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Managing end-stage carcinoid heart disease:A case report and literature review

World Journal of Gastrointestinal Oncology 2024年第3期16卷 1076-1083页

作者： Nikola Bulj Vedran Tomasic maja Cigrovski Berkovic Department of Cardiology University Hospital Centre“Sestre Milosrdnice“Zagreb 10000Croatia Division of Gastroenterology Department of Internal MedicineUniversity Hospital Centre“Sestre Milosrdnice”Zagreb 10000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients’quality of *** complications of GEP-NENs,primarily tricuspid and pulmonary valve disease,and right-sided heart failure,are the leading cause of death,even compared to metastatic *** SUMMARY We present a case of a 35-year-old patient with progressive dyspnea,back pain,polyneuropathic leg pain,and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver *** the initial presentation,serum biomarkers were not evaluated,and the patient received five cycles of doxorubicin,which he did not tolerate well,so he refused further therapy and was lost to *** 10 years,he presented to the emergency room with signs and symptoms of right-sided heart *** markers,serum chromogranin A,and urinary 5-hydroxyindoleacetic acid were extremely elevated(900 ng/mL and 2178µmol/L),and transabdominal ultrasound confirmed hepatic *** tomo-graphy(CT)showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and ***,an Octreoscan showed lesions in the heart,thoracic spine,duodenum,and ascendent colon.A standard trans-thoracic echocardiogram confirmed findings of carcinoid heart *** patient was not a candidate for valve *** started octreotide acetate treatment,and the dose escalated to 80 mg IM *** biochemical CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors,usually with liver metastases,which manifests as right-sided heart valve dysfunction leading to right-sided heart *** heart disease and tumor burden are major prognostic factors of poor surviva

关键词： Gastroenteropancreatic neuroendocrine neoplasms Carcinoid syndrome Carcinoid heart disease Diagnosis Treatment Case report

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Are treatment options used for adult-onset type 2 diabetes mellitus(equally)available and effective for children and adolescents?

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World Journal of Diabetes 2024年第4期15卷 623-628页

作者： Nevena Krnic Vibor Sesa Anna Mrzljak maja Cigrovski Berkovic Clinics for Pediatrics University Hospital Center ZagrebZagreb 10000Croatia Department of Gastroenterology and Hepatology University Hospital Centre ZagrebZagreb 10000Croatia University of Zagreb School of Medicine Zagreb 10000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

Youth-onset type 2 diabetes mellitus(T2DM),influenced by an increase in obesity,is a rising problem *** mechanisms of this early-onset T2DM include both peripheral and hepatic insulin resistance,along with increa-sed hepatic fasting glucose production accompanied by inadequate first and second-phase insulin ***,the incretin effect is *** initial presentation of type 2 diabetes can be dramatic and symptoms may overlap with those of type 1 diabetes ***,immediate therapy should address hyperglycemia and associated metabolic derangements irrespective of ultimate diabetes type,while further therapy adjustments are prone to patients’*** agents with proven glycemic and beyond glycemia benefits,such as Glucagon-like polypeptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors,used in the adult population of T2DM patients,might become increasingly important in the treatment ***,metabolic surgery is an option for markedly obese(body mass index>35 kg/m^(2))children and adolescents suffering from T2DM who have uncontrolled glycemia and/or serious comorbidities when lifestyle and pharmacologic interventions *** this mini-review,we will discuss the potential of treatment options considering new data available from randomized control trials,including individuals with adult-onset type diabetes mellitus.

关键词： Youth-onset type 2 diabetes mellitus Treatment Complications Glucose lowering agents Extra-glycemic benefit

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Challenges and pitfalls of youth-onset type 2 diabetes

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World Journal of Diabetes 2024年第5期15卷 876-885页

作者： Lavinia La Grasta Sabolic Sanda Marusic maja Cigrovski Berkovic Department of Pediatric Endocrinology and Diabetology University Hospital Centre Sestre MilosrdniceZagreb 10000Croatia School of Medicine Catholic University of CroatiaZagreb 10000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

The incidence and prevalence of youth-onset type 2 diabetes mellitus(T2DM)are *** rise in frequency and severity of childhood obesity,inclination to sedentary lifestyle,and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes ***,youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM,with greater insulin resistance and more rapid deterioration of beta cell ***,intermediate complications such as microalbuminuria develop in late childhood or early adulthood,while end-stage complications develop in *** to the lack of efficacy and safety data,several drugs available for the treatment of adults with T2DM have not been approved in youth,reducing the pharmacological treatment *** this mini review,we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

关键词： Youth-onset type 2 diabetes mellitus Insulin resistance Beta cell failure Risk factors Therapy Complications

