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OPTIMIZATION OF TREATMENT  FOR PATIENTS WITH LOCAL GASTRIC CANCER RELAPSE AFTER COMPLETE STOMACH  STUMP EXTIRPATIONS Oleg Kshivets, MD, PhD   Department of Surgery, Siauliai Public Hospital & Cancer Center, Siauliai,  Lithuania 2007 Gastrointestinal Cancers Symposium, January 19-21, 2007, Orlando, FL, the USA
Abstract OBJECTIVE:  The survival of patients with local relapse of gastric cancer (RGC) after subtotal gastrectomies takes several months. Repeated radical operations are extremely complex and remain the prerogative of several best surgeons of the world.  We examined the clinicomorphologic factors associated with the low- and high-risk of generalization of RGC (T1-4N0-2M0) after complete stomach stump extirpations (SSE). Relapses were diagnosed during 1-4 years after complete subtotal gastrectomies.   METHODS:  We analyzed data of 77 consecutive RGC patients (RGCP) (age=54.1±1.1 years; tumor size=9.0±0.4 cm) radically operated and monitored in 1975-2006 (males=54, females=23; combined SSE with resection of 1-5 adjacent organs: esophagus, pancreas, liver, diaphragm, colon transversum, splenectomies =63; T1=4, T2=10, T3=39, T4=24; N0=25, N1=4, N2=48; G1=12, G2=8, G3=58; adjuvant chemoimmunotherapy 5FU+taktivin/thymalin-AT=16). Variables selected for 5-year survival (5YS) study were input levels of 45 blood parameters, sex, age, TNMPG, cell type, tumor size, AT. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of RGCP 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:  For total of 77 RGCP overall LS was 964.3±154.6 days and cumulative 5YS reached 18.3%. 23 RGCP are alive, 8 RGCP lived more than 5 years and 4 – 10 years without RGC progressing. 53 RGCP died because of RGC LC during first 5 years after surgery. Cox modeling displayed that 5YS of RGCP after SSE significantly depended on: N0-2, T1-4, combined procedures, AT, histology, G1-3, blood monocytes, neutrophils, lymphocytes, eosinophils, ratio of lymphocytes to RGC cells, lymphoid infiltration of RGC, age, hemorrhage time, blood chlorides, RGC growth (P=0.049-0.000). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS of CECP and combined procedures (rank=1), G1-3 (2), gender (3), AT (4), RGC growth (5), age (6), N0-2 (7), weight (8), histology (9), blood monocytes (10), lymphocytes (11), neutrophils (12).     CONCLUSIONS:  Correct prediction of RGCP survival after SSE was 100% by discriminant analysis and neural networks computing (area under ROC curve=1.0; error=0.0011). AT significantly improved RGCP 5YS after SSE (P=0.046 by log-rank test).
Factors 1) Antropometric Factors……………….…….….. 4 2) Blood Analysis…………………………..…….. 26 3) Hemostasis Factors……………………..…….... 3 4) Cell Ratio Factors………………………….…... 9   6) Gastric  Cancer Relapse   Characteristics..…... 12 7) Biochemic Factors……………………………... 7 8) Treatment Characteristics…………………….. 3 9) Survival   Data………...………… … …………… 4 In All………………………...………………….. 68
Main Problem of Analysis of Alive Supersystems including Combinatorial Optimization (e.g. Cancer Patient Homeostasis, Search of Optimal Treatment Plan ):  Phenomenon of «Combinatorial Explosion» Number of Clinicomorphological Factors:……...….. 68 Number of Possible Combination for Random Search:……………..…………………. n!=68!=2.48e+96   Operation Time of IBM Blue Gene/L Supercomputer (135.5TFLOPS) ………………………… 5.8e+74 Years The Age of Our Universe………..... 1.3e+10 Years
Basis: NP     RP     P      n!   n*n*2(e+n)  or  n log n    n           AI     CSA+S+B     SM AI - Artificial Intelligence CSA - Complex System Analysis S - Statistics  B - Biometrics SM - Simulation Modeling
