Prognostic value of cyclin D1 overexpression in correlation with pRb and p53 status in non-small cell lung cancer (NSCLC).

PURPOSE: The aim of this study was to assess the impact of cyclin D1 overexpression (considered separately or jointly with previously assessed p53 and pRb statuses) on survival in a group of 111 surgically treated non-small cell lung cancer patients (NSCLC). METHODS: Cyclin D1 accumulation was assessed immunohistochemically, with the use of monoclonal antibody (DCS-6, DakoCytomation) and the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. RESULTS: Overexpression of cyclin D1 was found in 55 samples (49%), whereas the altered phenotypes cyclin D1+/p53+ or cyclin D1+/pRb- were found in 23 (22%) and 9 samples (9%), respectively. Statistical analysis was performed for different cut-off values and the only significant differences were found if samples with some expression of each protein were considered positive. There was no relationship between cyclin D1 overexpression and major clinicopathological factors, including p53 expression; however, there was a direct correlation between cyclin D1 and pRb protein expression (p=0.007). Cyclin D1 accumulation did not influence patients' survival. Of all possible cyclin D1/p53, cyclin D1/pRb and cyclin D1/p53/pRb phenotypes, patients with cyclin D1-/p53+ phenotype had shortened overall survival compared to other patients (p=0.027, HR=1.8). In the multivariate analysis, the only variable associated with shortened overall and disease-free survival was the stage of disease (p<0.001). CONCLUSIONS: These results suggest the lack of prognostic value of cyclin D1 overexpression in NSCLC patients.

Absence of prognostic significance of p21(WAF1/CIP1) protein expression in non-small cell lung cancer.

Prognostic value of p21WAF1/CIP1 expression in non-small-cell lung cancer patients (NSCLC) remains unclear. In this study the authors investigated the clinical significance of p21WAF1/CIP1 expression in a group of 117 NSCLC patients, who underwent curative pulmonary resection. Expression of p21WAF1/CIP1 protein was assessed immunohistochemically and samples showing>5% of positive tumor cells were considered positive. Seventy-six samples (65%) showed positive nuclear p21WAF1/CIP1 protein expression. There was no relationship between the expression of p21WAF1/CIP1 protein and major clinico-pathological factors, and neither there was an impact of p21WAF1/CIP1 protein expression on disease-free and overall survival. p21WAF1/CIP1 protein occurrence was not correlated with previously determined p53 protein expression and there was also no relationship between all possible p21WAF1/CIP1/p53 phenotypes and survival. In uni- and multivariate analysis only stage of disease was independent prognostic factors. These results suggest the lack of prognostic relevance of p21WAF1/CIP1 expression (analyzed separately or jointly with p53 protein) in surgically treated NSCLC patients.

[Thymectomy in myasthenia gravis]. / Znaczenie usuniecia grasicy u chorych na myasthenia gravis.

OBJECTIVES AND METHODS: To evaluate the results of thymectomy in myasthenia gravis we performed retrospective analysis of 82 consecutive patients in the mean age of 39 +/- 15 treated between 1991 and 2001. All patients underwent extended thymectomy by median sternotomy. Follow-up was assessed in 74 of 81(91.4%) patients, in the mean age of 39 +/- 15, discharged from the Department. RESULTS: Fifty three (71.6%) patients had symptoms of myasthenia gravis for less than 2 years. According to Osserman's classification 8 (10.8%) patients were assessed as class I, 32 (43.2%) as IIA 26 (35.2%) as IIB and 8 (10.8%) as IIC. In the postoperative period 8 (10.8%) patients had respiratory insufficiency, 5 (6.8%) were reoperated for bleeding. One patient died (1.4%) due to bilateral pneumonia and pulmonary insufficiency. After thymectomy the improvement of patient's clinical status was observed in 46 patients (86.4%) and complete remission was in 13 patients (17.6%). Prompt improvement after thymectomy (p = 0.008) and short duration of symptoms (p = 0.036) are positive predictive factors. Patients in class I had significantly better prognosis concerning complete remission (p = 0.036). Age, gender, histology of the thymus, and type of the thymoma had no influence on long time follow up. CONCLUSIONS: Extended thymectomy is a safe procedure leading to the improvement in majority of patients treated for myasthenia gravis.

Prognostic relevance of altered pRb and p53 protein expression in surgically treated non-small cell lung cancer patients.

