5YS of local advanced ECP after combined radical procedures significantly depended on: tumor characteristics, blood cell circuit, cell ratio factors, biochemical factors, hemostasis system, anthropometric data and adjuvant treatment. Optimal strategies for local advanced ECP are: 1) availability of very experienced thoracoabdominal surgeons because of complexity radical procedures; 2) aggressive en block surgery and adequate lymph node dissection for completeness; 3) precise prediction; 4) AT for ECP with unfavorable prognosis.

1. Local Advanced Esophageal Cancer
(T3-4N0-2M0): Artificial Intelligence,
Synergistics, Complex System Analysis and
Simulation of Alive Supersystems for Best
Management.
Kshivets Oleg Surgery Department, Bagrationovsk Hospital,
Bagrationovsk, Kaliningrad, Russia

2. ABSTRACT
OBJECTIVE: The survival of patients with local advanced of esophageal cancer (EC) takes several months. Radical operations are extremely
complex and remain the prerogative of several best thoracoabdominal surgeons of the world. The search of optimal treatment plan for EC patients
(ECP) with stage T3-4N0-2M0 was realized. We examined factors in terms of precise prediction of 5-year survival (5YS) of local advanced ECP after
complete (R0) combined esophagogastrectomies (E).
METHODS: We analyzed data of 313 consecutive ECP (age=56.2±9 years; tumor size=8.1±2.8 cm) radically operated and monitored in 1975-2024
(m=233, f=80; Lewis=122, Garlock=191, combined E with resection of trachea, bronchus, lung, aorta, VCS, pericardium, liver, pancreas, diaphragm,
colon, splenectomy=170; only surgery-S=217, adjuvant chemoimmunoradiotherapy-AT=96: 5FU+thymalin/taktivin +radiotherapy 45-50Gy; T3=185,
T4=128; N0=96, N1=38, N2=179, M0=313; G1=71, G2=57, G3=185; squamous=109, adenocarcinoma=194, mix=10. Variables selected for 5YS study were
input levels of 45 blood parameters, sex, age, TNMG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in
curves between groups of ECP were evaluated using a log-rank test. Multivariate Cox modeling, multi-factor clustering, discriminant analysis, structural
equation modeling, Monte Carlo, bootstrap, synergetics simulation and neural networks computing were used to determine any significant dependence.
RESULTS: Overall life span (LS) was 1243.6±1691.4 days and cumulative 5YS reached 29%, 10 years – 19.2%, 20 years – 13.3%. 55 ECP lived more
than 5 years (LS=4199.4±2295.3 days), 25 – more than 10 years (LS=6256.3±1884.8 days). 186 ECP died because of EC (LS=605.1±289.9 days). AT
significantly improved 5YS (56.8% vs. 22%) (P=0.0000). Cox modeling displayed that 5YS of ECP significantly depended on: Phase Transition N0-N12 in
terms of synergetics, G1-3, histology, AT, age, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), ESS,
prothrombin index, hemorrhage time, protein, residual nitrogen (P=0.000-0.033). Neural networks, genetic algorithm selection and bootstrap simulation
revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (2), healthy cells/CC (3), erythrocytes/CC (4), segmented neutrophils/CC (5),
eosinophils/CC (6), monocytes/CC (7), stick neutrophils/CC (8), lymphocytes/CC (9), leucocytes/CC (10). Correct prediction of 5YS was 100% by neural
networks computing.
CONCLUSIONS: 5YS of local advanced ECP after combined radical procedures significantly depended on: tumor characteristics, blood cell circuit,
cell ratio factors, biochemical factors, hemostasis system, anthropometric data and adjuvant treatment. Optimal strategies for local advanced ECP are:
1) availability of very experienced thoracoabdominal surgeons because of complexity radical procedures; 2) aggressive en block surgery and adequate
lymph node dissection for completeness; 3) precise prediction; 4) AT for ECP with unfavorable prognosis.

3. Data:
• Males…………………………………………………...233
• Females………..……………………………................80
• Age=56.2±9 years
• Tumor Size=8.1±2.8 cm
• Only Surgery.……………………………………........217
• Adjuvant Chemoimmunoradiotherapy
• (5FU+thymalin/taktivin, 5-6 cycles+ Radiotherapy
• 45-50Gy)………………………....................................96

4. :Radical Procedures
• Esophagogastrectomies Lewis (R0)…………………122
• Esophagogastrectomies Garlock (R0)………...........191
• Combined Esophagogastrectomies with Resection
• of Pancreas, Liver, Trachea, Lung, Aorta, Vena
• Cava Superior, Colon Transversum, Diaphragm,
Pericardium, Splenectomy (R0)……………...............170
• 2-Field Lymphadenectomy…………………………….186
• 3-Field Lymphadenectomy.………………………….…127

