Wojciech Dyszkiewicz

A novel method for the in vivo isolation of circulating tumor cells from peripheral blood of cancer patients using a functionalized and structured medical wire

The isolation of circulating tumor cells (CTCs) from the blood of patients afflicted with solid malignant tumors becomes increasingly important as it may serve as a ‘liquid biopsy’ with the potential of monitoring the course of the cancer disease and its response to cancer therapy, with subsequent molecular characterization. For this purpose, we functionalized a structured medical Seldinger guidewire (FSMW), normally used to obtain safe access to blood vessels and other organ cavities, with a chimeric monoclonal antibody directed to the cell surface expressed epithelial cell surface adhesion molecule (EpCAM). This medical device was optimized in vitro and its biocompatibility was tested according to the regulations for medical devices and found to be safe with no noteworthy side effects. Suitability, specificity and sensitivity of the FSMW to catch and enrich CTCs in vivo from circulating peripheral blood were tested in 24 breast cancer or non-small cell lung cancer (NSCLC) patients and in 29 healthy volunteers. For this, the FSMW was inserted through a standard venous cannula into the cubital veins of healthy volunteers or cancer patients for the duration of 30 min. After removal, CTCs were identified by immunocytochemical staining of EpCAM and/or cytokeratins and staining of their nuclei and counted. The FSMW successfully enriched EpCAM-positive CTCs from 22 of the 24 patients, with a median of 5.5 (0–50) CTCs in breast cancer (n=12) and 16 (2–515) CTCs in NSCLC (n=12). CTCs could be isolated across all tumor stages, including early stage cancer, in which distant metastases were not yet diagnosed, while no CTCs could be detected in healthy volunteers. In this observatory study, no adverse effects were noted. Evidently, the FSMW has the potential to become an important device to enrich CTCs in vivo for monitoring the course of the cancer disease and the efficacy of anticancer treatment.

Atrial fibrillation after surgery of the lung: clinical analysis of risk factors

OBJECTIVE The aim of this study was to determine which of the clinical parameters are the most valuable in predicting postoperative atrial fibrillation after lung surgery. MATERIALS AND METHODS Retrospective analysis was carried out on 298 patients after pulmonary resection necessitated mainly by lung cancer. The following parameters were investigated: age and sex, disturbances of cardiac rhythm, history of ischemic heart disease, diabetes and atherosclerosis, NYHA classification and type of surgical procedure. In addition, the duration of surgery, variations in oxygen saturation, changes in systemic blood pressure and heart-rate were noted intraoperatively. Statistical analysis was performed using Fishers exact test. RESULTS AND CONCLUSIONS Atrial fibrillation occurred in 25 cases (8.4%) and more frequently after pneumonectomy (24%). Other factors contributing to atrial fibrillation after lung surgery were: history of ischemic heart disease, congestive heart failure, intraoperative cardiac arrest and the need for rethoracotomy.

Early post-pneumonectomy complications in the elderly

OBJECTIVE The surgical treatment of non-small cell lung cancer (NSCLC) in elderly patients presents a serious challenge to thoracic surgeons. As there is considerable divergence of opinion about both the mortality and morbidity rates, it is important to set guidelines for proper patient selection. METHODS Early post-operative complications in 42 patients aged over 70 years who had undergone pneumonectomy because of NSCLC (Group I) were analyzed. The control group (Group II) consisted of 48 patients, also aged over 70 years, but who had undergone lobectomy or wedge resections. In both groups, the pre-operative conditions and 30-day morbidity and mortality were evaluated. RESULTS Postoperative complications occurred significantly more frequently in pneumonectomy patients (78.5%) than in Group II (58%). Transient or long-standing arrhythmias were noted in 20 patients (47.6%) from Group I and in 17 (35.4%) from Group II. Pulmonary complications occurred in 17 patients (40.4%) from Group I and 16 (33.3%) from Group II. The most important factors contributing to post-operative complications in pneumonectomy patients were performance status (WHO), chronic obstructive pulmonary disease (COPD) and elevated level of blood urea nitrogen (BUN). The highest impact on early mortality in pneumonectomy patients was exerted by COPD, arterial hypertension, formation of broncho-pleural fistula (BPF), the need for re-thoracotomy and high level of BUN. CONCLUSIONS (1) Pneumonectomy in patients over the age of 70 carries a considerable risk of severe post-operative complications and death, when compared to patients with less extensive pulmonary resections. (2) Elderly patients with impaired Performance Status (WHO 2 or more) and co-existing arterial hypertension, COPD and elevated level of BUN should be considered for pneumonectomy very carefully and cautiously.

Life-Threatening Aortic Hemorrhage During Pectus Bar Removal

This report presents an unusual case of late, aortic hemorrhage that occurred during the removal of the stabilizing bar 3 years after a Nuss operation. The primary reason for this complication was a rotation of the sternum bar, which caused chronic damage to the aorta and development of an aortomediastinal fistula. Cardiopulmonary bypass and implantation of an aortic prosthesis were required for successful treatment of this complication.