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Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

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World Journal of Gastroenterology 2024年第7期30卷 759-769页

作者： maja Cigrovski Berkovic Alessandro Coppola Vibor Sesa Anna Mrzljak Quirino Lai Department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Surgery Sapienza University of RomeRome 00185Italy Department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia Department of Medicine School of MedicineZagreb 10000Croatia General Surgery and Organ Transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor ***,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is *** this perspective,metformin is emerging as a molecule of *** studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR *** systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with *** To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of *** A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free *** A total of 13 studies(5674 patients)were included in this *** of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of *** T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS

关键词： Pancreatic neuroendocrine tumors Type 2 diabetes mellitus Prognosis Treatment Metformin

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Review of EU projects with a focus on environmental quality: Innovation, eco-innovation, and circular-economy elements

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International Journal of Innovation Studies 2024年第1期8卷 1-12页

作者： Jana Hojnik Mitja Ruzzier maja Konecnik Ruzzier Boris Sucic Brandon Soltwisch Matej Rus University of Primorska Faculty of ManagementIzolska Vrata 26000KoperSlovenia University of Ljubljana School of Economics and BusinessKardeljeva Ploscad 171000LjubljanaSlovenia Jozef Stefan Institute Energy Efficiency CentreJamova 391000LjubljanaSlovenia Tulane University Freeman School of Business6823 St Charles AveNew OrleansLA 70118USA University of Maribor Faculty of Economics and BusinessRazlagova 142000MariborSlovenia

The primary objective of this study is to delve into transnational projects conducted between 2014 and 2020,with a strong emphasis on environmental *** focus is directed toward projects that encompass either eco-innovation or feature elements intrinsic to a circular *** achieve this goal,we introduce a pioneering analytical framework tailored to dissect transnational projects,which intricately interweaves the diverse dimensions of environmental quality and innovation,facilitating a comparative assessment across various program *** approach aligns with the overarching mission of the four flagship initiatives,in which we evaluate the combined impacts on sustainability and *** evaluation considers three fundamental factors:(1)resource allocation,(2)innovation type,and(3)infusion of eco-innovation or circular economy *** methodology unfolds through a systematic,step-by-step ***,we meticulously handpick programs,specifically Interreg,Horizon,and Life projects,within the scope of TSG3(Environmental Quality).Each of these programs corresponds to one of the following four flagship initiatives:(1)overseeing and managing marine species,(2)fostering sustainable development in coastal and maritime zones,(3)safeguarding and elevating natural habitats and terrestrial ecosystems,and(4)formulating transnational contingency strategies for maritime *** an exhaustive review,we identify projects that either directly or indirectly champion eco-innovation or other facets of the circular ***,we uncover broader manifestations of innovation,eco-innovation,and circular economy *** the Oslo Manual as a guide,we methodically categorize these innovations into the product,process,organizational,and marketing *** the timeframe under scrutiny,a relatively modest subset of projects embraced eco-innovations and practices aligned with the circular *** findings culminate in

关键词： Environment Sustainability Eco-innovation Innovation EU projects Entrepreneurship

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Expect the unexpected:Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism

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World Journal of Clinical Cases 2024年第7期12卷 1200-1204页

作者： Ana Majic Tengg maja Cigrovski Berkovic Ivan Zajc Ivan Salaric Danko Müller Iva Markota Department of Endocrinology DiabetesMetabolic Diseases and Clinical PharmacologyClinical Hospital DubravaZagreb 10000Croatia Department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia Department of Oral Surgery Clinical Hospital DubravaZagreb 10000Croatia University of Zagreb School of Dental Medicine Zagreb 10000Croatia Clinical Department of Pathology and Cytology Clinical Hospital DubravaZagreb 10000Croatia

Hyperparathyroidism(HPT)is a condition in which one or more parathyroid glands produce increased levels of parathyroid hormone(PTH),causing disturbances in calcium *** commonly HPT presents with asymptomatic hypercalcemia but the clinical spectrum may include disturbances reflecting the combined effects of increased PTH secretion and *** tumors are rare,benign,tumor-like bone lesions,occurring in 1.5%to 4.5%of patients with HPT,as a complication of an uncontrolled disease pathway,and are nowadays rarely seen in clinical *** tumor can appear either as a solitary or multifocal lesion and usually presents as an asymptomatic swelling or a painful exophytic ***,it can cause a pathological fracture or skeletal pain and be radiologically described as a lytic bone *** diagnosis of a brown tumor in HPT is typically confirmed by assessing the levels of serum calcium,phosphorus,and *** when present,brown tumor is quite pathognomonic for HPT,the histologic finding often suggests a giant cell tumor,while clinical presentation might suggest other more frequent pathologies such as metastatic *** of brown tumors frequently focuses on managing the underlying HPT,which can often lead to regression and resolution of the lesion,without the need for surgical ***,in refractory cases or when dealing with large symptomatic lesions,surgical treatment may be necessary.

