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ARTFICIAL INTELLIGENCE, SYSTEM ANALYSIS AND SIMULATION MODELING IN PREDICTION OF  5-YEAR SURVIVAL OF CARDIOESOPHAGEAL CANCER  PATIENTS AFTER COMPLETE LEFT THORACOABDOMINAL ESOPHAGOGASTRECTOMIES   Oleg Kshivets, MD, PhD   Department of Surgery, Siauliai Public Hospital & Cancer Center, Lithuania The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Abstract ARTFICIAL INTELLIGENCE, SYSTEM ANALYSIS AND SIMULATION MODELING IN PREDICTION OF 5-YEAR SURVIVAL OF CARDIOESOPHAGEAL CANCER  PATIENTS AFTER COMPLETE LEFT THORACOABDOMINAL ESOPHAGOGASTRECTOMIES Oleg Kshivets  Department of Surgery, Siauliai Public Hospital & Cancer Center, Siauliai, Lithuania OBJECTIVE: We examined the clinicomorphologic factors associated with the low- and high-risk of generalization of cardioesophageal cancer (CEC) (T1-4N0-3M0) after complete esophagogastrectomies (EG) through left thoracoabdominal incision.     METHODS: We analyzed data of 150 consecutive CEC patients (CECP) (age=54.9±0.7 years; tumor size=6.9±0.2 cm) radically operated and monitored in 1975-2006 (males=116, females=34; combined EG with resection of pancreas, liver, diaphragm, colon transversum, splenectomies=49; lymphadenectomy D2=59, D3=91; esophagogastroanastomosis=89, esophagoenteroanastomosis=61; adenocarcinoma=125, squamos=19, mix=6; T1=16, T2=32, T3=58, T4=44; N0=59, N1=18, N2=71; N3=2; G1=42, G2=30, G3=78). Variables selected for 5-year survival (5YS) study were input levels of 45 blood parameters, sex, age, TNMPG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of CECP were evaluated using a log-rank test. Multivariate Cox modeling, multi-factor clustering, discriminant analysis, structural equation modeling, Monte Carlo, bootstrap simulation and neural networks computing were used to determine any significant dependence.     RESULTS: 44 CECP (life span: LS=3545.8±238.7 days) lived more than 5 years without any features of CEC progressing (5YS=29.3%). 106 CECP died because of generalization of CEC during the first 5 years after radical procedures (LS=593.5±32.6 days). Cox modeling displayed that 5YS of CECP (n=150) after complete EG significantly depended on: T1-4, combined procedures, histology, G1-3, blood lymphocytes, monocytes, neutrophils, lymphoid infiltration of CEC, age (P=0.000-0.038). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS of CECP and combined procedures (rank=1), N0-3 (2), histology (3), gender (4), CEC growth (5), type of operations (6), P1-4 (7), T1-4 (8), adjuvant chemoimmunotherapy (9), G1-3 (10), blood coagulation time (11), blood lymphocytes (12), thrombocytes (13), blood rest nitrogen (14), hemorrhage time (15), ESS (16), age (17), weight (18), blood chlorides (19), tumor size (20). CONCLUSIONS: Correct prediction of CECP survival after radical procedures was 90.7% by logistic regression (odds ratio=86.7), 96% by discriminant analysis and 100% by neural networks computing (area under ROC curve=1.0; error=0.0012).   The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Data Males…………………………………………….. 116 Females………..………………………………….. 34 Age=54.9±0.7 years Tumor Size=6.9±0.2 cm Only Surgery.…………………………………... 132 Adjuvant Chemoimmunotherapy (5FU+thymalin/taktivin, 5-6 cycles)……………. 18 The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Radical Procedures Proximal Esophagogastrectomies with Single-Stage Esophagogastroplasty.…………………. 81 Total Esophagogastrectomies with Single-Stage Esophagoenteroplasty..………..……………… 69 Combined Esophagogastrectomies with Resection of Diaphragm, Liver, Mesocolon, Colon Transversum, Splenectomy, Left Hemipancreatectomy,  etc……………………. 49 Lymphadenectomy D2………………………... 59 Lymphadenectomy D3………………………... 91 The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Schemas of Procedures The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Procedures
