This document describes a study examining optimal treatment strategies for non-small cell lung cancer (NSCLC) patients. The study reviewed data from 535 NSCLC patients who underwent complete surgical resection between 1985-2008. Patients received one of three treatments: surgery alone (316 patients), surgery plus postoperative radiotherapy (102 patients), or surgery plus adjuvant chemoimmunoradiotherapy (117 patients). The study found that adjuvant chemoimmunoradiotherapy resulted in significantly higher 5-year survival rates compared to radiotherapy or surgery alone, especially for patients with lymph node involvement. Overall 5-year survival for the entire group was 63.6%, demonstrating the benefit of aggressive surgical resection and adjuvant therapies.
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.
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.
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 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 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.
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
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 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.
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
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 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
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology. The aim of the journal is to provide a forum for cardiologists, researchers, physicians, and other health professionals to find most recent advances in the areas of cardiology and cardiovascular diseases.
Austin Journal of Clinical Cardiology accepts original research articles, review articles, case reports, clinical images and rapid communication on all the aspects of cardiology and circulatory system.
Austin Journal of Clinical Cardiology strongly supports the scientific upgradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Austin Journal of Clinical Cardiology is an open access, peer reviewed, scholarly journal dedicated to publish articles in all areas of cardiology and angiology
An Overview: Treatment of Lung Cancer on Researcher Point of ViewEswar Publications
Cancers is defined as the uncontrolled cell divisions. Cell does not grow maturely and destined to uncontrolled cell growth. When these cells of lungs grow uncontrolled it is called lung cancer. Nowadays mortality rate due to lung cancer is increasing day by day. Many treatment and diagnoses are now a day’s available to deal with lung cancer. Here we disused different method for diagnosis the common types of lung cancer Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Small Cell Lung Cancer Limited Stage, Small Cell Lung Cancer - Extensive Stage, Lung Adenocarcinoma, Squamous Cell Carcinoma,Bronchioloalveolar carcinoma (BAC), Metastatic lung cancer.
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.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...NainaAnon
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Clinics of Oncology | Oncology Journals | Open Access JournalEditorSara
Clinics of OncologyTM (ISSN 2640-1037) - Impact Factor 1.920* is a medical specialty that focuses on the use of operative techniques to investigate and resolve certain medical conditions caused by disease or traumatic injury.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...semualkaira
In this retrospective study we enrolled patients with upper rectal or sigmoid junction locally advanced tumors (stages II-III). At the first Institution patients received NCRT followed by surgery (study group); at the second Institution patients were referred to upfront surgery (control group). Overall survival was the main endpoint of the analysis. Local relapse and other clinical variables were also analyzed.
Similar to Kshivets O. Lung Cancer: Optimal Treatment Strategies (20)
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
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
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
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
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.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the 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 lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
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. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
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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Kshivets O. Lung Cancer: Optimal Treatment Strategies
1. The Open Lung Cancer Journal, 2009, 2, 12-23 12
Open Access
Lung Cancer: Optimal Treatment Strategies
Oleg Kshivets*
Department of Thoracic Surgery, Klaipeda University, Klaipeda, Lithuania
Abstract: Objective: Search of best treatment plan for non-small lung cancer (LC) patients (LCP) was realized.
Methods: In trial (1985-2008) the data of consecutive 535 LCP after complete resections (R0) (age=57.3±8.2 years; male-
482, female-53; tumor diameter: D=4.7±2.2 cm; pneumonectomies-222, lobectomies-313, combined procedures with re-
section of pericardium, atrium, aorta, VCS, carina, diaphragm, ribs-155; only surgery-S-316, adjuvant chemoimmunora-
diotherapy-AT-117: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy, postoperative radiotherapy 45-
50Gy-RT-102; squamous-341, adenocarcinoma-153, large cell-41; stage IA-105, IB-130, IIA-21, IIB-122, IIIA-116, IIIB-
41; T1-150, T2-230, T3-114, T4-41; N0-310, N1-118, N2-107; G1-126, G2-152, G3-257) were reviewed. Variables se-
lected for 5-year survival (5YS) study were input levels of blood, biochemic and hemostatic factors, sex, age, TNMG, D.
Survival curves were estimated by Kaplan-Meier method. Differences in curves between groups were evaluated using a
log-rank test. Neural networks computing, Cox regression, clustering, structural equation modeling, Monte Carlo and
bootstrap simulation were used to determine any significant regularity.
Results: For total of 535 LCP overall life span (LS) was 1723.3±1294.9 days and cumulative 5YS reached 63.6%, 10
years – 52.8%. 304 LCP (LS=2597.3±1037 days) lived more than 5 years without LC progressing. 186 LCP
(LS=559.8±383.1 days) died because of LC during first 5 years after surgery. 5YS of LCP with N1-2 was superior signifi-
cantly after AT (65.6%) compared with RT (39.5%) (P=0.0003 by log-rank test) and S (28.3%) (P=0.000). Cox modeling
displayed that 5YS significantly depended on: phase transition (PT)“early-invasive LC”, PT N0-N12, AT, age, weight,
histology, G, T, D, blood cell subpopulations, cell ratio factors, ESS, prothrombin index, heparin tolerance, recalcification
time, bilirubin, (P=0.000-0.046). Neural networks computing, genetic algorithm selection and bootstrap simulation re-
vealed relationships between 5YS and PT N0-N12 (rank=1), procedure type, G, T, histology, AT, PT “early-invasive LC”,
RT, S, sex, ESS, prothrombin index, fibrinogen, Hb, protein, weight, lymphocytes. Correct prediction of 5YS was 99.6%
by neural networks computing (error=0.045; urea under ROC curve=0.995).