关键词： Brown tumor Hyperparathyroidism Lytic bone lesions Giant cell tumor

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Splenic hamartomas in children

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World Journal of Clinical Cases 2024年第11期12卷 1909-1917页

作者： maja Milickovic Petar Rasic Sofija Cvejic Dejana Bozic Djordje Savic Tanja Mijovic Sava Cvetinovic Slavisa M Djuricic Department of Abdominal Surgery Mother and Child Health Care Institute of Serbia"Dr.Vukan Cupic"Belgrade 11000Serbia Faculty of Medicine University of BelgradeBelgrade 11000Serbia Department of Radiology The Children’s University HospitalBelgrade 11000Serbia Department of Clinical Pathology Mother and Child Health Care Institute of Serbia"Dr.Vukan Cupic"Belgrade 11000Serbia Faculty of Medicine University of Banja LukaBanja Luka 78000Bosnia and Herzegovina

Splenic hamartomas(SHs)are uncommon,benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images,at surgery,or at *** the first case description,in 1861,less than 50 pediatric SH cases have been reported in the *** this article,we have performed an analysis of all SH cases in children published in the literature to date and presented our case of an 8-year-old male with *** lesions in children were shown to cause symptoms more often than in the adult *** observed SH sizes in children ranged from a few millimeters to 18 cm,and the symptomatic lesions were mostly larger or *** most common clinical finding was *** of hypersplenism were present in children with a single SH larger than 4.5 cm(diameter range:4.5-18.0 cm)and in those with multiple hamartomas,ranging from a few millimeters to 5 *** percent of patients with available laboratory findings had hematological abnormalities such as anemia,thrombocytopenia,or *** symptoms and signs included abdominal pain,recurrent infections,fever,night sweats,lethargy,growth retardation,and weight *** use of multiple imaging modalities may suggest the preoperative diagnosis of a splenic mass in children and determine the therapeutic ***,the final diagnosis of SH relies on histopathological ***,including total or partial splenectomy(PS),is the mainstay of SH *** M et *** in children WJCC https://*** 1910 April 16,2024 Volume 12 Issue 11 Although total splenectomy carries a greater risk of overwhelming post-splenectomy infection than PS it has remained the most performed surgical procedure in children with *** the majority of pediatric patients with symptomatic SH,resolution of symptoms and resolution or improvement of cytopenias occurred after surgical treatment.

关键词： Splenic hamartoma Pediatric Splenoma Clinical features Radiological features Histopathology Treatment

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Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics requires promyelocytic leukemia protein

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World Journal of Gastroenterology 2008年第24期14卷 3819-3828页

作者： Maike Sieben Kerstin Herzer maja zeidler Vera Heinrichs Barbara Leuchs Martin Schuler Jan J Cornelis Peter R Galle Jean Rommelaere Markus Moehler First Department of Internal Medicine Johannes Gutenberg University of Mainz German Cancer Research Center Infection and Cancer ProgramDept.F010 and Institut National de la Santé et de la Recherche Médicale Unité 701 Department of Medicine (Cancer Research) West German Cancer CenterUniversity Hospital Essen

AIM: To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML). METHODS: The role of p53 and PML in regulating cy-totoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Further-more,H-1 PV infection was combined with cytostatic drug treatment. RESULTS: While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis,the cytotoxicity of H-1 PV was morepronounced in p53-negative than in p53-positive cells. Apoptosis rates in p53-negative cell lines treated by genotoxic drugs were further enhanced by a treatment with H-1 PV. In flow cytometric analyses,H-1 PV infection resulted in a reduction of the mitochondrial transmembrane potential. In addition,H-1 PV cells showed a significant increase in PML expression. Knocking down PML expression resulted in a striking reduction of the level of H-1 PV infected tumor cell death. CONCLUSION: H-1 PV is a suitable agent to circumvent the resistance of p53-negative HCC cells to genotoxic agents,and it enhances the apoptotic process which is dependent on functional PML. Thus,H-1 PV and its oncolytic vector derivatives may be considered as therapeutic options for HCC,particularly for p53-negative tumors.