One-Stage  Esophagogastroplasty or Esophagoenteroplasty
Schemas of Combined Procedures The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Schemas of D3 Lymphadenectomy The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Staging T1…… 16   N0..….. 59   G1………… 42 T2…… 32   N1…… 18   G2………… 30 T3…… 58   N2…… 71   G3………… 78 T4…… 44   N3…….. 2 exophytic growth………….. 53 endophytic growth……….... 85 mix growth..……………….. 12 adenocarcinoma…………… 93 squamos cell carcinoma…… 52 mix carcinoma………………. 5   The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Survival Rate 5-Year Survivors…………..……. 44 (29.3%)   10-Year Survivors………………. 18 (12.0%) Losses…………………………… 106 (70.7%) General Life Span=  1459.5 ±132 days For 5-Year Survivors=  3545.8±238.7 days For Losses=  593.5±32.6 days Cumulative 5-Year Survival……. 29.3% Cumulative 10-Year Survival…... 22.4% Cumulative 15-Year Survival…... 20.2% The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
General Cardioesophageal Cancer Patients Survival  after Complete Left Thoracoabdominal Esophagogastrectomies (Kaplan-Meier) ( n=150 ) The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Univariate Analysis in Prediction of Cardioesophageal Cancer Patients Survival  ( n=150 )
Results of Univariate Analysis in Prediction of Cardioesophageal Cancer Patients Survival  ( n=150 )
Results of Univariate Analysis in Prediction of Cardioesophageal Cancer Patients Survival  ( n=150 ) The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Cox Regression Modeling in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 )   Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper Eosinophils% 6.539 1 0.011 1.802 1.147 2.829 Stick.Neutrophils% 12.447 1 0.000 2.298 1.447 3.648 Seg.Neutrophils% 14.680 1 0.000 2.379 1.527 3.706 Lymphocytes% 11.949 1 0.001 2.212 1.410 3.469 Monocytes% 12.832 1 0.000 2.303 1.459 3.634 T1-4 12.579 3 0.006 T(1) 11.124 1 0.001 0.196 0.075 0.510 T(2) 6.870 1 0.009 0.349 0.159 0.767 T(3) 1.409 1 0.235 0.672 0.348 1.296 Ad.CHIT 0.648 1 0.421 0.744 0.362 1.529 Age 10.419 1 0.001 1.042 1.016 1.068 Comb.operation 15.523 6 0.017   The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Cox Regression Modeling in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 )   Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper Histology 15.864 2 0.000 Histology(1) 13.556 1 0.000 8.361 2.700 25.894 Histology(2) 15.753 1 0.000 9.631 3.147 29.473 Lymphocytes abs 5.423 1 0.020 6.126 1.332 28.166 Seg.Neutrophils abs 4.899 1 0.027 0.495 0.265 0.923 G1-3 6.539 2 0.038 G(1) 5.907 1 0.015 0.519 0.305 0.881 G(2) 3.578 1 0.059 0.565 0.313 1.021 LIT 32.081 3 0.000 LIT(1) 25.546 1 0.000 6.648 3.189 13.858 LIT(2) 23.429 1 0.000 5.804 2.848 11.829 LIT(3) 1.084 1 0.298 1.424 0.732 2.768   The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Discriminant Analysis   in  Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Discriminant Function Analysis Summary   Wilks' Lambda: 0.305 approx. F (61,88)=3.281  p< 0.0000   Wilks'  Partial  F-remove  P-level    Lambda  Lambda  (1,88)      LIT 0 .403 0.757 28.238 0.000 Comb.Operation 0.319 0.956 4.032 0.048 Erythrocytes   0 .319 0.956 4.012 0.048 Weight 0 .319 0.958 3.893 0.052 Glucose 0.318 0.962 3.503 0.065 Growth 0.312 0.979 1.904 0.171 G1-3 0.308 0.990 0.854 0.358 Ad.CHIT 0.307 0.995 0.402 0.528 T1-4 0.306 0.999 0.128 0.722 N0-3 0.306 0.999 0.064 0.801 The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Logistic Regression Analysis   in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 )   Est.  