Early Detection and Phase Transitions in System “Malignancy-Human Organism” Oleg Kshivets, M.D., Ph.D. Siauliai Cancer Center, Lithuania AACR Special Conference: The Biology and Genetics of Early Detection & Chemoprevention of Cancer Miami, Florida, The USA, 1999
31
Embed
Kshivets O. Cancer, Synergetics, Computer Sciences and Alive Supersystems
Early Detection and Phase Transition in Alive Supersystem "Cancer-Human Organism"
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Early Detection and Phase Transitions in System “Malignancy-
Human Organism”
Oleg Kshivets, M.D., Ph.D.Siauliai Cancer Center, Lithuania
AACR Special Conference: The Biology and Genetics of Early Detection & Chemoprevention of Cancer
Miami, Florida, The USA, 1999
Abstract:• EARLY DETECTION AND PHASE TRANSITIONS IN SYSTEM “MALIGNANCY-HUMAN
ORGANISM” • Oleg Kshivets Siauliai Cancer Center, Siauliai, Lithuania
• Purpose: This research studied homeostasis parameters, typical for two extreme states of phase transition: early malignancy (strategic purpose of early detection) and invasive cancer (C).
• Methods: Basis of this research was the data of 1524 cancer patients (CP) with pathologic stage (T1-4N0-2M0-1G1-4): 655 gastric CP (GCP), 525 lung CP (LCP) and 344 bladder CP (BCP) operated and monitored in clinic 1970-1998. All CP had preoperation examination including peripheral blood count, biochemical tests of venous blood using usual unified methods, clinical, anthropometric, X-ray examination, endoscopy, sonography, electrocardiography and also doctor’s examination, if required, computed tomography and radioisotope scanning. After operations the data of intraoperational investigation, information on character of surgery, complications, morphologic C characteristics (size, TNMG, growth, histology, etc.) was registrated. Representativeness of samplings was reached by means of randomization based on unrepeated random selection. Multiple correspondence analysis (A), clustering, A of variance, confirmatory factor A, structural equation modeling and Monte Carlo simulation were used to determine any significant overall regularities between malignancy and CP organism.
• Results: Using complex system analysis, simulation modeling in terms of synergetics, evoinformatics, statements from theories of Hopf, Landau, Turing and Marchuk it was discovered that system “C-patient’s homeostasis” consecutively passed through three phase transitions: 1) phase transition “norm--oncobackground”; 2) phase transition “oncobackground--early malignancy”; 3) phase transition “early malignancy--invasive C”. If diagnosis of first two phase transitions depended on outcomes of early detection and diagnosis, identification of third phase transition resulted in effectiveness of treatment process and 5-year survival of CP. It was also verified that most important figure of this transition for human was quantity of C cell population in organism and average critical threshold of this population was 4.189e+9 per human organism. Below such value there was a temporal dynamic equilibrium between C and patient’s homeostasis and 5-year survival of radically operated CP tended to be 100%. Excess over this threshold resulted in irreversible consequences when effectiveness of treatment went down up to 10-15%. It was discovered that phase transition of early malignancy into invasive C of any localization significantly depended on: 1) input level of blood cell circuit; 2) ratio of C cell population quantity to blood cell subpopulations in integral CP organism (cell ratio factors); 3) C characteristics (C cell population quantity in CP organism, TNMG); 4) some blood biochemical factors; 5) anthropometric data.
•
Samplings:
• Lung Cancer Patients (T1-4N0-2M0-1)…….525• Gastric Cancer Patients (T1-4N0-2M0-1)….655• Bladder Cancer Patients (T1-4N0-2M0-1)…344• In All .………………………...……………..1524
• Patients with Non-Malignant Pathology….3977 • Practically Healthy Old People…………...1464
Prognostic Role of Cancer DiameterBivariate Histogram: Life Span and Bladder Cancer Diameter (cm)
Life Span (day)Bladder Cancer Diameter (cm)
No of obs
-20000 2000400060008000100001200014000
12345678910111213
20
40
60
80
100
Bivariate Histogram: Life Span of LCP and Cancer Diameter
n=404
Main Problem of Analysis of Living Supersystems:
Phenomenon of «Combinatorial Explosion»
• Average Number of Routine Blood Parameters:…… 28• Number of Possible Combination • for Random Search:……………….... n!=28!=3.049e+29 • Computer Operation Time of The 7G Teracomputer
(1000TFLOPS) (The 21st Century)… 9.7 Million Years
MALIGNANCY OF THE II-III STAGES MALIGNANCY OF THE IV STAGE
Superoncoimmunology-1.0SUPERONCOIMMUNOLOGY-1.0
IMMUNODIAGNOSIS-1 IMMUNODIAGNOSIS-2
IMMUNODEFICIENCY NORMMALIGNANT NEOPLASM
POPULATION PHASE TRANSITION IMMUNOSTAGING
N M G
EARLY CANCER INVASIVE CANCER
Superoncoprognosis-1.0
SUPERONCOPROGNOSIS-1.0
PROGNOSIS SURVIVAL-2
PROG-1 PROG-2 PROG-3 E
SURVIVAL LESS 5 YEARS SURVIVAL MORE 5 YEARS
SURVIVAL-1
A B
C
Total Monitoring System
SOS-1.0HEALTHY PEOPLE
PRECANCER
PERSONS FOR SUSPICION OFMALIGNANCY
SOD-1.0
SOI-1.0NONMALIGNANT
PATHOLOGY
MALIGNANCY
SODM-1.0 EARLY CANCER
INVASIVE CANCER SOP-1.0
II-III STAGES IV STAGE
POPULATION OF THE COUNTRY
Conclusions:• 1. System “Cancer-patient’s homeostasis” consecutively passed
through three phase transitions: “norm-oncobackground”; “oncobackground-early malignancy”; “early malignancy-invasive cancer”.
