Lymph Node Metastases of Esophageal Cancer and Blood Cell Circuit

1. Lymph Node Metastases
of Esophageal Cancer
and Blood Cell Circuit
Kshivets Oleg, MD, PhD
Surgery Department, Roshal Hospital,
Roshal, Moscow, Russia

2. Abstract
• Lymph Node Metastases of Esophageal Cancer and Blood Cell Circuit
• Kshivets Oleg Surgery Department, Roshal Hospital, Moscow, Russia
• OBJECTIVE: Significance of blood cell circuit in terms of detection of esophageal cancer (EC) patients (ECP)
with lymph node metastases was investigated.
• METHODS: We analyzed data of 543 consecutive ECP (age=56.4±8.8 years; tumor size=6±3.5 cm) radically
operated (R0) and monitored in 1975-2019 (m=405, f=138; esophagogastrectomies (EG) Garlock=280, EG
Lewis=263, combined EG with resection of pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung,
trachea, pericardium, splenectomy=151; adenocarcinoma=308, squamous=225, mix=10; T1=126, T2=114,
T3=178, T4=125; N0=275, N1=69, N2=199; G1=157, G2=139, G3=247; early EC=107, invasive=436). Variables
selected for study were input levels of blood cell circuit, sex, age, TNMG. Differences between groups were
evaluated using discriminant analysis, clustering, nonlinear estimation, structural equation modeling, Monte
Carlo, bootstrap simulation and neural networks computing.
• RESULTS: It was revealed that separation of ECP with lymph node metastases (n=268) from ECP without
metastases (n=275) significantly depended on: erythrocytes (abs, total), leucocytes (total), segmented
neutrophils (total), eosinophils (%, abs, total), monocytes (%, abs, total), thrombocytes (abs), coagulation
time, protein, residual nitrogen, cell ratio factors (CRF) (ratio between cancer cells- CC and blood cells
subpopulations), T, G, tumor size, tumor growth, histology (P=0.045-0.000). Neural networks computing,
genetic algorithm selection and bootstrap simulation revealed relationships of lymph node metastases and
CRF: healthy cells/CC (rank=1), erythrocytes/CC (2), monocytes/CC (3), lymphocytes/CC (4), thrombocytes/CC
(5), segmented neutrophils/CC (6), eosinophils/CC (7), leucocytes/CC (8), stick neutrophils/CC (9). Correct
classification N0—N12 was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
• CONCLUSION: Lymph node metastases significantly depended on blood cell circuit.

3. Data:
• Males…………………………………….….405
• Females…….............................................138
• Age=56.4±8.8 years
• Tumor Size=6.0±3.5 cm

4. Radical Procedures:
• Esophagogastrectomies Lewis (R0)……………….…….263
• Esophagogastrectomies Garlock (R0)……….................280
• Combined Esophagogastrectomies with Resection of
Pancreas, Liver, Trachea, Lung, Aorta, Vena Cava
Superior, Colon Transversum, Diaphragm, Pericardium,
Splenectomy (R0)………………………………………..…..151
• 2-Field Lymphadenectomy…….……………..…………....374
• 3-Field
Lymphadenectomy.………………………………..…...……169

5. Staging:
• T1……..126 N0..……275 G1…………157
• T2……..114 N1…........69 G2…………139
• T3……..178 N2…......199 G3…………247
• T4……..125 N1-2…...268 M0…….…...543
• Adenocarcinoma………………………………………………………..308
• Squamous Cell Carcinoma……………………………………..……..225
• Mix………………….....…………………………………………................10
• Early Cancer……………………………...………………………….…..107
• Invasive Cancer…………………………..………………………..…....436

