Conclusions: 10-Year survival of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) anthropometric data; 10) surgery type. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
10-Year survival after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) tumor localization; 10) anthropometric data; 11) surgery type. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for ECP with unfavorable prognosis.
CONCLUSIONS: 10-Year survival after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) tumor localization; 10) anthropometric data; 11) surgery type. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for ECP with unfavorable prognosis.
10-Year survival of GCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) GC characteristics; 9) anthropometric data; 10) surgery type. Optimal diagnosis and treatment strategies for GC are: 1) screening and early detection of GC; 2) availability of experienced abdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunotherapy for GCP with unfavorable prognosis.
10-Year survival after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) tumor localization; 10) anthropometric data; 11) surgery type. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for ECP with unfavorable prognosis.
CONCLUSIONS: 10-Year survival after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) tumor localization; 10) anthropometric data; 11) surgery type. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for ECP with unfavorable prognosis.
10-Year survival of GCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) GC characteristics; 9) anthropometric data; 10) surgery type. Optimal diagnosis and treatment strategies for GC are: 1) screening and early detection of GC; 2) availability of experienced abdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunotherapy for GCP with unfavorable prognosis.
Kshivets O. Esophageal and Cardioesophageal Cancer SurgeryOleg Kshivets
5-YEAR SURVIVAL OF ESOPHAGEAL AND CARDIOESOPHAGEAL CANCER PATIENTS AFTER RADICAL SURGERY SIGNIFICANTLY DEPENDED ON PHASE TRANSITION “EARLY-INVASIVE CANCER”, LYMPH NODE METASTASES AND CELL RATIO FACTORS
Combined Esophagogastrectomies: Survival Outcomes in Patients with Local Adva...Oleg Kshivets
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 prognos
Gastric Cancer: 10-Year Survival
Kshivets Oleg Surgery Department, Roshal Hospital, Moscow, Russia
CONCLUSIONS: 10-Year survival of GCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) GC characteristics; 9) anthropometric data; 10) surgery type. Optimal diagnosis and treatment strategies for GC are: 1) screening and early detection of GC; 2) availability of experienced abdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunotherapy for GCP with unfavorable prognosis.
The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...daranisaha
To evaluate the benefit of radiotherapy, compared with other treatment in ocular marginal zone lymphoma, retrospectively we analyzed our experience, with the end-points: efficacy, measured for complete response, Progression-Free Survival (PFS) and Overall Survival
5-Year Survival of Lung Cancer Patients after Radical Surgery was Significantly Depended on Tumor Characteristics, Blood Cell Circuit, Cell Ratio Factors, Hemostasis System, Biochemic Homeostasis, Surgery Type, Adjuvant Treatment and Anthropometric Data
Kshivets O. Esophageal and Cardioesophageal Cancer SurgeryOleg Kshivets
5-YEAR SURVIVAL OF ESOPHAGEAL AND CARDIOESOPHAGEAL CANCER PATIENTS AFTER RADICAL SURGERY SIGNIFICANTLY DEPENDED ON PHASE TRANSITION “EARLY-INVASIVE CANCER”, LYMPH NODE METASTASES AND CELL RATIO FACTORS
Combined Esophagogastrectomies: Survival Outcomes in Patients with Local Adva...Oleg Kshivets
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 prognos
Gastric Cancer: 10-Year Survival
Kshivets Oleg Surgery Department, Roshal Hospital, Moscow, Russia
CONCLUSIONS: 10-Year survival of GCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) GC characteristics; 9) anthropometric data; 10) surgery type. Optimal diagnosis and treatment strategies for GC are: 1) screening and early detection of GC; 2) availability of experienced abdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunotherapy for GCP with unfavorable prognosis.
The Role of Radiotherapy in the Treatment of Early Stage Ocular Marginal Zone...daranisaha
To evaluate the benefit of radiotherapy, compared with other treatment in ocular marginal zone lymphoma, retrospectively we analyzed our experience, with the end-points: efficacy, measured for complete response, Progression-Free Survival (PFS) and Overall Survival
5-Year Survival of Lung Cancer Patients after Radical Surgery was Significantly Depended on Tumor Characteristics, Blood Cell Circuit, Cell Ratio Factors, Hemostasis System, Biochemic Homeostasis, Surgery Type, Adjuvant Treatment and Anthropometric Data
CONCLUSIONS: 10-Year survival of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) anthropometric data; 10) surgery type; 11) tumor localization. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
5-YEAR SURVIVAL OF UPPER THIRD ESOPHAGEAL CANCER PATIENTS WAS SIGNIFICANTLY SUPERIOR IN COMPARISON WITH MIDDLE AND LOWER THIRD ESOPHAGEAL CANCER PATIENTS AFTER RADICAL SURGERY AND STRONGLY DEPENDED ON PHASE TRANSITION EARLY-INVASIVE CANCER, LYMPH NODE METASTASES, CELL RATIO FACTORS AND ADJUVANT CHEMOIMMUNORADIOTHERAPY
Living Donor Liver Transplantation in Hepatocellular Carcinoma: How Far Can W...semualkaira
The expansion in Liver Transplantation (LT) selection criteria for
Hepatocellular Carcinoma (HCC) has shown acceptable results in
survival rate and tumor recurrence. Historical analysis of the results shows that the path taken so far is correct; however, there
are still doubts about the limit of this expansion. The acquisition
of new selection tools that measure the biological behavior of the
tumor, instead of the historic and simple preoperative morphological analysis, has been gaining strength in this expansion. In this
context, analyzing the ethical perspective in the use of grafts from
living donors is essential in order to seek a risk vs. benefit balance
for both donor and recipient.
Nowadays the problem of surgical treatment of Colorectal
Cancer (CRC) is becoming very important due to the high speed of increasing morbidity and mortality, which is registered almost in all economically developed countries in the world [1,2]. In 2012, more than one million new cases of CRC were detected on our planet and about half a million people died from this disease [1]. On the territory of Russia, a primary diagnosis of colorectal cancer is annually established in 6000 people, with the highest incidence rates in the North-West region (St. Petersburg and Leningrad region), where in the general structure of oncopathology, colorectal cancer is in the second
Introduction: Prediction of readmission as a result of either delayed presentation of infection, or worse an anastomotic leak is difficult. Efficient reduction in the length of stay and being able to predict problematic patients who may be readmitted or develop complications would be advantageous. To date,
other tests including CRP have proven to be insufficiently sensitive for this task.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...daranisaha
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...JohnJulie1
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...eshaasini
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...semualkaira
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Gastric Cancer: Сlinical Implementation of Artificial Intelligence, Synergeti...Oleg Kshivets
5-year survival of GCP after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) GC cell dynamics; 9) GC characteristics; 10) tumor localization; 11) anthropometric data; 12) surgery type. Optimal diagnosis and treatment strategies for GC are: 1) screening and early detection of GC; 2) availability of sufficient quantity of experienced abdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunotherapy for GCP with unfavorable prognosis.