Data Males……………………………………………… 54 Females………..………………………………….. 23 Age= 54.1±1.1 years Tumor Size= 9.0±0.4 cm Only Surgery...…………………………………… 61 Adjuvant Chemoimmunotherapy (5FU+thymalin/taktivin, 5-6 cycles)…………….. 16
Radical Procedures Stomach Stump Extirpations………………..……... 77 Combined Stomach Stump Extirpations with Resection of Liver, Pancreas, Esophagus, Diaphragm, Liver, Mesocolon, Colon Transversum, Jejunum, Splenectomy.………………………………….……... 63 Lymphadenectomy D2……………………………… 21 Lymphadenectomy D3……………………………… 56 In All….…………………………...………………….77
Schemas of Procedures
Schemas of Procedures
Schemas of Combined Procedures
Schemas of D3 Lymphadenectomy
Staging T1….….... 4   N0..….. 25   G1…………. 12 T2……... 10   N1…….. 4   G2…………... 8 T3……... 39   N2……. 48   G3………… 57 T4……... 24 Adenocarcinoma……....…...……………...……… 77
Survival Alive………..……………….………………. 23 (29.9%) 5-Year Survivors…………..………………... 8 (10.4%)   10-Year Survivors…………………………... 4 (5.2%) Losses from Cancer………………………... 53 (68.8%) General Life Span = 964.3 ±1356.4 days (SE=154.6) Life Span of 5-Year Survivors= 4457.5±1868.4 days Life Span of Losses= 563.0±62.3 days Cumulative 5-Year survival………………... 18.3% Cumulative 10-Year survival………………. 15.9%
General Survival  of Patients with Local Gastric Cancer Relapce after Complete  Stomach Stump Extirpations (Kaplan-Meier) ( n=77 )
Results of Univariate Analysis in Prediction of  Patients Survival with Local Gastric Cancer Relapse  ( n=77, P=0.046 by log-rank test )
Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=77 )  Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper Eosinophils% 13.425 1 0.000 0.023 0.003 0.174 Stick.Neutrophils% 10.189 1 0.001 0.054 0.009 0.325 Seg.Neutrophils% 11.582 1 0.001 0.044 0.007 0.266 Lymphocytes% 11.260 1 0.001 0.044 0.007 0.272 Monocytes% 8.361 1 0.004 0.076 0.013 0.435 Heamorrhage Time 20.967 1 0.000 1.087 1.049 1.126 Chlorides 8.347 1 0.004 0.885 0.814 0.961 Eosinophils abs 15.447 1 0.000 2.1e+13 4.8e+6 9.5e+19 Seg.Neutrophils abs 20.363 1 0.000 44.674 8.578 232.668 Monocytes abs 16.292 1 0.000 0.001 0.000 0.000
Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=77 )  Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper T1-4 37.175 3 0.000 T(1) 32.868 1 0.000 0.000 0.000 0.000 T(2) 3.892 1 0.049 0.098 0.010 0.985 T(3) 7.797 1 0.005 0.150 0.040 0.568 N0-2 31.930 3 0.000 N(1) 0.962 1 0.327 0.191 0.007 5.208 N(2) 4.593 1 0.032 0.033 0.001 0.747 N(3) 7.323 1 0.007 0.012 0.000 0.294 G1-3 9.381 2 0.009 G(1) 9.311 1 0.002 0.074 0.014 0.395 G(2) 0.144 1 0.705 0.769 0.198 2.987
Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=77 )  Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper Histology 39.326 2 0.000 Histology(1) 5.688 1 0.017 0.028 0.001 0.529 Histology(2) 0.167 1 0.682 1.809 0.106 30.974 Comb . Procedures 20.648 6 0.002 Comb.Procedures(1) 18.522 1 0.000 0.000 0.000 0.000 Comb.Procedures(2)  2.986 1 0.084 0.311 0.083 1.170 Comb.Procedures(3) 2.017 1 0.156 0.114 0.006 2.281 Comb.Procedures(4) 0.736 1 0.391 0.192 0.004 8.365 Comb.Procedures(5) 1.671 1 0.196 0.322 0.058 1.796 Comb.Procedures(6) 3.503 1 0.061 3.154 0.947 10.500
Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=77 )  Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper Growth 38.281 2 0.000 Growth(1) 11.422 1 0.001 18.725 3.424 102.406 Growth(2) 5.208 1 0.022 0.160 0.033 0.772 Monocytes tot 13.888 1 0.000 1031.7 26.830 4.0e+4 Eosinophils tot 5.486 1 0.019 0.056 0.005 0.625 Seg.Neutrophils tot  22.896 1 0.000 0.414 0.288 0.594 Lymphocytes/CC 6.774 1 0.009 65.078 2.804 1510.278 Age 3.869 1 0.049 1.047 1.000 1.095 Adjuvant CHIT 12.403 1 0.000 0.106 0.030 0.369