S.E. Wald    P Odds 95.0% C.I.for Odds Ratio    Ratio Lower Upper Const.B  18.24  9.25 3.89  0.049 8.3e+7 0.95 5.8e+12 Seg.Neut.%  -0.21  0.10 4.44  0035 0.81 0.67 0.99 Monocytes abs-5.46  2.51  4.74  0.030 0.00 0.00 0.608 LIT  1.99  0.42 22.38  0.000 7.28 3.18 16.70 G1-3  -0.59  0.42 2.02  0.155 0.55 0.24 1.26 Growth  1.54  0.71 4.75  0.029 4.69 1.15 19.04 Comb.Oper.  -0.47  0.16 8.75  0.003 0.63 0.46 0.86 T1-4  -0.26  0.48 0.29 0.589 0.77 0.30 1.99 N0-3  -0.20  0.40  0.26 0.613 0.817 0.370 1.80 Chi2=105.11; df=15;  P=0.0000 ; Odds ratio=86.70 The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Correspondence Analysis in Prediction of Cardioesophageal Cancer Patients Survival (n=150)   The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Multi-Factor Clustering of Clinicopathological Data in Prediction of Cardioesophageal Cancer Patients Survival (n=150) The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Neural Networks  in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 )   Baseline Errors=0.0012 Area under ROC curve=1 .00 Correct Classification Rate= 100%   Losses   5-year survivors   Total 106   44     Correct 106   44     Wrong  0   0 Genetic Algorithm Selection Useful for   L   ESS Haemor.Time  Protein  PI  D  Histology G1-3 Growth  Sabs   Survival  Yes  Yes  Yes  Yes  Yes  Yes  Yes  Yes  Yes  Yes Useful for   Lymabs  Comb.Oper.  P1-4  L/CC  S/CC  T1-4  N0-3  Chlorides  Stot Survival   Yes  Yes  Yes  Yes  Yes  Yes  Yes  Yes  Yes   The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of  Kohonen Self-Organizing  Neural Networks Computing  in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150)   The 60th Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Neural Networks Computing   in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 )   Error=0.0011; Area under ROC Curve=1.00; Correct Classification Rate=100% Factor Rank Error Ratio Comb.Operat. 1 0.199 159.5 N0-3 2 0.185 148.0 Histology 3 0.172 138.0 Sex 4 0.166 133.1 Growth  5 0.164 130.9 Oper. Type 6 0.153 122.6 P1-4 7 0.117 94.0 T1-4 8 0.109 87.2 Ad.CHIT 9 0.106 84.7 G1-3 10 0.071 57.1 Coag.Time 11 0.029 23.5 Lymph.% 12 0.029 23.2 Factor Rank Error Ratio Thr.tot 13 0.023 18.2 Rest Nitrogens 14 0.019 15.2 Haem.Time 15 0.007 5.6 ESS 16 0.005 3.8 Age 17 0.003 2.6 Weight 18 0.003 2.5 Chlorides 19 0.002 1.9 D 20 0.002 1.8 St.Neutr.tot 21 0.002 1.6 Protein 22 0.002 1.5 L/CC 23 0.002 1.4 Erythrocytes 24 0.002 1.4 The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Bootstrap Simulation  in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 )   Number of Samples=3333 Significant Factors Rank Kendall’s Tau-A   P< LIT 1 0.316 0.000 D 2 -0.196 0.000 P1-4 3 -0.189 0.000 Leucocytes/CC 4 0.188 0.000 HC/CC 5 0.187 0.000 Erythrocytes/CC 6 0.186 0.000 Lymphocytes/CC 7 0.185 0.000 T1-4 8 -0.184 0.000 N0-3 9 -0.176 0.000 Seg.Neutrophils/CC  10 0.167 0.000 Thrombocytes/CC 11 0.160 0.000 Monocytes/CC 12 0.146 0.000 The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Bootstrap