Local Advanced Esophageal Cancer (T3-4N0-2M0): Artificial Intelligence, Syner...Oleg Kshivets
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.
Esophageal Cancer: Artificial Intelligence, Synergetics, Complex System Analy...Oleg Kshivets
5-year survival of ECP after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC cell dynamics; 9) EC characteristics; 10) tumor localization; 11) anthropometric data; 12) surgery type. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for ECP with unfavorable prognosis.
Kshivets Oleg Optimization of Management for Esophageal Cancer Patients (T1-...Oleg Kshivets
Optimization of Management for Esophageal Cancer Patients (T1-4N0-2M0).
Kshivets Oleg Surgery Department, Bagrationovsk Hospital, Bagrationovsk, Kaliningrad, Russia
ABSTRACT
OBJECTIVE: 5-survival (5YS) and life span after radical surgery for esophageal cancer (EC) pa¬tients (ECP)(T1-4N0-2M0) - alive supersysems was analyzed. The importance must be stressed of using complex system analysis, artificial intelligence (neural networks computing), simulation modeling and statistical methods in combination, because the different approaches yield complementary pieces of prognostic information.
METHODS: We analyzed data of 563 consecutive ECP (age=56.6±8.9 years; tumor size=6±3.5 cm) radically operated (R0) and monitored in 1975-2024 (m=419, f=144; esophagogastrectomies (EG) Garlock=289, EG Lewis=274, combined EG with resection of pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung, trachea, pericardium, splenectomy=170; adenocarcinoma=323, squamous=230, mix=10; T1=131, T2=119, T3=185, T4=128; N0=285, N1=71, N2=207; G1=161, G2=143, G3=259; early EC=112, invasive=451; only surgery=428, adjuvant chemoimmunoradiotherapy-AT=135: 5-FU+thymalin/taktivin+radiotherapy 45-50Gy). 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 1915.4±2284.8 days and cumulative 5-year survival (5YS) reached 52.6%, 10 years – 46.3%, 20 years – 33.3%, 30 years – 27.5%. 193 ECP lived more than 5 years (LS=4309.1±2507.4 days), 105 ECP – more than 10 years (LS=5860.8±2469.2 days). 228 ECP died because of EC (LS=629.8±324.1 days). AT significantly improved 5YS (69% vs. 49.1%) (P=0.0007 by log-rank test). 5YS of ECP of upper/3 was significantly better than others (65.3% vs.50.3%) (P=0.003). Cox modeling displayed that 5YS of ECP significantly depended on: phase transition (PT) N0—N12 in terms of synergetics, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), T, G, histology, age, AT, localization, prothrombin index, hemorrhage time, residual nitrogen, protein (P=0.000-0.019). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and healthy cells/CC (rank=1), PT N0—N12 (2), PT early-invasive EC (3), erythrocytes/CC (4), thrombocytes/CC (5); segmented neutrophils/CC (6), stick neutrophils/CC (7), lymphocytes/CC (8), eosinophils/CC (9), monocytes/CC (10), leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5-year survival of ECP after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC cell dynamics; 9) EC characteristics; 10) tumor localization; 11) anthropometric data; 12) surgery type. Optimal diagnosis and trea
5-year survival of ECP after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) EC cell dynamics; 10) tumor localization; 11) anthropometric data; 12) surgery type. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for ECP with unfavorable prognosis.
OBJECTIVE: 5-survival (5YS) and life span after radical surgery for esophageal cancer (EC) pa¬tients (ECP) (T1-4N0-2M0) was analyzed. The importance must be stressed of using complex system analysis, artificial intelligence (neural networks computing), simulation modeling and statistical methods in combination, because the different approaches yield complementary pieces of prognostic information.
METHODS: We analyzed data of 557 consecutive ECP (age=56.6±8.9 years; tumor size=6±3.5 cm) radically operated (R0) and monitored in 1975-2023 (m=415, f=142; esophagogastrectomies (EG) Garlock=288, EG Lewis=269, combined EG with resection of pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung, trachea, pericardium, splenectomy=168; adenocarcinoma=319, squamous=228, mix=10; T1=130, T2=115, T3=184, T4=128; N0=282, N1=70, N2=205; G1=157, G2=142, G3=258; early EC=111, invasive=446; only surgery=425, adjuvant chemoimmunoradiotherapy-AT=132: 5-FU+thymalin/taktivin+radiotherapy 45-50Gy). 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 1876.9±2219.8 days and cumulative 5-year survival (5YS) reached 52%, 10 years – 45.5%, 20 years – 33.4%, 30 years – 26.9%. 187 ECP lived more than 5 years (LS=4271±2411.9 days), 99 ECP – more than 10 years (LS=5883±2296.6 days). 228 ECP died because of EC (LS=629.8±324.1 days). AT significantly improved 5YS (67.8% vs. 48.7%) (P=0.00084 by log-rank test). Cox modeling displayed that 5YS of ECP significantly depended on: phase transition (PT) N0—N12 in terms of synergetics, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), T, G, histology, age, AT, localization, prothrombin index, hemorrhage time, residual nitrogen, protein (P=0.000-0.019). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and
healthy cells/CC (rank=1), PT early-invasive EC (2); PT N0—N12 (3), erythrocytes/CC (4), thrombocytes/CC (5); stick neutrophils/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), eosinophils/CC (9), leucocytes/CC (10); monocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5-year survival of ECP after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) EC cell dynamics; 10) tumor localization; 11) anthropometric data; 12) surgery type. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5)AT
OBJECTIVE: 5-survival (5YS) and life span after radical surgery for esophageal cancer (EC) pa¬tients (ECP) (T1-4N0-2M0) was analyzed. The importance must be stressed of using complex system analysis, artificial intelligence (neural networks computing), simulation modeling and statistical methods in combination, because the different approaches yield complementary pieces of prognostic information.
