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Longitudinal changes in personalized platelet count metrics are good indicators of initial 3-year outcome in colorectal cancer

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World Journal of Clinical Cases 2022年第20期10卷 6825-6844页

作者： Zoltan Herold Magdolna Herold Julia Lohinszky Attila marcell szasz Magdolna Dank Aniko Somogyi Division of Oncology Department of Internal Medicine and OncologySemmelweis UniversityBudapest 1083Hungary Department of Internal Medicine and Hematology Semmelweis UniversityBudapest 1088Hungary

BACKGROUND Platelet count or complete blood count(CBC)-based ratios including lymphocyteto-monocyte(LMR),neutrophil-to-lymphocyte(NLR),hemoglobin-to-platelet(HPR),red blood cell count distribution width-to-platelet(RPR),and platelet-tolymphocyte(PLR)ratio are good predictors of colorectal cancer(CRC)*** change in time is not well documented,*** To investigate the effect of longitudinal CBC ratio changes on CRC survival and their possible associations with clinicopathological properties,comorbidities,and anamnestic *** A retrospective longitudinal observational study was conducted with the inclusion of 835 CRC patients,who attended at Semmelweis University,*** ratios and two additional newly defined personalized platelet count metrics(pPLT_(D)and pPLT_(S),the platelet counts relative to the measurement at the time of CRC diagnosis and to the one 4-6 wk after tumor removal surgery,respectively)were *** The 835 CRC patients had a total of 4608 measurements(5.52 visits/patient,in average).Longitudinal survival models revealed that the increases/decreases in LMR[hazard ratio(HR):0.4989,P<0.0001],NLR(HR:1.0819,P<0.0001),HPR(HR:0.0533,P=0.0038),pPLT_(D)(HR:4.9229,P<0.0001),and pPLT_(S)(HR:4.7568,P<0.0001)values were poor prognostic signs of disease-specific *** same was obtained for all-cause *** abnormal changes occurred within the first 3 years after the diagnosis of *** and PLR had an only marginal effect on diseasespecific(P=0.0675)and all-cause mortality(Bayesian 95%credible interval:0.90–186.05),*** LMR,NLR,and HPR are good metrics to follow the prognosis of the ***_(D)and pPLT_(S)perform just as well as the former,while the use of RPR and PLR with the course of the disease is not *** detection of the abnormal changes in pPLT_(D),pPLT_(S),LMR,NLR,or HPR may alert the practicing oncologist for further therapy decisions in a timely manner.

关键词： Personalized platelet count Lymphocyte-to-monocyte ratio Neutrophil-to-lymphocyte ratio Hemoglobin-to-platelet ratio Platelet-to-lymphocyte ratio Colorectal neoplasms

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High plasma CD40 ligand level is associated with more advanced stages and worse prognosis in colorectal cancer

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World Journal of Clinical Cases 2022年第13期10卷 4084-4096页

作者： Zoltan Herold Magdolna Herold Gyorgy Herczeg Agnes Fodor Attila marcell szasz Magdolna Dank Aniko Somogyi Division of Oncology Department of Internal Medicine and OncologySemmelweis UniversityBudapest H-1083Hungary Department of Internal Medicine and Hematology Semmelweis UniversityBudapest H-1088Hungar Department of General Surgery Szent Imre University Teaching HospitalBudapest H-1115Hungary

BACKGROUND Colorectal cancer(CRC)is often associated with elevated platelet count(>400×10^(9)/L),known as *** role of CD40 ligand(CD40L),a member of the tumor necrosis factor family,is controversial in *** CD40L is higher in CRC,but its relationship with disease staging and local and distant metastasis is not *** most of the circulating CD40L is produced by platelets,no previous study investigated its relationship with CRC-related *** To investigate the role of CD40L to predict the outcome of CRC and its relation to *** A total of 106 CRC patients and 50 age and sex-matched control subjects were enrolled for the *** data including comorbidities and histopathological data were *** measurements were performed at the time of CRC diagnosis and 1.5 mo and at least 6 mo after the surgical removal of the *** CD40L and thrombopoietin were measured via enzyme-linked immunosorbent assay,while plasma interleukin-6 was measured via electrochemiluminescence *** follow-ups were terminated on January 31,*** Plasma CD40L of CRC patients was tendentiously higher,while platelet count(P=0.0479),interleukin-6(P=0.0002),and thrombopoietin(P=0.0024)levels were significantly higher as opposed to the control *** of the 106 CRC patients(11.3%)had *** higher CD40L was found in the presence of distant metastases(P=0.0055)and/or thrombocytosis(P=0.0294).A connection was found between CD40L and platelet count(P=0.0045),interleukin-6(P=0.0130),and thrombocytosis(P=0.0155).CD40L was constant with the course of CRC,and all baseline differences persisted throughout the whole *** pre-and postoperative elevated platelet count,CD40L,and interleukin-6 level were associated with poor overall and disease-specific survival of *** negative effect of CD40L and interleukin-6 on patient survival remained even after the stra

