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Revolutionizing gastric cancer treatment:The potential of immunotherapy

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World Journal of Gastroenterology 2024年第4期30卷 286-289页

作者： Grigorios Christodoulidis konstantinos eleftherios koumarelas Marina Nektaria Kouliou Department of General Surgery University Hospital of LarissaLarissa 41110Greece

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

关键词： Immunotherapy Adaptive immunotherapy Tumor vaccines Chimeric antigen receptor therapy Tumor-infiltrating lymphocytes therapy Natural killer therapy Cytokine-induced killer therapy Engineered T cell receptor therapy Immune checkpoint inhibitors

Immune signature of small bowel adenocarcinoma and the role of tumor microenvironment

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World Journal of Gastroenterology 2024年第8期30卷 794-798页

作者： Grigorios Christodoulidis Marina Nektaria Kouliou konstantinos eleftherios koumarelas Department of General Surgery University Hospital of LarissaLarissa 41110Greece

In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.

关键词： Programmed cell death 1 Programmed cell death-ligand 1 Programmed death ligand Small bowel adenocarcinoma Tumor infiltrating lymphocytes Tumor microenvironment Microsatellite instability

Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 514-526页

作者： Stylianos Fiflis Grigorios Christodoulidis Menelaos Papakonstantinou Alexandros Giakoustidis Stergos Koukias Paraskevi Roussos Marina Nektaria Kouliou konstantinos eleftherios koumarelas Dimitrios Giakoustidis First Department of Surgery General Hospital PapageorgiouThessaloniki 56429Greece Department of General Surgery University Hospital of LarissaLarissa 41110Greece

BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed

关键词： Prognostic nutritional index Gastric adenocarcinoma Gastroesophageal junction cancer Prognosis Overall survival

Pivotal role of exosomes in diagnosis and treatment of esophageal cancer in a new era of precision medicine

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World Journal of Methodology 2024年第1期14卷 1-5页

作者： Grigorios Christodoulidis konstantinos eleftherios koumarelas Marina Nektaria Kouliou Department of General Surgery University Hospital of LarissaLarissa 41110Greece

In this editorial we comment on the article published by Ning et al,“Role of exosomes in metastasis and therapeutic resistance in esophageal cancer”.Esophageal cancer(EC)represents a significant global health concern,being the seventh most common and sixth in terms of mortality worldwide.Despite the advances in therapeutic modalities,the management of patients with EC remains challenging,with a 5-year survival rate of only 25%and a limited eligibility for curative surgery due to its late diagnosis.Conventional screening methods are impractical for the early detection of EC,given their either invasive or insensitive nature.The advent of liquid biopsy,with a focus on circulating tumor cells,circulating tumor DNA,and exosomes,heralds a non-invasive avenue for cancer detection.Exosomes,small vesicles involved in intercellular communication,are highlighted as potential biomarkers for EC diagnosis and prognosis.Along with a diverse cargo encompassing various types of RNA,DNA molecules,proteins,and metabolites,exosomes emerge as key players in tumorigenesis,tumor development,and metastasis.Their significance extends to carrying distinctive biomarkers,including microRNAs(miRNAs),long non-coding RNAs,and circular RNAs,underscoring their potential diagnostic and prognostic value.Furthermore,exosomes may be utilized for therapeutic purposes in the context of EC treatment,serving as efficient delivery vehicles for therapeutic agents such as chemotherapeutic medicines and miRNAs.In this editorial we delve into the applications of exosomes for the early detection and treatment of EC,as well as the future perspectives.

关键词： Exosomes Esophageal cancer Diagnostic methods Novel therapies

Billroth II anastomosis combined with brown anastomosis reduce reflux gastritis in gastric cancer patients

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World Journal of Methodology 2024年第1期14卷 71-79页

作者： Grigorios Christodoulidis Marina Nektaria Kouliou konstantinos eleftherios koumarelas konstantinos Argyriou Garyfallia Apostolia Karali konstantinos Tepetes Department of General Surgery University Hospital of LarissaLarissa 41110Greece Department of Gastroenterology University Hospital of LarissaLarissa 41334Greece