METHODS: We analyzed data of 557 consecutive ECP (age=56.6±8.9 years; tumor size=6±3.5 cm) radically operated (R0) and monitored in 1975-2023 (m=415, f=142; esophagogastrectomies (EG) Garlock=288, EG Lewis=269, combined EG with resection of pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung, trachea, pericardium, splenectomy=168; adenocarcinoma=319, squamous=228, mix=10; T1=130, T2=115, T3=184, T4=128; N0=282, N1=70, N2=205; G1=157, G2=142, G3=258; early EC=111, invasive=446; only surgery=425, adjuvant chemoimmunoradiotherapy-AT=132: 5-FU+thymalin/taktivin+radiotherapy 45-50Gy). 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 1876.9±2219.8 days and cumulative 5-year survival (5YS) reached 52%, 10 years – 45.5%, 20 years – 33.4%, 30 years – 26.9%. 187 ECP lived more than 5 years (LS=4271±2411.9 days), 99 ECP – more than 10 years (LS=5883±2296.6 days). 228 ECP died because of EC (LS=629.8±324.1 days). AT significantly improved 5YS (67.8% vs. 48.7%) (P=0.00084 by log-rank test). Cox modeling displayed that 5YS of ECP significantly depended on: phase transition (PT) N0—N12 in terms of synergetics, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), T, G, histology, age, AT, localization, prothrombin index, hemorrhage time, residual nitrogen, protein (P=0.000-0.019). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and
healthy cells/CC (rank=1), PT early-invasive EC (2); PT N0—N12 (3), erythrocytes/CC (4), thrombocytes/CC (5); stick neutrophils/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), eosinophils/CC (9), leucocytes/CC (10); monocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5-year survival of ECP after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) EC cell dynamics; 10) tumor localization; 11) anthropometric data; 12) surgery type. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant ch
5-year survival of GCP after radical procedures
significantly depended on: 1) PT “early-invasive
cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood
cell circuit; 5) biochemical factors; 6) hemostasis
system; 7) AT; 8) GC characteristics; 9) GC cell
dynamics; 10) tumor localization; 11) anthropometric
data; 12) surgery type. Best diagnosis and treatment
strategies for GC are: 1) screening and early detection
of GC; 2) availability of experienced abdominal
surgeons because of complexity of radical procedures;
3) aggressive en block surgery and adequate lymph
node dissection for completeness; 4) precise
prediction; 5) adjuvant chemoimmunotherapy for GCP
with unfavorable prognosis.
OBJECTIVE: 5-survival (5YS) and life span after radical surgery for non-small cell lung cancer (LC) pa¬tients (LCP) (T1-4N0-2M0) was analyzed.
METHODS: We analyzed data of 771 consecutive LCP (age=57.6±8.3 years; tumor size=4.1±2.4 cm) radically operated and monitored in 1985-2022 (m=662, f=109; upper lobectomies=278, lower lobectomies=178, middle lobectomies=18, bilobectomies=42, pneumonectomies=255, mediastinal lymph node dissection=771; combined procedures with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=194; only surgery-S=620, adjuvant chemoimmunoradiotherapy-AT=151: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=322, T2=255, T3=133, T4=61; N0=518, N1=131, N2=122, M0=771; G1=195, G2=243, G3=333; squamous=418, adenocarcinoma=303, large cell=50; early LC=215, invasive LC=556; right LC=413, left LC=358; central=291; peripheral=480. Variables selected for study were input levels of 45 blood parameters, sex, age, TNMG, cell type, tumor size. Regression modeling, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine significant dependence.
RESULTS: Overall life span (LS) was 2240.9±1748.8 days and cumulative 5-year survival (5YS) reached 73%, 10 years – 64.2%, 20 years – 43%. 503 LCP lived more than 5 years (LS=3126.6±1536 days), 145 LCP – more than 10 years (LS=5068.5±1513.2 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (77.7% vs.63.4%, P=0.00001 by log-rank test). AT significantly improved 5YS (64.4% vs. 34.8%) (P=0.00003 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.035). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), eosinophils/CC (4), erythrocytes/CC (5),healthy cells/CC (6), segmented neutrophils/CC (7), lymphocytes/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: PT early-invasive cancer; PT N0--N12; cell ratio factors; blood cell circuit; biochemical factors; hemostasis system; AT; LC characteristics; surgery type; anthropometric data.
OBJECTIVE: 5-survival (5YS) and life span after radical surgery for non-small cell lung cancer (LC) pa¬tients (LCP) (T1-4N0-2M0) was analyzed.
METHODS: We analyzed data of 771 consecutive LCP (age=57.6±8.3 years; tumor size=4.1±2.4 cm) radically operated and monitored in 1985-2022 (m=662, f=109; upper lobectomies=278, lower lobectomies=178, middle lobectomies=18, bilobectomies=42, pneumonectomies=255, mediastinal lymph node dissection=771; combined procedures with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=194; only surgery-S=620, adjuvant chemoimmunoradiotherapy-AT=151: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=322, T2=255, T3=133, T4=61; N0=518, N1=131, N2=122, M0=771; G1=195, G2=243, G3=333; squamous=418, adenocarcinoma=303, large cell=50; early LC=215, invasive LC=556; right LC=413, left LC=358; central=291; peripheral=480. Variables selected for study were input levels of 45 blood parameters, sex, age, TNMG, cell type, tumor size. Regression modeling, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine significant dependence.
RESULTS: Overall life span (LS) was 2240.9±1748.8 days and cumulative 5-year survival (5YS) reached 73%, 10 years – 64.2%, 20 years – 43%. 503 LCP lived more than 5 years (LS=3126.6±1536 days), 145 LCP – more than 10 years (LS=5068.5±1513.2 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (77.7% vs.63.4%, P=0.00001 by log-rank test). AT significantly improved 5YS (64.4% vs. 34.8%) (P=0.00003 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.035). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), eosinophils/CC (4), erythrocytes/CC (5),healthy cells/CC (6), segmented neutrophils/CC (7), lymphocytes/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data.
OBJECTIVE: 5-survival (5YS) and life span after radical surgery for non-small cell lung cancer (LC) pa¬tients (LCP) (T1-4N0-2M0) was analyzed.
METHODS: We analyzed data of 771 consecutive LCP (age=57.6±8.3 years; tumor size=4.1±2.4 cm) radically operated and monitored in 1985-2022 (m=662, f=109; upper lobectomies=278, lower lobectomies=178, middle lobectomies=18, bilobectomies=42, pneumonectomies=255, mediastinal lymph node dissection=771; combined procedures with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=194; only surgery-S=620, adjuvant chemoimmunoradiotherapy-AT=151: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=322, T2=255, T3=133, T4=61; N0=518, N1=131, N2=122, M0=771; G1=195, G2=243, G3=333; squamous=418, adenocarcinoma=303, large cell=50; early LC=215, invasive LC=556; right LC=413, left LC=358; central=291; peripheral=480. Variables selected for study were input levels of 45 blood parameters, sex, age, TNMG, cell type, tumor size. Regression modeling, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine significant dependence.
