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Oleg Kshivets, MD, PhD Siauliai Public Hospital, Siauliai, Lithuania

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<ul><li>5-YEAR SURVIVAL OF ESOPHAGEAL/CARDIOESOPHAGEAL CANCER PATIENTS AFTER RADICAL SURGERY SIGNIFICANTLY DEPENDED ON PHASE TRANSITION “EARLY-INVASIVE CANCER”, LYMPH NODE METASTASES AND CELL RATIO FACTORS </li></ul><ul><li>Oleg Kshivets Surgery Department, Siauliai Public Hospital, Lithuania </li></ul><ul><li> OBJECTIVE: We examined factors associated with low/high-risk of generalization of esophageal/cardioesophageal cancer (ECEC) (T1-4N0M1A) after complete (R0) esophagogastrectomies (EG). METHODS: We analyzed data of 407 consecutive ECEC patients (ECECP) (age=55.6±8.6 years; tumor size=6.7±3.3 cm) radically operated and monitored in 1975-2010 (m=305, f=102;EG Garlock=271, EG Lewis=136, combined EG with resection of pancreas, liver, diaphragm, colon transversum, lung, trachea, pericardium, splenectomy=125; adenocarcinoma=212, squamous=185, mix=10; T1=62, T2=96, T3=140, T4=109; N0=167, N1=56, M1A=184, G1=116, G2=96, G3=195; early ECEC=43, invasive=364). Multivariate Cox modeling, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine any significant dependence. RESULTS: Overall life span (LS) was 1612.6±2070.5 days and cumulative 5-year survival (5YS) reached 40%, 10 years – 32.7%, 20 years – 23.5%. 101ECECP lived more than 5 years without ECEC. 215ECECP died because of ECEC. Cox modeling displayed (Chi2=46.0, df=5, P=0.000) that 5YS of ECECP significantly depended on: phase transition (PT) early-invasive ECEC in terms of synergetics, PT N0--N1-M1A, cell ratio factors (CRF) (ratio between cancer cells – CC and blood cells subpopulations) (P=0.001-0.029). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive ECEC (rank=1), PT N0--N1-M1A (rank=2), healthy cells/CC, monocytes/CC, segmented neutrophils/CC, eosinophils/CC, stab neutrophils/CC, leucocytes/CC, lymphocytes/CC, thrombocytes/CC, erythrocytes/CC. Correct prediction of 5YS was 100% by neural networks computing. </li></ul><ul><li> CONCLUSIONS: 5YS of ECECP after radical procedures significantly depended on: 1) PT “early-invasive ECEC”; 2) PT N0--N1-M1A; 3) CRF. </li></ul>

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<ul><li>Males…………………………………………… ……………… 305 </li></ul><ul><li>Females……… …. ……………………………… ……………. 102 </li></ul><ul><li>Age=5 5 . 6 ± 8 . 6 years </li></ul><ul><li>Tumor Size= 6 . 7 ± 3 . 3 cm </li></ul><ul><li>Esophagogastrectomies Ivor-Lewis… …………... ... 136 </li></ul><ul><li>Esophagogastrectomies Garlock………………..….. 271 </li></ul><ul><li>Combined procedures with resection of pancreas, liver, diaphragm, VCS, colon transversum, lung, trachea, pericardium, splenectomy …………….…. 125 </li></ul>

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<ul><li>T1…….. 62 N0..….. 167 G1..……… 116 </li></ul><ul><li>T2…….. 96 N1……... 56 G2…..…….. 96 </li></ul><ul><li>T3…… 140 M1A…. 184 G3.….…… 195 </li></ul><ul><li>T4…… 109 </li></ul><ul><li>Early Cancer……………………………………….……. 43 </li></ul><ul><li>Invasive Cancer............................................. 364 </li></ul><ul><li>Adenocarcinoma……………………………………. 212 </li></ul><ul><li>Squamous Cell Carcinoma……..………………. 185 </li></ul><ul><li>Mix Carcinoma..……………………....................... 10 </li></ul>

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<ul><li>5-Year Survivors…………..…………. 101 (24.8%) </li></ul><ul><li>Losses…………………………………… 215 (52.8%) </li></ul><ul><li>General Life Span= 1612.6 ±2070.5 days </li></ul><ul><li>For 5-Year Survivors= 4404.4±2543.9 days </li></ul><ul><li>For Losses= 649.8±388.2 days </li></ul><ul><li>Cumulative 5-Year Survival…………….... 40.0% </li></ul><ul><li>Cumulative 10-Year Survival….............. 32.7% </li></ul>