Results of Discriminant Analysis   in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete  Stomach  Stump Extirpations  (n=61 ) Discriminant Function Analysis Summary   Wilks' Lambda: 0.579 approx. F (12,48)=2.910  p< 0.0042   Wilks'  Partial  F-remove  P-level    Lambda  Lambda  (1,48)      G1-3 .675 .858 7.941 .007 Comb.Oper.   .671 .863 7.615 .008 Adjuvant CHIT   .658 .879 6.589 .013 Prothrombin Index .615 .879 6.589 .088 Seg. Neutrophils .607 .954 2.298 .136
Results of Logistic Regression Analysis   in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=61 )     Est.  S.E. Wald   P Odds 95.0% C.I.for Odds Ratio    Ratio Lower Upper Const.B  12.47  8.33 2.24  .140 2.6e+5 0.01 4.7e+12 PI   -.07  .06 1.30  .259 .94 .83 1.05 Seg.Neut.abs  .08  .04  3.20  .078 2.20 .90 5.50 Age  -.18  .11 2.32  .134 .84 .66 1.06 G1-3   -3.32  1.37 5.86  .019 .04 .00 .57 Ad.CHIT   6.50  3.10 4.50  .038 675.5 1.40 3.1+5 Comb.Op.   -.66  .32 4.20  .045 .52 .27 .99 Chi2=30.342; df=6; P=0.00003; Odds ratio=156.0
SEPATH-Modeling  in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=61)
Neural Networks   in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=61 )     Baseline Errors=0.0011 Area under ROC curve=1 .00 Correct Classification Rate= 100% Losses   5-year survivors Total   53   8   Correct   53   8   Wrong  0   0 Genetic Algorithm Selection Useful for   S%   M%  ESS  Haemor.Time  St.abs  Sabs  Age  Histology  G1-3  Survival   Yes  Yes  Yes  Yes  Yes  Yes  Yes  Yes  Yes Useful for   Ad.CHIT   Comb.Oper.  Stot  Monocytes/CC  Growth Tumor Size Survival  Yes  Yes  Yes  Yes  Yes  Yes
Results of Neural Networks Computing   in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=61 )   Error=0.0011; Area under ROC Curve=1.00; Correct Classification Rate=100% Factor Rank Error Ratio Comb.Operat. 1 0.348 305.8 G1-3 2 0.316 278.0 Sex 3 0.224 196.8 Ad.CHIT 4 0.181 159.2 Growth  5 0.146 128.5 Age 6 0.121 106.7 N0-2 7 0.075 66.1 Weight 8 0.072 63.7 Histology 9 0.018 16.2 Monocytes% 10 0.014 12.1 Lymphocytes% 11 0.006 5.2 Seg.Neutr.tot 12 0.005 4.7 Factor Rank Error Ratio Haem.Time 13 0.005 4.5 Coag.Time 14 0.005 4.3 Seg.Neutr.abs 15 0.004 3.6 ESS 16 0.004 3.1 T1-4 17 0.003 3.0 Eosinophils% 18 0.003 2.2 Tumor Size 19 0.003 2.2 Seg.Neutr.% 20 0.002 1.9 St.Neutr.abs 21 0.002 1.7 Bilirubin 22 0.002 1.5 Clucose 23 0.001 1.2 Lymph . abs 24 0.001 1.2
Results of Bootstrap Simulation   in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=61 ) Number of Samples=3333 Significant Factors Rank Kendall’s Tau-A   P< Combined Operation 1 -0.109 0.000 G1-3 2 -0.109 0.000 Haemorrhage Time 3 -0.107 0.000 ESS 4 0.098 0.000 PI 5 -0.087 0.000 Chlorides 6 0.086 0.000 Age 7 -0.073 0.000 Seg.Neutrophils abs 8 0.072 0.000 Seg.Neutrophils tot 9 0.066 0.000 Tumor Size   10 0.064 0.000 Erythrocytes/CC 11 -0.063 0.000
Results of Bootstrap Simulation   in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=61 ) Number of Samples=3333 Significant Factors Rank Kendall’s Tau-A   P< Leucocytes 12 0.063 0.000 CI 13 -0.060 0.000 Seg.Neutrophils % 14 0.054 0.000 Leucocytes tot 15 0.051 0.000 Healthy Cells/CC 16 -0.050 0.000 Residual Nitrogen 17 0.043 0.000 Erythrocytes 18 -0.042 0.000 Sex 19 0.041 0.000 Adjuvant CHIT 20 0.040 0.001 Seg.Neutrophils/CC  21 0.040 0.001 Lymphocytes abs 22 0.036 0.002
Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpatins  (n=61 ) Classification of Cases by Logistic Regression, n=61 (5-Year Survivors--Losses)  Odds Ratio=33.5 Observed  Pred.Losses  Pred.Survivors  Correct Losses   52  1  98.1% 5-Year Survivors  2  6  75.0% Total  54  7  95.1% Classification of Cases by Discriminant Analysis, n=61 Observed  Pred.Losses  Pred.Survivors  Correct Losses   52  1  98.1% 5-Year Survivors  2  6  75.0% Total  54  7  95 .1% Classification of Cases by Neural Networks, n=61 Observed  Pred.Losses  Pred.Survivors  Correct Losses   53  0  100% 5-Year Survivors  0  8  100% Total  53  8  100 %
