Functional and Disability Outcomes in NSCLC Patients Post-Lobectomy Undergoing Pulmonary Rehabilitation: A Biopsychosocial Approach.

Worldwide, lung cancer remains the predominant cause of cancer cases and deaths and poses significant health challenges, with surgical resection being a key treatment. Post-surgery, patients often experience functional impairments. This study aimed to develop a comprehensive ICF version for assessing the functional profile and disability in lung cancer patients post-thoracic surgery undergoing pulmonary rehabilitation using the ICF and WHODAS 2.0 tool. We analyzed the correlation between the ICF Core Set and WHODAS 2.0 data to understand the impact on daily functioning. This study included 50 patients (23 F, 27 M) from the Clinic of Thoracic Surgery and Respiratory Rehabilitation in Lodz. Essential ICF codes were determined using the Delphi method, and assessments were conducted on the third day post-operation. Statistical analyses included various tests with α = 0.05. The results showed no impairments in voice functions (b310), respiration rates (b4400), and diaphragm functions (b4451), but there were significant issues with chest pain (b28011), respiratory muscle functions (b445), exercise tolerance (b455), and muscle endurance (b740). In Activities and Participation and Environmental Factors, most codes were not problematic, except for employment (d845, d850) and atmospheric pressure (e2252). Significant correlations were found between mobility limitations (d410, d460) and self-care (d510, d540) with the WHODAS 2.0 results. The comprehensive ICF Core Set effectively described the functional profile of post-surgery patients, confirming its utility and highlighting the impact of disability on daily functioning.

Assessment of the Functioning Profile of Patients with Lung Cancer Undergoing Lobectomy in Relation to the ICF Rehabilitation Core Set.

Lung cancer often presents with pain and breathlessness, frequently necessitating surgical procedures, such as lung lobectomy. A pivotal component of postoperative care is rehabilitation, aimed not only at improving the clinical condition but also at influencing the patient's functional profile. In a study conducted at the Clinic of Thoracic Surgery and Respiratory Rehabilitation in the Regional Multispecialist Center for Oncology and Traumatology of the Nicolaus Copernicus Memorial Hospital in Lodz, the effectiveness of rehabilitation intervention was assessed in 50 patients (n = 27 M, n = 23 F) postlobectomy due to early stage nonsmall cell lung cancer (NSCLC). The International Classification of Functioning, Disability, and Health-ICF Rehabilitation Core Set was used to evaluate the functional profile, the modified Laitinen scale for pain assessment, and the modified Borg scale for breathlessness evaluation. Additionally, lung-expansion time was monitored. The significance level of the statistical tests in this analysis was set at α = 0.05. The study employed an analysis of the normality of the distributions of the numerical variables, reporting of variable distributions, estimation of differences between groups, estimation of differences within groups, estimation of the independence of categorical variables, and regression analysis. The research confirmed that rehabilitation partially improves the functional profile of patients and reduces the sensation of breathlessness postsurgery. The study highlighted the need for future research with a larger number of participants and an extended observation period to gain a deeper understanding of the impact of rehabilitation on patients after lung lobectomy procedures.

Correlation of TIMP1-MMP2/MMP9 Gene Expression Axis Changes with Treatment Efficacy and Survival of NSCLC Patients.

In the course of lung cancer, normal cells are transformed into cancerous ones, and changes occur in the microenvironment, including the extracellular matrix (ECM), which is not only a scaffold for cells, but also a reservoir of cytokines, chemokines and growth factors. Metalloproteinases (MMPs) are among the elements that enable ECM remodeling. The publication focuses on the problem of changes in the gene expression of MMP2, MMP9 and tissue inhibitor of metalloproteinases (TIMP1) in the blood of NSCLC patients during therapy (one year after surgical resection of the tumor). The paper also analyzes differences in the expression of the studied genes in the tumor tissue, as well as data collected in publicly available databases. The results of blood tests showed no differences in the expression of the tested genes during therapy; however, changes were observed in cancerous tissue, which was characterized by higher expression of MMP2 and MMP9, compared to non-cancerous tissue, and unchanged expression of TIMP1. Nevertheless, higher expression of each of the studied genes was associated with shorter patient survival. Interestingly, it was not only the increased expression of metalloproteinase genes, but also the increased expression of the metalloproteinase inhibitor (TIMP1) that was unfavorable for patients.