OBJECTIVE: The prognostic value of pRb and p53 altered expression in non-small cell lung cancer (NSCLC) remains debatable. We assessed the occurrence of altered pRb and p53 protein expression, and the prognostic value of these assays considered as separate and combined variables in operable NSCLC. The study group included 195 NSCLC consecutive patients from one institution who underwent curative pulmonary resection between 1994 and 1999. METHODS: Expression of pRb and p53 was assessed immunohistochemically with the use of monoclonal antibodies (LM95.1 and Pab 1801, Oncogene Science, respectively). RESULTS: A lack of pRb and abnormal p53 protein expression were found in 57 (29%) and 92 samples (47%), respectively, whereas both abnormalities (pRb-/p53+) occurred in 24 samples (12%). There was no relationship between altered pRb/p53 expression and major clinico-pathological characteristics, neither was there a significant difference in disease-free and overall survival between particular groups of patients with tumors carrying four possible pRb/p53 phenotypes. In uni- and multivariate analysis, the only variable associated with shortened disease-free and overall survival was stage of disease (p < 0.001) and degree of tumor differentiation (p = 0.005). CONCLUSION: These results suggest that altered pRb and p53 expression does not provide prognostic information in operable NSCLC patients.

MDM2 gene amplification: a new independent factor of adverse prognosis in non-small cell lung cancer (NSCLC).

The prognostic impact of MDM2 amplification in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the occurrence of MDM2 amplification in surgically treated NSCLC patients. Molecular data were correlated with clinicopathological factors and evaluated for their prognostic value. The study group included 116 NSCLC patients who underwent pulmonary resection between 1996 and 1999. MDM2 amplification was assessed by real-time PCR using hybridization probe format on a LightCycler (Roche). The calculated ratio was a MDM2 value normalized to the amplification of the housekeeping gene phenylalaninhydroxylase (PAH). Survival curves were drawn according to the Kaplan-Meier method and compared with the use of the log-rank test. Multivariate analysis was based on Cox regression analysis. MDM2 amplification was found in 24 patients (21%). There was no relationship between MDM2 amplification and clinicopathological factors, such as sex, age and stage of disease, pT, pN, histology and tumor differentiation. Median disease-free survival (DFS) in patients with and without MDM2 amplification was 3 and 31 months, and 5-year DFS 24 and 33%, respectively (log-rank, P = 0.02). Likewise, median overall survival (OS) in patients with and without MDM2 amplification was 9 and 33 months, respectively, and 5-year OS 24 and 39%, respectively (log-rank, P = 0.01). The strong prognostic relevance of MDM2 amplification for both DFS and OS was confirmed in multivariate analysis (P < 0.01 for both comparisons). Our results suggest that MDM2 gene amplification analysis provides additional prognostic information in surgically treated NSCLC patients.

One step removal of dumb-bell tumors by postero-lateral thoracotomy and extended foraminectomy.

OBJECTIVE: Thoracic dumb-bell tumors are rare, usually benign tumors in the posterior mediastinum, consisting of intrathoracic and intraspinal parts. Surgical removal is the treatment of choice, performed by two teams - neurosurgeons and thoracic surgeons operating in a prescribed order. METHODS: Between 1994 and 1997 five patients had dumb-bell tumors removed in a one-step operation involving postero-lateral thoracotomy and extended foraminectomy. This operating method, rarely described in the medical literature, consists of intrathoracic and intraspinal parts being performed by a thoracic team independently or with the assistance of a neurosurgeon. Initially the intrathoracic part is resected, followed by an extensive widening of the intervertebral foramen to an appropriate extension and the removal of the remaining intraspinal part of the tumor. RESULTS: Four postero-lateral thoracotomies and one incision over a huge tumor in the thoraco-lumbal region, without entering the pleural cavity, were performed. In one patient postoperative, transient leakage of the cerebral fluid was observed. No form of late complications or neurologic sequelae have been reported within a 5-year follow-up. CONCLUSIONS: One-step removal of a dumb-bell tumor by postero-lateral thoracotomy and extended foraminectomy is a safe surgical procedure that can be performed by the thoracic team alone. Early and late surgical results confirm the appropriateness and usefulness of the method.

[Long-term results after resection of IIIA-N2 non-small cell lung cancer and complementary mediastinal irradiation]. / Odlegle wyniki leczenia operacyjnego chorych na niedrobnokomórkowego raka pluca w stadium IIIA-N2 poddanych uzupelniajacej radioterapii sródpiersia.