Ratio Lymphocytes to Cancer Cells Populations   in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations  (n=61 )
Conclusions: Optimal treatment strategies for p atients with local gastric cancer relapse are: 1) dynamic monitoring  of  gastric cancer patients after gastrectomies for  early detection of local cancer relapce;  2) availability of very experienced surgeons because of baffling complexity repeated radical procedures; 3) aggressive en block surgery for completeness;  4) precise prediction;  5) adjuvant chemioimmunotherapy for patients with  unfavorable prognosis.
Oleg Kshivets, M.D., Ph.D.  Consultant Thoracic/Abdominal/General Surgeon & Surgical Oncologist  Department of Surgery, Siauliai Public Hospital & Cancer Center Address: Tilzes:42-16, LT78206 Siauliai, Lithuania Tel. (37041)416614  e-mail:  kshivets@yahoo.com  http//:myprofile.cos.com/Kshivets

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Kshivets O. Gastric Cancer Relapse Surgery

  • 1. OPTIMIZATION OF TREATMENT FOR PATIENTS WITH LOCAL GASTRIC CANCER RELAPSE AFTER COMPLETE STOMACH STUMP EXTIRPATIONS Oleg Kshivets, MD, PhD Department of Surgery, Siauliai Public Hospital & Cancer Center, Siauliai, Lithuania 2007 Gastrointestinal Cancers Symposium, January 19-21, 2007, Orlando, FL, the USA
  • 2. Abstract OBJECTIVE: The survival of patients with local relapse of gastric cancer (RGC) after subtotal gastrectomies takes several months. Repeated radical operations are extremely complex and remain the prerogative of several best surgeons of the world. We examined the clinicomorphologic factors associated with the low- and high-risk of generalization of RGC (T1-4N0-2M0) after complete stomach stump extirpations (SSE). Relapses were diagnosed during 1-4 years after complete subtotal gastrectomies. METHODS: We analyzed data of 77 consecutive RGC patients (RGCP) (age=54.1±1.1 years; tumor size=9.0±0.4 cm) radically operated and monitored in 1975-2006 (males=54, females=23; combined SSE with resection of 1-5 adjacent organs: esophagus, pancreas, liver, diaphragm, colon transversum, splenectomies =63; T1=4, T2=10, T3=39, T4=24; N0=25, N1=4, N2=48; G1=12, G2=8, G3=58; adjuvant chemoimmunotherapy 5FU+taktivin/thymalin-AT=16). Variables selected for 5-year survival (5YS) study were input levels of 45 blood parameters, sex, age, TNMPG, cell type, tumor size, AT. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of RGCP 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: For total of 77 RGCP overall LS was 964.3±154.6 days and cumulative 5YS reached 18.3%. 23 RGCP are alive, 8 RGCP lived more than 5 years and 4 – 10 years without RGC progressing. 53 RGCP died because of RGC LC during first 5 years after surgery. Cox modeling displayed that 5YS of RGCP after SSE significantly depended on: N0-2, T1-4, combined procedures, AT, histology, G1-3, blood monocytes, neutrophils, lymphocytes, eosinophils, ratio of lymphocytes to RGC cells, lymphoid infiltration of RGC, age, hemorrhage time, blood chlorides, RGC growth (P=0.049-0.000). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS of CECP and combined procedures (rank=1), G1-3 (2), gender (3), AT (4), RGC growth (5), age (6), N0-2 (7), weight (8), histology (9), blood monocytes (10), lymphocytes (11), neutrophils (12).     CONCLUSIONS: Correct prediction of RGCP survival after SSE was 100% by discriminant analysis and neural networks computing (area under ROC curve=1.0; error=0.0011). AT significantly improved RGCP 5YS after SSE (P=0.046 by log-rank test).
