Kshivets O. Lung Cancer Surgery

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  • LYMPH NODE METASTASES OF LUNG CANCER AND IMMUNE SYSTEMOleg Kshivets, MD, PhD Siauliai Cancer Center, Siauliai, LithuaniaThe Second International Chicago Symposium on Malignancies of The Chest and Head & NeckChicago, Illinois, The USA, 2001

  • Abstract: LYMPH NODE METASTASES OF LUNG CANCER AND IMMUNE SYSTEM Oleg Kshivets Siauliai Cancer Center, Siauliai, Lithuania Purpose: Significance of immune cell and humoral circuit in terms of detection of lung cancer (LC) patients (LCP) with lymph node metastases was investigated. Methods: In trial (1987-1998) consecutive cases after surgery, monitored 533 LCP (males 472, females 61; age=57.40.4 years; pneumonectomies -181, upper lobectomies - 138, lower lobectomies - 67, upper/lower bilobectomies - 24, middle lobectomies 6, segmentectomies 76, exploratory thoracotomies and biopsies - 41) with pathologic stage I-IV (stage I 48, stage II 47, stage III - 321; stage IV 117; squamous cell LC - 294, adenocarcinoma - 171, large cell LC 48, small cell LC - 20; T1 - 116, T2 - 168, T3 125, T4 - 124; N0 148, N1 - 144, N2 - 159; N3 82; G1 88, G2 166, G3 279; M0 438; M1 - 95) were reviewed. Variables selected for study were input levels of immunity blood parameters, sex, age, TNMG. Thawed aliquoted samples were evaluated for IgG, IgM, IgA, natural antibodies, circulating immune complexes. The percentage, absolute count and total population number (per human organism) of T-lymphocytes (CD3), B-lymphocytes (CD19), helper T-lymphocytes (CD4), suppressor/cytotoxic T-lymphocytes (CD8), killer cells (O-cells, K-cells or CD16), precursor T-cells (CD1), activated T-cells (CDw26), monocytes (CD64, CD13), helper/inducer T-lymphocytes (CD4+2H), contrsuppressor T-lymphocytes (CD8+VV), CD4/CD8, leukocytes, lymphocytes, polymorphonuclear and sticknuclear leukocytes were estimated. The laboratory blood studies also included input levels of NST (tests of oxygen dependent metabolism of neutrophils spontaneous and stimulated by Staphylococcus aureus or by Streptococcus pyogenes), index of stimulation of leukocytes by Staphylococcus aureus or Streptococcus pyogenes, index of thymus function, phagocytic number, phagocyte index, index of complete phagocytosis. Differences between groups were evaluated using multiple regression analysis, multi-factor clustering, structural equation modelling and Monte Carlo simulation. Results: It was revealed that separation of LCP with lymph node metastases (males 343, females 42; age=57.20.4 years; T1-4N1-3M0-1; tumor size=6.10.1 cm; n=385) from LCP without metastases (males 129, females 19; age=57.90.6 years; T1-3N0M0, tumor size=3.50.2 cm; n=148) significantly (P=0.000000) depended on: 1) level of immune cell circuit (2=31263.7; Df=560); 2) value of monocyte and macrophage circuit (2=233.9; Df=14); 3) level of humoral immunity (2=183.66; Df=9); 4) neutrophils circuit (2=7261.35; Df=77); 5) value of cell ratio factors (ratio of LC cell population to immune cell subpopulations in integral LCP organism) (2=6907.08; Df=104); 6) LC characteristics (T1-4, M0-1,G1-3, histology, tumor size) (2=1103.58; Df=27). It was also founded that most important factors of metastases of LC in lymph nodes were cell ratio factors (T=-5.761; P=0.0000000) and LC characteristics (T=9.666; P=0.0000000). Key words: Lung Cancer, Immunity, Lymph Node Metastases