Conclusion: Optimal treatment strategies for LCP are: 1) screening and early detection of LC; 2) availability of experi-
enced surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymphadenec-
tomy for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable progno-
sis.
INTRODUCTION after clinical trials showed approximately 5-15% improve-
ment in overall survival for those with higher risk disease,
Lung Cancer is a global problem of the mankind. In the
especially for stage II-IIIA [4,5]. Generally, cancer has im-
world 1.5 million new patients with lung cancer are diag-
munosuppressive effects on patient’s immune circuit [6].
nosed each year, from which 85-90% have already died. Ap- Surgery, chemotherapy and irradiation themselves perturb
proximately 80-85% of these tumors are non-small cell his-
baseline immune circuit [7]. Clinically, in the total popula-
tological type, including adenocarcinomas, squamous cell
tion it is known that poor baseline cytotoxic function of pa-
and large cell carcinomas. Non-small cell lung cancer (LC)
tient immune cells correlates with a higher long-term rate of
is the main cause of death from cancer, and real 5-year sur-
cancer relapses and generalization after radical procedures
vival (5YS) across all stages of the disease is approximately
[8].
14% in the USA and 10% in Europe [1,2]. At the present,
radical surgery is generally regarded as the best treatment One of the most perspective directions developed to en-
option, but only approximately 30-50% of tumors are suit- hance the efficacy of surgery is the combination of chemo-
able for potentially curative resection depending on quality therapy, irradiation and immunotherapy or gene therapy
of diagnostics of LC and aggression and skill of regional which offers the advantage of exposing LC cell population
thoracic surgeons [1,3]. Adjuvant chemotherapy has recently for drugs and immune factors, thus obviating cancer cell-
become a new standard of care for patients with LC (LCP) cycle cytotoxic and host-immunoprotective effects [1,9].
Nevertheless, very few studies have demonstrated convinc-
ing clinical results. We developed optimal treatment strate-
*Address correspondence to this author at the Thoracic Surgery Department, gies that incorporate bolus chemotherapy, irradiation and
Klaipeda University Hospital, Vingio: 16, P/D 1017, Klaipeda, LT95188, immunotherapy after radical, aggressive en-block surgery
Lithuania; Tel: (370)60878390; E-mail: kshivets003@yahoo.com
and mediastinal lymph node dissection.
1876-8199/09 2009 Bentham Open
2. Fiber Deposition in Human Lungs The Open Lung Cancer Journal, 2009, Volume 2 13
PATIENTS AND METHODS in 105, IB – in 130, IIA - in 21, IIB – in 122, IIIA - in 116
and IIIB – in 41 patients; the pathological T stage was T1 in
We performed a review of prospectively collected data-
150, T2 - in 230, T3 - in 114, T4 - in 41 cases; the pathologi-
base of European patients undergoing the complete (R0)
cal N stage was N0 in 310, N1 - in 118, N2 - in 107 patients.
pulmonary resections for LC between August 1985 and No-
The tumor differentiation was graded as G1 in 126, G2 - in
vember 2008. 535 consecutive LCP (male – 482, female – 152, G3 - in 257 cases.
53; age=57.3±8.2 years, tumor size=4.7±2.2 cm)
(mean±standard deviation) entered this trial. Patients were After surgery postoperative chemoimmunoradiotherapy
not considered eligible if they had N3 lymph node metasta- or radiotherapy were accomplished LCP in ECOG perform-
sis, stage IV (nonregional lymph nodes metastases, distant ance status 0 or 1.
metastases, carcinomatous pleurisy, carcinomatosis), previ- All patients (535 LCP) were divided between the three
ous treatment with chemotherapy, immunotherapy or radio- protocol treatment: 1) surgery and adjuvant chemoim-
therapy or if there were two primary tumors at the time of munoradiotherapy (117 LCP – group A) (age=57.7±9.0
diagnosis. LCP after non-radical procedures and patients, years; males - 108, females - 9; tumor size=5.5±2.5 cm); 2)
who died postoperatively, were excluded to provide a homo- surgery and postoperative radiotherapy (102 LCP – group B)
geneous patient group. The preoperative staging protocol (age=57.7±7.5 years; males - 91, females - 11; tumor
included clinical history, physical examination, complete size=4.7±2.1 cm); 3) surgery alone without any adjuvant
blood count with differentials, biochemistry and electrolyte treatment (316 LCP – group C) (age=57.1±8.1 years; males-
panel, chest X-rays, röntgenoesophagogastroscopy, com- 283, females - 33; tumor size=4.3±2.1 cm) – the control
puted tomography scan of thorax, abdominal ultrasound, group. All patients completed adjuvant therapy (chemoim-
fibrobronchoscopy, electrocardiogram. Computed tomogra- munoradiotherapy or radiotherapy).