The authors present a retrospective evaluation of long-term results of treatment of patients with IIIA-N2 non-small cell lung cancer (NSCLC), operated and subjected to complementary irradiation of mediastinum in the years 1987-1990. 60 patients were observed: 10 women and 50 men, aged 37-74 years (mean age 56). In all patients a radical resection of lung parenchyma with the primary tumour and mediastinal lymphadenectomy were performed. The one-year survival was 63% (38 patients), three-year survival--15% (9 patients) and five-year survival 13% (8 patients). It was found that the five year-survival in patients with IIIA-N2 NSCLC, in whom a combined therapy was applied (surgery and irradiation), was low, and the most common cause of death in the first three years of follow-up were distant metastases. Moreover it was observed that the number of mediastinal lymph node groups had a great influence on the time of survival.

Loss of heterozygosity at chromosomes 3p and 17p in primary non-small cell lung cancer.

BACKGROUND: Loss of heterozygosity (LOH) of selected regions at chromosomes 3p and 17p in non-small cell lung cancer (NSCLC) and the association of these abnormalities with major clinical parameters and prognosis were studied. MATERIALS AND METHODS: The study group included 92 consecutive primary NSCLC tumours and four microsatellite markers from chromosome 3p and three markers from 17p were analyzed. RESULTS: LOH of at least one locus was found in 83% of all analyzed tumours. Most frequently deletion (58%) was found at locus D3S1481 (3p14.2). Sequence deletions of D17S520 (17p12) and TP53 (17p13.1) occurred in 52% of tumours. LOH occurrence at 3p and 17p was more frequent in squamous cell carcinomas compared to adenocarcinomas (89% vs. 75%), but this difference was not significant. CONCLUSION: No significant association was found between LOH on any analyzed loci and tumour stage (TNM) and grade (G). There was no correlation between LOH and survival.

[Effect of neoadjuvant chemotherapy on complications in patients undergoing surgical treatment for non small cell lung cancer]. / Wplyw przedoperacyjnej chemioterapii na powiklania po leczeniu operacyjnym chorych na niedrobnokomórkowego raka pluca.

Neoadjuvant chemotherapy before resection is being the standard of care for stage IIIA non-small cell lung cancer in many institutions. The risk of complications in patients undergoing thoracotomy after induction chemotherapy remain controversial. We reviewed our experience. From 1998 to 2003, 29 patients underwent pulmonary resection after induction chemotherapy for advanced non-small cell lung cancer. Pneumonectomies were performed for 16 (55.2%) patients (2 right sleeve pneumonectomy and 1 pneumonectomy with wedge excision of tracheal carina), lobectomies for 11 (37.9%) patients (3 right upper sleeve lobectomy), segmentectomies for 1 (3.45%) patient and explorative thoracotomy for 1 (3.45%) patient. There were 3 (10.3%) postoperative deaths, all after right pneumonectomy; 2 caused by pneumonia of the left lung, 1 caused by pulmonary embolism in patient after re-thoracotomy for hemothorax. The postoperative complications included pneumonia in 2 patients, postoperative bleeding in 2, hemothorax in 1, prolonged intubation in 1, vocal cord paralysis in 2, cardiac arrhythmia in 2, atelectasis in 1 and residual air space in 1, resulting in 41,4% morbidity. Most of complications occurred after right pneumonectomy (45.5%). The mortality of patients who had received induction chemotherapy was higher than that of a comparative group of 1529 who underwent lung resection or only exploration without induction chemotherapy during the same period, and the difference was significant (10.3% vs 4.1%; p = 0.01). Morbidity differences were. not significant (p = 0.94).

[Anaerobic bacteria in bronchoalveolar lavage fluid (BAL) after thoracic surgery]. / Wystepowanie bakterii beztlenowych w popluczynach pecherzykowo-oskrzelikowych u chorych po operacjach torakochirurgicznych.

Purpose of this study was to find out what kind of anaerobic bacteria were in lower respiratory tract and how often they were present there considering patients after thoracic surgery. Also, what is susceptibility of bacteria to antibiotics. Research covered 30 patients after operation. Material for research was bronchoalveolar lavage (BAL) taken during bronchoscopy. Collected sample was cultivated in anaerobic and aerobic conditions. Anaerobic bacteria were found in 28 samples (93%). Totally there were 100 anaerobic bacteria strains. The most common Gram-negative rods were from genus Prevotella (24 strains, 24%) and Bacteroides (15 strains, 15%). Gram-negative bacteria except Bacteroides characterised biggest susceptibility to imipenem, piperacillin/tazobactam, amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin, clindamycin and metronidazol. Bacteroides were susceptible to imipenem, piperacillin/tazobactam and metronidazol. Among Gram-positive anaerobic bacteria mostly were isolated from cocci Peptostreptococcus (18 strains, 18%) and were susceptible to all antibiotics. Gram-positive rods were in most cases represented by Actinomyces (12 strains 12%) and were highly susceptible to all antibacterial means except metronidazol (100% is resistant).