RESULTS: Overall life span (LS) was 2240.9±1748.8 days and cumulative 5-year survival (5YS) reached 73%, 10 years – 64.2%, 20 years – 43%. 503 LCP lived more than 5 years (LS=3126.6±1536 days), 145 LCP – more than 10 years (LS=5068.5±1513.2 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (77.7% vs.63.4%, P=0.00001 by log-rank test). AT significantly improved 5YS (64.4% vs. 34.8%) (P=0.00003 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.035). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), eosinophils/CC (4), erythrocytes/CC (5),healthy cells/CC (6), segmented neutrophils/CC (7), lymphocytes/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data.
OBJECTIVE: 5-survival (5YS) and life span after radical surgery for esophageal cancer (EC) pa¬tients (ECP) (T1-4N0-2M0) was analyzed.
METHODS: We analyzed data of 556 consecutive ECP (age=56.5±8.9 years; tumor size=6±3.5 cm) radically operated (R0) and monitored in 1975-2022 (m=415, f=141; esophagogastrectomies (EG) Garlock=287, EG Lewis=269, combined EG with resection of pancreas, liver, diaphragm, aorta, VCS, colon transversum, lung, trachea, pericardium, splenectomy=167; adenocarcinoma=318, squamous=228, mix=10; T1=129, T2=115, T3=184, T4=128; N0=281, N1=70, N2=205; G1=157, G2=141, G3=258; early EC=110, invasive=446; only surgery=424, adjuvant chemoimmunoradiotherapy-AT=132: 5-FU+thymalin/taktivin+radiotherapy 45-50Gy). 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 1877±2221.6 days and cumulative 5-year survival (5YS) reached 52%, 10 years – 45%, 20 years – 33.4%, 30 years – 27%. 186 ECP lived more than 5 years (LS=4283.3±2412.6 days), 99 ECP – more than 10 years (LS=5883±2296.6 days). 227 ECP died because of EC (LS=631.8±323.4 days). AT significantly improved 5YS (60.3% vs. 42%) (P=0.0029 by log-rank test). Cox modeling displayed that 5YS of ECP significantly depended on: phase transition (PT) N0—N12 in terms of synergetics, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), T, G, histology, age, AT, localization, prothrombin index, hemorrhage time, residual nitrogen, protein (P=0.000-0.021). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and P PT early-invasive EC (rank=1); healthy cells/CC (2), erythrocytes/CC (3), PT N0—N12 (4) thrombocytes/CC (5); segmented neutrophils/CC (6), stick neutrophils/CC (7), lymphocytes/CC (8), monocytes/CC (9); leucocytes/CC (10); eosinophils/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5-year survival of ECP after radical procedures significantly depended on: 1) PT “early-invasive cancer”; 2) PT N0--N12; 3) Cell Ratio Factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) EC characteristics; 9) tumor localization; 10) anthropometric data; 11) surgery type. Optimal diagnosis and treatment strategies for EC are: 1) screening and early detection of EC; 2) availability of experienced thoracoabdominal surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for ECP with unfavorable prognosis.
Survival of Lung Cancer Patients after Lobectomies was Significantly Superior...Oleg Kshivets
OBJECTIVE: This study aimed to determine surgery type influence for 5-year survival (5YS) of non-small cell lung cancer (LC) patients (LCP) after complete en block (R0) lobectomies and pneumonectomies.
METHODS: We analyzed data of 765 consecutive patients (age=57.6±8.3 years; tumor size=4.1±2.4 cm) radically operated (R0) and monitored in 1985-2022 (m=659, f=106; bi/lobectomies=512, pneumonectomies=253, mediastinal lymph node dissection=765; combined procedures with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=192; only surgery-S=616, adjuvant chemoimmunoradiotherapy-AT=149: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=318, T2=255, T3=133, T4=59; N0=514, N1=131, N2=120, M0=765; G1=194, G2=241, G3=330; squamous=417, adenocarcinoma=298, large cell=50; early LC=212, invasive LC=553. Multivariate Cox modeling, discriminant analysis, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine any significant dependence.
RESULTS: Overall life span (LS) was 2240.1±1751.6 days and cumulative 5-year survival (5YS) reached 72.8%, 10 years – 64.2%, 20 years – 42.9%. 499 LCP lived more than 5 years (LS=3126.8±1540 days), 143 LCP – more than 10 years (LS=5083.3±1518.6 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (77.6% vs.63.1%, P=0.00001 by log-rank test). AT significantly improved 5YS (64.4% vs. 34.8%) (P=0.00003 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). 5YS of LCP after Lobectomies (77.6%) was significantly superior in comparison with LCP after pneumonectomies (63%) (P=0.00001 by log-rank test). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12(rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), segmented neutrophils/CC (7), lymphocytes/CC (8), monocytes/CC (9); stick neutrophils/CC (10), leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) surgery type: lobectomy/pneumonectomy; 10) anthropometric data.
• Gastric cancer prognosis and cell ratio factors Oleg Kshivets
OBJECTIVE: We examined cell ratio factors (CRF) significantly affecting gastric cancer (EC) patients GCP) survival. CRF - ratio between cancer cells (CC) and blood cells subpopulations.
METHODS: We analyzed data of 799 consecutive GCP (T1-4N0-2M0) (age=57.1±9.4 years; tumor size=5.4±3.1 cm) radically operated (R0) and monitored in 1975-2022 (m=558, f=241; total gastrectomies=173, distal gastrectomies=461; proximal gastrectomies=165; combined gastrectomies=247 with resection of esophagus, pancreas, liver, duodenum, diaphragm, colon transversum, splenectomy, etc; only surgery-S=624, adjuvant chemoimmunotherapy-AT=175 (5-FU + thymalin/taktivin); T1=238, T2=220, T3=184, T4=157; N0=437, N1=109, N2=253, M0=799; G1=222, G2=164, G3=413. Variables selected for prognosis 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 GCP were evaluated using a log-rank test. Multivariate Cox modeling, discriminant analysis, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine any significant dependence.
RESULTS: Overall life span (LS) was 2128.9±2300.3 days and cumulative 5-year survival (5YS) reached 58.4%, 10 years – 51.9%, 20 years – 39%, 30 years – 27.2%. 318 GCP lived more than 5 years (LS=4304.5±2290.6 days), 169 GCP – more than 10 years (LS=5919.5±2020 days). 290 GCP died because of GC (LS=651±347.2 days). Cox modeling displayed that G CP survival significantly depended on CRF: healthy cells/CC, erythrocytes/CC, monocytes/CC, phase transition (PT) in terms of synergetics early—invasive cancer; PT N0--N12, age, G1-3, hemorrhage time, ESS, sex, AT, prothrombin index, residual nitrogen. Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early—invasive cancer (rank=1); PT N0--N12 (2); healthy cells/CC (3), erythrocytes/CC (4), thrombocytes/CC (5), monocytes/CC (6), segmented neutrophils/CC (7), leucocytes/CC (8), lymphocytes/CC (9), stick neutrophils/CC (10), eosinophils/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: GCP survival after radical procedures significantly depended on CRF.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
2. World Journal of Advanced Research and Reviews, 2021, 12(02), 246–260
247
procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise
prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Keywords: Lung cancer; 10—Year survival; Surgery; Prognosis.