phy scan of abdomen, liver and bone radionuclide scan were
performed whenever needed. Mediastinoscopy was not used. After complete resections 102 LCP received radiotherapy
All LCP were diagnosed with histologically confirmed LC. (60CO; ROKUS, Russia) with a total tumor dose 45-50 Gy
All had measurable tumor and ECOG performance status 0 starting 2-4 weeks after surgery (group B). Radiation con-
or 1. Before any treatment each patient was carefully exam- sisted of single daily fractions of 180-200 cGy 5 days
ined by a medical panel composed of thoracic surgeon, che- weekly. The treatment volume included the ipsilateral hilus,
motherapeutist, radiologist and pneumologist to confirm the the supraclavicular fossa and the mediastinum from the in-
stage of disease. All patients signed a written informed con- cisura iugularis to 5-7 cm below the carina. The lower medi-
sent form approved by the local Institutional Review Board. astinum was included in cases of primary tumors in the
lower lobes. The resected tumor bed was included in all pa-
The initial treatment was started with surgery. Radical tients. Parallel-opposed AP-PA fields were used. All fields
procedure was performed through standard thoracotomy. were checked using the treatment planning program COSPO
Complete anatomical resections (lobectomies, bilobectomies, (St.Petersburg, Russia). Doses were specified at middepth
pneumonectomies) were performed in all patients. All 535 for parallel-opposed technique or at the intersection of cen-
LCP routinely underwent complete systematic hilar and me- tral axes for oblique technique. No prophylactic cranial irra-
diastinal lymph node dissection. All mediastinal stations diation was used.
were numbered separately by the surgeon according to the
American Joint Committee on Cancer Classification. Com- Adjuvant chemoimmunoradiotherapy consisting of che-
plete resection (R0) was defined as removal of the primary motherapy (by CAV till 1998, since 1999 chemotherapy by
tumor and all accessible hilar and mediastinal lymph nodes, gemzar and cisplatin), immunotherapy and thoracic radio-
with no residual tumor left behind (resection of all macro- therapy was applied to 117 patients (group A). 1 cycle of
scopic tumor and resection margins free of tumor at micro- bolus chemotherapy by CAV was initiated 14 days after sur-
scopic analysis). Before surgery all patients underwent pul- gery and consisted of cyclophosphamid 500 mg/m2 intrave-
monary function testing in order to determine the volume of nously (IV) on day 1, doxorubicin 50 mg/m2 IV on day 1,
the lungs which can be removed without consequences. For vincristin 1.4 mg/m2 IV on day 1. Chemotherapy by gemzar
prophylaxis of postoperative respiratory failure LCP were 1250 mg/m2 IV on day 1, 8, 15 and cisplatin 75 mg/m2 on
operated, if the preoperative forced expiratory lung volume day 1 was initiated on 14 day after surgery. Immunotherapy
in 1 second was more 2.0 L and maximum voluntary ventila- consisted thymalin or taktivin 20 mg intramuscularly on days
tion was more 35% (especially pneumonectomy). The pre- 1, 2, 3, 4 and 5. Cycle of immunotherapy was repeated every
sent analysis was restricted to LCP with complete resected 21-28 days (4-6 courses). These immunomodulators were
tumors with negative surgical resection margins and with produced by Pharmaceutics of Russian Federation (Novosi-
N0-N2 nodes. Surgical complete resection consisted of birsk) and approved by Ministry of Health of Russian Fed-
pneumonectomy in 222, upper lobectomy in 179, lower eration. Thymalin and taktivin are preparations from calf
lobectomy in 100, upper/lower bilobectomy in 26 and mid- thymus, which stimulate proliferation of blood T-cell and B-
dle lobectomy in 8 patients. Among these, 155 LCP under- cell subpopulations and their response [10]. The importance
went combined and extensive radical procedures with the of using immunotherapy must be stressed, because immune
resection of pericardium, atrium, aorta, vena cava superior, dysfunctions of the cell-mediated and humoral response
vena azygos, carina, trachea, diaphragm, liver, chest wall, were induced by tumor, surgical trauma, chemotherapy and
ribs, etc. All LCP were postoperatively staged according to radiation [1,7,8]. Such immune deficiency induced generali-
the TNMG-classification. Histological examination showed zation of LC and compromised the long-term therapeutic
squamous cell LC in 341, adenocarcinoma - in 153 and large result. In this sense immunotherapy shielded human organ-
cell LC - in 41 patients. The pathological TNM stage IA was ism from side and adverse effects of basic treatment. Chest
radiotherapy (45-50 Gy) was administered 7 days after one
3. 14 The Open Lung Cancer Journal, 2009, Volume 2 Robert Sturm
cycle chemoimmunotherapy at a daily dose of 1.8-2 Gy. No 1785.8±1192.2 days (95% CI, 1653.9-1917.8) (P=0.100 by
prophylactic cranial irradiation was used. Two to three log-rank for group A and P=0.00027 for group B). The over-
weeks after completion of radiotherapy 3-4 courses of che- all 5-year survival of LCP with N0-2 for group A was 71%
motherapy by CAV were repeated every 21-28 days. Cycle and was significantly superior compared to 42.5% for group
of chemotherapy by gemzar and cisplatin was repeated every B (P=0.00002). The overall 5-year survival for group C was
14 days (4-5 courses). During chemoimmunotherapy antie- 61.9% (P=0.100 for group A and P=0.00027 for group B).