BACKGROUND The surgeon performing a distal gastrectomy,has an arsenal of reconstruction techniques at his disposal,Billroth II among them.Braun anastomosis performed during a Billroth II procedure has shown evidence of superiority over typical Billroth II,in terms of survival,with no impact on postoperative morbidity and mortality.AIM To compare Billroth II vs Billroth II and Braun following distal gastrectomy,regarding their postoperative course.METHODS Patients who underwent distal gastrectomy during 2002-2021,were separated into two groups,depending on the surgical technique used(Billroth II:74 patients and Billroth II and Braun:28 patients).The daily output of the nasogastric tube(NGT),the postoperative day that NGT was removed and the day the patient started per os feeding were recorded.Postoperative complications were at the same time noted.Data were then statistically analyzed.RESULTS There was difference in the mean NGT removal day and the mean start feeding day.Mean total postoperative NGT output was lower in Braun group(399.17 mL vs 1102.78 mL)and it was statistically significant(P<0.0001).Mean daily postoperative NGT output was also statistically significantly lower in Braun group.According to the postoperative follow up 40 patient experienced bile reflux and alkaline gastritis from the Billroth II group,while 9 patients who underwent Christodoulidis G et al.Billroth II and Braun compared with Billroth II WJM https://*** 2 March 20,2024 Volume 14 Issue 1 Billroth II and Braun anastomosis were presented with the same conditions(P<0.05).CONCLUSION There was evidence of superiority of Billroth II and Braun vs typical Billroth II in terms of bile reflux,alkaline gastritis and NGT output.

关键词： Billroth II Billroth II and Braun Reconstruction techniques Gastrectomy Distal gastrectomy

Double role of depression in gastric cancer:As a causative factor and as consequence

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World Journal of Gastroenterology 2024年第10期30卷 1266-1269页

作者： Grigorios Christodoulidis koumarelas konstantinos-eleftherios Kouliou Marina-Nektaria Department of General Surgery University Hospital of LarissaLarissa 41110Greece

In this editorial we comment on the article“Hotspots and frontiers of the rela-tionship between gastric cancer and depression:A bibliometric study”.Gastric cancer(GC)is a common malignancy in the digestive system with increased mortality and morbidity rates globally.Standard treatments,such as gastrectomy,negatively impact patients'quality of life and beyond the physical strain,GC patients face psychological challenges,including anxiety and depression.The prevalence of depression can be as high as 57%,among gastrointestinal cancer patients.Due to the advancements in treatment effectiveness and increased 5-year overall survival rates,attention has shifted to managing psychological effects.However,the significance of managing the depression doesn’t lie solely in the need for a better psychological status.Depression leads to chronic stress acti-vating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis,leading release of catecholamines inducing tumor proliferation,migration,and metastasis,contributing to GC progression.The dysregulation of neurotrans-mitters and the involvement of various signaling pathways underscore the complex interplay between depression and GC.Comprehensive strategies are required to address the psychological aspects of GC,including region-specific interventions and increased monitoring for depression.Understanding the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex disease.In this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.

关键词： Gastric cancer Depression Anxiety Chronic stress Pathogenesis of gastric cancer

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery:A systematic review

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World Journal of Cardiology 2024年第1期16卷 27-39页

作者： Christos Kourek Marios Kanellopoulos Vasiliki Raidou Michalis Antonopoulos eleftherios Karatzanos Irini Patsaki Stavros Dimopoulos Medical School of Athens National and Kapodistrian University of AthensAthens 15772Greece Clinical Ergospirometry Exercise and Rehabilitation LaboratoryEvangelismos HospitalAthens 10676Greece Intensive Care Unit Onassis Cardiac Surgery CenterKallithea 17674Greece Department of Physiotherapy University of West AtticaAthens 12243Greece

BACKGROUND Lack of mobilization and prolonged stay in the intensive care unit(ICU)are major factors resulting in the development of ICU-acquired muscle weakness(ICUAW).ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery,and may be a risk factor for prolonged duration of mechanical ventilation,associated with a higher risk of readmission and higher mortality.Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay.Neuromuscular electrical stimulation(NMES)is an alternative modality of exercise in patients with muscle weakness.A major advantage of NMES is that it can be applied even in sedated patients in the ICU,a fact that might enhance early mobilization in these patients.AIM To evaluate safety,feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery.METHODS We performed a search on Pubmed,Physiotherapy Evidence Database(PEDro),Embase and CINAHL databases,selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials(RCTs)that included implementation of NMES in patients before after cardiac surgery.RCTs were assessed for methodological rigor and risk of bias via the PEDro.The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function.RESULTS Ten studies were included in our systematic review,resulting in 703 participants.Almost half of them performed NMES and the other half were included in the control group,treated with usual care.Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery.Functional capacity was assessed in 8 studies via 6MWT or other indices,and improved only in 1 study before and in 1 after cardiac surgery.Nine studies explored the effects of NMES on muscle strength

关键词： Neuromuscular electrical stimulation Cardiac surgery coronary artery bypass grafting Heart valve replacement Peak VO2 Safety

Photofermentative hydrogen production by immobilized Rhodopseudomonas sp. S16-VOGS3 cells in photobioreactors

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Energy Reviews 2024年第1期3卷 39-48页

作者： Isabela C.Moia Aikaterini Kanaropoulou Demetrios F.Ghanotakis Pietro Carlozzi eleftherios Touloupakis Research Institute on Terrestrial Ecosystems National Research CouncilVia Madonna del Piano 1050019Sesto FiorentinoFIItaly Department of Chemistry University of CreteVoutes Campus70013 HeraklionGreece