The Interaction between Four Polymorphisms and Haplotype of ABCB1, the Risk of Non-Small Cell Lung Cancer, and the Disease Phenotype.

P-glycoprotein, product of the ABCB1 (ATP binding cassette subfamily B member 1) gene, has been reported to play an important role in multiple drug resistance during cancer therapy. However, its influence on non-small cell lung cancer (NSCLC) risk has not been clearly defined. The aim of the present study was to examine the association between clinicopathological factors and SNPs T-129C, C1236T, G2677T/A, and C3435T, as well as its haplotype, and to investigate the role of ABCB1 polymorphisms in NSCLC development. The study included 80 patients who suffered from NSCLC and underwent surgery to remove the tumour and 96 healthy controls. The tissues were genotyped by PCR-RFLP and sequencing methods, and the haplotype frequencies in both groups were estimated. The SNP C3435T was identified as a NSCLC risk factor. The presence of mutated allelic variant T (p=0.0103) or homozygote TT (p=0.0099) was observed significantly more often in cancer patients than in healthy controls. The two groups also demonstrated a highly significant difference in common haplotype frequency (p=0.01). The T-129-T1236-T2677-T3435 haplotype was found to be most closely associated with NSCLC risk. Although the investigated polymorphisms were not related to demographic features, clinicopathological lung tumour characteristics, or blood morphology indices, marginally significant correlations were found with some variables: C1236T with age of disease onset (p=0.0410); C3435T with smoking status (p=0.0561). As the findings indicate, lung cancer and control groups demonstrate significantly different patterns of -129/1236/2677/3435 haplotype distribution; T-T-T-T haplotype contributes to NSCLC susceptibility, and this effect is probably mainly dependent on C3435T. So far, similar studies were published in other populations.

HMGA1 gene expression level in cancer tissue and blood samples of non-small cell lung cancer (NSCLC) patients: preliminary report.

The study aimed to assess the HMGA1 gene expression level in NSCLC patients and to evaluate its association with selected clinicopathological features and overall survival of patients. The expression of the HMGA1, coding non-histone transcription regulator HMGA1, was previously proved to correlate with the ability of cancer cells to metastasize the advancement of the disease. The prognostic value of the HMGA1 expression level was demonstrated in some neoplasms, e.g., pancreatic, gastric, endometrial, hepatocellular cancer, but the knowledge about its role in non-small cell lung cancer (NSCLC) is still limited. Thus, the HMGA1 expression level was evaluated by real-time PCR method in postoperative tumor tissue and blood samples collected at the time of diagnosis, 100 days and 1 year after surgery from 47 NSCLC patients. Mean HMGA1 expression level in blood decreased systematically from the time of cancer diagnosis to 1 year after surgery. The blood HMGA1 expression level 1 year after surgery was associated with the tobacco smoking status of patients (p= 0.0230). Patients with high blood HMGA1 expression levels measured 100 days after surgery tend to have worse overall survival than those with low expression levels (p= 0.1197). Tumor HMGA1 expression level was associated with neither features nor the overall survival of NSCLC patients. Moreover, no correlation between HMGA1 expression level measured in tumor tissue and blood samples was stated. Blood HMGA1 mRNA level could be a promising factor in the prognostication of non-small cell lung cancer patients.

Prognostic value of selected platelet parameters of patients operated for non-small cell lung cancer.