1. Introduction
In the world, lung cancer is the number 1 killer today, despite the astronomical efforts of humankind to fight it. It seems
strange that there are no data on 10-year survival in the literature, which is extremely important for optimizing the
treatment and diagnostic process. In the world, 2.2 million new patients with lung cancer were diagnosed each year,
from which 79-90% have already died. Approximately 80-85% of these tumors are non-small cell histological type,
including adenocarcinomas, squamous cell and large cell carcinomas. Non-small cell lung cancer (LC) is the main cause
of death from cancer, and real 5-year survival (5YS) across all stages of the disease is approximately 21% in the USA
and 16% in Europe [1,6]. At the present, radical surgery is generally regarded as the best treatment option, but only
approximately 30-50% of tumors are suitable for potentially curative resection depending on quality of diagnostics of
LC and aggression and skill of regional thoracic surgeons [1, 4, 5, 23]. Adjuvant chemotherapy has recently become a
new standard of care for patients with LC (LCP) after clinical trials showed approximately 5-15% improvement in
overall survival for those with higher risk disease, especially for stage II-IIIA [3,4,5]. Generally, cancer has
immunosuppressive effects on patient’s immune circuit [2,6,11]. Surgery, chemotherapy and irradiation themselves
perturb baseline immune circuit [7]. Clinically, in the total population it is known that poor baseline cytotoxic function
of patient immune cells correlates with a higher long-term rate of cancer relapses and generalization after radical
procedures [8].
One of the most perspective directions developed to enhance the efficacy of surgery is the combination of chemotherapy,
irradiation and immunotherapy or gene therapy which offers the advantage of exposing LC cell population for drugs
and immune factors, thus obviating cancer cell-cycle cytotoxic, check-point inhibitors and host-immunoprotective
effects [1,2,9]. Nevertheless, it seems strange that there are no data on 10-year survival of LCP in the literature, which
is extremely important for optimizing the treatment and diagnostic process. We developed optimal treatment strategies
that incorporate bolus chemotherapy, irradiation and immunotherapy after radical, aggressive en-block surgery and
mediastinal lymph node dissection.
2. Patients and methods
We performed a review of prospectively collected database of European patients undergoing the complete (R0)
pulmonary resections for LC between August 1985 and November 2021. 768 consecutive LCP (male – 660, female –
108; age=57.6±8.3 years, tumor size=4.1±2.4 cm) (mean±standard deviation) entered this trial. Patients were not
considered eligible if they had N3 lymph node metastasis, stage IV (nonregional lymph nodes metastases, distant
metastases, carcinomatous pleurisy, carcinomatosis), previous treatment with chemotherapy, immunotherapy or
radiotherapy or if there were two primary tumors at the time of diagnosis. LCP after non-radical procedures and
patients, who died postoperatively, were excluded to provide a homogeneous patient group. The preoperative staging
protocol included clinical history, physical examination, complete blood count with differentials, biochemistry and
electrolyte panel, chest X-rays, röntgenoesophagogastroscopy, computed tomography scan of thorax, abdominal
ultrasound, fibrobronchoscopy, electrocardiogram. Computed tomography scan of abdomen, liver and bone
radionuclide scan were performed whenever needed. Mediastinoscopy was not used. All LCP were diagnosed with
histologically confirmed LC. All had measurable tumor and ECOG performance status 0 or 1. Before any treatment each
patient was carefully examined by a medical panel composed of thoracic surgeon, chemotherapeutist, radiologist and
pneumologist to confirm the stage of disease. All patients signed a written informed consent form approved by the local
Institutional Review Board.
The initial treatment was started with surgery. Radical procedure was performed through standard thoracotomy.
Complete anatomical resections (lobectomies, bilobectomies, pneumonectomies) were performed in all patients. All
768 LCP routinely underwent complete systematic hilar and mediastinal lymph node dissection. All mediastinal stations
were numbered separately by the surgeon according to the American Joint Committee on Cancer Classification.
Complete resection (R0) was defined as removal of the primary tumor and all accessible hilar and mediastinal lymph
nodes, with no residual tumor left behind (resection of all macroscopic tumor and resection margins free of tumor at
microscopic analysis). Before surgery all patients underwent pulmonary function testing in order to determine the
volume of the lungs which can be removed without consequences. For prophylaxis of postoperative respiratory failure
LCP were operated, if the preoperative forced expiratory lung volume in 1 second was more 2.0 L and maximum
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voluntary ventilation was more 35% (especially pneumonectomy). The present analysis was restricted to LCP with
complete resected tumors with negative surgical resection margins and with N0-N2 nodes. Surgical complete resection
consisted of pneumonectomy in 254, upper lobectomy in 277, lower lobectomy in 177, upper/lower bilobectomy in 42
and middle lobectomy in 18 patients. Among these, 193 LCP underwent combined and extensive radical procedures
with the resection of pericardium, atrium, aorta, vena cava superior, vena azygos, carina, trachea, diaphragm, liver, chest
wall, ribs, etc. All LCP were postoperatively staged according to the TNMG-classification. Histological examination
showed squamous cell LC in 417, adenocarcinoma - in 301 and large cell LC - in 50 patients. The pathological TNM stage
IA was in 257, IB – in 154, IIA - in 42, IIB – in 130, IIIA - in 133 and IIIB – in 52 patients; the pathological T stage was T1
in 320, T2 - in 255, T3 - in 133, T4 - in 60 cases; the pathological N stage was N0 in 516, N1 - in 131, N2 - in 121 patients.
The tumor differentiation was graded as G1 in 194, G2 - in 243, G3 - in 331 cases. Early LC was in 214, invasive LC – in
554; right LC - in 412, left LC – in 356; central LC – in 290; peripheral LC – in 478.
After surgery postoperative chemoimmunoradiotherapy and radiotherapy were accomplished LCP in ECOG
performance status 0 or 1.
All patients (768 LCP) were divided between the two protocol treatment: 1) surgery and adjuvant
chemoimmunoradiotherapy (150 LCP – group A); 2) surgery alone without any adjuvant treatment (618 LCP – group
B) – the control group. All patients completed adjuvant therapy (chemoimmunoradiotherapy or radiotherapy).