metics were administered. Gastrointestinal side effects, par-
It is necessary to pay attention to the two very important
ticularly nausea and vomiting, were mild, and chemoim-
prognostic phenomenas. First, we found 98.3% 5-years sur-
munoradiotherapy was generally well tolerated. Severe leu-
vival for LCP with early cancer (T1N0, n=62) versus 59.1%
kopenia, neutropenia, anemia and trombocytopenia occurred
for other LCP (n=473) after lobectomies and pneumonecto-
infrequently. There were no treatment-related deaths. mies (P=0.000 by log-rank test) (Fig. 2). Early lung cancer
A follow-up examination was, generally, done every 3 was defined, based on the final histopathologic report of the
month for the first 2 years, every 6 month after that and resection specimen, as tumor limited up to 2 cm in diameter
yearly after 5 years, including a physical examination, a with N0 [1]. Patients with early LC did not receive adjuvant
complete blood count, blood chemistry, and chest roent- treatment. Correspondingly, the overall 10-year survival for
genography. Zero time was the data of surgical procedures. LCP with the early cancer was 77.1% and was significantly
No one was lost during the follow-up period and we re- better compared to 48.2% for other patients.
garded the outcome as death through personal knowledge,
Second, we observed excellent 5-year survival of LCP
physician's reports, autopsy or death certificates. Survival
with N0 (79.3%, n=310) as compared with 5-year survival of
time (days) was measured from the date of surgery until
LCP with N1-N2 (42.2%) after radical procedures (P=0.000
death or the most-recent date of follow-up for surviving pa-
by log-rank test) (Fig. 3). Accordingly, the overall 10-year
tients. survival for LCP with N0 reached 64.9% and was signifi-
Variables selected for 5-year survival and life span study cantly superior compared to 33.7% for LCP with lymph node
were the input levels of 45 blood parameters, sex, age, metastasis. Owing to the relatively high frequency of distant
TNMG, cell type, and tumor size. Survival curves were es- failure after surgical resection of LC with lymph nodal me-
timated by the Kaplan-Meier method. Differences in curves tastasis, it has been generally accepted that nodal metastasis
between groups of LCP were evaluated using a log-rank test. would be an indicator of systemic metastasis [18,19]. Conse-
Multivariate proportional hazard Cox regression, structural quently, at least two separate subsets of patients can be de-
equation modeling (SEPATH), Monte Carlo simulation, fined from present study: those with N0 status (n=310) and
bootstrap simulation and neural networks computing were those with N1-2 involvement (n=225). These factors must be
used to determine any significant dependence [11-17]. Neu- taken into account in system analysis of LCP survival and
ral networks computing, system, biometric and statistical are particularly cogent when attempting to translate obtained
analyses were conducted using CLASS-MASTER program results into patient’s treatment strategies.
(Stat Dialog, Inc., Moscow, Russia), SANI program (Stat
There are no statistical significant differences were found
Dialog, Inc., Moscow, Russia), DEDUCTOR program
in 5-year survival and life span of LCP with N0 status be-
(BaseGroup Labs, Inc., Riazan, Russia), SPSS (SPSS Inc.,
tween groups A (76.8%, n=52) and B (58.1%, n=37)
Chicago, IL, USA), STATISTICA and STATISTICA Neural
(P=0.070), A and C (78.1%, n=221) (P=0.723), but 5-year
Networks program (Stat Soft, Inc., Tulsa, OK, USA),
survival in group C was significantly better than in group B
MATHCAD (MathSoft, Inc., Needham, MA, USA), SIM- (P=0.016).
STAT (Provalis Research, Inc., Montreal, QC, Canada). All
tests were considered significant if the resulting P value was Regarding LCP with N1-2 metastases 5-year survival
less than 0.05. was much better for group A (65.6%, n=65) compared to
group C (28.3%, n=95) (P=0.000) and was superior with
RESULTS respect to group B (37.6%, n=65) (P=0.00025) (Fig. 4). No
significant differences were found in 5-year survival of LCP
For the entire sample of 535 patients overall life span with N1-2 between groups B and C (P=0.768).
(LS) was 1723.3±1294.9 days (mean ±standard deviation)
(95% CI, 1613.3-1833.2; median=1843). General cumulative All parameters were analyzed in a multivariate Cox
5 year survival reached 63.6%, 10-year survival – 52.8%. model. In accordance with this Cox model (global
2
327 LCP (61.1%) were alive till now, 304 LCP (56.8%) =309.44; Df=32; P=0.000), the twenty seven variables
lived more than 5 years (LS=2597.3±1037.0 days) without significantly explained survival of LCP after surgery: LC
any features of LC progressing. 186 LCP (34.8%) died be- characteristics, adjuvant chemoimmunoradiotherapy, age,
cause of LC during the first 5 years after surgery and blood cell subpopulations, hemostasis parameters, cell
(LS=559.8±383.1 days) (Fig. 1). ratio factor (ratio between blood cell subpopulations and
cancer cell population), etc. (Table 1).