5. Staging:
• T3……186 N0..…...96 G1………….71
• T4……128 N1….....38 G2………….57
• M0…..313 N2…....179 G3…………185
• Adenocarcinoma…………………………….194
• Squamos Cell Carcinoma…………………..110
• Mix………………….....…………………...........10

6. Survival Rate:
• Alive………………………………………......105 (33.5%)
• 5-Year Survivors…………..…………..……..55 (17.6%)
• 10-Year Survivors…………………………....25 (8%)
• Losses………………………………………..186 (59.4%)
• General Life Span=1243.6±1691.4 days
• For 5-Year Survivors=4199.4±2295.3 days
• For 10-Year Survivors=6256.3±1884.8 days
• For Losses=605.1±289.9 days
• Cumulative 5-Year Survival……………………….29%
• Cumulative 10-Year Survival…………………......19.2%
• Cumulative 20-Year Survival…………………......13.3%

7. General Esophageal Cancer Patients (T3-4)
Survival after Complete
Esophagogastrectomies (Kaplan-Meier)
(n=313):
Survival Function
5YS=29%; 10YS=19.2%; 20YS=13.3%
Complete Censored
-5 0 5 10 15 20 25 30 35
Years after Esophagogastrectomies
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
1.2
Cumulative
Proportion
Surviving

8. Results of Univariate Analysis of Phase
Transition N0—N1-2 in Prediction of
Esophageal Cancer Patients (T3-4) Survival
(n=313):
Cumulative Proportion Surviving (Kaplan-Meier)
P=0.00354
Complete Censored
0 5 10 15 20 25 30 35
Years after Esophagogastrectomies
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
N0
N1-2

9. Results of Univariate Analysis of
Localization
(Cardioesophageal vs. Esophageal) in
Prediction of Esophageal Cancer
Patients (T3-4) Survival (n=313): Cumulative Proportion Surviving (Kaplan-Meier)
P=0.00109
Complete Censored
0 5 10 15 20 25 30 35
Years after Esophagogasrectomies
-0.1
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
Esophageal Cancer Patients
Cardioesophageal Cancer Patients

10. Results of Univariate Analysis of Adjuvant
Treatment (Adjuvant
Chemoimmunoradiotherapy vs Surgery
along) in Prediction of Esophageal
Cancer Patients (T3-4) Survival (n=313):
Cumulative Proportion Surviving (Kaplan-Meier)
P=0.0000
Complete Censored
0 5 10 15 20 25 30 35
Years after Esophagogastrectomies
-0.1
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Cumulative
Proportion
Surviving
only Surgery
Adjuvant Chemoimmunoradiotherapy

11. Results of Cox Regression Modeling in
Prediction of Esophageal Cancer Patients
(T3-4) Survival after Complete
Esophagogastrectomies (n=313):
Cox Regression, ECP (T3-4N0-2), n=313
Parameter
Estimate
Standard
Error
Chi-square P value
95% Lower
CL
95% Upper
CL
Eosinophils (%) 1.450 0.63707 5.17929 0.022858 0.201 2.698
Stick Neutrophils (%) 1.594 0.64188 6.16669 0.013018 0.336 2.852
Segmented Neutrophils (%) 1.616 0.63118 6.55406 0.010465 0.379 2.853
Lymphocytes (%) 1.640 0.63515 6.66400 0.009838 0.395 2.884
Monocytes (%) 1.717 0.64700 7.04410 0.007953 0.449 2.985
ESS -0.017 0.00751 5.03756 0.024803 -0.032 -0.002
Hemorrhage Time 0.001 0.00047 4.52166 0.033468 0.000 0.002
Residual Nitrogen 0.058 0.01241 22.03938 0.000003 0.034 0.083
Protein 0.032 0.01054 8.96255 0.002756 0.011 0.052
Prothrombin Index 0.038 0.00802 22.68268 0.000002 0.022 0.054
Phase Transition N0---N12 0.513 0.19200 7.13876 0.007544 0.137 0.889
Age 0.031 0.01019 9.40805 0.002160 0.011 0.051
Histology -0.444 0.15086 8.65327 0.003265 -0.739 -0.148
G1-3 0.282 0.10138 7.76029 0.005341 0.084 0.481
Leucocytes (tot) 22.981 4.89333 22.05549 0.000003 13.390 32.571
Eosinophils (tot) -22.335 4.85003 21.20792 0.000004 -31.841 -12.829
Stick Neutrophils (tot) -22.207 4.86970 20.79526 0.000005 -31.751 -12.662
Lymphocytes (tot) -23.049 4.93130 21.84678 0.000003 -32.714 -13.384
Segmented Neutrophils (tot) -23.024 4.88779 22.18959 0.000002 -32.604 -13.444
Monocytes (tot) -23.043 4.86741 22.41275 0.000002 -32.583 -13.503
Leucocytes/Cancer Cells -157.315 28.43656 30.60461 0.000000 -213.050 -101.581
Eosinophils/Cancer Cells 156.586 28.69089 29.78630 0.000000 100.353 212.819
Segmented Neutrophils/Cancer Cells 157.829 28.43487 30.80849 0.000000 102.098 213.560
Stick Neutrophils/Cancer Cells 153.093 28.44108 28.97477 0.000000 97.350 208.837
Lymphocytes/Cancer Cells 156.884 28.52403 30.25085 0.000000 100.978 212.790
Monocytes/Cancer Cells 155.948 28.15775 30.67366 0.000000 100.760 211.136
Esophageal/Cardioesophageal Cancer 0.440 0.17284 6.47954 0.010912 0.101 0.779
Adjuvant Chemoimmunoradiotherapy -0.874 0.21985 15.81752 0.000070 -1.305 -0.4435