Background: Platelets play a vital role in the neoplastic process. Platelet parameters are hence an important source of information concerning ongoing neoplastic disease. The aim of the study is to assess the impact of selected platelet parameters on the survival of patients with non-small cell lung cancer (NSCLC). Methods: The study included 532 (174 female and 358 male) patients aged 36-84 years (mean age 63.6 years) operated on due to NSCLC, staged IA-IIIA. Before the operation, all patients received a blood morphology test. The following parameters were subjected to statistical analysis: platelet count, mean platelet volume (MPV) parameter, platelet distribution width (PDW) parameter, platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation (SII) index. These findings were compared with the clinical data of the patients, and the probability of overall survival was analyzed. Results: The univariate analysis revealed a correspondence between PDW, MPV, PLR and SII index and patient survival. The multivariate analysis including patient clinical data found the following factors to have negative prognostic value for patients operated on due to NSCLC: male sex, advancement stage of neoplastic disease and Charlson Comorbidity Index (CCI) above 4, and PLR >144. Conclusions: PDW value, PLR and SII index are independent prognostic factors. In the multi-factor model, male sex, the advancement stage of the neoplastic disease, CCI above 4 and PLR lower than 144 had the greatest prognostic value.

Changes in the expression of membrane type-matrix metalloproteinases genes (MMP14, MMP15, MMP16, MMP24) during treatment and their potential impact on the survival of patients with non-small cell lung cancer (NSCLC).

The analysis concerned the comparison of the expression of membrane type matrix metalloproteinases genes in the blood and tissue of NSCLC patients during the course of the disease and comparison to the control group. Blood and neoplastic tissue taken from 45 patients diagnosed with non-small cell lung cancer was a research material. The expression level of MMP14, MMP15, MMP16 and MMP24 was evaluated by qPCR and the results were compared with controls. The expression of MMP14 and MMP24 before tumor removal surgery and 100 days after was lower than in the control group. Interestingly, one year after surgery the levels of expression of these genes were identical to those in the control group. This suggests that the expression of metalloproteinase genes changes in the course of cancer and that effective treatment results in the normalization of gene expression. Lower expression of MMP15 in the blood of patients with more advanced cancer disease was observed, confirming the suppressive nature of changes in the blood. It has also been demonstrated that higher expression of MMP14 and MMP15 in the tissue is associated with more advanced stage of disease development or more invasive nature of the lesion. There is a noticeable increase of expression level in the environment surrounding the tumor, while a lower can be observed in the blood. This may indicate that changes in the expression of metalloproteinases in cancer are much more complex than merely the tumor tissue, which may also account for the inadequacies of metalloproteinase inhibitors.

The Prognostic Significance of Preoperative Platelet-to-Lymphocyte and Neutrophil-to-Lymphocyte Ratios in Patients Operated for Non-Small Cell Lung Cancer.

INTRODUCTION: The aim of the study was to determine the prognostic significance of PLR and NLR ratios in patients operated due to non-small cell lung cancer. MATERIAL: The study group consisted of 532 (174 women, 358 men) patients with non-small cell lung cancer (NSCLC) staged IA-IIIA. The mean age was 63.6 years (range 36 to 84 years). Together with platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR), the following factors were included in the statistical analysis: age, sex, smoking history, the number of leukocytes, neutrophils, and platelets, histopathology, T-stage, N-stage, concomitant diseases according to the Charlson Comorbidity Index (CCI), type of operation, adjuvant chemotherapy, and overall survival. RESULTS: Univariate analysis showed an association between the value of PLR and NLR and the length of survival. Multivariate analysis found that the stage of advancement of the neoplastic disease (p=0.00003), adjuvant chemotherapy (p=0.009), CCI > 4 (0.00008), and PLR > 144 (p=0.001) were negative prognostic factors for survival > 2 years; however, this effect diminishes in patients surviving more than 5 years. CONCLUSION: PLR might serve as a prognostic factor in patients affected by NSCLC with expected two-year overall survival.

Clinical significance of HRAS and KRAS genes expression in patients with non-small-cell lung cancer - preliminary findings.