For 117 LCP with N0-2 status in adjuvant chemoim-
munoradiotherapy arm (group A), overall LS was For comparative purposes, clinicomorphological vari-
1845.8±1631.6 days (95% CI, 1547.0-2144.5). For 102 LCP ables of LCP (n=490: 304 5-year survivors and 186 losses)
with N0-2 status in postoperative radiotherapy arm (group were tested by neural networks computing (4-layer percep-
B), overall LS was 1388.8±1110.1 days (95% CI, 1170.8- tron) (Fig. 5). To obtain a more exact analysis 45 patients
1606.8) (P=0.00002 by log-rank for group A). For 316 LCP being alive less than 5 years after radical procedures without
with N0-2 status in the control (group C), overall LS was relapse were excluded from the sample. Multilayer
4. Fiber Deposition in Human Lungs The Open Lung Cancer Journal, 2009, Volume 2 15
S u rvi va l Fu n cti o n
L un g Can ce r P ati e n ts a fter L o be cto m i e s/P n eu m on e cto m i e s, n=5 35
Cu m u l ati ve 5 -Y ea r S urviva l=6 3.6 % , 1 0 -Y ea r S urviva l=5 2.8 %
Co m p l e te Cen so red
1 .2
1 .1
1 .0
0 .9
0 .8
0 .7
0 .6
Cumulative Proportion Su
0 .5
0 .4
-5 0 5 10 15 20 25
Y e a rs a fte r L o be cto m ie s/P n e um on e cto m i e s
Fig. (1). General cumulative survival of LCP with stage T1-4N0-2M0, n=535 after radical procedures: cumulative 5-year survival=63.6%,
10-year survival=52.8%.
Cumulative Proportion Surviving (Kaplan-Meier)
5YS of Early LCP=98.3% vs.5YS of Invasive LCP=59.1%
P=0.000 by Log-Rank T est
Complete Censored
1.0
Invasive LCP, n=473
Early LCP, n=62
0.9
0.8
0.7
0.6
0.5
Cumulative Proportion
0.4
0.3
0 2 4 6 8 10 12 14 16 18 20 22
Years after Lobectomies/Pneumonectomies
Fig. (2). Survival of LCP with early cancer (n=62) was significantly better compared with invasive cancer (n=473) (P=0.000 by log-rank
test).
5. 16 The Open Lung Cancer Journal, 2009, Volume 2 Robert Sturm
Cumulative Proportion Surviving (Kaplan-Meier)
5YS of LCP with N0=79.3% vs. 5YS of LCP with N1-2=42.2%;
P=0.000 by Log-Rank T est
Complete Censored
1.0
0.9 LCP with N1-2, n=225
LCP with N0, n=310
0.8
0.7
0.6
0.5
0.4
Cumulative Proportion
0.3
0.2
0 2 4 6 8 10 12 14 16 18 20 22
Years after Lobectomies/Pneumonectomies
Fig. (3). Survival of LCP with N0 (n=310) was significantly better compared with N1-N2 metastases (n=225) (P=0.000 by log-rank test).
Cumulative Proportion Surviving (Kaplan-Meier) : LCP with N1-2, n=225
5YS of LCP with N1-2 after Ad. CHIRT=65.6% vs. 5Y S of LCP with N1-2=28.3% (P=0.00002);
5YS of LCP with N1-2 vs. 5YS of LCP with N1-2 afte r p/o RT=37.6% (P=0.00025);
5YS of LCP with N1-2 vs. 5YS of LCP with N1-2 afte r p/o RT (P=0.768)
Complete Censored
1.0
0.9 LCP with N1-2 after Surgery alone, n95
LCP with N1-2 after p/o RT, n=65
0.8 LCP with N1-2 after Ad. CHIRT, n=65
0.7
0.6
0.5
0.4
0.3
Cumulative Proportion S
0.2
0.1
0 2 4 6 8 10 12 14 16 18
Years after Lobectomies/Pneumonectomies
Fig. (4). 5-year survival of LCP with N1-2 after lobectomies and pneumonectomies in group A (adjuvant chemoimmunoradiotherapy:
65.6%, n=65) was significantly better than in group B (postoperative radiotherapy: 37.6%, n=65) (P=0.00025 by log-rank test) and in group
C (only surgery: 28.3%, n= 95) (P=0.000).