Adjuvant chemoimmunoradiotherapy consisting of chemotherapy (by CAV till 1998, since 1999 chemotherapy by
gemzar and cisplatin), immunotherapy and thoracic radiotherapy was applied to 150 patients (group A). 1 cycle of bolus
chemotherapy by CAV was initiated 14 days after surgery and consisted of cyclophosphamid 500 mg/m2 intravenously
(IV) on day 1, doxorubicin 50 mg/m2 IV on day 1, vincristin 1.4 mg/m2 IV on day 1. Chemotherapy by gemzar 1250
mg/m2 IV on day 1, 8, 15 and cisplatin 75 mg/m2 on day 1 was initiated on 14 day after surgery. Immunotherapy
consisted thymalin or taktivin 20 mg intramuscularly on days 1, 2, 3, 4 and 5. Cycle of immunotherapy was repeated
every 21-28 days (4-6 courses). These immunomodulators were produced by Pharmaceutics of Russian Federation
(Novosibirsk) and approved by Ministry of Health of Russian Federation. Thymalin and taktivin are preparations from
calf thymus, which stimulate proliferation of blood T-cell and B-cell subpopulations and their response [13]. The
importance of using immunotherapy must be stressed, because immune dysfunctions of the cell-mediated and humoral
response were induced by tumor, surgical trauma, chemotherapy and radiation [1,2,3,11]. Such immune deficiency
induced generalization of LC and compromised the long-term therapeutic result. In this sense immunotherapy shielded
human organism from side and adverse effects of basic treatment. Chest radiotherapy was administered 7 days after
one cycle chemoimmunotherapy at a daily dose of 1.8-2 Gy (60CO; ROKUS, Russia) with a total tumor dose 45-50 Gy. The
treatment volume included the ipsilateral hilus, the supraclavicular fossa and the mediastinum from the incisura
iugularis to 5-7 cm below the carina. The lower mediastinum was included in cases of primary tumors in the lower
lobes. The resected tumor bed was included in all patients. Parallel-opposed AP-PA fields were used. All fields were
checked using the treatment planning program COSPO (St.Petersburg, Russia). Doses were specified at middepth for
parallel-opposed technique or at the intersection of central axes for oblique technique. No prophylactic cranial
irradiation was used. No prophylactic cranial irradiation was used. Two to three weeks after completion of radiotherapy
3-4 courses of chemotherapy by CAV were repeated every 21-28 days. Cycle of chemotherapy by gemzar and cisplatin
was repeated every 14 days (4-5 courses). During chemoimmunotherapy antiemetics were administered.
Gastrointestinal side effects, particularly nausea and vomiting, were mild, and chemoimmunoradiotherapy was
generally well tolerated. Severe leukopenia, neutropenia, anemia and trombocytopenia occurred infrequently. There
were no treatment-related deaths.
A follow-up examination was, generally, done every 3 month for the first 2 years, every 6 month after that and yearly
after 5 years, including a physical examination, a complete blood count, blood chemistry, and chest roentgenography.
Zero time was the data of surgical procedures. No one was lost during the follow-up period and we regarded the
outcome as death through personal knowledge, physician's reports, autopsy or death certificates. Survival time (days)
was measured from the date of surgery until death or the most-recent date of follow-up for surviving patients.
Variables selected for 10YS and life span study were sex, age, TNM, cell type, tumor size. Survival curves were estimated
by the Kaplan-Meier method. Differences in curves between groups of LCP were evaluated using a log-rank test.
Multivariate proportional hazard Cox regression, structural equation modeling (SEPATH), Monte Carlo simulation and
neural networks computing were used to determine any significant dependence [14-18]. Neural networks computing,
system, biometric and statistical analyses were conducted using CLASS-MASTER program (Stat Dialog, Inc., Moscow,
Russia), SANI program (Stat Dialog, Inc., Moscow, Russia), STATISTICA and STATISTICA Neural Networks program (Stat
Soft, Inc., Tulsa, OK, the USA), DEDUCTOR program (BaseGroup Labs, Inc., Riazan, Russia), SPSS (SPSS Inc., Chicago, IL,
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USA), Table Curve3D (Systat Software Inc., San Hose, CA, USA), SIMSTAT2.6 (Provalis Research, Montreal, Canada). All
tests were considered significant when the resulting P value was less than 0.05.
3. Results
For the entire sample of 768 patients overall life span (LS) was 2244.9±1750.3 days (mean ±standard deviation).
General cumulative 5 year survival reached 72.9%, 10-year survival – 64.3%, 20-year survival – 43.1%. 502 LCP lived
more than 5 years (LS=3128.7±1536.8 days) without any features of LC progressing, 145 LCP – more than 10 years after
surgery (LS=5068.5±1513.2 days). 199 LCP died because of LC during the first 5 years after surgery (LS=562.7±374.5
days) (Fig. 1).
Figure 1 General cumulative survival of LCP with stage T1-4N0-2M0, n=768 after radical procedures: cumulative 10-
year survival=64.3%, 20-year survival=43.1%
Figure 2 10-year survival of LCP with early cancer 93.9% (n=214) was significantly better compared with invasive
cancer 51.8% (n=554) (P=0.0000 by log-rank test)
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It is necessary to pay attention on the five very important prognostic phenomenons. First, 93.9% 10-year survival
(10YS) for LCP with the early cancer as against 51.8% for the others LCP after surgery (P=0.000 by log-rank test) (Fig.2).
Early lung cancer was defined, based on the final histopathologic report of the resection specimen, as tumor limited up
to 2 cm in diameter with N0 [1,24]. Patients with early LC did not receive adjuvant treatment.
Second, good 10YS for LCP with N0 (78.3%) as compared with LCP with N1-2 (10YS was 35.2%) after radical procedures
(P=0.000 by log-rank test) (Fig.3).
Figure 3 10-year survival of LCP with N0 78.3% (n=516) was significantly better compared with LCP with N1-N2
metastases 35.2% (n=252) (P=0.0000 by log-rank test)
Figure 4 10-year survival of LCP with N1-2 after adjuvant chemoimmunoradiotherapy in group A 52.4%, n=88 was
significantly better than in group B (only surgery) 27.7%, n=164 (P=0.00002 by log-rank test)
Third, for the AT significantly improved 10YS (52.4% vs. 27.7%) (P=0.00002 by log-rank test) only for LCP with N1-2
(Fig.4).
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Fourth, we revealed 73.4% 10YS for female LCP versus 63.4% for male LCP after surgery (P=0.0289 by log-rank test)
(Fig.5).
Figure 5 10-year survival of LCP after lobectomies 72% (n=514) was significantly better compared with LCP after
pneumonectomies 46.9% (n=254) (P=0.00002 by log-rank test)
Figure 6 10-year survival of females LCP after surgery 73.4% (n=108) was significantly better compared with males
LCP after surgery 63.4% (n=660) (P=0.0289 by log-rank test)
In the fifth we found 72% 10YS for LCP after lobectomies versus 46.9% for LCP after pneumonectomies (P=0.00002 by
log-rank test) (Fig.6).