6. Survival Rate:
• Alive……………………………………....................................284 (52.3%)
• 5-Year Survivors……………………………………………..…183 (33.7%)
• 10-Year Survivors………………………...................................98 (18%)
• Losses……………………..………………………………….….224 (41.3%)
• General Life Span=1892.4±2241 days
• For 5-Year Survivors=4311±2419.7 days
• For 10-Year Survivors=5903.4±2299.4 days
• For Losses=629.2±320.1 days
• Cumulative 5-Year Survival for N0-N12…………………….………51.9%
• Cumulative 5-Year Survival for N0…………..…………….………...73.9%
• Cumulative 5-Year Survival for N12………………………………....27.5%

7. Results of Univariate Analysis of Phase Transition N0—N1-2 in Prediction of
Esophageal Cancer Patients Survival (n=543):
Cumulative Proportion Surviving (Kaplan-Meier)
5-Year Survival of ECP with N0=73.9%; 5-Year Survival of ECP with N1-2=27.5%
P=0.00000 by Log-Rank Test
Complete Censored
0 5 10 15 20 25 30 35 40
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
CumulativeProportionSurviving
ECP with N1-2, n=268
ECP with N0, n=275

8. Results of T-testing for Recognition of Lymph Node
Metastases of Esophageal Cancer (n=543):
Variable
Mean
N1-2
Mean
N0
t-value p
Std.Dev.
N1-2
Std.Dev.
N0
Erythrocytes abs 3.9321 4.0480 -2.2878 0.022537 0.6013 0.5793
Eosinophils (%) 2.6119 1.9564 3.3211 0.000957 2.6603 1.8830
Monocytes (%) 3.8657 4.5855 -3.0755 0.002208 2.6670 2.7834
Thrombocytes abs 246.2164 230.4255 2.9488 0.003328 66.1781 58.4573
Coagulation Time 312.5082 267.4299 3.9177 0.000101 142.3578 125.4249
Residual Nitrogen 20.3224 14.5305 9.0438 0.000000 6.7240 8.1151
Protein 70.8358 72.4509 -2.2802 0.022987 8.6025 7.8958
Tumor Size 7.5955 4.4353 11.8861 0.000000 3.0092 3.1813
Eosinophils abs 0.1547 0.1172 2.9204 0.003641 0.1776 0.1169
Monocytes abs 0.2354 0.2933 -2.9455 0.003363 0.2100 0.2461
Erythrocytes tot 18.2003 19.4827 -2.8855 0.004063 4.9583 5.3829
Leucocytes tot 27.4540 29.6694 -2.0117 0.044743 11.8452 13.7212
Eosinophils tot 0.7306 0.5542 2.6457 0.008389 0.9488 0.5603
Segmented Neutrophils tot 17.4354 19.3848 -2.4926 0.012978 7.8233 10.2115
Monocytes tot 1.1030 1.4007 -3.0025 0.002801 1.0883 1.2166
Erythrocytes/Cancer Cells 2.7901 8.4450 -11.1571 0.000000 1.4259 8.1770
Thrombocytes/Cancer Cells 170.5577 466.2988 -10.3004 0.000000 84.0484 462.6386
Leucocytes/Cancer Cells 4.1185 12.4827 -10.0883 0.000000 2.1669 13.4031
Eosinophils/Cancer Cells 0.1048 0.2369 -5.2310 0.000000 0.1228 0.3951
Stick Neutrophils/Cancer Cells 0.0944 0.2351 -5.6168 0.000000 0.1358 0.3874
Segmented Neutrophils/Cancer Cells 2.6124 8.0388 -10.3172 0.000000 1.4583 8.4888
Lymphocytes/Cancer Cells 1.1451 3.3509 -8.0249 0.000000 0.7599 4.4367
Monocytes/Cancer Cells 0.1639 0.6135 -7.2323 0.000000 0.1598 1.0054
Healthy Cells/Cancer Cells 10.1004 28.9642 -11.4397 0.000000 4.6453 26.6020
Weight 65.7948 68.4364 -2.2476 0.025003 12.7561 14.5469