Simulation  in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 )   Number of Samples=3333 Significant Factors Rank Kendall’s Tau-A   P< Eosinophils/CC 13 0.124 0.000 Operation Type 14 -0.119 0.000 G1-3 15 -0.119 0.000 Histology 16 -0.118 0.000 Chlorides 17 0.106 0.000 Coagulation Time 18 -0.096 0.000 Growth 19 -0.092 0.000 Stick Neutrophils/CC 20 0.068 0.000 Protein 21 0.063 0.000 Combined Operation  22 0.048 0.000 Rest Nitrogens 23 0.042 0.001 Colour Index 24 0.041 0.000 The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Results of Bootstrap Simulation  in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 )   Number of Samples=3333 Significant Factors Rank Kendall’s Tau-A   P< ESS 25 0.038 0.002 Erythrocytes tot 26 0.038 0.002 Thrombocytes 27 -0.033 0.005 Adjuvant CHIT 28 0.031 0.005 Eosinophils tot 29 0.028 0.018 Leucocytes tot 30 0.027 0.023 Sex 31 0.027 0.023 Weight 32 0.026 0.024 Haemorrhage Time 33 0.026 0.024 Monocytes tot   34 0.024 0.05 The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Classification of Cases by Logistic Regression, n=150,  Odds Ratio=86.7 Observed  Pred.Losses  Pred.Survivors  Correct Losses   102  4  96.2% 5-Year Survivors  10  34  77.3% Total  112  38  90.7% Classification of Cases by Discriminant Analysis, n=150 Observed  Pred.Losses  Pred.Survivors  Correct Losses   105  1  99.1% 5-Year Survivors  5  39  88.6% Total  110  44  96 .0% Classification of Cases by Neural Networks, n=150, Errors=0.0012 Observed  Pred.Losses  Pred.Survivors  Correct Losses   106  0  100% 5-Year Survivors  0  44  100% Total  106  44  100 % The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Ratio of Lymphocytes to Cancer Cells & Glucose Level  in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 )   The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Prognostic SEPATH-Model of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies, n=150   The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Holling-Tenner Models of Cardioesophageal  Cancer Cell Population and  Cytotoxic Cell Population Dynamics
Cardioesophageal Cancer Dynamics
Conclusions: 5-year survival and life span  of cardioesophageal cancer patients after complete esophagogastrectomies significantly depended on:  1) cell ratio factors: ratio of cancer cell population to blood cell subpopulations in integral patient organism; 2) cancer characteristics (cancer cell population number, TNMG-system);  3) the data of blood cell circuit, biochemical homeostasis and hemostasis system; 4) character of surgical procedure; 5) anthropometric data. The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Conclusions: Optimal treatment strategies for cardioesophageal  cancer patients are: 1) screening and early detection of cardioesophageal cancer;  2) availability of very experienced surgeons because of complexity of radical procedures; 3) aggressive en block surgery for completeness;  4) precise prediction;  5) adjuvant chemioimmunotherapy for patients with  unfavorable prognosis.  The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA
Address: Oleg Kshivets  M.D., Ph.D., Consultant Thoracic, Abdominal, General Surgeon & Surgical Oncologist  Surgery Department, Siauliai Public Hospital & Cancer Center Tilzes:42-16, LT78206 Siauliai, Lithuania Tel. 37041-416614 e-mail: kshivets@yahoo.com  http//:myprofile.cos.com/Kshivets The 60 th  Annual Meeting of Society of Surgical Oncology  March 15-18, 2007, Washington , DC, the USA