  • 3. Factors 1) Antropometric Factors……………….…….….. 4 2) Blood Analysis…………………………..…….. 26 3) Hemostasis Factors……………………..…….... 3 4) Cell Ratio Factors………………………….…... 9 6) Gastric Cancer Relapse Characteristics..…... 12 7) Biochemic Factors……………………………... 7 8) Treatment Characteristics…………………….. 3 9) Survival Data………...………… … …………… 4 In All………………………...………………….. 68
  • 4. Main Problem of Analysis of Alive Supersystems including Combinatorial Optimization (e.g. Cancer Patient Homeostasis, Search of Optimal Treatment Plan ): Phenomenon of «Combinatorial Explosion» Number of Clinicomorphological Factors:……...….. 68 Number of Possible Combination for Random Search:……………..…………………. n!=68!=2.48e+96 Operation Time of IBM Blue Gene/L Supercomputer (135.5TFLOPS) ………………………… 5.8e+74 Years The Age of Our Universe………..... 1.3e+10 Years
  • 5. Basis: NP  RP  P   n!  n*n*2(e+n) or n log n  n    AI  CSA+S+B  SM AI - Artificial Intelligence CSA - Complex System Analysis S - Statistics B - Biometrics SM - Simulation Modeling
  • 6. Data Males……………………………………………… 54 Females………..………………………………….. 23 Age= 54.1±1.1 years Tumor Size= 9.0±0.4 cm Only Surgery...…………………………………… 61 Adjuvant Chemoimmunotherapy (5FU+thymalin/taktivin, 5-6 cycles)…………….. 16
  • 7. Radical Procedures Stomach Stump Extirpations………………..……... 77 Combined Stomach Stump Extirpations with Resection of Liver, Pancreas, Esophagus, Diaphragm, Liver, Mesocolon, Colon Transversum, Jejunum, Splenectomy.………………………………….……... 63 Lymphadenectomy D2……………………………… 21 Lymphadenectomy D3……………………………… 56 In All….…………………………...………………….77
  • 10. Schemas of Combined Procedures
  • 11. Schemas of D3 Lymphadenectomy
  • 12. Staging T1….….... 4 N0..….. 25 G1…………. 12 T2……... 10 N1…….. 4 G2…………... 8 T3……... 39 N2……. 48 G3………… 57 T4……... 24 Adenocarcinoma……....…...……………...……… 77
  • 13. Survival Alive………..……………….………………. 23 (29.9%) 5-Year Survivors…………..………………... 8 (10.4%) 10-Year Survivors…………………………... 4 (5.2%) Losses from Cancer………………………... 53 (68.8%) General Life Span = 964.3 ±1356.4 days (SE=154.6) Life Span of 5-Year Survivors= 4457.5±1868.4 days Life Span of Losses= 563.0±62.3 days Cumulative 5-Year survival………………... 18.3% Cumulative 10-Year survival………………. 15.9%
  • 14. General Survival of Patients with Local Gastric Cancer Relapce after Complete Stomach Stump Extirpations (Kaplan-Meier) ( n=77 )
  • 15. Results of Univariate Analysis in Prediction of Patients Survival with Local Gastric Cancer Relapse ( n=77, P=0.046 by log-rank test )
  • 16. Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=77 ) Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper Eosinophils% 13.425 1 0.000 0.023 0.003 0.174 Stick.Neutrophils% 10.189 1 0.001 0.054 0.009 0.325 Seg.Neutrophils% 11.582 1 0.001 0.044 0.007 0.266 Lymphocytes% 11.260 1 0.001 0.044 0.007 0.272 Monocytes% 8.361 1 0.004 0.076 0.013 0.435 Heamorrhage Time 20.967 1 0.000 1.087 1.049 1.126 Chlorides 8.347 1 0.004 0.885 0.814 0.961 Eosinophils abs 15.447 1 0.000 2.1e+13 4.8e+6 9.5e+19 Seg.Neutrophils abs 20.363 1 0.000 44.674 8.578 232.668 Monocytes abs 16.292 1 0.000 0.001 0.000 0.000