The early and late results of combined off-pump coronary artery bypass grafting and pulmonary resection in patients with concomitant lung cancer and unstable coronary heart disease

OBJECTIVE The aim of this study was to analyze the early and long-term results of simultaneous surgical treatment of both coronary heart disease (CHD) and lung cancer. METHODS Twenty-five patients with the diagnoses of both non-small cell lung cancer (NSCLC) and unstable angina were operated on between 2001 and 2006 in the Department of Cardiothoracic Surgery at the University of Medical Sciences in Poznań, Poland. Myocardial revascularization was performed simultaneously with the lung resection. The mean patient age was 63 years. The majority (18 patients) were male and the stage of lung cancer was predominantly AJCC II. Most of the patients were classified as stage II or III CCS and the predominant pathology was a two-vessel disease. Fifteen lobectomies, six pneumonectomies and four wedge resections were performed together with the aortocoronary graft implantation (mean: 1.9 graft per patient). RESULTS There were no postoperative deaths or perioperative myocardial infarctions (MI). The most frequent complications were as follows: atrial fibrillation (24%), atelectasis (12%) and residual pneumothorax (12%). All the patients were followed up for 8-60 months. Within this period, eight patients (32%) died, mostly due to the cancer relapse. The local recurrence of lung cancer and distant metastases were the only factors statistically influencing the late survival. No patient in the entire follow-up period had a MI. In three patients, the symptoms of recurrent angina occurred and one of them underwent a coronary stent implantation. CONCLUSIONS Simultaneous off-pump myocardial revascularization and lung resection is a safe and effective treatment when unstable CHD and lung cancer coexist. In selected patients, this combined procedure may be an alternative to the two-stage approach, surgical or non-surgical (cardiologic) interventions preceding the pulmonary resection. The only statistically significant factor having an impact on long-term survival is the recurrence of the cancer.

Lower preoperative fluctuation of heart rate variability is an independent risk factor for postoperative atrial fibrillation in patients undergoing major pulmonary resection

OBJECTIVES The following study presents a special independent atrial fibrillation (AF) risk factor-preoperative fluctuation of heart rate variability (HRV), as well as other perioperative AF risk factors in patients qualified for pneumonectomy and undergoing pneumonectomy or lobectomy for lung cancer. METHODS The prospective study was performed in patients who had undergone anatomical resection for non-small-cell lung cancer. A total of 117 patients (92 men and 25 women) qualified for statistical research. In order to determine the risk factors, all patients were divided into two groups: Group A-98 patients without AF and Group B-19 patients with AF during the perioperative time. A number of different risk factors of AF have been analysed and further divided into preoperative, operative and postoperative. RESULTS Postoperative AF occurred in 19 patients (16%), all of them were male. The patients with higher short-term HRV parameters (SD1, RMSSD), slower mean heart rate and those with a lower fluctuation of HRV-related parameters (HRV Afternoon, Night, Day (A/N/D)) before the operation, were more prone to AF. Postoperative risk of AF was higher in patients with a higher number of ventricular ectopic beats before the operation, a higher number of supraventricular and ventricular ectopic beats and a higher maximal heart rate after the operation. Statistical analysis revealed that male gender and the extent of pulmonary resection, particularly left pneumonectomy, constituted significant risk factors. AF was more often observed in patients who had ASA physical status score of III, in comparison with ASAI and ASAII patients. CONCLUSIONS Along with other concomitant AF risk factors presented in this work, the evaluation of the fluctuation tendencies of HRV parameters should be taken into consideration before any major lung resection. The balance disturbance between the sympathetic and parasympathetic nervous systems is responsible for AF.

Susceptibility loci in lung cancer and COPD: association of IREB2 and FAM13A with pulmonary diseases.

Genome-wide association studies have identified loci at 15q25 (IREB2) and 4q22 (FAM13A), associated with lung cancer (LC) and chronic obstructive pulmonary disease (COPD). The aim of our research was to determine the association of IREB2 and FAM13A SNPs with LC and severe/very severe COPD patients. We examined IREB2 variants (rs2568494, rs2656069, rs10851906, rs13180) and FAM13A (rs1903003, rs7671167, rs2869967) among 1.141 participants (468 LC, 149 COPD, 524 smoking controls). The frequency of the minor IREB2 rs2568494 AA genotype, was higher in LC vs controls (P = 0.0081, OR = 1.682). The FAM13A rs2869967 was associated with COPD (minor CC genotype: P = 0.0007, OR = 2.414). The rs1903003, rs7671167 FAM13A variants confer a protective effect on COPD (both P < 0.002, OR < 0.405). Haplotype-based tests identified an association of the IREB2 AAAT haplotype with LC (P = 0.0021, OR = 1.513) and FAM13A TTC with COPD (P = 0.0013, OR = 1.822). Cumulative genetic risk score analyses (CGRS), derived by adding risk alleles, revealed that the risk for COPD increased with the growing number of the FAM13A risk alleles. OR (95% CI) for carriers of ≥5 risk alleles reached 2.998 (1.8 to 4.97) compared to the controls. This study confirms that the IREB2 variants contribute to an increased risk of LC, whereas FAM13A predisposes to increased susceptibility to COPD.

Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first‑line platinum and pemetrexed therapy in NSCLC patients

AbstractPurpose We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy.MethodsThe following polymorphisms in DNA isolated from 115 patients were analyzed: various number of 28-bp tandem repeats in 5′-UTR region of TS gene, single nucleotide polymorphism (SNP) within the second tandem repeat of TS gene (G>C); 6-bp deletion in 3′-UTR region of the TS (1494del6); 677C>T SNP in MTHFR; 19007C>T SNP in ERCC1. Molecular examinations’ results were correlated with disease control rate, progression-free survival (PFS) and overall survival.ResultsPolymorphic tandem repeat sequence (2R, 3R) in the enhancer region of TS gene and G>C SNP within the second repeat of 3R allele seem to be important for the effectiveness of platinum and pemetrexed in first-line chemotherapy. The insignificant shortening of PFS in 3R/3R homozygotes as compared to 2R/2R and 2R/3R genotypes were observed, while it was significantly shorter in patients carrying synchronous 3R allele and G nucleotide. The combined analysis of TS VNTR and MTHFR 677C>T SNP revealed shortening of PFS in synchronous carriers of 3R allele in TS and two C alleles in MTHFR. The strongest factors increased the risk of progression were poor PS, weight loss, anemia and synchronous presence of 3R allele and G nucleotide in the second repeat of 3R allele in TS. Moreover, lack of application of second-line chemotherapy, weight loss and poor performance status and above-mentioned genotype of TS gene increased risk of early mortality.ConclusionThe examined polymorphisms should be accounted as molecular predictor factors for pemetrexed- and platinum-based front-line chemotherapy in non-squamous NSCLC patients.

Evaluation of serum amino acid profiles’ utility in non-small cell lung cancer detection in Polish population

OBJECTIVES Data from studies performed in Japanese and Korean populations suggest that free amino acid profiles have the potential to aid in non-small cell lung cancer (NSCLC) detection. However, there is still no data regarding abnormalities of free amino acids and their usefulness in NSCLC detection in European populations. The aim of the study was an evaluation of utility of amino acid profiles in NSCLC detection in Polish patients. MATERIALS AND METHODS Levels of 31 free amino acids were determined in 153 serum samples applying a liquid chromatography-tandem mass spectrometry-based methodology. Patients with I stage lung cancer represented a significant part of the studied group (46.7%). The obtained metabolite profiles along with clinical data were subjected to multivariate statistical tests. RESULTS The presented study indicated that the increased serum level of phenylalanine and decreased level of citrulline are among the most robust cancer signatures in blood of NSCLC group. In addition, increased levels of aspartic acid and β-alanine were also recognized as important features of NSCLC. Amino acid selected based on studies of Asian patients were found to have insufficient specificity in NSCLC detection in the studied population. Therefore, we proposed a new set of 6 amino acids (aspartic acid, β-alanine, histidine, asparagine, phenylalanine and serine), which ensured higher accuracy in sample classification (from 90.3% to 77.1% depending of histological type). CONCLUSION We indicated that some of the free amino acid alterations occur in serum of NSCLC patients in early stage of disease and thus they can be valuable components of a blood multi-marker panel for NSCLC detection.

Video-assisted thoracic surgery pneumonectomy: the first case report in Poland.

Minimally invasive video-assisted thoracic surgery (VATS) lobectomy has proved to be equal and in some aspects superior to open lobectomy in T1 and T2 lung cancers. Indications for VATS pneumonectomy however are still not clearly defined and strictly limited. The minimally invasive VATS pneumonectomy can be undertaken in patients with centrally located tumors without extended invasion of the large pulmonary vessels, chest wall, pericardium, mediastinal structures or proximal part of the main bronchus and when sleeve resection is not feasible (T2). We present a case of a patient who underwent left VATS pneumonectomy due to left lung cancer. Based on the preoperative examinations any kind of less extensive resection than pneumonectomy was excluded. Our VATS technique consisted of three incisions: two ports and a 5-6 cm long utility incision without any kind of rib spreading. The whole of the procedure was controlled on the monitor via a thoracoscope and the technique of resection was described in detail. Total surgery time was 130 min and blood loss was 150 ml. The chest tube was removed on the 2nd post-operative day and the patient was discharged home on the 8th postoperative day. The final histopathological examination confirmed squamous cell lung cancer (T2aN0M0 stage IB). In the authors’ opinion VATS pneumonectomy should be performed only in centers with extensive experience in minimally invasive VATS lobectomy. Despite limited indications for VATS pneumonectomy, if the patients fulfill the VATS pneumonectomy inclusion criteria they may gain from all the advantages of minimally invasive techniques.