9. ResuIts of GLZ Analysis in Recognition of
Lymph Node Metastases of Esophageal
Cancer (n=543):
Effect
N0---1_2 - Test of all effects (ECP, n=543)
Distribution : BINOMIAL, Link function: LOGIT
Modeled probability that N0---N1_2 = N0
Degr. of
Freedom
Wald
Stat.
p
Intercept 1 8.54062 0.003473
Leucocytes 1 12.80606 0.000345
Segmented Neutrophils (%) 1 8.33307 0.003893
Residual Nitrogen 1 16.57739 0.000047
Eosinophils abs 1 7.55421 0.005987
Lymphocytes abs 1 8.08126 0.004473
Thrombocytes tot 1 22.93402 0.000002
Thrombocytes/Cancer Cells 1 38.68893 0.000000
Tumor Growth 2 40.52006 0.000000

10. Results of Neural Networks Computing in
Recognition of Lymph Node Metastases in
Esophageal Cancer Patients (n=543):
Neural Networks: n=543;
Baseline Error=0.000;
Area under ROC Curve=1.000;
Correct Classification Rate=100%
Rank Sensitivity
Healthy Cells/Cancer Cells 1 12920
Erythrocytes/Cancer Cells 2 11262
Monocytes/Cancer Cells 3 7345
Lymphocytes/Cancer Cells 4 6154
Thrombocytes/Cancer Cells 5 6102
Segmented Neutrophils/Cancer Cells 6 4350
Eosinophils/Cancer Cells 7 4268
Leucocytes/Cancer Cells 8 3294
Stick Neutrophils/Cancer Cells 9 3026

11. Results of Bootstrap Simulation in Recognition of Lymph
Node Metastases in Esophageal Cancer Patients (n=543):
Significant Factors
(Number of Samples=3333)
Ran
k
Kendal
Tau-A
P<
Tumor Size 1 0.273 0.000
T1-4 2 0.268 0.000
Healthy Cells/Cancer Cells 3 -0.265 0.000
Monocytes/Cancer Cells 4 -0.244 0.000
Lymphocytes/Cancer Cells 5 -0.241 0.000
Erythrocytes/Cancer Cells 6 -0.223 0.000
Leucocytes/Cancer Cells 7 -0.219 0.000
Tumor Growth 8 0.218 0.000
Segmented Neutrophils/Cancer Cells 9 -0.215 0.000
Residual Nitrogen 10 0.199 0.000
Phase Transition Early---Invasive Cancer 11 0.195 0.000
Thrombocytes/Cancer Cells 12 -0.177 0.000
Esophageal/Cardioesophageal Cancer 13 0.162 0.000
Procedure Type 14 0.151 0.000
Coagulation Time 15 0.123 0.000
Combined Procedure 16 -0.112 0.000
Histology 17 0.098 0.001
Monocytes tot 18 -0.089 0.01
Monocytes abs 19 -0.083 0.01
Monocytes (%) 20 -0.082 0.01
Hemoglobin 21 -0.069 0.05
Erythrocytes tot 22 -0.067 0.05
Bilirubin 23 -0.063 0.05

12. Results of Kohonen Self-Organizing Neural Networks
Computing in Recognition of Lymph Node
Metastases of Esophageal Cancer Patients (n=543):

13. Equation Models in Recognition of Lymph Node
Metastases of Esophageal Cancer Patients (n=543):

14. SEPATH-Model in Recognition of Lymph Node
Metastases of Esophageal Cancer Patients (n=543):

15. LYMPH NODE METASTASES OF ESOPHAGEAL
CANCER SIGNIFICANTLY DEPENDED ON:
1) BLOOD CELL CIRCUIT;
2) CELL RATIO FACTORS;
3) BIOCHEMICAL FACTORS;
4) HEMOSTASIS SYSTEM;
5) CANCER CHARACTERISTICS;
6) TUMOR LOCALIZATION;
7) ANTHROPOMETRIC DATA;
8) SURGERY.
Conclusion:

16. 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