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Kshivets O. Cardioesophageal Cancer Surgery

  • 1. ARTFICIAL INTELLIGENCE, SYSTEM ANALYSIS AND SIMULATION MODELING IN PREDICTION OF 5-YEAR SURVIVAL OF CARDIOESOPHAGEAL CANCER PATIENTS AFTER COMPLETE LEFT THORACOABDOMINAL ESOPHAGOGASTRECTOMIES Oleg Kshivets, MD, PhD Department of Surgery, Siauliai Public Hospital & Cancer Center, Lithuania The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 2. Abstract ARTFICIAL INTELLIGENCE, SYSTEM ANALYSIS AND SIMULATION MODELING IN PREDICTION OF 5-YEAR SURVIVAL OF CARDIOESOPHAGEAL CANCER PATIENTS AFTER COMPLETE LEFT THORACOABDOMINAL ESOPHAGOGASTRECTOMIES Oleg Kshivets Department of Surgery, Siauliai Public Hospital & Cancer Center, Siauliai, Lithuania OBJECTIVE: We examined the clinicomorphologic factors associated with the low- and high-risk of generalization of cardioesophageal cancer (CEC) (T1-4N0-3M0) after complete esophagogastrectomies (EG) through left thoracoabdominal incision.     METHODS: We analyzed data of 150 consecutive CEC patients (CECP) (age=54.9±0.7 years; tumor size=6.9±0.2 cm) radically operated and monitored in 1975-2006 (males=116, females=34; combined EG with resection of pancreas, liver, diaphragm, colon transversum, splenectomies=49; lymphadenectomy D2=59, D3=91; esophagogastroanastomosis=89, esophagoenteroanastomosis=61; adenocarcinoma=125, squamos=19, mix=6; T1=16, T2=32, T3=58, T4=44; N0=59, N1=18, N2=71; N3=2; G1=42, G2=30, G3=78). Variables selected for 5-year survival (5YS) study were input levels of 45 blood parameters, sex, age, TNMPG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of CECP were evaluated using a log-rank test. Multivariate Cox modeling, multi-factor clustering, discriminant analysis, structural equation modeling, Monte Carlo, bootstrap simulation and neural networks computing were used to determine any significant dependence.     RESULTS: 44 CECP (life span: LS=3545.8±238.7 days) lived more than 5 years without any features of CEC progressing (5YS=29.3%). 106 CECP died because of generalization of CEC during the first 5 years after radical procedures (LS=593.5±32.6 days). Cox modeling displayed that 5YS of CECP (n=150) after complete EG significantly depended on: T1-4, combined procedures, histology, G1-3, blood lymphocytes, monocytes, neutrophils, lymphoid infiltration of CEC, age (P=0.000-0.038). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS of CECP and combined procedures (rank=1), N0-3 (2), histology (3), gender (4), CEC growth (5), type of operations (6), P1-4 (7), T1-4 (8), adjuvant chemoimmunotherapy (9), G1-3 (10), blood coagulation time (11), blood lymphocytes (12), thrombocytes (13), blood rest nitrogen (14), hemorrhage time (15), ESS (16), age (17), weight (18), blood chlorides (19), tumor size (20). CONCLUSIONS: Correct prediction of CECP survival after radical procedures was 90.7% by logistic regression (odds ratio=86.7), 96% by discriminant analysis and 100% by neural networks computing (area under ROC curve=1.0; error=0.0012). The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 3. Data Males…………………………………………….. 116 Females………..………………………………….. 34 Age=54.9±0.7 years Tumor Size=6.9±0.2 cm Only Surgery.…………………………………... 132 Adjuvant Chemoimmunotherapy (5FU+thymalin/taktivin, 5-6 cycles)……………. 18 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 4. Radical Procedures Proximal Esophagogastrectomies with Single-Stage Esophagogastroplasty.…………………. 81 Total Esophagogastrectomies with Single-Stage Esophagoenteroplasty..………..……………… 69 Combined Esophagogastrectomies with Resection of Diaphragm, Liver, Mesocolon, Colon Transversum, Splenectomy, Left Hemipancreatectomy, etc……………………. 49 Lymphadenectomy D2………………………... 59 Lymphadenectomy D3………………………... 91 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 5. Schemas of Procedures The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 7. One-Stage Esophagogastroplasty or Esophagoenteroplasty
