Konrad Pawełczyk

Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) and lung cancer are widespread lung diseases. Cigarette smoking is a high risk factor for both the diseases. COPD may increase the risk of developing lung cancer. Thus, it is crucial to be able to distinguish between these two pathological states, especially considering the early stages of lung cancer. Novel diagnostic and monitoring tools are required to properly determine lung cancer progression because this information directly impacts the type of the treatment prescribed. In this study, serum samples collected from 22 COPD and 77 lung cancer (TNM stages I, II, III, and IV) patients were analyzed. Then, a collection of NMR metabolic fingerprints was modeled using discriminant orthogonal partial least squares regression (OPLS-DA) and further interpreted by univariate statistics. The constructed discriminant models helped to successfully distinguish between the metabolic fingerprints of COPD and lung cancer patients (AUC training=0.972, AUC test=0.993), COPD and early lung cancer patients (AUC training=1.000, AUC test=1.000), and COPD and advanced lung cancer patients (AUC training=0.983, AUC test=1.000). Decreased acetate, citrate, and methanol levels together with the increased N-acetylated glycoproteins, leucine, lysine, mannose, choline, and lipid (CH3-(CH2)n-) levels were observed in all lung cancer patients compared with the COPD group. The evaluation of lung cancer progression was also successful using OPLS-DA (AUC training=0.811, AUC test=0.904). Based on the results, the following metabolite biomarkers may prove useful in distinguishing lung cancer states: isoleucine, acetoacetate, and creatine as well as the two NMR signals of N-acetylated glycoproteins and glycerol.

Serum and whole blood Zn, Cu and Mn profiles and their relation to redox status in lung cancer patients

Disturbed redox status may be critical to lung cancerogenesis, however little research has been conducted on general changes in total redox status in lung cancer. Levels and activities of antioxidants, especially enzymatic ones, are related to trace element concentration. Trace element status is often disturbed in cancers, however no studies concerning the association between redox and trace element status have been performed for lung cancer. We hypothesized that disturbed redox status in lung cancer patients is partially determined by trace elements while their distribution amongst blood compartments may differ compared to healthy subjects. Blood samples from lung cancer patients (n=44) and control subjects (n=44) were collected to assess redox and trace element status. Serum and whole blood Cu and Mn levels were determined with GF-AAS, and Zn-with F-AAS. In serum the total antioxidant status (TAS) was determined with the commercial kit TAS (Randox, UK), total oxidant status (TOS) was determined based on the method developed by Erel and the oxidative stress index (OSI) was calculated. Total protein (T-Prot), albumin (Alb), uric acid (UA) and total bilirubin (T-Bil) concentrations were measured with an auto-analyser (Konelab 20i, Thermoscientific, USA), SOD and CAT activity - with commercially available kits (Cayman, USA). The level of TAS, T-Prot, Alb, T-Bil, the activity of SOD, the concentration of whole blood Mn as well as serum and whole blood Zn were lower while TOS, OSI, serum Cu levels and serum Cu:Zn ratios were higher in lung cancer patients compared to the control group. In the lung cancer group TAS correlated positively with Alb and UA, serum Zn and negatively with whole blood Mn. Additionally, SOD positively correlated with the whole blood Mn and Cu:Zn ratio, while CAT - negatively with the whole blood Cu:Zn ratio. In the lung cancer sub-group at clinical stage I-II, TOS additionally negatively correlated with whole blood Zn, and CAT negatively with serum Cu and Cu:Zn ratio. In advanced lung cancer, we found a positive correlation between TAS and serum Zn, and a negative one - with serum Cu:Zn ratio. We observed a similar correlation between endogenous non-enzymatic antioxidants and TAS in the control group, however considerably fewer correlations between trace elements and antioxidants were observed. This study supports the hypothesis that disturbed redox status in lung cancer patients is linked with alterations in trace element status regarding Zn, Mn and Cu. Moreover, the type of biological fluid influences both - alterations in the metal profile and relationships with redox status parameters.