• 2. Most important figure of this transition for human was quantity of cancer cell population in organism and average critical threshold of this population was 4.189e+9 per human organism.
• 3. Phase transition of early malignancy into invasive cancer of any localization significantly depended on: input level of blood cell circuit; ratio of cancer cell population quantity to blood cell subpopulations in integral cancer patient’s organism (cell ratio factors); malygnancy characteristics (cancer cell population quantity in organism, TNMG); some blood biochemical factors and anthropometric data.
Patents:1. Kshivets O.M. Method of Screening and Differential Diagnosis of Malignant
Neoplasms// Patent from 27.04.92.-N2045072.-28pp.. 2. Kshivets O.M. Method of Prognosis of Survival Rate of Radically Operated
Oncopatients// Patent from 10.02.94.-N2101704.-24pp. .3. Kshivets O.M. Method of Prognosis of Survival Rate of Non-Radically Operated
Oncopatients// Patent from 14.03.94.-N2104536.-10pp. .4. Kshivets O.M. Method of Early and Differential Immunodiagnosis of Malignancies//
Patent from 24.10.95.-N2107290.-12pp. .5. Kshivets O.M. Method of Immunodiagnosis of Distant Metastases of Oncopatients//
Patent from 06.10.95.-N2107295.-8pp. .6. Kshivets O.M. Method of Immunodiagnosis of Generalization of Oncopatients// Patent
from 09.10.95.-N2107294.-12pp. .7. Kshivets O.M. Method of Immunodiagnosis of Early and Invasive Oncopathology for
Patients// Patent from 04.05.95.-N2107293.-14pp. .8. Kshivets O.M. Method of Differential Diagnosis of Oncopathology and Pre-Cancer or
Non-Malignant Pathology// Patent from 08.11.94.-N2114431.-18pp.
Patents:. 9.Kshivets O.M. Method of Measuring the Size of Malignant Neoplasms and Total Quantity of
Malignant Cells in Oncopatient’s Organism Based on the Homeostasis Parameters// Application for Patent from 04.05.95.-N95107201/012623.-8pp. (Positive Decision).
.10. Kshivets O.M. Method of Diagnosis of Distant Metastases of Oncopatients// Application for Patent from 03.11.95.-N95118236/032006.-12pp. (Positive Decision).
.11. Kshivets O.M. Method of Diagnosis of Generalization of Oncopatients// Application for Patent from 20.10.95.-N95117904/031312.-12pp. (Positive Decision).
.12. Kshivets O.M. Method of Diagnosis of Early and Invasive Oncopathology for a Single Patient// Application for Patent from 06.10.95.-N95117338/029690.-13pp. (Positive Decision).
.13. Kshivets O.M. Method of Diagnosis of Malignant Neoplasms Metastasizing in Regional Lymphatic Nodules of a Concrete Patient// Application for Patent from 29.09.95.-N95116510/028981.-10pp. (Positive Decision).
.14. Kshivets O.M. Method of Measuring the Size of the Malignancy and Total Quantity of Malignant Cells in the Oncopatient’s Organism Based on the Immunogram// Application for Patent from 04.05.95.-N95107200/012622.-9pp. (Positive Decision).
.15. Kshivets O.M. Method of Immunodiagnosis of Regional Metastases of Oncopatients// Application for Patent from 06.10.95.-N95117049/029707.-9pp. (Positive Decision).
Address:• Oleg Kshivets, M.D.,
Ph.D.• Thoracic Surgeon• Department of Surgery• Siauliai Cancer Center• Tilzes:42-16, Siauliai, LT78206, Lithuania• Tel. (37041)416614• [email protected] • [email protected]• http//:myprofile.cos.com/Kshivets