BACKGROUND: The RAS family protooncogenes, including KRAS, NRAS and HRAS, encode proteins responsible for the regulation of growth, differentiation and survival of many cell types. The HRAS and KRAS oncogene mutations are well defined, however, the clinical significance of RAS expressions in non-small-cell lung cancer (NSCLC) is still uncertain. METHODS: A total of 39 whole blood samples of NSCLC (the investigated group), collected at three points of time: at the time of diagnosis, 100 days and 1 year after the surgery as well as 35 tissue samples obtained during the surgery were included in this study. HRAS and KRAS genes mRNA expression were assessed using quantitative real-time polymerase chain reaction techniques. RESULTS: Increased relative HRAS mRNA level in blood was found significantly more frequently in the group of smokers (p = 0.008). Patients with squamous cell carcinoma subtypes of NSCLC were more likely to show an overexpression of HRAS gene in blood, but not statistically significant (p = 0.065). In tumor tissue overexpression of HRAS gene was associated with adenocarcinoma subtype (p = 0.049). No statistically significant associations were found for the expression of KRAS with any clinicopathological parameters, except the age of patients, within the study. There were no differences between the relative HRAS and KRAS genes expression levels in blood samples taken from the same patients during the 3 observation points, as well as between blood collected from patients before surgery and tissue samples obtained during operation. CONCLUSION: The potential associations between high HRAS expression levels, age, smoking status and histological type of cancer were observed, which emphasizes the need for further study of the RAS family. Therefore, subsequent research involving larger numbers of patients and a longer follow-up, as well as multicenter study are necessary to confirm our findings.

Prognostic Factors Determining Survival of Patients Operated for Non-Small Cell Lung Cancer with Consideration Given to Morphological Parameters of Blood.

INTRODUCTION: Prognostic biomarkers are the area of high interest in non-small cell lung cancer (NSCLC). Inflammatory blood markers can be routinely determined from complete blood counts which are inexpensive and reliable. The aim of the study was to determine prognostic parameters which, in early diagnostics, best determine survival of patients, operated on due to NSCLC. MATERIALS: The study was conducted on 532 (174 females and 358 males) patients, operated on due to NSCLC, in stages IA - III, aged 36-84 years (the mean age: 63.6 years). The following parameters were subjected to a statistical analysis, conducted in order to determine prognostic values of the number of leukocytes, neutrophils, monocytes, platelets, haemoglobin, RDW-CV and MCV, calculated values of PLR, NLR, and LMR ratios, age, sex, smoking, histopathological diagnosis, T stage, N stage, the Charlson Comorbidity Index (CCI), type of surgery, and potential complications. RESULTS: The univariate analysis revealed an impact of NLR, PLR, and LMR values, RDW-CW and CCI ranges, and also the number of monocytes on patients' overall survival (OS). The multivariate analysis identified six independent negative prognostic factors: male sex (0.001), CCI > 4 (p=0.000007), RDW-CV > 14.5% and PLR > 144 (p=0.000001, p= 0.001, respectively), the number of metastatic N2 lymphatic nodes (p=0.0003), and existence of post-operative complications (p=0.008). CONCLUSION: Patients' sex, RDW and PLR values, Charlson index, the number of involved N2 nodes by cancer and postoperative complications are independent and significant prognostic factors in patients operated on due to NSCLC.

Prognostic value of red blood cell distribution width-standard deviation (RDW-SD) in patients operated on due to non-small cell lung cancer.

BACKGROUND: The aim of the study was to determine a survival prognostic value of selected blood morphological rates of patients, operated on due to non-small cell lung cancer (NSCLC). METHODS: The study was conducted on 532 patients, surgically treated due to NSCLC, in stages IA-IIIA, 174 females and 358 males, mean age 63.6 years (36-84 years) were included in the study. Blood parameters and clinical factors were included in statistical analysis, in order to determine potential prognostic values of red blood cell distribution width-standard deviation (RDW-SD), mean corpuscular volume (MCV) of red cell and hemoglobin. Factors contained: age, sex, smoking history, histopathological diagnosis, T category, N category, age-adjusted Charlson Comorbidity Index (CCI), number of lymphocytes, neutrophils, monocytes, platelets, the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), kind of surgery, patient survival. RESULTS: The univariate analysis revealed a dependence of the value of RDW-SD and CCI values, the number of monocytes, NLR and PLR values, neoplasia stage and the overall survival. The multivariate analysis confirmed that not only N2 category and the value of CCI above 4 are negative prognostication factors, but also RDW-SD above 43 fL (P=0.00007) and PLR above 138 (P=0.001) are such negative factors of survival prognosis. CONCLUSIONS: RDW-SD is an independent and significant prognostic factor of patients' survival operated on due to NSCLC.