The influence of blood transfusion on survival in operated non-small cell lung cancer patients.

BACKGROUND: It has been postulated that allogeneic transfusions have immunosuppressive effects that can promote tumor growth and metastasis formation. Despite the variety of publications on this controversial topic, the influence of blood transfusion on survival is not yet clearly identified. The impact of autologous blood transfusion on survival has only occasionally been analyzed in cancer patients. OBJECTIVE: To determine the effect of perioperative allogeneic and autologous blood transfusions on survival in non-small cell lung cancer patients treated with curative pulmonary resection. METHODS: Of 493 consecutive patients, 185 (37.5%) received allogeneic blood products and 145 (29.4%) received autologous blood products, whereas 163 patients (33.1%) received no blood products. Survival analysis included univariate log-rank test and multivariate Cox regression model. RESULTS: Three-year survival probabilities in allogeneic, autologous, and nontransfused groups were 40%, 48%, and 61%, respectively, and the estimated 5-year survival probabilities were 34%, 38%, and 48%, respectively. In the univariate analysis there was a reduced survival in allogeneic versus nontransfused group (P <.01). In the multivariate analysis stage (P <.01), initial hemoglobin level (P =.01) and sedimentation rate (P =.03) remained significant factors, whereas the type of blood transfusion (allogeneic versus autologous) was no longer significant. There was no significant impact of transfusion in the multivariate analysis when patients in stage III or patients who underwent pneumonectomy were excluded. CONCLUSION: Neither allogeneic nor autologous blood transfusion has independent, adverse survival impact in non-small cell lung cancer patients treated with radical pulmonary resection.

[Microorganisms isolated from clinical specimens of patients from the Department of Thoracic Surgery]. / Drobnoustroje izolowane z materialów klinicznych torakochirurgicznej chorych z kliniki.

The clinical specimens received from patients hospitalized in Department of Thoracic Surgery between 1997 and 2001 were microbiologically examined. The main specimen for microbiological examination was pleural fluid (median 34%). The frequency of specimens from bronchial tree increased significantly (from 4% to 26%) with concurrent decrease of sputum (from 29% to 6%). Among isolated pathogens, Gram negative rods were the most frequent (median 48%) and Pseudomonas sp. was the main pathogen among them. Occurrence of staphylococci was median 22% and Staphylococcus aureus, with a little decrease in analyzed period, was still the main Gram positive pathogen. Simultaneously the occurrence of MRSA in the last three years dropped three times. The number of isolations of yeasts have risen from 5.8% to 10.3%.

[Infections in patients after thoracic surgery]. / Zakazenia u chorych po operacjach torakochirurgicznych.

UNLABELLED: Purpose of this paper was estimation of occurrence of postoperative complications caused by most common infection agents. Research covered 1662 hospitalised patients during 2000-2001. Clinical records of patients and results from bacteriological research were analysed. Analysis of etiological agents were based on 779 clinical samples. In postoperative period infection was observed in 138 patients (9.2%). Among them 158 episodes of infection occurred. Totally for 138 patients, 158 infections were observed in postoperative period. 9% of all (1662)-operated patients had postoperative infections. In that number were: 98 (6.5%)--bronchopulmonary infection, 25 (1.7%)--empyema, 21 (1.4%)--wound infections, 10 (0.7%)--urinary tract infection, 4 (0.3%)--sepsis. All those complications caused 14 deaths. CONCLUSIONS: 1. Thoracic surgeries were connected with quite high risk of postoperative infections. 2. The most common postoperative complication was bronchopneumonia. 3. The most common etiological agent in thoracic surgery infections was Pseudomonas aeruginosa.

[Results of treatment for chronic pleural empyema]. / Wyniki leczenia przewleklego ropniaka oplucnej.