  • 8. Schemas of Combined Procedures The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 9. Schemas of D3 Lymphadenectomy The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 10. Staging T1…… 16 N0..….. 59 G1………… 42 T2…… 32 N1…… 18 G2………… 30 T3…… 58 N2…… 71 G3………… 78 T4…… 44 N3…….. 2 exophytic growth………….. 53 endophytic growth……….... 85 mix growth..……………….. 12 adenocarcinoma…………… 93 squamos cell carcinoma…… 52 mix carcinoma………………. 5 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 11. Survival Rate 5-Year Survivors…………..……. 44 (29.3%) 10-Year Survivors………………. 18 (12.0%) Losses…………………………… 106 (70.7%) General Life Span= 1459.5 ±132 days For 5-Year Survivors= 3545.8±238.7 days For Losses= 593.5±32.6 days Cumulative 5-Year Survival……. 29.3% Cumulative 10-Year Survival…... 22.4% Cumulative 15-Year Survival…... 20.2% The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 12. General Cardioesophageal Cancer Patients Survival after Complete Left Thoracoabdominal Esophagogastrectomies (Kaplan-Meier) ( n=150 ) The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 13. Results of Univariate Analysis in Prediction of Cardioesophageal Cancer Patients Survival ( n=150 )
  • 14. Results of Univariate Analysis in Prediction of Cardioesophageal Cancer Patients Survival ( n=150 )
  • 15. Results of Univariate Analysis in Prediction of Cardioesophageal Cancer Patients Survival ( n=150 ) The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 16. Results of Cox Regression Modeling in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper Eosinophils% 6.539 1 0.011 1.802 1.147 2.829 Stick.Neutrophils% 12.447 1 0.000 2.298 1.447 3.648 Seg.Neutrophils% 14.680 1 0.000 2.379 1.527 3.706 Lymphocytes% 11.949 1 0.001 2.212 1.410 3.469 Monocytes% 12.832 1 0.000 2.303 1.459 3.634 T1-4 12.579 3 0.006 T(1) 11.124 1 0.001 0.196 0.075 0.510 T(2) 6.870 1 0.009 0.349 0.159 0.767 T(3) 1.409 1 0.235 0.672 0.348 1.296 Ad.CHIT 0.648 1 0.421 0.744 0.362 1.529 Age 10.419 1 0.001 1.042 1.016 1.068 Comb.operation 15.523 6 0.017 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 17. Results of Cox Regression Modeling in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper Histology 15.864 2 0.000 Histology(1) 13.556 1 0.000 8.361 2.700 25.894 Histology(2) 15.753 1 0.000 9.631 3.147 29.473 Lymphocytes abs 5.423 1 0.020 6.126 1.332 28.166 Seg.Neutrophils abs 4.899 1 0.027 0.495 0.265 0.923 G1-3 6.539 2 0.038 G(1) 5.907 1 0.015 0.519 0.305 0.881 G(2) 3.578 1 0.059 0.565 0.313 1.021 LIT 32.081 3 0.000 LIT(1) 25.546 1 0.000 6.648 3.189 13.858 LIT(2) 23.429 1 0.000 5.804 2.848 11.829 LIT(3) 1.084 1 0.298 1.424 0.732 2.768 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 18. Results of Discriminant Analysis in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Discriminant Function Analysis Summary Wilks' Lambda: 0.305 approx. F (61,88)=3.281 p< 0.0000 Wilks' Partial F-remove P-level Lambda Lambda (1,88) LIT 0 .403 0.757 