The impact of ABCB1 gene polymorphism and its expression on non-small-cell lung cancer development, progression and therapy - preliminary report.

The ABCB1 gene belongs to ATP binding cassette (ABC) transporter genes that has been previously implicated in cancer progression and drug response. This study aimed to evaluate the association between the SNP 3435 and the expression of the ABCB1 gene in lung cancer patients in the Polish population in comparison to clinicopathological parameters and treatment. 150 RNA and 47 DNA samples were isolated from 49 lung cancer cases including both tissue samples and blood taken from the same patients at three time points: diagnosis, 100 days and one year after the surgical intervention. Qualitative and real-time PCR analysis of expression were done, also genotyping by PCR-RFLP. Mutant homozygous TT and allele T are present statistically significantly more frequently in the group of patients with lung cancer. There is no difference with expression level in lung cancer tissue and blood sample taken from the same patients before surgical treatment. On the basis of blood samples analysis it was observed that the expression level of ABCB1 mRNA was growing in time. Higher levels were marked after 100 days and one year after the surgical intervention. The complementary pharmacological treatment induced higher expression levels of ABCB1. The presented data suggest an important role of ABCB1 in lung cancer, the increasing level of ABCB1 mRNA which can be connected with induction of multidrug resistance mechanism is also significant, that observation must be confirmed in further analysis.

Prognostic value of neutrophil-to-lymphocyte, platelet-to-lymphocyte and lymphocyte-to-monocyte ratio ratios in patients operated on due to non-small cell lung cancer.

BACKGROUND: The aim of the study was to determine a prognostic value of the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR) and the lymphocyte to monocyte ratio (LMR) ratios for survival of patients, operated on due to non-small cell lung cancer (NSCLC). METHODS: The study was conducted on 532 patients, operated on due to NSCLC, in stages IA-IIIA. A total of 174 females and 358 males, aged 36-84 years (the mean age: 63.6 years) were included in the study. The following factors were subject to a statistical analysis, conducted for determination of potential prognostic values of NLR, PLR and LMR ratios: age, sex, nicotinism, the number of leukocytes, neutrophils, monocytes, platelets, histopathological diagnosis, T category, N category, the Charlson comorbidity index (CCI), kind of surgery, patient survival. RESULTS: The single-factor analysis revealed a relationship between NLR, PLR and LMR values, CCI values, the number of monocytes and the length of survival. The multi-factor analysis confirmed that for patients with expected 2-year survival, PLR above 138 (P=0.0008) is another negative prognostic factor, apart from the stage of the neoplastic disease and CCI above 4. For 5-year survival, such a relationship was not observed. CONCLUSIONS: The PLR ratio is an independent and significant prognostic factor for expected, over 2-year survival of patients operated on due to NSCLC.

Five-year survival analysis and prognostic factors in patients operated on for non-small cell lung cancer with N2 disease.

BACKGROUND: The aim of the study is to analyse 5-year survival and prognostic factors in patients operated due to lung cancer with postoperatively confirmed metastases to N2 group nodes. METHODS: In the years 2007-2015, 1,148 patients with lung cancer were treated surgically. A postoperative histopathological study confirmed N2 feature in 150 patients. One hundred and ten patients, in whom a 5-year survival analysis was possible to perform, were included in such analysis. The patients underwent the following procedures: pneumonectomy, 31 patients; lobectomy, 61; bilobectomy, 10; and wedge resection, 8. All patients were subjected to supplementary treatment after the surgery. RESULTS: Five-year survival was achieved in 23 patients (21%). The patients' survival did not depend on the type of surgery, type of tumour, its location or presence of metastases in N1 nodes (P=0.82, P=0.51, P=0.36 and P=0.23, respectively). A statistically significant correlation was observed (P=0.01) between the 5-year survival of a patient and the occurrence of metastases only in one group of lymph nodes of the N2 feature (22 patients, 20%). Involvement of three or more mediastinal nodal groups resulted in survival shorter than 5-year. CONCLUSIONS: (I) In patients with the N2 feature, the type of performed surgery, type of tumour and the occurrence of metastases in the lymph nodes of the lung hilum do not affect 5-year survival; (II) involvement of only one nodal group allows to achieve 5-year survival in 20% of patients; (III) involvement of three and more nodal groups with the N2 feature results in decreased 5-year survival.