Total antioxidant status in lung cancer is associated with levels of endogenous antioxidants and disease stage rather than lifestyle factors – preliminary study

Aim of the study Decreased total antioxidant capacity (TAC) has been reported in different neoplasms, including lung cancer. However, no study concerning the relationship between endogenous antioxidants, lifestyle factors, and TAC has been conducted among lung cancer patients. The purpose of the study was to investigate the associations between endogenous antioxidants, severity of disease, lifestyle factors, and TAC in lung cancer patients. Material and methods The study was conducted among 59 lung cancer patients. The levels of total antioxidant status (ATBS method), endogenous antioxidants, and C-reactive protein were measured in patients’ sera automatically. Dietary habits of the subjects were evaluated based on the Food Frequency Questionnaire (FFQ) on the day of admission to hospital. Results We found a positive correlation between serum albumin, uric acid (UA), and TAC and a negative correlation between CRP and TAC. Moreover, TAC was significantly positively associated with disease stage. We did not find any significant relationship between the frequency of selected food consumption and TAC in lung cancer patients, except for a positive correlation between the frequency of refined cereal products consumption and TAC level. Smoking status did not correlate with TAC. Conclusions Total antioxidant status of lung cancer patients results from their disease stage and levels of endogenous antioxidants rather than from lifestyle factors. The lack of influence of diet and smoking on the TAC presumably result from disturbed homeostasis in which cancer, while developing, could determine the redox state to a greater extent than lifestyle factors.

Treatment of Recurrent Primary Spontaneous Pneumothorax – Own Experience

UNLABELLED Primary spontaneous pneumothorax could be a serious therapeutic problem in case of recurrence. Lack of therapeutic standards sometimes leads to delay in definitive surgical treatment and could cause respiratory complications. The aim of the study was the evaluation of treatment results in patients with recurrence of primary spontaneous pneumothorax and looking for optimal therapeutic method after first recurrence (surgical treatment vs. pleural drainage). MATERIAL AND METHODS Between 01.01.2009 and 31.07.2010 fifty four patients with recurrent primary spontaneous pneumothorax was hospitalized in Wrocław Thoracic Surgery Centre (24.3% of all patients with pneumothorax). The recurrence was treated surgically in 24 cases, in 30 pleural drainage was performed: simple drainage (n=14) or drainage with chemical pleurodesis (n=16). Mean age of patients treated without surgery was higher than surgically treated (p=0,012). RESULTS In surgery group no recurrence was found, in drainage group 11 recurrences occurred (p=0.0009). In group of 11 patients with second recurrence, pleurodesis was performed four times (36%) vs. 12 times (63%) in 19 patients without a recurrence of the disease. 70% of non-surgically treated patients vs. 50% of surgically treated were afraid of recurrence (p=0.01). Among 11 patients in drainage group, nine underwent surgery at the second episode of recurrence. CONCLUSIONS The optimal treatment method in case of first recurrence of primary spontaneous pneumothorax is surgical treatment. When it is not possible chemical pleurodesis should be performed during pleural drainage. Most of the patients after second recurrence are treated surgically anyway. The surgical treatment significantly reduces patients fears for future recurrence of the disease. Younger patients are most often surgically treated.

Systemic redox status in lung cancer patients is related to altered glucose metabolism

Altered systemic redox status is often observed in lung cancer. However, detailed information on factors other, than smoking, which influence this perturbation is rather scarce. Elevated oxidative stress has been linked with disturbances in glucose metabolism before, but such associations have not been investigated in lung cancer. The aim of this study was to evaluate the relationship between systemic parameters of glucose metabolism and redox status in lung cancer patients (LC). Biochemical variables related to circulating glucose, i.e. glucose, insulin, c-peptide, fructosamine (FA), and glucose metabolism, i.e. β-hydroxybutyrate (BHB), lactate (LACT), non-esterified fatty acids (NEFAs), as well as redox status i.e. total antioxidant status (TAS) and total oxidant status (TOS) were determined for LC (n = 122) and control subjects (CS) (n = 84). HOMA-IR and the oxidative stress index (OSI) were calculated. LC patients had an altered redox status and glucose metabolism compared to CS. Positive correlations in LC were observed between TOS, OSI and circulating glucose as well as FA, while TAS positively correlated with BHB and NEFAs. In contrast, in metastatic LC, NEFAs and BHB positively correlated with OSI. Smoking status additionally stratified the observed relationships. In conclusion, we found that parameters related to circulating glucose or non-enzymatic glycation were correlated with oxidative stress (TOS and OSI), while metabolites such as BHB and NEFAs were correlated with antioxidant capacity (TAS). Metastasis prevalence and smoking seem to influence these correlations. However, the detailed mechanism of this relationship requires further research, in particular as regards the surprising positive correlation between NEFAs and TAS.