28.238 0.000 Comb.Operation 0.319 0.956 4.032 0.048 Erythrocytes 0 .319 0.956 4.012 0.048 Weight 0 .319 0.958 3.893 0.052 Glucose 0.318 0.962 3.503 0.065 Growth 0.312 0.979 1.904 0.171 G1-3 0.308 0.990 0.854 0.358 Ad.CHIT 0.307 0.995 0.402 0.528 T1-4 0.306 0.999 0.128 0.722 N0-3 0.306 0.999 0.064 0.801 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 19. Results of Logistic Regression Analysis in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Est. S.E. Wald P Odds 95.0% C.I.for Odds Ratio Ratio Lower Upper Const.B 18.24 9.25 3.89 0.049 8.3e+7 0.95 5.8e+12 Seg.Neut.% -0.21 0.10 4.44 0035 0.81 0.67 0.99 Monocytes abs-5.46 2.51 4.74 0.030 0.00 0.00 0.608 LIT 1.99 0.42 22.38 0.000 7.28 3.18 16.70 G1-3 -0.59 0.42 2.02 0.155 0.55 0.24 1.26 Growth 1.54 0.71 4.75 0.029 4.69 1.15 19.04 Comb.Oper. -0.47 0.16 8.75 0.003 0.63 0.46 0.86 T1-4 -0.26 0.48 0.29 0.589 0.77 0.30 1.99 N0-3 -0.20 0.40 0.26 0.613 0.817 0.370 1.80 Chi2=105.11; df=15; P=0.0000 ; Odds ratio=86.70 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 20. Results of Correspondence Analysis in Prediction of Cardioesophageal Cancer Patients Survival (n=150) The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 21. Results of Multi-Factor Clustering of Clinicopathological Data in Prediction of Cardioesophageal Cancer Patients Survival (n=150) The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 22. Neural Networks in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Baseline Errors=0.0012 Area under ROC curve=1 .00 Correct Classification Rate= 100% Losses 5-year survivors Total 106 44 Correct 106 44 Wrong 0 0 Genetic Algorithm Selection Useful for L ESS Haemor.Time Protein PI D Histology G1-3 Growth Sabs Survival Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Useful for Lymabs Comb.Oper. P1-4 L/CC S/CC T1-4 N0-3 Chlorides Stot Survival Yes Yes Yes Yes Yes Yes Yes Yes Yes The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 23. Results of Kohonen Self-Organizing Neural Networks Computing in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150) The 60th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 24. Results of Neural Networks Computing in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Error=0.0011; Area under ROC Curve=1.00; Correct Classification Rate=100% Factor Rank Error Ratio Comb.Operat. 1 0.199 159.5 N0-3 2 0.185 148.0 Histology 3 0.172 138.0 Sex 4 0.166 133.1 Growth 5 0.164 130.9 Oper. Type 6 0.153 122.6 P1-4 7 0.117 94.0 T1-4 8 0.109 87.2 Ad.CHIT 9 0.106 84.7 G1-3 10 0.071 57.1 Coag.Time 11 0.029 23.5 Lymph.% 12 0.029 23.2 Factor Rank Error Ratio Thr.tot 13 0.023 18.2 Rest Nitrogens 14 0.019 15.2 Haem.Time 15 0.007 5.6 ESS 16 0.005 3.8 Age 17 0.003 2.6 Weight 18 0.003 2.5 Chlorides 19 0.002 1.9 D 20 0.002 1.8 St.Neutr.tot 21 0.002 1.6 Protein 22 0.002 1.5 L/CC 23 0.002 1.4 Erythrocytes 24 0.002 1.4 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 25. Results of Bootstrap Simulation in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Number of Samples=3333 Significant Factors Rank Kendall’s Tau-A P< LIT 1 0.316 0.000 D 2 -0.196 0.000 P1-4 3 -0.189 0.000 Leucocytes/CC 4 0.188 0.000 HC/CC 5 0.187 0.000 Erythrocytes/CC 6 0.186 0.000 Lymphocytes/CC 7 0.185 0.000 T1-4 8 -0.184 0.000 N0-3 9 -0.176 0.000 Seg.Neutrophils/CC 10 0.167 0.000 Thrombocytes/CC 11 0.160 0.000 Monocytes/CC 12 0.146 0.000 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 26. Results of Bootstrap Simulation