Transthoracic versus transhiatal esophagectomy - influence on patient survival.

AIM: To evaluate the survival of patients after surgery of the esophagus/cardia using the transthoracic and transhiatal methods. MATERIAL AND METHODS: In the years 2007-2011, 102 patients were radically treated for cancer of the esophagus/cardia: 24 women and 78 men at the average age of 59.5. There were 38 transthoracic procedures and 64 transhiatal procedures. All patients had a conduit made from the stomach, led through lodges in the esophagus and combined with the stump of the esophagus in the neck following the Collard method. Two-pole lymphadenectomies were performed in all patients. RESULTS: Patients after transthoracic procedures had statistically more (p < 0.05) lymph nodes removed than patients after transhiatal procedures. The 5-year survival rates in transhiatal and transthoracic procedures did not statistically differ, being 8% and 0% respectively. The length of patient survival was influenced by metastases in the nearby lymph nodes (p < 0.0001) and the presence of adenocarcinoma. CONCLUSIONS: Surgical access (transhiatal and transthoracic surgery) does not affect the 5-year survival rates. Transhiatal surgery allows a greater number of lymph nodes to be removed. The main factor influencing the 5-year survival rate is the presence of metastases in the nearby lymph nodes.

Expression profiles of cancer stem cell markers: CD133, CD44, Musashi-1 and EpCAM in the cardiac mucosa-Barrett's esophagus-early esophageal adenocarcinoma-advanced esophageal adenocarcinoma sequence.

INTRODUCTION: Barrett's esophagus (BE), which develops as a result of gastroesophageal reflux disease, is a preneoplastic condition for esophageal adenocarcinoma (EAC). A new hypothesis suggests that cancer is a disease of stem cells, however, their expression and pathways in BE - EAC sequence are not fully elucidated yet. AIMS: We used a panel of putative cancer stem cells markers to identify stem cells in consecutive steps of BE-related cancer progression. METHODS: Immunohistochemistry was performed on formalin-fixed, paraffin-embedded blocks from 58 patients with normal cardiac mucosa (n=5), BE (n=14), early EAC (pT1) from mucosal resection (n=17) and advanced EAC (pT1-T4) from postoperative specimens (n=22). Expression of the CD133, CD44, Musashi-1 and EpCAM was analyzed using respective monoclonal antibodies. RESULTS: All markers showed a heterogeneous expression pattern, mainly at the base of the crypts of Barrett's epithelium and EAC, with positive stromal cells in metaplastic and dysplastic lesions. Immuno-expression of EpCAM, CD44 and CD133 in cardiac mucosa was significantly lower (mean immunoreactivity score (IRS)=1.2; 0.0; 0.4; respectively) compared to their expression in Barrett's metaplasia (mean IRS=4.3; 0.14; 0.7; respectively), in early adenocarcinoma (mean IRS=4.4; 0.29; 1.3; respectively) and in advanced adenocarcinoma (mean IRS=6.6; 0.7; 2.7; respectively) (p<0.05). On the contrary, Musashi-1 expression was higher in BE and early ADC compared to GM and advanced ADC (NS). CONCLUSION: Our results suggest that the stem cells could be present in premalignant lesions. EpCAM, CD44 and CD133 expression could be candidate markers for BE progression, whereas Musashi-1 may be a marker of the small intestinal features of Barrett's mucosa.