6. Fiber Deposition in Human Lungs The Open Lung Cancer Journal, 2009, Volume 2 17
Table 1. Results of Multivariate Proportional Hazard Cox Regression Modeling in Prediction of LCP Survival After Lobectomies
and Pneumonectomies (n=535)
Variables in the Equation B SE Wald df P
Phase Transition “Early---Invasive LC” 0.691 0.214 10.378 1 0.001
Phase Transition “N0---N1-2” 0.576 0.103 31.153 1 0.000
Tumor Size 0.097 0.047 4.338 1 0.037
T 23.881 3 0.000
T(1) -1.250 0.299 17.494 1 0.000
T(2) -1.161 0.244 22.695 1 0.000
T(3) -0.844 0.233 13.073 1 0.000
G 10.178 2 0.006
G(1) -0.326 0.132 6.132 1 0.013
G(2) 0.071 0.121 0.340 1 0.560
Histology 10.753 2 0.005
Histology(1) -0.024 0.117 0.041 1 0.840
Histology(2) 0.678 0.209 10.510 1 0.001
Age 0.021 0.006 11.644 1 0.001
Weight -0.063 0.017 13.263 1 0.000
Adjuvant Chemoimmunoradiotherapy -0.687 0.145 22.566 1 0.000
Thrombocytes (abs) -0.012 0.005 6.933 1 0.008
Thrombocytes (tot) 0.003 0.001 12.261 1 0.000
Leucocytes (tot) -0.566 0.159 12.680 1 0.000
Stab Neutrophils (tot) 0.911 0.197 21.450 1 0.000
Segmented Neutrophils (tot) 0.539 0.158 11.596 1 0.001
Lymphocytes (tot) 0.554 0.165 11.294 1 0.001
Monocytes (tot) 0.652 0.208 9.791 1 0.002
ESS -0.010 0.004 8.133 1 0.004
Prothrombin Index 0.030 0.005 36.651 1 0.000
Recalcification Time -0.004 0.001 6.789 1 0.009
Fibrinogen 0.066 0.035 3.661 1 0.056
Heparin Tolerance 0.003 0.001 34.347 1 0.000
Bilirubin 0.043 0.016 7.203 1 0.007
Leucocytes/Cancer Cells 1.878 0.574 10.697 1 0.001
Stab Neutrophils/Cancer Cells -3.293 0.735 20.089 1 0.000
Segmented Neutrophils/Cancer Cells -1.761 0.573 9.463 1 0.002
Lymphocytes/Cancer Cells -2.104 0.609 11.949 1 0.001
Monocytes/Cancer Cells -2.087 0.738 7.984 1 0.005
Healthy Cells/Cancer Cells 0.042 0.021 3.976 1 0.046
perceptron was trained by Levenberg-Marquardt method. All of these differences and discrepancies were further
Obviously, analyzed data provide significant information investigated by structural equation modeling (SEPATH) as
about LC prediction. High accuracy of classification – 99.6% well as Monte Carlo simulation. From the data, summarized
(5-year survivors vs losses) was achieved in analyzed sample in Fig. (9) it could be recognized that the nine clusters sig-
(baseline error=0.045, are under ROC curve=0.995). In other nificantly predicted 5-year survival and life span of LCP
words it remains formally possible that reviled the seventeen after complete pulmonary resections: 1) phase transition
factors might predate neoplastic generalization: N-status “early LC—invasive LC” (P=0.002); 2) phase transition “LC
(rank=1), procedure type, G, T, histology, adjuvant chemo- with N0—LC with N1-2” (P=0.000); 3) cell ratio factors
immunoradiotherapy, “early-invasive LC”, radiotherapy, (P=0.000); 4) LC characteristics (P=0.000); 5) blood cell
surgery along, sex, ESS, prothrombin index, fibrinogen, he- circuit (P=0.014); 6) biochemical homeostasis (P=0.047); 7)
moglobin, protein, weight, lymphocytes (Table 2). Genetic surgery (P=0.000); 8) adjuvant chemoimmunoradiotherapy
algorithm selection and bootstrap simulation confirmed sig- (P=0.000), and 9) postoperative radiotherapy (P=0.000) (Fig.
nificant dependence between 5-year survival of LCP after 9). It is necessary to pay attention, that both phase transitions
radical procedures and all recognized variables (Tables 3 and strictly depend on blood cell circuit (P=0.000) and cell ratio
4). Moreover, bootstrap simulation confirmed the paramount factors (P=0.000).
value of cell ratio factors and the two very special patient’s
homeostasis states: patients with early LC and N-1-2 status. DISCUSSION
It is necessary to note a very important law: both transi- Optimal treatment of LC is a global problem. On the one
tions of the early cancer into the invasive cancer, as well as hand, the lung cancer surgery demands masterly, precise and
the cancer with N0 into the cancer with N1-N2, have the aggressive surgical technique, especially for LCP with stage
phase character. These results testify by mathematical T3-4N0-2 and always will remain the privilege of very expe-
(Holling-Tenner) and imitating modeling of system “EC— rienced thoracic surgeons [2,3]. Actual surgical removal of
patient homeostasis” in terms of synergetics (Figs. 6, 7). This tumor and lymph node metastases remains basic manage-
also proves the first results received earlier in the work [1]. ment of this very aggressive cancer giving the real chance
Presence of the two phase transitions is evidently shown on for cure in spite of extensive research over the last 30 years
Kohonen self-organizing neural networks maps (Fig. 8). in terms of chemotherapy, radiotherapy, immunotherapy and
7. 18 The Open Lung Cancer Journal, 2009, Volume 2 Robert Sturm
Fig. (5). Configuration of neural networks: 4-layer perceptron.