UNLABELLED: The aim of the study was to assess the results of the treatment in 97 patients with chronic pleural empyema treated in the department of thoracic surgery between 1988 and 1997. The majority of patients were between 30 and 50 years old. Most of the group were men and more than a half had a concomitant disease, which may predispose to empyema development. Nevertheless all the empyemas were in the chronic phase 1/3 of patients were successfully treated only with closed chest tube drainage and the remaining group with lung decortication. The Gram-negative bacterial flora dominated in the culture from empyema sac. Spirometric values and blood gas analysis showed significant reduction of lung function before the treatment. We found the relation between an early institution of closed tube drainage and the shorter stay at the hospital. Moreover in a significant proportion of patients pleural drainage was a sufficient way of treatment. CONCLUSIONS: Drainage of the empyema should be performed at early phase of the disease. It should be recommended that pleural drainage precede the surgical management of empyema. Delate of surgical intervention is the main cause of the high mortality rate in empyema following esophageal perforation.

[Evaluation of anaerobic flora in lung neoplasms]. / Ocena flory beztlenowej guzów nowotworowych pluca.

Purpose of this study was to analyse the kind and frequency of anaerobic bacteria in the lower respiratory tract as well as susceptibility of the bacteria to antibiotics. Material from 35 patients with lung tumour derived from tumour and post-tumoural area sample. Collected sample was cultivated in anaerobic and aerobic conditions. Anaerobic bacteria were found in 23 (66%) samples. Totally there were 44 isolated of anaerobic bacteria strains. The most common G-negative strains belonged to genus of Bacteroides (11 strains); two types dominated: Bacteroides gracilis (4 strains) Bacteroides fragilis (4 strains). Among G-positive anaerobic bacteria most common were Peptostreptococcus (9 strains). G-positive rods were represented by Propionibacterium genus (8 strains). The susceptibility of anaerobic bacteria was estimated towards mostly used antibacterial drugs. Results suggest that most of bacteria were susceptible for imipenem, piperacillin/tazobactam, amoxicillin/clavulanate, ampicillin/sulbactam, metronidazole, piperacillin and clindamycin. Bacteria were less susceptible to roxitromycin and examined cephalosporins. Most of the strains were resistant for cefuroxime.

[P53 and P16 gene mutations in non-small cell lung cancer]. / Mutacje genów p53 i p16 w niedrobnokomórkowym raku pluca.

The aim of this study was to assess prospectively the occurrence of p53 and p16 mutations (considered separately and together) in NSCLC in terms of their clinical and prognostic relevance. Study group included 87 patients who underwent pulmonary resection for cure. p53 and p16 mutations were found in 22 (25%) and 14 (16%) cases, respectively. In eight patients (9%) both mutations were present, and the tendency for their common occurrence was significant (p = 0.02). There was no relation between mutation and clinical characteristics. Median survival in the entire group was 17 months and the 3-year survival probability--41%. There was no correlation between the occurrence of any mutation (considered separately or together) and survival. These results indicate that p53 and p16 gene mutations tend to occur together in NSCLC, however these alterations seem not to have noteworthy clinical and prognostic significance.

Decortication in chronic pleural empyema - effect on lung function.

OBJECTIVE: The aim of the present study is to evaluate the lung function before and after the lung decortication in patients with chronic pleural empyema (CPE). METHODS: Twenty-six patients with diagnosis of CPE were evaluated in a prospective manner by lung perfusion scintigraphy, blood gas analysis and spirometry before and 35 weeks (+/-17) after the lung decortication. RESULTS: Preoperative scintigraphy showed reduction of lung perfusion on the affected side to 24.5% (+/-12.6%) in 11 right side empyemas (predicted value 55%) and to 18% (+/-8%) in 15 left side empyemas (predicted value 45%). The postoperative measurements showed improvement in perfusion to 45.2% (+/-7.7%) in patients with right side empyema and 34.1% (+/-8.5%) with the left side affection. The preoperative vital capacity (VC) was reduced to 62.3% (+/-13.8%) of the predicted value and forced expiratory volume in 1s (FEV1) to 50% (+/-15.5%) of the predicted value. Postoperatively, slight improvement was achieved to 79.8 % (+/-12.9%) for VC and 69.2% (+/-12.7%) for FEV1. Blood gas analysis showed decreased values in majority of the patients before operation and significant improvement in postoperative evaluation. CONCLUSIONS: Perfusion and spirometry improves significantly in patients with CPE after the lung decortication but function of the affected lung remains impaired. There was no influence of the age, gender, side of the disease, bacteriology or duration of the empyema before operation on lung function.