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All parameters were analyzed in a multivariate Cox model. In accordance with this Cox model the sixteen variables
significantly explained 10-year survival of LCP after surgery: phase transition (PT) early—invasive LC, PT N0---N12, LC
characteristics (histology, G1-3), adjuvant chemoimmunoradiotherapy, blood cell subpopulations, hemostasis
parameters, cell ratio factor (ratio between blood cell subpopulations and cancer cell population), etc. (Table 1).
Table 1 Results of multivariate proportional hazard Cox regression modeling in prediction of LCP survival after
lobectomies and pneumonectomies (n=768)
Cox Proportional Hazards Results,
LCP T1-4N0-2M0, n=768
Parameter Estimate Standard Error Chi-square P value
Thrombocytes/Cancer Cells -0.00550 0.001579 12.14276 0.000493
Healthy Cells/Cancer Cells 0.07391 0.024958 8.77037 0.003062
Adjuvant Chemoimmunoradiotherapy -1.13036 0.201727 31.39806 0.000000
Phase Transition N0---N12 1.12121 0.144416 60.27584 0.000000
Phase Transition Early-Invasive Cancer -1.47130 0.341717 18.53830 0.000017
Histology 0.35066 0.084684 17.14621 0.000035
G1-3 0.36443 0.087580 17.31503 0.000032
Color Index -2.18363 0.917025 5.67018 0.017256
Glucose -0.32526 0.078234 17.28559 0.000032
Prothrombin Index 0.03372 0.006854 24.20847 0.000001
Bilirubin 0.05124 0.018274 7.86319 0.005045
Recalcification Time -0.00444 0.001711 6.73236 0.009468
Heparin Tolerance 0.00392 0.000662 35.06287 0.000000
Thrombocytes (tot) 0.00172 0.000341 25.43339 0.000000
Monocytes -0.05039 0.024421 4.25828 0.039059
Weight -0.03451 0.008725 15.64460 0.000076
For comparative purposes, clinicomorphological variables of LCP (n=344: 145 10-year survivors and 199 losses) were
tested by neural networks computing (4-layer perceptron) (Fig. 7) (Table 2). To obtain a more exact analysis 424
patients being alive less than 10 years after radical procedures without relapse were excluded from the sample.
Obviously, analyzed data provide significant information about LC prediction. High accuracy of classification (10-year
survivors vs. losses) was achieved 100% (baseline error=0.000, area under ROC curve=1.0). In other words, it remains
formally possible that at least 11 of these factors might predate neoplastic generalization: PT early—invasive LC
(rank=1), thrombocytes/CC (2), PT N0—N12 (3), segmented neutrophils/CC (4), healthy cells/CC (5), lymphocytes/CC
(6), erythrocytes/CC (7), stick neutrophils/CC (8), eosinophils/CC (9), leucocytes/CC (10), monocytes/CC (11).
Moreover, bootstrap simulation confirmed the paramount value of Cell Ratio Factors, PT N0---N12 and PT early---
Invasive GC (Table 3). It is necessary to note a very important law: both transitions of the early cancer into the invasive
cancer, as well as the cancer with N0 into the cancer with N1-N2, have the phase character. These results testify by
mathematical and imitating modeling of system “LC—patient homeostasis” in terms of synergetics (Fig. 9-12). This also
proves the first results received earlier in the work [9,24] (Fig. 8). Presence of the two phase transitions is evidently
shown on Kohonen self-organizing neural networks maps (Fig. 13).
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Figure 7 Configuration of neural networks: 4-layer perceptron
Figure 8 Lung Cancer Dynamics: Presence of the two phase transitions “early lung cancer—invasive lung cancer” and
“lung cancer with N0—cancer with N1-2” in terms of synergetics
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Figure 9 Prognostic equation model of 10-year survival of lung cancer patients (n=344), blood Lymphocytes/Cancer
Cells and blood glucose (P=0.000)
Figure 10 Prognostic equation model of 10-year survival of lung cancer patients (n=344), blood Monocytes/Cancer
Cells and blood glucose (P=0.000)
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Figure 11 Prognostic equation model of 10-year survival of lung cancer patients (n=344), phase transition early—
invasive lung cancer and blood lymphocytes (P=0.000)
Figure 12 Prognostic equation model of 10-year survival of lung cancer patients (n=344), phase transition N0---N12
and blood lymphocytes (P=0.000)
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Figure 13 Results of Kohonen self-organizing neural networks computing in prediction of 10-year survival of LCP
after surgery (n=344)
Figure 14 Significant networks between LCP (n=344) survival, cancer characteristics, blood cell circuit, cell ratio
factors, hemostasis system, biochemic and anthropometric data, phase transition “early cancer—invasive cancer”,
phase transition “cancer with N0—cancer with N1-2” and treatment protocols (SEPATH model)
Table 2 Results of neural networks computing in prediction of 10-year survival of LCP after lobectomies and
pneumonectomies (n=344: 145 10-year survivors and 199 losses)
Neural Networks: n=344;
Baseline Error=0.000;
Area under ROC Curve=1.000;
Correct Classification Rate=100%
Rank Sensitivity
Phase Transition Early--Invasive Cancer 1 11646
Thrombocytes/Cancer Cells 2 7184
Phase Transition N0--N12 3 6656
Segmented Neutrophils/Cancer Cells 4 4154
Healthy Cells/Cancer Cells 5 4407
Lymphocytes/Cancer Cells 6 3993
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Erythrocytes/Cancer Cells 7 3370
Stick Neutrophils/Cancer Cells 8 2963
Eosinophils/Cancer Cells 9 2224
Leucocytes/Cancer Cells 10 1566
Monocytes/Cancer Cells 11 1206
All of these differences and discrepancies were further investigated by structural equation modeling (SEPATH) as well
as Monte Carlo simulation. From data, summarized in Fig. 14 it was revealed that the ten clusters significantly predicted
10YS and life span of LCP with N0-2 status (n=344): 1) PT early--invasive LC; 2) PT N0—N12; 3) Cell Ratio Factors; 4)
LC characteristics; 5) blood cell circuit; 6) biochemical homeostasis; 7) hemostasis system; 8) surgery type; 9) adjuvant
chemoimmunoradiotherapy; 10) anthropometric data.