  • 17. Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=77 ) Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper T1-4 37.175 3 0.000 T(1) 32.868 1 0.000 0.000 0.000 0.000 T(2) 3.892 1 0.049 0.098 0.010 0.985 T(3) 7.797 1 0.005 0.150 0.040 0.568 N0-2 31.930 3 0.000 N(1) 0.962 1 0.327 0.191 0.007 5.208 N(2) 4.593 1 0.032 0.033 0.001 0.747 N(3) 7.323 1 0.007 0.012 0.000 0.294 G1-3 9.381 2 0.009 G(1) 9.311 1 0.002 0.074 0.014 0.395 G(2) 0.144 1 0.705 0.769 0.198 2.987
  • 18. Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=77 ) Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper Histology 39.326 2 0.000 Histology(1) 5.688 1 0.017 0.028 0.001 0.529 Histology(2) 0.167 1 0.682 1.809 0.106 30.974 Comb . Procedures 20.648 6 0.002 Comb.Procedures(1) 18.522 1 0.000 0.000 0.000 0.000 Comb.Procedures(2) 2.986 1 0.084 0.311 0.083 1.170 Comb.Procedures(3) 2.017 1 0.156 0.114 0.006 2.281 Comb.Procedures(4) 0.736 1 0.391 0.192 0.004 8.365 Comb.Procedures(5) 1.671 1 0.196 0.322 0.058 1.796 Comb.Procedures(6) 3.503 1 0.061 3.154 0.947 10.500
  • 19. Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=77 ) Factors Wald df P Exp(B) 95%CI for Exp(B) Lower Upper Growth 38.281 2 0.000 Growth(1) 11.422 1 0.001 18.725 3.424 102.406 Growth(2) 5.208 1 0.022 0.160 0.033 0.772 Monocytes tot 13.888 1 0.000 1031.7 26.830 4.0e+4 Eosinophils tot 5.486 1 0.019 0.056 0.005 0.625 Seg.Neutrophils tot 22.896 1 0.000 0.414 0.288 0.594 Lymphocytes/CC 6.774 1 0.009 65.078 2.804 1510.278 Age 3.869 1 0.049 1.047 1.000 1.095 Adjuvant CHIT 12.403 1 0.000 0.106 0.030 0.369
  • 20. Results of Discriminant Analysis in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=61 ) Discriminant Function Analysis Summary Wilks' Lambda: 0.579 approx. F (12,48)=2.910 p< 0.0042 Wilks' Partial F-remove P-level Lambda Lambda (1,48) G1-3 .675 .858 7.941 .007 Comb.Oper. .671 .863 7.615 .008 Adjuvant CHIT .658 .879 6.589 .013 Prothrombin Index .615 .879 6.589 .088 Seg. Neutrophils .607 .954 2.298 .136
  • 21. Results of Logistic Regression Analysis in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=61 ) Est. S.E. Wald P Odds 95.0% C.I.for Odds Ratio Ratio Lower Upper Const.B 12.47 8.33 2.24 .140 2.6e+5 0.01 4.7e+12 PI -.07 .06 1.30 .259 .94 .83 1.05 Seg.Neut.abs .08 .04 3.20 .078 2.20 .90 5.50 Age -.18 .11 2.32 .134 .84 .66 1.06 G1-3 -3.32 1.37 5.86 .019 .04 .00 .57 Ad.CHIT 6.50 3.10 4.50 .038 675.5 1.40 3.1+5 Comb.Op. -.66 .32 4.20 .045 .52 .27 .99 Chi2=30.342; df=6; P=0.00003; Odds ratio=156.0
  • 22. SEPATH-Modeling in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=61)
  • 23. Neural Networks in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=61 ) Baseline Errors=0.0011 Area under ROC curve=1 .00 Correct Classification Rate= 100% Losses 5-year survivors Total 53 8 Correct 53 8 Wrong 0 0 Genetic Algorithm Selection Useful for S% M% ESS Haemor.Time St.abs Sabs Age Histology G1-3 Survival Yes Yes Yes Yes Yes Yes Yes Yes Yes Useful for Ad.CHIT Comb.Oper. Stot Monocytes/CC Growth Tumor Size Survival Yes Yes Yes Yes Yes Yes