  • The Main Characteristics of The Study PopulationsLung Cancer Patients (males 472, females 61; age=57.40.4 years)..533Stage I.....48Stage II....47Stage III.321Stage IV.117

    *

  • Procedures (n=533)Pneumonectomy181Upper Lobectomy.138Lower Lobectomy...67Upper/Lower Bilobectomy.24Middle Lobectomy6Segmentectomy...76Exploratory Thoracotomy, Biopsy...41 Combined & Extensive Procedures with Resection of Pericardium, Left Atrium, Aorta, Vena Cava Superior, Vena Azygos, Carina, Trachea, Diaphragm, Chest Wall, Ribs, etc. ..55

  • Lung Cancer Patients Characteristics (n=533)Squamous Cell..294Adenocarcinoma...171Large Cell48Small Cell.20T1...116T2168T3125T4124N0148

    N1...144N2...159N3.82G1.88G2...166G3...279M0...438M1.95

    *

  • Immune Testing:

    Factors of T-, B-, K-cell Circuit:

    Lymphocytes (%); Lymphocytes (abs)*109/l; Lymphocytes (tot) *109

    T-cells (%); T-cells (abs)*109/l; T-cells (tot)*109

    B-cells (%); B-cells (abs)*109/l; B-cells (tot)*109

    K-cells (%); K-cells (abs)*109/l; K-cells (tot)*109

    CD1 (%); CD1 (abs)*109/l; CD1 (tot)*109

    CDw26 (%); CDw26 (abs)*109/l; CDw26 (tot)*109

    CD4+2H (%); CD4+2H (abs)*109/l; CD4+2H (tot) *109

    CD8+VV (%); CD8+VV (abs)*109/l; CD8+VV (tot) *109

    CD4 (%); CD4 (abs)*109/l; CD4 (tot) *109

    CD8 (%); CD8 (abs)*109/l; CD8 (tot) *109

    CD4/CD8

    Index Thymus Function

    Factors of Monocyte and Macrophage Circuit:

    Monocytes (%); Monocytes (abs)*109/l; Monocytes (tot) *109

    Phagocyte Index; Phagocyte Number

    Index Complete Phagocytosis

    Factors of Humoral Immunity:

    IgG (g/l); IgM (g/l); IgA (g/l)

    Natural Antibodies

    Circulating Immune Complexes

    Factors of Neutrophil Circuit:

    NST spontaneous

    NST stimulated Staphylococcus aureus

    NST stimulated Streptococcus Pyogenes

    Index Stimulation by Staphylococcus aureus

    Index Stimulation by Streptococcus Pyogenes

    Leukocytes (abs)*109/l; Leukocytes (tot)*109

    Stick Neutrophils (%); Stick Neutrophils (abs)*109/l

    Stick Neutrophils (tot)*109

    Segmented Neutrophils (%); Segmented Neutrophils (abs)*109/l; Segmented Neutrophils (tot)*109

  • Significant Immune Data in Detection of Lung Cancer Lymph Node Metastases (n=533)

    NN

    Factors

    N0

    n=148

    N1-3

    n=385

    P

    Mean

    SD

    Mean

    SD

    1

    2

    B-cells (abs)*109/l

    B-cells (tot)*109

    0.36

    1.76

    0.37

    1.84

    0.31

    1.48

    0.18

    0.92

    0.027*

    0.020*

    3

    CD4+2H (abs)*109/l

    CD4+2H (tot) *109

    0.59

    2.83

    0.41

    1.89

    0.51

    2.46

    0.34

    1.78

    0.018*

    0.037*

    4

    5

    CD8 (%)

    CD8 (tot) *109

    14.03

    1.17

    8.20

    0.89

    12.50

    1.01

    7.79

    0.78

    0.045*

    0.045*

    6

    Lymphocytes (%)