Table 2. Results of Neural Networks Computing in Prediction of 5-Year Survival of LCP After Lobectomies and Pneumonecto-
mies (n=490: 304 5-Year Survivors and 186 Losses)
Sample n=490
NN Factors Rank
Error Ratio
Phase Transition “N0---N1-2” 1 0.387 8.652
1
Procedure Type 2 0.312 6.908
2
G 3 0.282 6.238
3
T 4 0.210 4.655
4
Histology 5 0.194 4.294
5
Adjuvant Chemoimmunoradiotherapy 6 0.187 4.143
6
Phase Transition “Early---Invasive Cancer” 7 0.178 3.932
7
Postoperative Radiation Therapy 8 0.155 3.429
8
Surgery Along 9 0.150 3.309
9
Gender 10 0.143 3.173
10
ESS 11 0.120 2.655
11
Prothrombin Index 12 0.102 2.259
12
Fibrinogen 13 0.089 1.966
13
Hemoglobin 14 0.085 1.877
14
Protein 15 0.080 1.773
15
Weight 16 0.078 1.720
16]17
Lymphocytes (%) 17 0.066 1.46
Baseline Error 0.045
Area under ROC Curve 0.995
Correct Classification Rate (%) 99.6
8. Fiber Deposition in Human Lungs The Open Lung Cancer Journal, 2009, Volume 2 19
Table 3. Results of Neural Networks Genetic Algorithm Se- Central goal of the present research was to estimate the
lection in Prediction of 5-Year Survival of LCP Af-
efficiency of complete lobectomies, bilobectomies and
ter Lobectomies and Pneumonectomies (n=490: 304
5-Year Survivors and 186 Losses)
pneumonectomies with adequate lymph node dissection and
adjuvant chemoimmunoradiotherapy after radical surgery.
The importance must be stressed of using complex system
NN LCP, n=490 Useful for analysis, artificial intelligence (neural networks computing),
Factors 5-Year Survival simulation modeling and statistical methods in combination,
because the different approaches yield complementary pieces
1 Phase Transition “N0---N1-2” Yes
2 Phase Transition “Early---Invasive Cancer” Yes of prognostic information. Not stopping in details on these
3 Adjuvant Chemoimmunoradiotherapy Yes supermodern technologies because of the journal limit rules,
4 Lymphocytes (tot) Yes great advantage of the artificial intelligence methods is the
5 Monocytes (tot) Yes opportunity to find out hidden interrelations which cannot be
6 Eosinophils (tot) Yes
7 Erythrocytes (tot) Yes
calculated by analytical and system methods. Meanwhile,
8 Tumor Size Yes huge merit of simulation modeling is the identification of
9 T Yes dynamics of any supersystem, including alive supersystem
10 G Yes like human homeostasis, on the hole in time [1,11-17].
11 Erythrocyte/Cancer Cells Yes
12 Leucocytes/Cancer Cells Yes Now all LC experts have come to a common opinion,
13 Eosinophils/Cancer Cells Yes that, first of all, it is necessary to operate LCP at any possi-
14 Stab Neutrophils/Cancer Cells Yes bility if, on the one hand, the performance status of the pa-
15 Segmented Neutrophils/Cancer Cells Yes
16 Healthy Cells/Cancer Cells Yes tient is eligible, and, on the other hand, a tumor is probably
17 Postoperative Radiotherapy Yes removable. Certainly, the experience, the art and the aggres-
18 Surgery Along Yes sion of the concrete thoracic surgeon plays the huge role
19 Gender Yes here. If there is a small LC, practically any thoracic surgeon
20 Weight Yes
21 Prothrombin Index Yes
can successfully fulfill the radical operation.
22 Protein Yes As one regards the early LC, everything becomes quite
23 Procedure Type Yes
24 ESS Yes
clear, because for these patients only radical surgery is abso-
25 Coagulation Time Yes lutely sufficient. 5-year survival of patients with early LC
26 Hemorrhage Time Yes after lobectomies reaches 90-100% and there is no necessity
27 Glucose Yes in adjuvant treatment. From this follows the paramount im-
portance of screening and early detection of LC.
The situation becomes complicated at once if we have
gene therapy [4,9,18,19]. On the other hand, effectiveness of
local advanced LC and, unfortunately, such patients make up
complete lobectomy and pneumonectomy already reached its the majority. Without radical procedures these LCP usually
limit and leaves much to be desired: the average real 5-year
perish in several months in spite of the current achievements
survival rate of radically operated LCP even after combined
in chemotherapy and radiotherapy. Only very skilled sur-
and extensive procedures is 30-45% and practically is not
geons are capable to perform such combined operation ade-
improved during the past 25-30 years, as the great majority
quately. In case of success 25-45% of patients with locally
of patients has already LC with stage IIIA-IIIB. And finally,
advanced LC live 5 and more years [1,2].
