József Furák

Prognostic significance of endogenous adhesion/growth-regulatory lectins in lung cancer

Objective: To determine the expression of endogenous adhesion/growth-regulatory lectins and their binding sites using labeled tissue lectins as well as the binding profile of hyaluronic acid as an approach to define new prognostic markers. Methods: Sections of paraffin-embedded histological material of 481 lungs from lung tumor patients following radical lung excision processed by a routine immunohistochemical method (avidin-biotin labeling, DAB chromogen). Specific antibodies against galectins-1 and -3 and the heparin-binding lectin were tested. Staining by labeled galectins and hyaluronic acid was similarly visualized by a routine protocol. After semiquantitative assessment of staining, the results were compared with the pT and pN stages and the histological type. Survival was calculated by univariate and multivariate methods. Results: Binding of galectin-1 and its expression tended to increase, whereas the parameters for galectin-3 decreased in advanced pT and pN stages at a statistically significant level. The number of positive cases was considerably smaller among the cases with small cell lung cancer than in the group with non-small-cell lung cancer, among which adenocarcinomas figured prominently with the exception of galectin-1 expression. Kaplan-Meier computations revealed that the survival rate of patients with galectin-3-binding or galectin-1-expressing tumors was significantly poorer than that of the negative cases. In the multivariate calculations of survival lymph node metastases (p < 0.0001), histological type (p = 0.003), galectin-3-binding capacity (p = 0.01), galectin-3 expression (p = 0.03) and pT status (p = 0.003) proved to be independent prognostic factors, not correlated with the pN stage. Conclusion: The expression and the capacity to bind the adhesion/growth regulatory galectin-3 is defined as an unfavorable prognostic factor not correlated with the pTN stage.

Bronchioloalveolar lung cancer: Occurrence, surgical treatment and survival

OBJECTIVEnThe prevalence of pulmonary adenocarcinoma has risen worldwide. Bronchioloalveolar carcinoma (BAC) was studied with regard to whether it exhibits a similar tendency, and its typical features were analysed.nnnMETHODSnBetween 1992 and 2001, 278 lung resections were carried out for adenocarcinoma. Of these, 67 (24.1%) proved to involve BAC. Whereas BAC accounted for 6.9% of the cases in 1992, in 2001 the proportion was 46.9%. There were 37 men (55.2%) and 30 women (44.7%); the average age was 60.5 years. 58.2% of them had no complaints. Of the 26 non-smokers, 69.2% were women; of the 41 smokers, 29.2% were women. In consequence of the tumour, 49 lobectomies, three bilobectomies, six pneumonectomies and nine wedge resections were performed.nnnRESULTSnThe surgical mortality was 1.6%. The pathology revealed that 26 (38.8%) tumours were in stage I/A. In 15 cases (22.4%), tuberculosis (TB) could be revealed besides the BAC: by skin tests in four cases, by CT in three cases, by case history in four cases, and by pathology in four cases. For the overall group of 67 patients, the 5-year survival rate was 61.9%, and the mean survival time was 75.7 months. The 5-year survival rate among the women (74%) was significantly better than that among the men (37%) (P=0.030). There was no significant difference in survival with regard to the multiple BAC (85%). The 5-year survival rate was significantly worse in the mixed BAC group (20%) than in the non-mucinous (62.7%) and in mucinous (59%) group. The overall 5-year survival rate among the smokers and TB patients was 61 and 79%, respectively, which is higher than that among the non-smokers (47%) and non-TB patients (56%). The survival rate for the wedge resection cases was 37%, which was lower than that for the cases involving major resections (60%) (P=0.939).nnnCONCLUSIONnBAC has a favourable survival, particularly in women. In spite of this, resection smaller than lobectomy is recommended only as a compromise. A multiple appearance does not imply a worse survival. The best survival rate was found in the non-mucinous BAC among the histological groups. TB seems to be frequent among BAC patients.