A rare case of calcifying fibrous pseudotumor of the pleura with an accompanying vascular anomaly in the pulmonary ligament

A 27-year old man without any significant comorbidities was admitted to the Department of Thoracic Surgery for the diagnosis and treatment of an operable tumor found accidentally during a routine examination. Tomography revealed a paraspinal tumorous lesion on the left side of the thoracic wall (Figs. 1, 2). The tumor was described as heterogeneous with calcifications in almost 1/4 of its volume. The examination did not show any additional vessels or atypical branches of the main artery. The presentation of the tumor in magnetic resonance indicated a benign, extrapleural lesion with calcifications, modeling the adjacent lung parenchyma, tangent to the descending aorta and intercostal artery, with no infiltration of the neighboring structures (Fig. 3). The patient was qualified for tumor resection with the use of video-assisted thoracoscopy. A polycyclic tumorous lesion adjoined to the surface of the lower lobe of the left lung was revealed intraoperatively. Taking into consideration the size and location of the lesion, a decision was made to mobilize the lung by releasing the pulmonary ligament. When a superficial incision of the ligament was performed, an artery was damaged – most likely a branch of the aorta. Conversion to classic anterolateral thoracotomy was performed due to massive hemorrhage. The bloody fluid accumulated in the pleural cavity was evacuated, and pressure was applied to the site of the bleeding. The damaged artery was sewn with vascular sutures on its distal section and the aortic wall. The tumor was excised within normal lung parenchymal margins. Due to significant blood loss, 3 units of packed red blood cells were administered; additional 3 units were administered postoperatively. Other blood derivatives, cryoprecipitate and fresh-frozen plasma (FFP), had to be used as well. A significant decrease in cardiopulmonary parameters necessitated the administration

Assessment of adequacy of intraoperative nodal staging and factors influencing the lack of its compliance with recommendations in the surgical treatment of non-small cell lung cancer (NSCLC)

Background Adequate pathological status of lymph nodes sampled during resection of NSCLC determines prognosis and decides on further therapeutic actions. The areas of analysis are the factors affecting evaluation of pN accuracy, and the convergence of recommendations with actual intraoperative sampling of lymph nodes. Methods The data of 3,215 patients with NSCLC consecutively operated with the intention of radical resection in 2007-2017, were analyzed. Accuracy of nodal sampling and influencing factors were compared with Union for International Cancer Control (UICC) guidelines, which recommend that to confirm pN0 status at least six lymph nodes/stations free of the disease must be removed. Three should be sampled from mediastinum (including subcarinal) and three from N1 stations. Results A significant number of patients were found to have an adequate staging, especially after 2009, in terms of recommended quantity of nodes/nodal stations (P<0.0001). Age ≥64 (P=0.048), left side (P<0.0001), sublobar resection (P<0.0001), T1 tumors (P=0.019) are the factors affecting inadequacy of staging. Patients with inaccurate staging were found to have a considerably lower pN1 (7.2% vs.15.9%, P<0.001) and pN2 (9.7% vs.13.4%, P<0.001) status. Survival of patients with inadequate staging were found to be significantly worse (P=0.0002), which resulted in worse survival of those patients in stage I (P=0.00004), stage II (P=0.023) and stage III (P=0.031) of NSCLC. Conclusions UICC recommendations led to an increased adequacy of nodal sampling. The factors affecting insufficient number of sampled nodes include advanced age, left side, sublobar resections and T1 stage. Inaccuracy of intraoperative nodal staging results in incorrect prognosis.