关键词： CD40 ligand Colorectal neoplasms Interleukin-6 Thrombocytosis Thrombopoietin

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Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system

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World Journal of Gastrointestinal Oncology 2021年第9期13卷 1109-1120页

作者： Zoltan Herold a marcell szasz Magdolna Dank Division of Oncology Department of Internal Medicine and OncologySemmelweis UniversityBudapest H-1083Hungary

Hepatopancreatobiliary tumors are challenging to treat,and the advanced or metastatic forms have a very low 5-year survival *** drug combinations have been tested,and new therapeutic approaches have been introduced in the last decades,including radiofrequency and heat based *** is the artificial heating of tumors by various biophysical methods that may possess immunostimulant,tumoricidal,and chemoradiotherapy sensitizer *** whole-body and regional hyperthermia studies have been conducted since the 1980s after the introduction of deep-seated tumor hyperthermia *** of the effects of hyperthermia in hepatocellular and pancreatic cancer are known from several *** in biliary cancers is a less investigated *** local and overall responses to treatment,increased progression-free and overall survival,and improved laboratory and quality-of-life results are associated with hyperthermia in all three tumor *** the evolution of chemotherapeutic agents and the introduction of newer techniques,the combination of adjuvant hyperthermia with those therapies is advantageous and has not been associated with an increase in alarming adverse ***,despite the many positive effects of hyperthermia,its use is still only known at the experimental level,and its concomitant utilization in routine cancer treatment is not certain because of the lack of thorough clinical studies.

关键词： Hyperthermia induced Carcinoma hepatocellular Cholangiocarcinoma Gallbladder neoplasms Pancreatic neoplasms

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Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases

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World Journal of Gastroenterology 2023年第18期29卷 2850-2863页

作者： Heinrich Steinhoff Miklos Acs Sebastian Blaj Magdolna Dank Magdolna Herold Zoltan Herold Jonas Herzberg Patricia Sanchez-Velazquez Tim Strate Attila marcell szasz Pompiliu Piso Department of General and Visceral Surgery Hospital Barmherzige BrüderRegensburg 93049Germany Division of Oncology Department of Internal Medicine and OncologySemmelweis UniversityBudapest 1083Hungary Department of Internal Medicine and Hematology Semmelweis UniversityBudapest 1088Hungary Department of Surgery Krankenhaus Reinbek St.Adolf-StiftReinbek 21465Germany Department of General Surgery Hospital del MarBarcelona 08003Spain

BACKGROUND Advanced gastric cancer with synchronous peritoneal metastases(GC-PM)is associated with a poor *** cytoreductive surgery with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC)is a promising approach,only a limited number of Western studies *** To investigate the clinicopathological outcomes of patients who underwent CRSHIPEC for *** A retrospective analysis of patients with GC-PM was *** patients were seen at the Department of General and Visceral Surgery,Hospital Barmherzige Brüder,Regensburg,Germany between January 2011 and July 2021 and underwent *** laboratory results,the use of neoadjuvant trastuzumab,and the details of CRS-HIPEC,including peritoneal carcinomatosis index,completeness of cytoreduction,and surgical procedures were ***-specific(DSS),and overall survival(OS)of patients were *** A total of 73 patients were included in the *** treated with neoadjuvant trastuzumab(n=5)showed longer DSS(P=0.0482).Higher white blood cell counts(DSS:P=0.0433)and carcinoembryonic antigen levels(OS and DSS:P<0.01),and lower hemoglobin(OS and DSS:P<0.05)and serum total protein(OS:P=0.0368)levels were associated with shorter *** HIPEC duration was associated with more advantageous median survival times[60-min(n=59):12.86 mo;90-min(n=14):27.30 mo],but without statistical *** obtain additional data from this observation,further separation of the study population was ***,propensity score-matched patient pairs(n=14 in each group)were *** different DSS was found between patient pairs(hazard ratio=0.2843;95%confidence interval:0.1119-0.7222;P=0.0082).Second,those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity(median survival:12.68 mo vs 24.02 mo),or had to undergo the procedure before 2016(median survival:12.68 mo vs 27.30 mo;P=0.0493)were removed from the orig

关键词： Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Peritoneal metastasis Stomach neoplasms Gastric cancer

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Supportive and Palliative Care in Cancer Therapies—Path from Tumor-Driven Therapies to Patient-Driven Ones

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International Journal of Clinical Medicine 2022年第7期13卷 287-359页