关键词：细小病毒细胞凋亡 p53 白血病

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B7 homolog 3 in pancreatic cancer

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World Journal of Gastroenterology 2024年第31期30卷 3654-3667页

作者： Dijana Perovic Marija Dusanovic Pjevic Vladimir Perovic Milka Grk Milica Rasic maja Milickovic Tanja Mijovic Petar Rasic Institute of Human Genetics Faculty of MedicineUniversity of BelgradeBelgrade 11000Serbia Institute of Microbiology and Immunology Faculty of MedicineUniversity of BelgradeBelgrade 11000Serbia Department of Abdominal Surgery Mother and Child Health Care Institute of Serbia“Dr.Vukan Cupic”Belgrade 11000Serbia Faculty of Medicine University of BelgradeBelgrade 11000Serbia

Despite advances in cancer treatment,pancreatic cancer(PC)remains a disease with high mortality rates and poor survival *** B7 homolog 3(B7-H3)checkpoint molecule is overexpressed among many malignant tumors,including PC,with low or absent expression in healthy *** modulating various immunological and nonimmunological molecular mechanisms,B7-H3 may influence the progression of ***,the impact of B7-H3 on the survival of patients with PC remains a subject of ***,most available scientific data recognize this molecule as a suppressive factor to antitumor immunity in ***,it has been demonstrated that B7-H3 stimulates the migration,invasion,and metastasis of PC cells,and enhances resistance to *** preclinical models of PC,B7-H3-targeting monoclonal antibodies have exerted profound antitumor effects by increasing natural killer cell-mediated antibodydependent cellular cytotoxicity and delivering radioisotopes and cytotoxic drugs to the tumor ***,PC treatment with B7-H3-targeting antibody-drug conjugates and chimeric antigen receptor T cells is being tested in clinical *** review provides a comprehensive analysis of all PC-related studies in the context of B7-H3 and points to deficiencies in the current data that should be overcome by future research.

关键词： B7 homolog 3 Pancreatic cancer Prognosis Signaling pathways Immunotherapy

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Levels of evidence and grades of recommendation supporting European society for medical oncology clinical practice guidelines

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Oncology Research 2024年第5期32卷 807-815页

作者： MARKO SKELIN BRUNA PERKOV-STIPIČIN SANJA VUŠKOVIĆ MARINAŠANDRK PLEHAČEK ANE BAŠIĆ DAVIDŠARČEVIĆ maja ILIĆ IVAN KREČAK Pharmacy Department General Hospital ofŠibenik-Knin CountyŠibenikCroatia2 Faculty of MedicineUniversity of RijekaRijekaCroatia3 Undergraduate Study in NursingUniversity of Applied SciencesŠibenikCroatia4 Department of OncologyUniversity Hospital Center ZagrebZagrebCroatia5 Pharmacies JoukhadarSveta NedeljaCroatia6 Pharmacies Prima PharmeZagrebCroatia7 Pharmacy DepartmentGeneral Hospital ZadarZadarCroatia8 Pharmacy DepartmentGeneral Hospital PulaPulaCroatia9 Department of Internal MedicineGeneral Hospital ofŠibenik-Knin CountyŠibenikCroatia

Background:The European Society for Medical Oncology(ESMO)guidelines are among the most comprehensive and widely used clinical practice guidelines(CPGs)***,the level of scientific evidence supporting ESMO CPG recommendations has not been systematically *** study assessed ESMO CPG levels of evidence(LOE)and grades of recommendations(GOR),as well as their trends over time across various cancer ***:We manually extracted every recommendation with the Infectious Diseases Society of America(IDSA)classification from each *** examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer ***:Among the 1,823 recommendations in the current CPG,30%were classified as LOEⅠ,and 43%were classified as GOR ***,there was a slight decrease in LOEⅠ(−2%)and an increase in the proportion of GOR A(+1%)in the current CPG compared to previous *** proportion of GOR A recommendations based on higher levels of evidence such as randomized trials(LOEⅠ–Ⅱ)shows a decrease(71%vs.63%,p=0.009)while recommendations based on lower levels of evidence(LOEⅢ–Ⅴ)show an increase(29%vs.37%,p=0.01)between previous and current *** the current versions,the highest proportion of LOEⅠ(42%)was found in recommendations related to pharmacotherapy,while the highest proportion of GOR A recommendations was found in the areas of pathology(50%)and diagnostic(50%)*** variability in LOEⅠand GOR A recommendations and their changes over time was observed across different cancer ***:One-third of the current ESMO CPG recommendations are supported by the highest level of *** well-designed randomized clinical trials are needed to increase the proportion of LOEⅠand GOR A recommendations,ultimately leading to improved outcomes for cancer patients.

关键词： ESMO guidelines Clinical practice guidelines Level of evidence Grade of recommendation

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