Kshivets sso2013

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  • 1.Cardioesophageal andEsophageal Cancer:Optimization ofManagementOleg Kshivets, MD, PhD

2. Abstract:Oleg KshivetsCardioesophageal and Esophageal Cancer:Optimization of ManagementOBJECTIVE: Search of best treatment plan for cardioesophageal/esophageal cancer (CEC) patients(CECP) was realized. METHODS: We analyzed data of 411 consecutive CECP (age=55.68.7 years; tumor size=6.73.3 cm)radically operated (R0) and monitored in 1975-2012 (m=307, f=104; esophagogastrectomy- EGGarlock=271, EG Lewis=140, combined EG with resection of pancreas, liver, diaphragm, colontransversum, lung, trachea, pericardium, splenectomy=127; adenocarcinoma=216, squamous=185, mix=10;T1=62, T2=99, T3=141, T4=109; N0=170, N1=57, M1A=184, G1=116, G2=98, G3=197; early CEC=43,invasive=368; esophageal cancer=139, cardioesophageal cancer=272): only surgery-S=327, adjuvanttreatment-AT=84 (chemoimmunoradiotherapy=36: 5-FU+thymalin/taktivin +radiotherapy 45-50Gy,adjuvant chemoimmunotherapy=48). Survival curves were estimated by the Kaplan-Meier method.Differences in curves between groups of CECP were evaluated using a log-rank test. Cox modeling,clustering, SEPATH, Monte Carlo, bootstrap simulation and neural networks computing were used todetermine any significant dependence. RESULTS: For total of 411 CECP overall life span (LS) was 1632.22141.6 days, (median=783 days) andcumulative 5-year survival (5YS) reached 40.1%, 10 years 32.9%, 20 years 24%. 102 CECP lived morethan 5 years without CEC progressing. 216 CECP died because of CEC during the first 5 years aftersurgery. 5YS was superior significantly after AT (61.7%) compared with S (36.2%) (P=0.000 by log-ranktest). Cox modeling displayed that 5YS significantly depended on: phase transition (PT) early-invasiveCEC in term of synergetics, PT N0-N1M1A, AT, cell ratio factors (P=0.000-0.038). Neural networkscomputing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS andPT early-invasive CEC (rank=1), PT N0-N1M1A (rank=2), AT (3), segmented neutrophils/cancer cells-CC)(4), lymphocytes/CC (5), monocytes/CC (6). Correct prediction of 5YS was 100% by neural networkscomputing.CONCLUSIONS: Optimal management strategies for CECP are: 1) screening and early detection; 2)availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3)aggressive en block surgery and adequate lymphadenectomy for completeness; 4) high-precisionprediction; 5) adjuvant treatment for CECP with unfavorable prognosis. 3. Data: Males.307 Females.........104 Age=55.68.7 years Tumor Size=6.73.3 cm Only Surgery....327 Adjuvant Chemoimmunoradio/Chemoimmunotherapy(5FU+thymalin/taktivin, 5-6 cycles+RT 45-50Gy)..84 4. Radical Procedures: Left Thoracoabdominal Esophagogastrectomies(Garlock)....271 Right Thoracoabdominal Esophagogastrectomies (Ivor Lewis)....140 Combined Esophagogastrectomies with Resection of Diaphragm, Pericardium, Lung, Liver,Pancreas, etc.......127 2-Field Lymphadenectomy...303 3-Field Lymphadenectomy...108 5. Staging: T162 N0..170 G1116 T299 N157 G2..98 T3..141 N2..184 G3197 T4..109 M1..0 Adenocarcinoma..................................216 Squamos Cell Carcinoma185 Mix Carcinoma...10 Early Cancer43 Invasive Cancer.368 6. Survival Rate: Alive....170 (41%) 5-Year Survivors...102 (24.8%) 10-Year Survivors...54 (13%) Losses.216 (52.6%) General Life Span=1632.22141.6 days For 5-Year Survivors=4491.32679.0 days For 10-Year Survivors=6228.62632.2 days For Losses=648.6387.8 days Cumulative 5-Year Survival..40.1% Cumulative 10-Year Survival32.9% 7. General Esophageal/Cardioesophageal Cancer Patients Survivalafter Complete Esophagogastrectomies (Kaplan-Meier) (n=411) 8. Results of Univariate Analysis of Phase Transition EarlyInvasiveCancer in Prediction of Esophageal/Cardioesophageal CancerPatients Survival (n=411) 9. Results of Univariate Analysis of Phase Transition N0N1-2 inPrediction of Esophageal/Cardioesophageal Cancer PatientsSurvival (n=411) 10. Results of Univariate Analysis of Adjuvant Therapy in Predictionof Esophageal/Cardioesophageal Cancer Patients Survival (n=411) 11. Results of Univariate Analysis of Tumor Localization in Prediction ofEsophageal/Cardioesophageal Cancer Patients Survival (n=411) 12. Results of Univariate Analysis of Tumor Hystology in Prediction ofEsophageal/Cardioesophageal Cancer Patients Survival (n=411) 13. Results of Univariate Analysis of Tumor Growth in Prediction ofEsophageal/Cardioesophageal Cancer Patients Survival (n=411) 14. Results of DiscriminantFanction Analysis inPrediction ofEsophageal/CardioesophagealCancer Patients Survival afterSurgery (n=318) 15. Results of Multi-Factor Clusteringof Clinicopathological Data inPrediction ofEsophageal/CardioesophagealCancer Patients Survival afterComplete Esophagectomies (n=318) 16. Results of Cox Regression Modeling inPrediction ofEsophageal/Cardioesophageal CancerPatients Survival after Surgery (n=411) 17. Results of Neural Networks Computingin Prediction ofEsophageal/Cardioesophageal CancerPatients Survival after CompleteEsophagogastrectomies (n=318) 18. Results of Bootstrap Simulation inPrediction ofEsophageal/CardioesophagealCancer Patients Survival afterComplete Esophagectomies(n=318) 19. Holling-Tenner Models ofEsophageal/Cardioesophageal CancerCell Population and Cytotoxic Cell Population Dynamics 20. Results of Kohonen Self-Organizing NeuralNetworks Computing in Prediction ofEsophageal/Cardioesophageal Cancer PatientsSurvival after Complete Esophagogastrectomies (n=318) 21. Esophageal/CardioesophagealCancer Dynamics 22. Results of Structurul Equation Modelingin Prediction ofEsophageal/Cardioesophageal Cancer Patients Survival afterEsophagectomies, n=318 23. Conclusions: Optimal management strategies for esophageal andcardioesophageal cancer patients are: 1) screening and early detection; 2) availability of experienced thoracoabdominalsurgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph nodedissection for completeness; 4) high-precision prediction; 5) adjuvant treatment for esophageal andcardioesophageal cancer patients with unfavorableprognosis. 24. Address:Oleg Kshivets, M.D., Ph.D.Consultant Thoracic, Abdominal,General Surgeon & SurgicalOncologist e-mail: okshivets@yahoo.com skype: okshivetshttp: //www.ctsnet.org/home/okshivets