One of the most important solutions to overcome energy and environmental problems and to replace the fossil fuel-based economy could be the use of photosynthetic microorganisms.The use of photosynthetic microorganisms is a potential alternative to energy generation from fossil fuels because they efficiently produce hydrogen(H_(2)).Immobilization of photosynthetic microorganisms is used for many biotechnological applications such as H_(2) production.This method appears attractive because it restricts cell movement in an entrapped matrix.Immobilization of Rhodopseudomonas sp.S16-VOGS3 cells is a promising way to improve H_(2) production.In this work,the ability of immobilized Rhodopseudomonas sp.S16-VOGS3 cells to produce H_(2) was investigated in two types of PBRs.The PBRs used in this work were a cylindrical one with 0.2 L working volume(C-PBR)and a flat Roux type with 0.6 L working volume(FRT-PBR).The calcium alginate beads prepared were resistant to culture mixing and showed little leakage of cells,and the immobilized cells continued the photofermentation process in both PBRs.The immobilized cells in the C-PBR produced 936.8 mL of H_(2) with an average H_(2) production rate of 2.99 mL/h.The average productivity was 126.4μL(H_(2))/mg(cells)/h or 14.96 mL(H_(2))/L(culture)/h,and the light conversion efficiency was 2.37%.The immobilized cells in the FRT-PBR produced a total of 662.2 mL of H_(2) with an average H_(2) production rate of 1.55 mL/h.The average productivity was 31.1μL(H_(2))/mg(cells)/h or 2.58 mL(H_(2))/L(culture)/h,and the light conversion efficiency was 0.52%.The more uniform and therefore more efficient degree of bacterial cell mixing achieved in the C-PBR with cylindrical configuration played an important role compared to the FRT-PBR.In the FRT-PBR,the beads were aggregated at the bottom,which limited light penetration and resulted in low H_(2) production efficiency.

关键词： Photobioreactor Rhodopseudomonas sp.S16-VOGS3 Photofermentation Hydrogen production Calcium alginate

Effects of combined aerobic,resistance and inspiratory training in patients with pulmonary hypertension:A systematic review

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World Journal of Critical Care Medicine 2024年第2期13卷 168-179页

作者： Christos Kourek Antonia Zachariou eleftherios Karatzanos Michalis Antonopoulos Theodora Soulele Andreas Karabinis Serafim Nanas Stavros Dimopoulos Department of Clinical Ergospirometry Exercise and Rehabilitation Laboratory1^(st)Department of Critical Care MedicineEvangelismos HospitalNational and Kapodistrian University of AthensAthens 10676Greece Department of Cardiology 417 Army Share Fund Hospital of AthensAthens 11521Greece Cardiac Surgery ICU Onassis Cardiac Surgery centerAthens 17674AtticaGreece Cardiac Surgery ICU Onassis Cardiac Surgery CenterAthens 17674Greece Cardiac Surgery Intensive Care Unit Onassis Cardiac Surgery CenterAthens 17674Greece Department of Clinical Ergospirometry Exercise and Rehabilitation LaboratoryNational and Kapodistrian University of AthensAthens 10676Greece

BACKGROUND Pulmonary hypertension(PH)is a serious progressive disorder of the modern world,characterized by endothelial dysfunction and impaired vasoreactivity.Patients with PH usually present exercise intolerance from the very early stages and reduced exercise capacity.Exercise training has been shown to have beneficial effects in patients with cardiovascular comorbidities.However,data regarding the effects of combined exercise training programs in patients with PH still remains limited.AIM To investigate the effects of combined exercise training programs on exercise capacity and quality of life in patients with PH.METHODS Our search included all available randomized controlled trials(RCTs)regarding combined aerobic,resistance and inspiratory training programs in patients with PH in 4 databases(Pubmed,PEDro,Embase,CINAHL)from 2012 to 2022.Five RCTs were included in the final analysis.Functional capacity,assessed by peak VO_(2)or 6-min walking test(6MWT),as well as quality of life,assessed by the SF-36 questionnaire,were set as the primary outcomes in our study.RESULTS Peak VO_(2)was measured in 4 out of the 5 RCTs while 6MWT was measured in all RCTs.Both indices of functional capacity were significantly increased in patients with PH who underwent combined exercise training compared to the controls in all of the included RCTs(P<0.05).Quality of life was measured in 4 out of 5 RCTs.Although patients improved their quality of life in each group,however,only 2 RCTs demonstrated further improvement in patients performing combined training compared to controls.CONCLUSION By this systematic review,we have demonstrated that combined aerobic,resistance and inspiratory exercise training is safe and has beneficial effects on aerobic capacity and quality of life in patients with PH.Such exercise training regimen may be part of the therapeutic strategy of the syndrome.

关键词： Pulmonary hypertension Exercise training Peak VO2 Functional capacity Quality of life