modern TNM-classification is based only on cancer charac-
teristics and does not take into account at all the features of The most widely accepted treatment strategy for lymph
extremely complex alive supersystem – the patient’s organ- node metastasis is the subsequent initiation of multimodality
ism. Therefore the prediction of LC is rather inexact and treatment, including surgery, adjuvant/neoadjuvant chemo-
affected by big errors. therapy or chemoradiation [3-5]. Apparently from present
research we have here the two qualitatively various states of
Table 4. Results of Bootstrap Simulation in Prediction of 5-Year Survival of LCP After Lobectomies and Pneumonectomies
(n=490: 304 5-Year Survivors and 186 Losses)
LCP, n=490 Number of Samples=3333
NN Rank P<
Significant Factors Kendall’Tau-A
1 Phase Transition “N0---N1-2” 1 -0.188 0.000
2 Eosinophils/Cancer Cells 2 0.124 0.000
3 Erythrocytes/Cancer Cells 3 0.123 0.000
4 Monocytes/Cancer Cells 4 0.122 0.000
5 Lymphocytes/Cancer Cells 5 0.121 0.000
6 Healthy Cells/Cancer Cells 6 0.121 0.000
7 Thrombocytes/Cancer Cells 7 0.094 0.01
8 Phase Transition “Early---Invasive Cancer” 8 -0.090 0.01
9 Tumor Size 9 -0.088 0.01
10 T 10 -0.087 0.01
11 G 11 -0.071 0.05
9. 20 The Open Lung Cancer Journal, 2009, Volume 2 Robert Sturm
Fig. (6). Results of Holling-Tenner modeling of system “LC—Lymphocytes” in prediction of LCP survival after lobectomies and pneu-
monectomies (dynamics of early cancer: Lymphocytes/Cancer Cells=1/1; dynamics of cancer with N0: Lymphocytes/Cancer Cells=3/4;
dynamics of cancer with N1-N2: Lymphocytes/Cancer Cells=2/3; cancer generalization: Lymphocytes/Cancer Cells=1/10).
Fig. (7). Presence of the two phase transitions “early cancer—invasive cancer” and “cancer with N0—cancer with N1-2” in terms of syner-
getics.
10. Fiber Deposition in Human Lungs The Open Lung Cancer Journal, 2009, Volume 2 21
Fig. (8). Results of Kohonen self-organizing neural networks computing in prediction of LCP survival after lobectomies/pneumonectomies
(n=490). The black curve line stand for 5-year survivors above and for losses below. Top figure: the area under the dark-color shadow stand
for early LCP and the area under the weak-colored shadow stand for invasive LCP. Bottom figure: the area under the dark-color shadow
stand for LCP with N0 and the area under the weak-colored shadow stand for LCP with N1-2.
11. 22 The Open Lung Cancer Journal, 2009, Volume 2 Robert Sturm
Fig. (9). Significant networks between LCP (n=490) 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 network model).
a patient’s homeostasis. LC with N0 is the local oncopathol- metastases; 2) surgery and chemoradiotherapy can result
ogy and a panacea is the complete lobectomy or pneumonec- immunosuppressive state, which can be improved by immu-
tomy. Lymph node metastasis is a chain reaction or phase notherapy; 3) radical operated LCP with stage IIA-IIIB are
transition in terms of synergetics and the disease gets the thought to be potentially good candidates for adjuvant
system character. Therefore this state should be treated by chemoimmunoradiotherapy as the majority of these patients
the methods influencing on whole organism after operation: would be expected to have LC progressing.
chemotherapy and immunotherapy. At that radical surgical
Concerning LCP with N0 further investigations will be
removal of LC and lymph node metastasis plays a paramount required to determine efficiency, compatibility and tolerance
role again, allowing to decrease sharply the number of can-
of new drugs and immunomodulators after surgery. The re-
cer cell population in patient’ organism and to warn possible
sults of the present research will offer guidance for the de-
deadly complications (e.g., profuse hemorrhage). Theoreti-
sign of future studies.
cally chemoimmunotherapy is the most effective when used
in patients with a relatively low residual malignant cell In conclusion, optimal treatment strategies for LCP are:
population (approximately 1 billion cancer cells per patient) 1) screening and early detection of LC; 2) availability of
in terms of hidden micrometastasis [1]. This is typical clini- experienced surgeons because of complexity of radical pro-
cal situation for LCP with N1-2 after complete pulmonary cedures; 3) aggressive en block surgery and adequate lym-
resections. Present research only confirmed this axiom. In phadenectomy for completeness; 4) precise prediction; 5)
the given situation high-precision prediction of LCP survival adjuvant chemoimmunoradiotherapy for LCP with unfavor-
after surgery, which allows to select concrete patients for able prognosis.
adjuvant treatment and to cut huge financial expenses, has a
great value. REFERENCES
In summary, when adjuvant chemoimmunoradiotherapy [1] Kshivets O. Expert system in diagnosis and prognosis of malignant
is applied to complete lobectomies and pneumonectomies for neoplasms. Dissertation for Sc.D., Tomsk, 1995; 486.
[2] Bedrettin Yildizeli, Philippe G. Dartevelle, Elie Fadel et al. Results
LC with N1-2, the following benefits should be considered: of primary surgery with T4 non-small cell lung cancer during a 25-
1) possibility of total elimination of residual hidden micro- year period in single center: the benefit is worth the risk. The An-
nuals of Thoracic Surgery 2008; 86: 1065-75.