  • 24. Results of Neural Networks Computing in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=61 ) Error=0.0011; Area under ROC Curve=1.00; Correct Classification Rate=100% Factor Rank Error Ratio Comb.Operat. 1 0.348 305.8 G1-3 2 0.316 278.0 Sex 3 0.224 196.8 Ad.CHIT 4 0.181 159.2 Growth 5 0.146 128.5 Age 6 0.121 106.7 N0-2 7 0.075 66.1 Weight 8 0.072 63.7 Histology 9 0.018 16.2 Monocytes% 10 0.014 12.1 Lymphocytes% 11 0.006 5.2 Seg.Neutr.tot 12 0.005 4.7 Factor Rank Error Ratio Haem.Time 13 0.005 4.5 Coag.Time 14 0.005 4.3 Seg.Neutr.abs 15 0.004 3.6 ESS 16 0.004 3.1 T1-4 17 0.003 3.0 Eosinophils% 18 0.003 2.2 Tumor Size 19 0.003 2.2 Seg.Neutr.% 20 0.002 1.9 St.Neutr.abs 21 0.002 1.7 Bilirubin 22 0.002 1.5 Clucose 23 0.001 1.2 Lymph . abs 24 0.001 1.2
  • 25. Results of Bootstrap Simulation in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=61 ) Number of Samples=3333 Significant Factors Rank Kendall’s Tau-A P< Combined Operation 1 -0.109 0.000 G1-3 2 -0.109 0.000 Haemorrhage Time 3 -0.107 0.000 ESS 4 0.098 0.000 PI 5 -0.087 0.000 Chlorides 6 0.086 0.000 Age 7 -0.073 0.000 Seg.Neutrophils abs 8 0.072 0.000 Seg.Neutrophils tot 9 0.066 0.000 Tumor Size 10 0.064 0.000 Erythrocytes/CC 11 -0.063 0.000
  • 26. Results of Bootstrap Simulation in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=61 ) Number of Samples=3333 Significant Factors Rank Kendall’s Tau-A P< Leucocytes 12 0.063 0.000 CI 13 -0.060 0.000 Seg.Neutrophils % 14 0.054 0.000 Leucocytes tot 15 0.051 0.000 Healthy Cells/CC 16 -0.050 0.000 Residual Nitrogen 17 0.043 0.000 Erythrocytes 18 -0.042 0.000 Sex 19 0.041 0.000 Adjuvant CHIT 20 0.040 0.001 Seg.Neutrophils/CC 21 0.040 0.001 Lymphocytes abs 22 0.036 0.002
  • 27. Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpatins (n=61 ) Classification of Cases by Logistic Regression, n=61 (5-Year Survivors--Losses) Odds Ratio=33.5 Observed Pred.Losses Pred.Survivors Correct Losses 52 1 98.1% 5-Year Survivors 2 6 75.0% Total 54 7 95.1% Classification of Cases by Discriminant Analysis, n=61 Observed Pred.Losses Pred.Survivors Correct Losses 52 1 98.1% 5-Year Survivors 2 6 75.0% Total 54 7 95 .1% Classification of Cases by Neural Networks, n=61 Observed Pred.Losses Pred.Survivors Correct Losses 53 0 100% 5-Year Survivors 0 8 100% Total 53 8 100 %
  • 28. Ratio Lymphocytes to Cancer Cells Populations in Prediction of Patients Survival with Local Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=61 )
  • 29. Conclusions: Optimal treatment strategies for p atients with local gastric cancer relapse are: 1) dynamic monitoring of gastric cancer patients after gastrectomies for early detection of local cancer relapce; 2) availability of very experienced surgeons because of baffling complexity repeated radical procedures; 3) aggressive en block surgery for completeness; 4) precise prediction; 5) adjuvant chemioimmunotherapy for patients with unfavorable prognosis.
  • 30. Oleg Kshivets, M.D., Ph.D. Consultant Thoracic/Abdominal/General Surgeon & Surgical Oncologist Department of Surgery, Siauliai Public Hospital & Cancer Center Address: Tilzes:42-16, LT78206 Siauliai, Lithuania Tel. (37041)416614 e-mail: kshivets@yahoo.com http//:myprofile.cos.com/Kshivets

Editor's Notes

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