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<ul><li>Factors Wald df P </li></ul><ul><li>Phase Transition Early-Invasive LC 5 . 864 1 0.0 15 </li></ul><ul><li>Phase Transition N0—N1-2 11 . 871 1 0.00 1 </li></ul><ul><li>Leucocytes/Cancer Cells 5 . 844 1 0.0 16 </li></ul><ul><li>Segmented Neutrophils/Cancer Cells 4 . 794 1 0.0 29 </li></ul><ul><li>Monocytes/Cancer Cells 4 . 998 1 0. 025 </li></ul><ul><li> </li></ul>

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<ul><li>Discriminant Function Analysis Summary </li></ul><ul><li>Wilks' Lambda: 0. 703 approx. F ( 8 , 307 )= 16 . 179 p< 0.0000 ; </li></ul><ul><li>Correct Classification Rate=78.5% </li></ul><ul><li> Wilks' -Lambda P </li></ul><ul><li>Phase Transition Early-Invasive Lung Cancer 0.714 0.029 </li></ul><ul><li>Phase Transition N0—N1-2 0 . 744 0.00 0 </li></ul><ul><li>Erythrocytes/Cancer Cells 0. 718 0.0 12 </li></ul><ul><li>Leucocytes/Cancer Cells 0.719 0.010 </li></ul><ul><li>Segmented Neutrophils/Cancer Cells 0.719 0.010 </li></ul><ul><li>Lymphocytes/Cancer Cells 0.716 0.018 </li></ul><ul><li>Monocytes/Cancer Cells 0.714 0.029 </li></ul><ul><li>Healthy Cells/Cancer Cells 0.720 0.008 </li></ul>

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<ul><li> 5-Year Survivors Losses </li></ul><ul><li>Baseline Errors=0.000 Total 215 101 </li></ul><ul><li>Area under ROC Curve=1.0 Correct 215 101 </li></ul><ul><li>Correct Classification Rate=100% Wrong 0 0 </li></ul><ul><li> </li></ul>

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<ul><ul><li>Factor Rank Sensitivity </li></ul></ul><ul><li>Phase Transition Early-Invasive Cancer 1 49239 </li></ul><ul><li>Phase Transition N0---N12 2 15916 </li></ul><ul><li>Healthy Cells/Cancer Cells 3 6775 </li></ul><ul><li>Monocytes/Cancer Cells 4 5656 </li></ul><ul><li>Segmented Neutrophils/Cancer Cells 5 4612 </li></ul><ul><li>Eosinophils/Cancer Cells 6 4176 </li></ul><ul><li>Stab Neutrophils/Cancer Cells 7 3601 </li></ul><ul><li>Leucocytes/Cancer Cells 8 3469 </li></ul><ul><li>Lymphocyte/Cancer Cells 9 3136 </li></ul><ul><li>Thrombocytes/Cancer Cells 10 2925 </li></ul><ul><li>Erythrocytes/Cancer Cells 11 2885 </li></ul>

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<ul><ul><li>Factor Useful for 5-Year Survival </li></ul></ul><ul><li>Phase Transition Early-Invasive Cancer Yes </li></ul><ul><li>Phase Transition N0---N1M1A Yes </li></ul><ul><li>Leucocyte/Cancer Cells Yes </li></ul><ul><li>Monocyte/Cancer Cells Yes </li></ul><ul><li>Healthy Cells/Cancer Cells Yes </li></ul>

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<ul><li>Number of Samples=3333 </li></ul><ul><li>Significant Factors Rank Kend . Tau-A P </li></ul><ul><li>Healthy Cells/Cancer Cells 1 0. 230 0.0 00 </li></ul><ul><li>Erythrocytes/Cancer Cells 2 0. 226 0.0 00 </li></ul><ul><li>Leucocytes / Cancer Cells 3 0. 215 0.0 00 </li></ul><ul><li>Lymphocytes/Cancer Cells 4 0. 205 0.0 00 </li></ul><ul><li>Thrombocytes / Cancer Cells 5 0. 202 0.0 00 </li></ul><ul><li>Segmented Neutrophils/Cancer Cells 6 0.190 0.0 00 </li></ul><ul><li>Eosinophils/Cancer Cells 7 0.1 75 0.0 00 </li></ul><ul><li>Phase Transition N0—N1M1A 8 - 0.1 72 0.0 00 </li></ul><ul><li>Monocytes/Cancer Cells 9 0. 158 0.0 00 </li></ul><ul><li>Phase Transition Early-Invasive Cancer 10 -0.125 0.001 </li></ul><ul><li>Stab Neutrophils/Cancer Cells 1 1 0. 083 0.0 48 </li></ul>

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<ul><li>5-year survival and life span of esophageal and cardioesophageal cancer patients after complete esophagogastrectomies significantly depended on: </li></ul><ul><li>1) phase transition early—invasive cancer; </li></ul><ul><li>2) phase tranzition N0---N1M1A; </li></ul><ul><li>3) cell ratio factors: ratio of cancer cell population to blood cell subpopulations in integral patient organism. </li></ul>