    30.57

    10.78

    27.07

    11.10

    0.001*

    7

    8

    NST spontaneous

    NST stimulated Streptococcus Pyogenes

    7.33

    9.55

    6.30

    8.63

    9.16

    11.73

    9.15

    9.71

    0.026*

    0.017*

    9

    Index Stimulation by Streptococcus pyogenes

    1.46

    1.23

    1.87

    1.87

    0.013*

    10

    11

    12

    13

    Leukocytes (abs)*109/l

    Segmented Neutrophils (%)

    Segmented Neutrophils (abs)*109/l

    Segmented Neutrophils (tot)*109

    5.94

    61.78

    3.69

    17.84

    2.32

    11.14

    1.60

    8.20

    6.45

    65.17

    4.25

    20.12

    2.53

    11.49

    1.96

    9.30

    0.031*

    0.002*

    0.002*

    0.009*

    15

    16

    17

    18

    19

    20

    21

    22

    23

    24

    25

    26

    27

    28

    29

    T-cells/Cancer Cells

    B-cells/Cancer Cells

    K-cells/Cancer Cells

    CD1/Cancer Cells

    CDw26/Cancer Cells

    CD4+2H/Cancer Cells

    CD8+VV/Cancer Cells

    CD4/Cancer Cells

    CD8/Cancer Cells

    Leukocytes/Cancer Cells

    Eosinophils/Cancer Cells

    Lymphocytes/Cancer Cells

    Monocytes/Cancer Cells

    Stick Neutrophils/Cancer Cells

    Segmented Neutrophils/Cancer Cells

    1.76

    0.73

    1.02

    0.31

    0.19

    1.11

    1.13

    1.40

    0.47

    10.99

    0.31

    3.43

    0.40

    0.12

    6.72

    1.60

    1.24

    1.79

    0.52

    0.33

    1.08

    1.36

    1.29

    0.58

    8.72

    0.37

    3.94

    0.50

    0.20

    5.25

    0.78

    0.28

    0.47

    0.14

    0.09

    0.47

    0.47

    0.64

    0.19

    5.62

    0.31

    1.52

    0.18

    0.08

    3.65

    0.62

    0.22

    0.43

    0.21

    0.14

    0.41

    0.49

    0.57

    0.17

    3.09

    0.27

    1.09

    0.21

    0.14

    2.09

    0.000000*

    0.000000*

    0.000000*

    0.000000*

    0.000002*

    0.000000*

    0.000000*

    0.000000*

    0.000000*

    0.000000*

    0.000053*

    0.000000*

    0.000000*

    0.004333*

    0.000000*

  • Results of Logistic Regression Modeling in Detection of Lymph Node Metastases of Lung Cancer (n=533)

    NN

    Significant Immune Factors: (2=47.281; Df=14; P=0.00002; n=533;

    Estimate

    1

    2

    3

    4

    5

    6

    7

    8

    9

    10

    11

    12

    13

    14

    Const.B0

    CD4+2H (abs)*109/l

    CD4+2H (tot)*109

    CD8 (%)

    CD8 (tot) *109

    B-cells (abs)*109/l

    B-cells (tot)*109

    NST spontaneous

    NST stimulated Streptococcus pyogenes

    Index Stimulation by Streptococcus pyogenes

    Leukocytes (abs)*109/l

    Lymphocytes (%)

    Segmented Neutrophils (%)

    Segmented Neutrophils (abs)*109/l

    Segmented Neutrophils (tot)*109

    -2.60217

    -4.62834

    0.82

    -0.01852

    -0.04143

    1.64540

    -0.62571

    0.06071

    -0.02167

    0.26358

    0.48

    0.01332

    0.03823

    -0.02550

    -0.09027

  • Correlation between Lymph Node Metastasis & Lung Cancer Characteristics (n=533)

  • T- & B-cell Circuit in Detection of Lung Cancer Lymph Node Metastases (n=533)

  • CD8- & CD4-cell Circuit in Detection of Lung Cancer Lymph Node Metastases (n=533)

  • Lymphocytes & Monocy