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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

Role and function of granin proteins in diabetes mellitus

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World Journal of Diabetes 2021年第7期12卷 1081-1092页

作者： zoltan herold Marton Doleschall Aniko Somogyi Division of Oncology Department of Internal Medicine and OncologySemmelweis UniversityBudapest 1083Hungary Department of Internal Medicine and Hematology Semmelweis UniversityBudapest 1088Hungary Molecular Medicine Research Group Eotvos Lorand Research Network and Semmelweis UniversityBudapest 1089Hungary

The granin glycoprotein family consists of nine acidic proteins;chromogranin A(CgA),chromogranin B(CgB),and secretogranin II–*** are produced by a wide range of neuronal,neuroendocrine,and endocrine cells throughout the human *** major intracellular function is to sort peptides and proteins into secretory granules,but their cleavage products also take part in the extracellular regulation of diverse biological *** contribution of granins to carbohydrate metabolism and diabetes mellitus is a recent research *** is associated with glucose homeostasis and the progression of type 1 ***-14,CgA10-19,and CgA43-52 are peptide derivates of CgA,and act as CD4+or CD8+autoantigens in type 1 diabetes,whereas pancreastatin(PST)and catestatin have regulatory effects in carbohydrate ***,PST is related to gestational and type 2 *** has a crucial role in physiological insulin *** II and III have angiogenic activity in diabetic retinopathy(DR),and are novel targets in recent DR *** studies are beginning to investigate the potential use of granin derivatives as drugs to treat diabetes based on the divergent relationships between granins and different types of diabetes.

关键词： Granin Chromogranin A Chromogranin B Diabetes Mellitus Mice Inbred nonobese diabetic Secretogranin III

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

New therapeutic approaches for type 1 diabetes:Disease-modifying therapies

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World Journal of Diabetes 2022年第10期13卷 835-850页

作者： Geza Nagy Tekla Evelin Szekely Aniko Somogyi Magdolna herold zoltan herold Department of Internal Medicine and Hematology Semmelweis UniversityBudapest H-1088Hungary Division of Oncology Department of Internal Medicine and OncologySemmelweis UniversityBudapest H-1083Hungary

It has been 100 years since the first successful clinical use of insulin, yet it remains the only treatment option for type 1 diabetes mellitus(T1DM) patients. Advances in diabetes care, such as insulin analogue therapies and new devices, including continuous glucose monitoring with continuous subcutaneous insulin infusion have improved the quality of life of patients but have no impact on the pathogenesis of the disease. They do not eliminate long-term complications and require several lifestyle sacrifices. A more ideal future therapy for T1DM, instead of supplementing the insufficient hormone production(a consequence of β-cell destruction), would also aim to stop or slow down the destructive autoimmune process. The discovery of the autoimmune nature of type 1 diabetes mellitus has presented several targets by which disease progression may be altered. The goal of disease-modifying therapies is to target autoimmune mechanisms and prevent β-cell destruction. T1DM patients with better β-cell function have better glycemic control, reduced incidence of long-term complications and hypoglycemic episodes. Unfortunately, at the time symptomatic T1DM is diagnosed, most of the insulin secreting β cells are usually lost. Therefore, to maximize the salvageable β-cell mass by disease-modifying therapies, detecting autoimmune markers in an early, optimally presymptomatic phase of T1DM is of great importance. Diseasemodifying therapies, such as immuno-and regenerative therapies are expected to take a relevant place in diabetology. The aim of this article was to provide a brief insight into the pathogenesis and course of T1DM and present the current state of disease-modifying therapeutic interventions that may impact future diabetes treatment.

关键词： Type 1 diabetes Mesenchymal stem cell Immunotherapy Islet cells Autoimmunity Regenerative medicine

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

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