Surgical intervention for pulmonary tuberculosis: analysis of indications and perioperative data relating to diagnostic and therapeutic resections

OBJECTIVEnTo analyze the data on patients operated on for pulmonary tuberculosis (TB) with (Group I) or without (Group II) a correct TB diagnosis and preoperative anti-TB treatment.nnnMETHODSnBetween 1980 and 1997, 144 resections for TB (Groups I+II) were performed. The 80 patients in Group I underwent therapeutic resections: 32 cases involved recurrent cavities or tuberculomas, three involved post-TB bronchiectasis, 13 involved progression of cavities or tuberculomas, and 32 involved persistent tuberculomas after 6 months of anti-TB therapy. The 64 patients in Group II were operated on for a suspicion of malignancy in 49 cases, for cavitary lesions with haemophthysis in six cases, for multiple lesions in seven cases, and for recurrent hydrothorax in two cases.nnnRESULTSnGroups I and II included 0 and five pneumonectomies, 32 and 29 lobectomies, 48 and 20 wedge resections, 0 and nine videothoracoscopic biopsies, and 0 and one hilar lymphadenectomy, respectively. In Groups I and II, the mean duration of postoperative hospitalization was 13.2 and 10.4 days, and the frequency of postoperative pneumothorax was 11.25 and 4.6%, respectively. The incidence of bronchopleural fistula was 1.25 and 0%, the mortality was 0 and 3.1%, and the morbidity was 53.7 and 35.9% in Groups I and II, respectively. Two patients with active disease died in Group II. Pathology demonstrated that the frequency of acid-fast bacilli in Groups I and II was 40 and 25%, respectively.nnnCONCLUSIONSnPatients without a correct preoperative TB diagnosis underwent more extensive parenchyma resection. Postoperative complications increased when acid-fast bacilli were present. The lack of preoperative anti-TB treatment did not involve a higher risk of minor complications, but death occurred only in this group.

Immunophenotypic profiling of nonsmall cell lung cancer progression using the tissue microarray approach.

This study, using tissue microarrays, aimed at the immunomorphologic profiling of nonsmall cell lung cancer (NSCLC) cases to reveal clinically relevant disease groups and biomarkers associated with patients survival and tumor progression including brain metastatic potential. Donor tissue blocks were form 59 patients, including 33 primary tumors without distant metastasis and 26 brain metastatic primary tumors as well as the brain metastases. Sections were immunostained for 29 markers targeting molecules of cell adhesion, cell growth, cell cycle, and apoptosis regulation. β-Catenin expression was the only independent prognostic marker associated with better outcome. Elevated expression of collagen XVII, CD44v6, and caspase-9, and the reduced production of β-catenin and cellular apoptosis susceptibility protein were significantly associated with the metastatic potential of primary NSCLC. Expression of positive cell cycle regulators cyclin D1 and cyclin D3 was also increased in metastatic primary tumors. Metastatic tumor progression into the brain was accompanied by prominent p16, syndecan-1, p53 (DO7), and caspase-3 protein levels. Hierarchical clustering of complex immunoprofiles based on the differentially expressed markers grouped NSCLCs of the poorest outcome with high correlation including 2/3 of brain metastases of mixed histology. The brain metastatic potential of NSCLCs may be linked to the elevated levels of cyclinD1, cyclinD3, p16, p53, caspase-3, caspase-9, CD44v6, and collagen XVII and the down-regulation of β-catenin and cellular apoptosis susceptibility protein. Unsupervised immunoprofiles based on differentially expressed biomarkers may help selecting lung cancers with aggressive behavior.