作者： Carrie Anne Minnaar Andras szasz Sun Young Lee Gyula Peter Szigeti Attila marcell szasz Domokos Mathe Wits Donald Gordon Medical Center Department of Radiation Oncology Johannesburg South Africa Department of Radiation Sciences University of the Witwatersrand Gauteng South Africa Biotechnics Department Hungarian University of Agriculture and Life Sciences Godollo Hungary Department of Radiation Oncology Jeonbuk National University Medical School Jeonbuk Republic of Korea Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital Jeonju Republic of Korea Semmelweis University Innovation Center Budapest Hungary Division of Oncology 1st Department of Internal Medicine and Oncology Semmelweis University Budapest Hungary Department of Biophysics and Radiation Biology Faculty of Medicine Semmelweis University Budapest Hungary

Cancer patients frequently report a set of symptoms including fatigue, pain, and physiological and social distress. Families and other personal lay relations give proposals to take supportive drugs and supplemental nutrients, without professional knowledge about their actions. Internet search engines and social networks serve up most of the treatment proposals, opening wide possibilities for quackeries and predatory money-making practices. Medical professionals have a responsibility to clear this field and concentrate on patients’ well-being and personal needs. According to our approach, the integration of supportive and palliative care with conventional therapies needs a change of paradigm from tumour-driven to patient-driven treatment actions. Supportive/palliative care includes a broad spectrum of applied methods, including medications, nourishments, electrical effects, and psycho and social supports. Our goal is to discuss the possibilities for combining conventional oncotherapies with additional supportive/palliative care and to give suggestions on a professional basis.

关键词： Cancer Vitamins Minerals Fungi Immune Phytomedicine Complexity Electric-Stimuli Hyperthermia mEHT

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Heating Preciosity—Trends in Modern Oncological Hyperthermia

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Open Journal of Biophysics 2017年第3期7卷 116-144页

作者： Oliver szasz marcell A. szasz Carrie Minnaar Andras szasz Biotechnics Department Faculty of Engineering St. István University Godollo Hungary Cancer Center Semmelweis University Budapest Hungary Department of Radiation Sciences University of the Witwatersrand Johannesburg South Africa Faculty of Information Technology and Bionics Pazmany P. Catholic University Budapest Hungary

The use of hyperthermia as a treatment in oncology is a common topic for debate. Some researchers expect a breakthrough in oncological treatments with hyperthermia, whereas others have disregarded the method. Serious questions concerning hyperthermia have arisen. Should homogeneous (isothermal) or heterogeneous (selective) heating being used? When we use selective heating (heterogeneity), should the entire tumour be targeted or should the malignant cells be individually selected? Does the mechanism involve thermal cell death or thermally-assisted cell death? Is the goal necrosis or apoptosis? Is hyperthermia safe as a monotherapy or does it have to be combined with conventional treatments? When the selection is local, how do we act on disseminated cells that represent a high risk of life threatening metastases? When local heating is the focus, how should it be carried out with measured and controlled? Our objective is to show how precise, selective heat transfer is necessary to remove malignant cells and, consequently, how hyperthermia as part of the immune-oncology can change the game in this promising field of oncological therapies.

关键词： Heating Preciosity Hyperthermia Oncology Immune Effects Bystander-Effect Abscopal Effect

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Electrokinetics of Temperature for Development and Treatment of Effusions

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Advances in Bioscience and Biotechnology 2017年第11期8卷 434-449页

作者： Oliver szasz Gyula Peter Szigeti Attila marcell szasz Department of Biotechnics Istvan University Budaors Hungary Institute of Human Physiology and Clinical Experimental Research Semmelweis University Budapest Hungary Cancer Center Semmelweis University Budapest Hungary

Introduction: Hyperthermia is a complementary therapy in oncology having various pros and contras for its application. Ascites, pleural effusion, edema and other electrolyte accumulations are frequently excluded from the treatability of the patients with heating locally or systemically. The special gathering of electrolytes is sometimes contraindicated, at times not mentioned in the clinical protocols. However, it is certainly challenging in the oncology where micro and macro edemas, as well as larger electrolyte accumulations (e.g. ascites, pleural effusion), are very frequent. Methods: Excluding patients with accumulation of free electrolytes limits the applications of hyperthermia. To find a solution we are studying the microvasculature and fluid dynamism together with the electric field effects, including the injury currents. The hyperthermia method which we investigate is the modulated electro-hyperthermia (mEHT). We use the Starling’s equation and the injury current in the frame of non-equilibrium thermodynamics and in connection with the biologically closed electric circuits. Results: It is shown that mEHT, unlike the conventional hyperthermia, is applicable for patients who have edema and other free-electrolytes in the volume which is targeted. The heterogeneous heating (unlike the homogeneous, isothermal conventional hyperthermia) promotes the development of tumor-specific immune actions, and so has less adverse-effects, and longer survival time for patients in advanced, metastatic cancers too. Conclusion: mEHT is well applicable in cases of ascites, pleural effusion, edema and other electrolyte accumulations when a patient is treated in complex (complementary) oncological therapy.

