Kshivets O. Gastric Cancer Relapse Surgery

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  • OPTIMIZATION OF TREATMENT FOR PATIENTS WITH LOCAL GASTRIC CANCER RELAPSE AFTER COMPLETE STOMACH STUMP EXTIRPATIONSOleg Kshivets, MD, PhD Department of Surgery, Siauliai Public Hospital & Cancer Center, Siauliai, Lithuania2007 Gastrointestinal Cancers Symposium, January 19-21, 2007, Orlando, FL, the USA

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  • 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=54.11.1 years; tumor size=9.00.4 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 964.3154.6 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).

  • Factors1) Antropometric Factors....42) Blood Analysis....263) Hemostasis Factors......34) Cell Ratio Factors....9 6) Gastric Cancer Relapse Characteristics.....127) Biochemic Factors...78) Treatment Characteristics..39) 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 ExplosionNumber of Clinicomorphological Factors:.....68Number of Possible Combination for Random Search:...n!=68!=2.48e+96 Operation Time of IBM Blue Gene/L Supercomputer (135.5TFLOPS) 5.8e+74 YearsThe 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 SMAI - Artificial IntelligenceCSA - Complex System AnalysisS - Statistics B - BiometricsSM - Simulation Modeling

  • DataMales54Females....23Age=54.11.1 yearsTumor Size=9.00.4 cmOnly Surgery...61Adjuvant Chemoimmunotherapy (5FU+thymalin/taktivin, 5-6 cycles)..16

  • Radical ProceduresStomach Stump Extirpations.....77Combined Stomach Stump Extirpations with Resection of Liver, Pancreas, Esophagus, Diaphragm, Liver, Mesocolon, Colon Transversum, Jejunum, Splenectomy.....63Lymphadenectomy D221Lymphadenectomy D356In All.....77

  • Schemas of Procedures

  • Schemas of Procedures

  • Schemas of Combined Procedures

  • Schemas of D3 Lymphadenectomy

  • StagingT1.....4 N0....25 G1.12T2...10 N1..4 G2...8T3...39 N2.48 G357T4...24Adenocarcinoma..........77

  • SurvivalAlive....23 (29.9%)5-Year Survivors.....8 (10.4%) 10-Year Survivors...4 (5.2%)Losses from Cancer...53 (68.8%)General Life Span=964.31356.4 days (SE=154.6)Life Span of 5-Year Survivors=4457.51868.4 daysLife Span of Losses=563.062.3 daysCumulative 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)

    FactorsWalddfPExp(B)95%CI for Exp(B)LowerUpperEosinophils%13.42510.0000.0230.0030.174Stick.Neutrophils%10.18910.0010.0540.0090.325Seg.Neutrophils%11.58210.0010.0440.0070.266Lymphocytes%11.26010.0010.0440.0070.272Monocytes%8.36110.0040.0760.0130.435Heamorrhage Time20.96710.0001.0871.0491.126Chlorides8.34710.0040.8850.8140.961Eosinophils abs15.44710.0002.1e+134.8e+69.5e+19Seg.Neutrophils abs20.36310.00044.6748.578232.668Monocytes abs16.29210.0000.0010.0000.000

  • Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=77)

    FactorsWalddfPExp(B)95%CI for Exp(B)LowerUpperT1-437.17530.000T(1)32.86810.0000.0000.0000.000T(2)3.89210.0490.0980.0100.985T(3)7.79710.0050.1500.0400.568N0-231.93030.000N(1)0.96210.3270.1910.0075.208N(2)4.59310.0320.0330.0010.747N(3)7.32310.0070.0120.0000.294G1-39.38120.009G(1)9.31110.0020.0740.0140.395G(2)0.14410.7050.7690.1982.987

  • Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=77)

    FactorsWalddfPExp(B)95%CI for Exp(B)LowerUpperHistology39.32620.000Histology(1)5.68810.0170.0280.0010.529Histology(2)0.16710.6821.8090.10630.974Comb.Procedures20.64860.002Comb.Procedures(1)18.52210.0000.0000.0000.000Comb.Procedures(2) 2.98610.0840.3110.0831.170Comb.Procedures(3)2.01710.1560.1140.0062.281Comb.Procedures(4)0.73610.3910.1920.0048.365Comb.Procedures(5)1.67110.1960.3220.0581.796Comb.Procedures(6)3.50310.0613.1540.94710.500

  • Results of Cox Regression Modeling in Prediction of Patients Survival with Gastric Cancer Relapse after Complete Stomach Stump Extirpations (n=77)

    FactorsWalddfPExp(B)95%CI for Exp(B)LowerUpperGrowth38.28120.000Growth(1)11.42210.00118.7253.424102.406Growth(2)5.20810.0220.1600.0330.772Monocytes tot13.88810.0001031.726.8304.0e+4Eosinophils tot5.48610.0190.0560.0050.625Seg.Neutrophils tot 22.89610.0000.4140.2880.594Lymphocytes/CC6.77410.00965.0782.8041510.278Age3.86910.0491.0471.0001.095Adjuvant CHIT12.40310.0000.1060.0300.369

  • 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) G1-3.675.8587.941.007Comb.Oper. .671.8637.615.008Adjuvant CHIT .658.8796.589.013Prothrombin Index.615.8796.589.088Seg. Neutrophils.607.9542.298.136

  • 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 POdds95.0% C.I.for Odds Ratio RatioLowerUpperConst.B 12.47 8.332.24 .1402.6e+50.014.7e+12PI -.07 .061.30 .259.94.831.05Seg.Neut.abs .08 .04 3.20 .0782.20.905.50Age -.18 .112.32 .134.84.661.06G1-3 -3.32 1.375.86 .019.04.00.57Ad.CHIT 6.50 3.104.50 .038675.51.403.1+5Comb.Op. -.66 .324.20 .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

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