in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Number of Samples=3333 Significant Factors Rank Kendall’s Tau-A P< Eosinophils/CC 13 0.124 0.000 Operation Type 14 -0.119 0.000 G1-3 15 -0.119 0.000 Histology 16 -0.118 0.000 Chlorides 17 0.106 0.000 Coagulation Time 18 -0.096 0.000 Growth 19 -0.092 0.000 Stick Neutrophils/CC 20 0.068 0.000 Protein 21 0.063 0.000 Combined Operation 22 0.048 0.000 Rest Nitrogens 23 0.042 0.001 Colour Index 24 0.041 0.000 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 27. Results of Bootstrap Simulation in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Number of Samples=3333 Significant Factors Rank Kendall’s Tau-A P< ESS 25 0.038 0.002 Erythrocytes tot 26 0.038 0.002 Thrombocytes 27 -0.033 0.005 Adjuvant CHIT 28 0.031 0.005 Eosinophils tot 29 0.028 0.018 Leucocytes tot 30 0.027 0.023 Sex 31 0.027 0.023 Weight 32 0.026 0.024 Haemorrhage Time 33 0.026 0.024 Monocytes tot 34 0.024 0.05 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 28. Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) Classification of Cases by Logistic Regression, n=150, Odds Ratio=86.7 Observed Pred.Losses Pred.Survivors Correct Losses 102 4 96.2% 5-Year Survivors 10 34 77.3% Total 112 38 90.7% Classification of Cases by Discriminant Analysis, n=150 Observed Pred.Losses Pred.Survivors Correct Losses 105 1 99.1% 5-Year Survivors 5 39 88.6% Total 110 44 96 .0% Classification of Cases by Neural Networks, n=150, Errors=0.0012 Observed Pred.Losses Pred.Survivors Correct Losses 106 0 100% 5-Year Survivors 0 44 100% Total 106 44 100 % The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 29. Ratio of Lymphocytes to Cancer Cells & Glucose Level in Prediction of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies (n=150 ) The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 30. Prognostic SEPATH-Model of Cardioesophageal Cancer Patients Survival after Complete Esophagogastrectomies, n=150 The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 31. Holling-Tenner Models of Cardioesophageal Cancer Cell Population and Cytotoxic Cell Population Dynamics
  • 33. Conclusions: 5-year survival and life span of cardioesophageal cancer patients after complete esophagogastrectomies significantly depended on: 1) cell ratio factors: ratio of cancer cell population to blood cell subpopulations in integral patient organism; 2) cancer characteristics (cancer cell population number, TNMG-system); 3) the data of blood cell circuit, biochemical homeostasis and hemostasis system; 4) character of surgical procedure; 5) anthropometric data. The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 34. Conclusions: Optimal treatment strategies for cardioesophageal cancer patients are: 1) screening and early detection of cardioesophageal cancer; 2) availability of very experienced surgeons because of complexity of radical procedures; 3) aggressive en block surgery for completeness; 4) precise prediction; 5) adjuvant chemioimmunotherapy for patients with unfavorable prognosis. The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA
  • 35. Address: Oleg Kshivets M.D., Ph.D., Consultant Thoracic, Abdominal, General Surgeon & Surgical Oncologist Surgery Department, Siauliai Public Hospital & Cancer Center Tilzes:42-16, LT78206 Siauliai, Lithuania Tel. 37041-416614 e-mail: kshivets@yahoo.com http//:myprofile.cos.com/Kshivets The 60 th Annual Meeting of Society of Surgical Oncology March 15-18, 2007, Washington , DC, the USA