关键词： Effusion Ascites Edema Modulated Electro-Hyperthermia mEHT

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The Growth of Healthy and Cancerous Tissues

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Open Journal of Biophysics 2020年第3期10卷 113-128页

作者： Gyula Peter Szigeti Attila marcell szasz Andras szasz Innovation Center Semmelweis University Budapest Hungary Division of Oncology Department of Internal Medicine and Oncology Semmelweis University Budapest Hungary Department of Biotechnics St. Istvan University Budaors Hungary

The structure of the tissues is formed in a self-similar manner, forming fractal structures in their transport networks. The structure exhibits allometric forming and so-called scaling behavior. This is a basic growth model fine-tuned by various connections of the cells (junctions and adherent connections), intended to direct material and energy transports between them. This secondary control of cell metabolism decreases primary metabolic transport through the free surfaces of the cells. The cellular network is formed by triggering the endogenous electric fields, which are dominantly governed by cell membrane potential. Proliferation exhibits a different electric pattern due to the low cell-membrane potential and resulting negativity relative to its environment. This potential change characterizes cells in normal proliferation and a cluster of cells (a tumor) in the case of cancerous development. This latter has certain similarities to the leakage transport of liquid in porous media, substituting the pressure with endogenous tumor potential. The average survival of a tumor depends on the kind of available metabolic transport and the fractal dimensions of the newly built angiogenic network.

关键词： Endogenous Potential Metabolic Scaling Competition Cooperation Self-Time Tumor Survival

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Parametrization of Survival Measures (Part III) Clinical Evidences in Single Arm Studies with Endpoint of Overall Survival

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International Journal of Clinical Medicine 2020年第6期11卷 389-419页

作者： Andras szasz Gyula P. Szigeti marcell A. szasz Biotechnics Department Faculty of Mechanical Engineering St. Istvan University Budaors Hungary Innovation Center Semmelweis University Budapest Hungary Cancer Center Semmelweis University Budapest Hungary

Many clinical trials have prospective or retrospective data-sets without comparison to the control-group formed by the same cohort as the active one. The measured single arm naturally contains the relevant information, however, in most of the cases, it is impossible to obtain it from the complex survival curve without a reference. In our previous articles [1] [2], we had shown that the self-similar Weibull distribution fits the self-organized biological mechanisms well, and so it is the best option to study the single-arm survival curves, where self-organizing process is actively present. With the Weibull decomposition of the survival curve, we can fit at least two subgroups of patients. The weighted sum of the decomposed fractions could be optimized analytically and determining the best parameters of the components and the best composition ratio of the weighted sum is also possible. In this part of our series of articles, we will show how the method works in a real clinical environment through modulated electro-hyperthermia (mEHT) as a complementary method, applied curatively when no other conventional curative therapies are available. The decomposed function of the non-responding group provides an excellent agreement with the historical controls in pancreatic cancer and non-small-cell-lung-cancer studies. In the case of glioblastoma multiform, the historical missing control from the institute where the treatment was made does not allow a comparison. We used a modified Hardin-Jones-Pauling statistical estimation and had shown in single arm clinical trials for advanced pancreas, non-small cell lung cancer and glioblastoma multiforme, that this estimation is applicable, and it is corresponding with the historical arm and with the non-responding group where this comparison was available.

关键词： Single-Arm-Study Weibull-Decomposition Hardin-Jones-Pauling-Estimation Modulated Electro-Hyperthermia (mEHT) Glioblastoma Multiform Pancreatic Carcinoma Non-Small-Cell Lung Cancer

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Parametrization of Survival Measures (Part II): Single Arm Studies

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International Journal of Clinical Medicine 2020年第5期11卷 348-373页

In some clinical applications in oncology randomized, double armed, and double-blind trials are not possible. In case of device applications, double-blinded conditions are nonrealistic, and with many times the randomization also has complications due to the high-line treatments where the reference cohort is not available;the active “arm” has mainly palliative initiative. Sometimes highly personalized therapies block the collection of the homogeneous group and limit its double-arm randomization. Our objective is to discuss the situations of the single arm evaluation and to give methods for the mining of information from this to increase the level of evidence of the measured dataset. The basic idea of the data-separation is the appropriate parameterization of the non-parametric Kaplan-Meier survival pattern by the poly-Weibull fit.

关键词： Single-Arm Clinical Trial Survival-Time Decomposition of Survival Curves Personalized Treatment Observational Trial

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