Metachronous Lung Cancer: Clinical Characteristics and Effects of Surgical Treatment

The occurrence of a second lung tumor after surgical removal of lung cancer usually indicates a lung cancer metastasis, but sometimes a new lesion proves to be a new primary lung cancer, i.e., metachronous lung cancer. The goal of the present study was to conduct a clinical evaluation of patients with metachronous lung cancer and lung cancer metastasis, and to compare the early and distant outcomes of surgical treatment in both cancer types. There were 26 age-matched patients with lung cancer metastases and 23 patients with metachronous lung cancers, who underwent a second lung cancer resection. We evaluated the histological type of a resected cancer, the extent of thoracosurgery, the frequency of early postoperative complications, and the probability of 5-year survival after the second operation. The findings were that metachronous lung cancer was adenocarcinoma in 52% of patients, with a different histopathological pattern from that of the primary lung cancer in 74% of patients. In both cancer groups, mechanical resections were the most common surgery type (76% of all cases), with anatomical resections such as segmentectomy, lobectomy, or pneumectomy being much rarer conducted. The incidence of early postoperative complications in metachronous lung cancer and lung cancer metastasis (30% vs. 31%, respectively) and the probability of 5-year survival after resection of either cancer tumor (60.7% vs. 50.9%, respectively) were comparable. In conclusion, patients undergoing primary lung cancer surgery require a long-term follow-up due to the risk of metastatic or metachronous lung cancer. The likelihood of metachronous lung cancer and pulmonary lung cancer metastases, the incidence of postoperative complications, and the probability of 5-year survival after resection of metachronous lung cancer or lung cancer metastasis are similar.

Left main bronchus separation after blunt trauma

Tracheobronchial damage is very rare in clinical practice and represents no more than 1% of all injuries caused by blunt trauma. Nearly 80% of patients die before reaching the hospital. Most ruptures are observed in the right main bronchus and are located within 2 cm of the carina trachea. The highest mortality rate applies to patients with bilateral bronchial injuries. Nonspecific symptoms, additionally masked by complaints regarding other damaged organs, delay the diagnosis and surgical treatment. The aim of this article is to present one particular clinical case and to discuss it in conjunction with a literature review.

The usefulness of routinely used malnutrition screening tools in predicting anemia in lung cancer patients

BACKGROUND Anemia and malnutrition are frequently observed during lung cancer development, and the associations between them have been researched. However, no study concerning the utility of routinely used nutritional screening tools in predicting anemia in lung cancer has been performed. OBJECTIVES The aim of this study was to assess the usefulness of routinely used malnutrition screening tools in predicting anemia in lung cancer patients. MATERIAL AND METHODS Eighty-five male patients were recruited to this study. Blood counts, serum iron concentration, total iron binding capacity (TIBC) and serum transferrin saturation (STS), measurements of selected anthropometric parameters, Mini Nutritional Assessment (MNA) and Glasgow Prognostic Score (GPS) were performed for the subjects. To evaluate the differences in the distribution of hematological and iron status parameters according to nutritional status, a t-test (Mann-Whitney U test for non-parametric data) and an analysis of variance (ANOVA) were performed. Tukeys post hoc test was performed for intergroup comparison of parametric data. The sensitivity, specificity, positive and negative predictive values of MNA and GPS were compared to blood counts and biochemical parameters of iron status. RESULTS Using the MNA test, we observed that ca. 60% of subjects had deteriorated nutritional status. About half of the patients had inflammation cumulated with malnutrition. A similar part of the subjects had anemia. The MNA test showed a significant difference in the distribution of Hb and Htc, while GPS showed the distribution of Fe and TIBC among lung cancer patients. We did not observe any influence of fat-free mass index (FFMI) on hematological and iron status parameters. The MNA test had very high specificity and positive predictive values (PPV) for all the hematological parameters evaluated as well as GPS for serum Fe concentration and TIBC. CONCLUSIONS Our data demonstrates that an evaluation of nutritional status with the MNA test can provide additional predictive information regarding anemia, while GPS may do the same with type of anemia in lung cancer patients.