Table 3 Results of bootstrap simulation in prediction of 10-year survival of LCP after lobectomies and
pneumonectomies (n=344: 145 10-year survivors and 199 losses)
Bootstrap Simulation n=344
Significant Factors
(Number of Samples=3333)
Rank Kendall’Tau-
A
P<
Lymphocytes/Cancer Cells 1 0.269 0.000
Leucocytes/Cancer Cells 2 0.223 0.000
Healthy Cells/Cancer Cells 3 0.211 0.000
Erythrocytes/Cancer Cells 4 0.193 0.000
Thrombocytes/Cancer Cells 5 0.192 0.000
Lymphocytes (tot) 6 0.183 0.000
Segmented Neutrophils/Cancer
Cells
7 0.173 0.000
Tumor Size 8 -0.118 0.000
Monocytes/Cancer Cells 9 0.111 0.000
PT Early---Invasive Cancer 10 0.107 0.000
Lymphocytes (%) 11 0.105 0.000
Segmented Neutrophils (%) 12 -0.102 0.000
Lymphocytes (abs) 13 0.096 0.000
Prothrombin Index 14 -0.094 0.001
T1-4 15 -0.094 0.001
PT N0---N12 16 -0.092 0.001
Procedures Type 17 0.087 0.01
Histology 18 0.076 0.01
Stick Neutrophils/Cancer Cells 19 0.073 0.01
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Eosinophils/Cancer Cells 20 0.067 0.05
Age 21 -0.067 0.05
Fibrinogen 22 -0.052 0.05
4. Discussion
Optimal treatment of LC is a global problem. On the one hand, the lung cancer surgery demands masterly, precise and
aggressive surgical technique, especially for LCP with stage T3-4N0-2 and always will remain the privilege of very
experienced thoracic surgeons [4,5]. Actual surgical removal of tumor and lymph node metastases remains basic
management of this very aggressive cancer giving the real chance for cure in spite of extensive research over the last 30
years in terms of chemotherapy, radiotherapy, immunotherapy and gene therapy [2,6,12,21,22]. On the other hand, the
effectiveness of complete lobectomy and pneumonectomy already reached its limit and leaves much to be desired: the
average real 5-year survival rate of radically operated LCP even after combined and extensive procedures is 30-45%
and practically is not improved during the past 25-30 years, as the great majority of patients has already LC with stage
IIIA-IIIB. And finally, modern TNM-classification is based only on cancer characteristics and does not take into account
at all the features of extremely complex alive supersystem – the patient’s organism. Therefore the prediction of LC is
rather inexact and affected by big errors.
Central goal of the present research was to estimate the efficiency of complete lobectomies, bilobectomies and
pneumonectomies with adequate lymph node dissection and adjuvant chemoimmunoradiotherapy after radical
surgery. The importance must be stressed of using complex system analysis, artificial intelligence (neural networks
computing), simulation modeling and statistical methods in combination, because the different approaches yield
complementary pieces of prognostic information. Not stopping in details on these supermodern technologies because
of the journal limit rules, great advantage of the artificial intelligence methods is the opportunity to find out hidden
interrelations which cannot be calculated by analytical, statistical and system methods. Meanwhile, huge merit of
simulation modeling is the identification of dynamics of any supersystem, including alive supersystem like human
homeostasis, on the hole in time [1,14-20,24].
Now all LC experts have come to a common opinion, that, first of all, it is necessary to operate LCP at any possibility if,
on the one hand, the performance status of the patient is eligible, and, on the other hand, a tumor is probably removable.
Certainly, the experience, the art and the aggression of the concrete thoracic surgeon plays the huge role here. If there
is a small LC, practically any thoracic surgeon can successfully fulfill the radical operation.
As one regards the early LC, everything becomes quite clear, because for these patients only radical surgery is absolutely
sufficient. 5-year and 10-year survival of patients with early LC after lobectomies reaches 90-100% and there is no
necessity in adjuvant treatment. From this follows the paramount importance of screening and early detection of LC.
The situation becomes complicated at once if we have local advanced LC and, unfortunately, such patients make up the
majority. Without radical procedures these LCP usually perish in several months in spite of the current achievements
in chemotherapy, radiotherapy and immunotherapy. Only very skilled surgeons are capable to perform such combined
operation adequately. In case of success 25-45% of patients with locally advanced LC live 5 and more years [1,4,23].
The most widely accepted treatment strategy for lymph node metastasis is the subsequent initiation of multimodality
treatment, including surgery, adjuvant/neoadjuvant chemotherapy, chemoradiation or chemoimmunoradiotherapy[3-
5,8]. Apparently from present research we have here the two qualitatively various states of a patient’s homeostasis. LC
with N0 is the local oncopathology and a panacea is the complete lobectomy or pneumonectomy. Lymph node
metastasis is a chain reaction or phase transition in terms of synergetics and the disease gets the system character [24].
Therefore this state should be treated by the methods influencing on whole organism after operation: chemotherapy
and immunotherapy. At that radical surgical removal of LC and lymph node metastasis plays a paramount role again,
allowing to decrease sharply the number of cancer cell population in patient’ organism and to warn possible deadly
complications (e.g., profuse hemorrhage). Theoretically chemoimmunotherapy is the most effective when used in
patients with a relatively low residual malignant cell population (approximately 1 billion cancer cells per patient) in
terms of hidden micrometastasis [1]. This is typical clinical situation for LCP with N1-2 after complete pulmonary
resections. Present research only confirmed this axiom. In the given situation high-precision prediction of LCP survival
after surgery, which allows to select concrete patients for adjuvant treatment and to cut huge financial expenses, has a
great value.
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In summary, when adjuvant chemoimmunoradiotherapy is applied to complete lobectomies and pneumonectomies for
LC with N1-2, the following benefits should be considered: 1) possibility of total elimination of residual hidden
micrometastases; 2) surgery and chemoradiotherapy can result immunosuppressive state, which can be improved by
immunotherapy; 3) radical operated LCP with stage IIA-IIIB are thought to be potentially good candidates for adjuvant
chemoimmunoradiotherapy as the majority of these patients would be expected to have LC progressing.
Concerning LCP with N0 further investigations will be required to determine efficiency, compatibility and tolerance of
new drugs, immunomodulators and check-point inhibitors after surgery. The results of the present research will offer
guidance for the design of future studies.
Optimal treatment strategies for LCP are: 1) screening and early detection of LC; 2) availability of experienced thoracic
surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymphadenectomy
for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Conclusion
10-Year survival of LCP after radical procedures significantly depended on:1) phase transition early-invasive cancer; 2)
phase transition N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7)
adjuvant chemoimmunoradiotherapy; 8) lung cancer characteristics; 9) anthropometric data;10) surgery type.
Compliance with ethical standards
Disclosure of conflict of interest
No conflict of interest.
Statement of informed consent
All patients signed a written informed consent included in the study, approved by the local Institutional Review Board.
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