12. Results of Neural Networks and Monte Carlo
Computing in Prediction of Esophageal Cancer
Patients (T3-4) Survival after Complete
Esophagogastrectomies (n=241):
Corect Classification Rate=100%
Error=0.000
Area under ROC Curve=1.000
Neural Networks: Baseline Error=0.000
Area under ROC Curve=1.000; Correct
Classification Rate=100%; n=241
Rank Sensitivity
Phase Transition N0---N12 1 701
Eosinophils/Cancer Cells 2 491
Stick Neutrophils/Cancer Cells 3 269
Healthy Cells/Cancer Cells 4 176
Erythrocytes/Cancer Cells 5 175
Monocytes/Cancer Cells 6 151
Lymphocytes/Cancer Cells 7 124
Thrombocytes/Cancer Cells 8 100
Segmented Neutrophils/Cancer Cells 9 30
Leucocytes/Cancer Cells 10 24

13. Results of Bootstrap Simulation in Prediction
of Esophageal Cancer Patients Survival (T3-4)
after Complete Esophagogastrectomies (n=241):
Bootstrap Simulation:
Number of Samples=3333
Rank Kendall
Tau
P<
Hemorrhage Time 1 -0.171 0.05
Blood Chlorides 2 0.171 0.05
Esophageal/Cardioesophageal Cancer 3 -0.151 0.05
Prothrombin Index 4 -0.146 0.05
Phase Transition N0---N12 5 -0.144 0.05
Protein 6 -0.142 0.05

14. Results of Kohonen Self-Organizing
Neural Networks Computing in
Prediction of Esophageal Cancer Patients (T3-4) Survival after Complete Esophagogastrectomies
(n=241):

15. Esophageal Cancer Cell Dynamics:

16. Prognostic Equation Models of
Esophageal Cancer Patients (T3-4)
Survival after Complete
Esophagogastrectomies (n=241):

17. Prognostic Equation Models of
Esophageal Cancer Patients (T3-4)
Survival after Complete
Esophagogastrectomies (n=241):

18. Prognostic Equation Models of
Esophageal Cancer Patients (T3-4)
Survival after Complete
Esophagogastrectomies (n=241):

19. Prognostic Equation Models of
Esophageal Cancer Patients (T3-4)
Survival after Complete
Esophagogastrectomies (n=241):

20. SEPATH Modeling in Prediction of
Esophageal Cancer Patients (T3-4)
Survival after Complete
Esophagogastrectomies (n=241):

21. 5-year survival of ECP after radical
procedures significantly depended on:
1) PT N0--N12;
2) Cell Ratio Factors;
3) Blood Cell Circuit;
4) Biochemical Factors;
5) Hemostasis System;
6) Adjuvant Treatment;
7) EC Characteristics;
8) EC Cell Dynamics;
9) Tumor Localization;
10) Anthropometric Data;
11) Surgery Type.
Conclusion:

22. Optimal treatment strategies for
local advanced ECP (T3-4) are:
1) Availability of Sufficient
Quantity of Very Experienced
Thoracoabdominal Surgeons
because of Extreme Complexity of
Radical Procedures;
2) Aggressive en block Combined
Surgery and Adequate Lymph
Node Dissection for
Completeness;
3) Precise Prediction;
4) Adjuvant
Chemoimmunoradiotherapy for
ECP with Unfavorable Prognosis.
Conclusion:

23. Address:
Oleg Kshivets,
M.D.,Ph.D.
Consultant Thoracic, Abdominal,
General Surgeon & Surgical
Oncologist
• e-mail: okshivets@yahoo.com
• skype: okshivets
• http: //www.ctsnet.org/home/okshivets