sputum from patients with NSCLC

Aberrant methylation of CpG islands is an important pathway for regulation of gene expression. Recent data suggest that epigenetic abnormalities may occur very early in lung carcinogenesis. We studied the promoters of the four genes, HOX A9, p16(INK4a) (p16), MAGE A1 and MAGE B2 by methylation-specific PCR in matched normal tissue, tumour, and cytological negative sputum samples obtained from 22 patients with non-small cell lung cancer (NSCLC). We further report methylation abnormalities in sputum samples from 56 smokers with differential cytology readouts (negative, inflammatory changes, suspicious, and cancer). Our method was successfully performed on formalin-fixed and paraffin-embedded (FFPE) samples, and was fit to study only few cells obtained by a convenient non-invasive sputum collection and handling. The promoters of MAGE A1 and MAGE B2 had abnormal methylation patterns in, respectively, 50% and 41% of the cytologically negative sputum samples from NSCLC patients, whereas methylation abnormalities of p16 was observed in 27% of negative sputum samples. Interestingly, 95.5% (21 of 22) of the cytologically negative sputum samples from NSCLC patients had abnormal methylation in at least one of the four genes indicating a high sensitivity of this marker system. Moreover, a higher frequency of methylation abnormalities was observed in sputum samples from smokers with high cytological grade compared to low cytological grade. We conclude that the identification of abnormal gene methylation of a limited number of markers in FFPE sputum samples is feasible and may be investigated as a potential system for population-based screening of early stages of lung cancer.     

Evaluation of the clinical pathway for laparoscopic cholecystectomy

Clinical pathways are comprehensive systematized patient care plans for specific procedures. The clinical pathway for laparoscopic cholecystectomy was implemented in our department in March 2002. The aim of this study is to evaluate the clinical pathway for this procedure 1 year after implementation. A study was conducted on all the patients included in the clinical pathway since its implementation. The assessment criteria include degree of compliance, indicators of clinical care effectiveness, financial impact, and survey-based indicators of satisfaction. The results are compared to a series of patients undergoing surgery the year prior to implementation of the clinical pathway. As our hospital has a system of cost management, we analyzed the mean cost per procedure before and after clinical pathway implementation. Evaluation was made of a series of 160 consecutive patients who underwent surgery during the period 1 year prior to development of the clinical pathway and met the accepted inclusion criteria. The mean length of hospital stay was 3.27 days, and the mean cost per procedure before pathway implementation was 2149 (+/-768) euros. One year after implementation of the pathway, 140 patients were included (i.e., an inclusion rate of 100%). The mean length of hospital stay of the patients included in the clinical pathway was 2.2 days. The degree of compliance with stays was 66.7 per cent. The most frequent reasons for noncompliance were staff-dependent, followed by patient-dependent causes (oral intolerance, pain, etc.). The mean cost in the series of patients included in the clinical pathway was 1845 (+/-618) euros. Laparoscopic cholecystectomy is an ideal procedure for commencing the systemization of clinical pathways. Results show that it has significantly reduced the length of hospital stay and mean cost per procedure with no increased morbidity and with a high degree of patient satisfaction.     

The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism

Factor VIII (FVIII), von Willebrand factor (vWF) and the ABO blood groups have been associated with thrombosis. The ABO locus has functional effects on vWF and FVIII levels and is genetically correlated with FVIII, vWF and thrombosis. We carried out a case-control study to assess the role of FVIII, vWF and ABO types on thrombotic risk. We analyzed 250 patients with venous thrombosis and 250 unrelated controls. FVIII, vWF and other factors related to thrombophilia were measured, ABO groups were analyzed by genotyping. FVIII and vWF were higher in non-O individuals. Group O was more frequent in the controls (44.3% v 23.3%; difference 21.1%; 95% CI: 13.0-29.3%) and Group A in patients (59.2% v. 41.5%; difference 17.7%, 95% CI: 9.1-26.4%). Individuals carrying the A1 allele had a higher risk of thrombosis (OR 2.6; 95% CI, 1.8-3.8). The risk attributed to vWF disappeared after adjusting for the ABO group. Patients with FVIII above the 90th percentile had a high thrombotic risk (adjusted OR 3.7; 95% CI, 2.1-6.5), and a high risk of recurrence (OR 2.3; 95% CI: 1.3-4.1). In conclusion, high FVIII levels and non-O blood groups, likely those with the A1 allele, are independent risk factors for venous thromboembolism and should be considered in evaluating of thrombophilia.     

Orthodontic extrusion anchored in osseointegrated implants: a case report

Rapid orthodontic extrusion is indicated for cases involving biological space invasion of the periodontal ligament in which the surgical increase of the clinical crown can compromise esthetics or the support of the adjacent teeth. This article presents the case report of a tooth with radicular perforation 1.0 mm below the bone crest. A procedure to restore the biological distances was necessary. Rapid orthodontic extrusion of the affected tooth, with anchorage in the adjacent osseointegrated implants, was selected.