Postoperative paraplegia after resection of a giant posterior mediastinal tumour. Importance of the blood supply in the upper spinal cord

A 10-cm diameter tumour was revealed in the left upper posterior mediastinum in a 15-year-old female. After exclusion of the possibility of a dumbbell tumour and confirmation of a ganglioneurinoma, an encapsulated, but vascularised tumour was removed via a left posterolateral thoracotomy from the level of the first-third costo-vertebral angle, without intraoperative complications. Following surgery, acute paraplegia was diagnosed, with a spinal cord lesion at the high thoracic level. Magnetic resonance imaging did not reveal any disorder in the spinal cord. In response to medical treatment, the patients locomotor and sensation functions normalised within six months. On revising the preoperative computed tomography, we found dilated vessels passing through the tumour and the hypoplastic vertebral artery on the left side. This finding led us to suspect that the spinal cord circulation was partially supplied by the arteries passing through the tumour, which were clipped during surgery. Verification of the blood supply of the spinal cord is therefore highly recommended before resection of a giant tumour from the posterior mediastinum.

Development of brain metastasis 5 years before the appearance of the primary lung cancer: "messenger metachronous metastasis".

We report a patient with a brain metastasis that presented 5 years before the primary adenocarcinoma of the lung from which it originated. The metastasis and the primary tumor were removed. To confirm their common origin, we used comparative genomic hybridization. We have named this type of metastasis messenger metachronous metastasis. The patient remains well 79 months after the brain metastasectomy and 18 months after the lung surgery.

Multiple costal cartilage graft reconstruction for the treatment of a full-length laryngotracheal stenosis after an inhalation burn

After suffering an inhalation burn, a 22-year-old male was intubated for seven days. Full-length massive scar formation in the upper airway necessitated tracheostomy five months later. After this, the stenosis became complete in the cricoid region, and a long cannula was needed to maintain the severely damaged middle-distal trachea. After unsuccessful laser dilatation, the more stenotic 3xa0cm distal tracheal segment was resected, but two months later the stenosis recurred. As resection was ineffective, tracheoplasty was performed via a right-sided thoracotomy; the re-stenotized trachea was incised in length and successfully extended with 5xa0cm long, oval-shaped rib cartilage. Three months later, the complete cricotracheal stenosis was fixed by combined laryngofissure and cricoid laminotomy with two 6xa0cm×2.5xa0cm cartilage pieces sutured into the incisions. The middle portion of the trachea was expanded with a similar graft inserted into the anterior wall below the tracheostomy. The fixing T-tube was removed three months later, and the patient had an adequate airway two years after the last procedure. We conclude that multiple cartilage graft reconstruction can be successful even after the development of an extremely long airway stenosis following inhalation burn injury.

Claudin-1 Protein Expression Is a Good Prognostic Factor in Non-Small Cell Lung Cancer, but only in Squamous Cell Carcinoma Cases.

The aim of the study was to investigate the correlation between claudin (CLDN) protein expression and clinicopathological parameters as well as survival in histological subtypes of non-small cell lung cancer. Archived surgical resection specimens of 137 pathologic stage I primary bronchial cancers including 49 adenocarcinomas of non-lepidic variants (ADC), 46 adenocarcinomas of lepidic variants (L-ADC), and 42 squamous cell carcinomas (SCC) were examined. Immunohistochemistry (IHC) using antibodies against CLDN1,-2,-3,-4,-7 proteins as well as semiquantitative estimation (IHC scores 0–5) were performed. Claudin IHC scores of L-ADC differed significantly from ADC (CLDN1: pxa0=xa00.009, CLDN2: pxa0=xa00.005, CLDN3: pxa0=xa00.004, CLDN4: pxa0=xa00.001, CLDN7: pxa0<xa00.001, respectively) and SCC (CLDN1: pxa0<xa00.001, CLDN3: pxa0<xa00.001, CLDN7: pxa0<xa00.001, respectively). Highly significant CLDN3-CLDN4 parallel expression could be demonstrated in ADC and L-ADC (pxa0<xa00.001 in both), which was not observed in SCC (pxa0=xa00.131). ADC and SCC showed no correlation with smoking, whereas in case of L-ADC heavier smoking correlated with higher CLDN3 expression (pxa0=xa00.020). Regarding claudin expression and survival, in SCC significant correlation could be demonstrated between CLDN1 IHC positivity and better survival (pxa0=xa00.038). In NSCLC as a whole, high CLDN2 expression proved to be a better prognostic factor when compared with cases where CLDN2 IHC score was 0–1 vs. 2–5 (pxa0=xa00.009), however, when analyzed separately, none of the histological subgroups showed correlation between CLDN2 expression and overall survival. The claudin expression pattern was significantly different not only between the SCC–ADC and SCC–L-ADC but also between the L-ADC and ADC histological subgroups, which strongly underlines that L-ADC represents a distinct entity within the ADC group. CLDN1 overexpression is a good prognostic factor in NSCLC, but only in the SCC subgroup.

Treatment decision based on the biological behavior of pulmonary benign metastasizing leiomyoma.

Benign metastasizing leiomyoma (BML) is a rare disease in women undergoing surgery for uterine leiomyoma. About 100 cases have been reported in the literature, none of which describe the biological behavior of lesions. The authors present the case of a 36-year-old, asymptomatic woman who had undergone uterus extirpation seven years earlier for leiomyoma of the uterus. Routine chest radiography revealed multiple nodules in both lungs. Biopsy verified metastases from the original uterine leiomyoma. During a 41-month interval, 87 lesions were removed in seven operations, through mini-thoracotomy [four left-sided (42 lesions); and three right-sided (45 lesions)] by cautery resection and suturing of the parenchyma (n=83), or by wedge resection (n=4). In between the procedures, the patient received continuous oncological treatment (VIP protocol: etoposide, ifosfamide, cisplatin). Mean hospital stay was 5.14 days. Respiratory function tests performed after the last surgery showed near-normal results (FVC: 77%, FEV1: 64%, FEV1/FVC: 0.83). Over time, a decrease in number of newly developed BML nodules was observed. Mean surgical sensitivity [rate of lesions appearing on computerized tomography (CT) and removed during each surgery] of the seven metastasectomies was 95% (range: 40-150%). Pathological examination of the nodules proved that, despite continuous oncological treatment, there were no signs of necrosis, thrombosis, or fibrosis. The number of mitoses within the nodules did not change. According to our surgical results and the fact that oncological treatment did not have a significant effect on the course of the disease, we conclude that in the management of multiple BML lesions, surgically removing as many lesions as possible is advised.

Evaluation of grading systems in stage I lung adenocarcinomas: a retrospective cohort study

Aims There is no internationally accepted grading system for lung adenocarcinoma despite the new WHO classification. The architectural grade, the Kadota grade and the Sica score were evaluated and compared with overall (OS) and disease-free survival (DFS). Methods Comprehensive histological subtyping was used in a series of resected stage I lung adenocarcinoma to identify subtypes of adenocarcinomas, the architectural grade, the Kadota grade, the Sica grade, the mitotic count, nuclear atypia, the presence of lymphovascular, vascular and airway propagation, necrosis, and micropapillary or solid growth pattern in any percentage. Statistical models fitted included Kaplan-Meier estimates and Cox proportional hazard regression models. Results 261 stage I adenocarcinomas were included. The 5-year survivals of different subtypes were as follows: lepidic (n=40, OS: 92.5%; DFS 91.6%), acinar (n=54, OS: 81.8%; DFS: 68.6%), papillary (n=49, OS: 73.6%; DFS: 61.0%), solid (n=95, OS: 64.7%; DFS: 57.8%) and micropapillary (n=23, OS: 34.8%; DFS: 33.5%). Concerning the architectural grade, there were significant differences between OS and DFS of low and intermediate (pOS=0.005, pDFS<0.001), low and high (pOS<0.001, pDFS<0.001) and intermediate and high grades (pOS=0.002, pDFS<0.001). Low-grade and intermediate grade tumours did not differ in survival according to Kadota grade and Sica grade. In the multivariable model, architectural grade was found to be an independent prognostic marker. In another model, architectural pattern proved to be superior to architectural grade. Conclusions Of the three grading systems compared, the architectural grade makes the best distinction between the outcome of low-grade, intermediate-grade and high-grade stage I adenocarcinomas.