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

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;Pci=0.78-2.90;Prepresents 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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Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer:A meta-analysis and systematic review

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Asian Journal of Urology 2024年第2期11卷 191-207页

作者： Stefano Salciccia Marco Frisenda Giulio Bevilacqua Pietro Viscuso Paolo Casale Ettore De Berardinis Giovanni Battista Di Pierro Susanna Cattarino Gloria Giorgino Davide Rosati Francesco Del Giudice alessandro Sciarra Gianna Mariotti alessandro Gentilucci Department of Urology Sapienza Rome UniversityPoliclinico Umberto I00161 RomeItaly Department of Urology Humanitas20089 RozzanoMIItaly

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic ***: A literature search process was performed following the Preferred reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect ***: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [ci]: −0.03-0.15) and between high and low PLR cases increased to 0.30 (95% ci: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% ci: 0.78-1.88) and between high and low PLR was 1.47 (95% ci: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% ci: 1.44-2.13) and between high and low PLR was 1.05 (95% ci: 0.87-1.24).Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

关键词： Prostatic neoplasm Neutrophil-to-lymphocyte ratio Platelet-to-lymphocyteratio Meta-analysis Radical prostatectomy Metastatic

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The challenge of molecular selection in liver-limited metastatic colorectal cancer for surgical resection: a systematic review and meta-analysis in the context of current and future approaches

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Oncology Research 2024年第9期32卷 1407-1422页

作者： ROSSANA RONCATO JERRY POLESEL FEDERICA TOSI ELENA PERUZZI ERIKA BRUGUGNOLI CLAUDIA LAURIA PANTANO MARIA FURFARO FILIPPO DI GIROLAMO alessandro NANI ARIANNA PANI NOEMI MILAN ELENA DE MATTIA ANDREA SARTORE-BIANCHI ERIKA CECCHIN Experimental and Clinical Pharmacology Unit Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAviano33081Italy Department of Medicine(DMED) University of UdineUdine33100Italy Unit of Cancer Epidemiology Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAviano33081Italy Department of Oncology and Hemato-Oncology Universitàdegli Studi di MilanoMilan20122Italy Department of Hematology Oncologyand Molecular MedicineGrande Ospedale Metropolitano NiguardaMilan20122Italy Oncology Pharmacy Unit IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino AmadoriMeldola47014Italy Pharmacy Unit Fondazione IRCCS Istituto Tumori di MilanoMilan20122Italy Department of Pharmacy Ca’Foncello Treviso Regional HospitalPiazzale Ospedale 1Treviso31100Italy Department of Medical Surgical and Health Sciences University of TriesteTrieste34127Italy Hospital Pharmacy Cattinara HospitalAzienda Sanitaria Universitaria Giuliano IsontinaTrieste34148Italy Department of Oncology and Onco-Hematology Postgraduate School of Clinical Pharmacology and ToxicologyUniversity of MilanMilan20122Italy

Objectives:Treatment of metastatic colorectal cancer(mCRC)includes resection of liver metastases(LM),however,no validated biomarker identifies patients most likely to benefit from this *** meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC(i.e.,RAS,BRAF,SMAD4,PIK3CA)as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM ***:A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM,stratified according to RAS,BRAF,PIK3CA,and SMAD4 mutational *** ratios(HRs)from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were *** search was conducted in numerous databases,including MEDLINE(PubMed),Embase,Cumulative Index to Nursing and Allied Health Literature(ciNAHL)(EBSCO host),and WHO Global Index Medicus,through March 18th,***-analyses,editorials,letters to the editor,case reports,studies on other primary cancers,studies with primary metastatic sites other than the liver,studies lacking specific oncological outcome variables or genetic data,non-English language studies,and studies omitting residual disease data from liver metastasectomy were *** remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically ***:RAS mutation status was negatively associated with overall survival(OS)(HR,1.68;95%ci,1.54–1.84)and recurrence free survival(RFS)(HR,1.46;95%ci,1.33–1.61).A negative association was also found for BRAF regarding OS(HR,2.64;95%ci,2.15–3.24)and RFS(HR,1.89;95%ci,1.32–2.73)and SMAD4 regarding OS(HR,1.93;95%ci,1.56–2.38)and RFS(HR,1.95;95%ci,1.31–2.91).For PIK3CA only three studies were eligible and no significant associati

关键词： Metastasectomy Liver metastases RAS BRAF SMAD4 PIK3CA Colorectal

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ABCG5-positivity in tumor buds is an indicator of poor prognosis in node-negative colorectal cancer patients

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World Journal of Gastroenterology 2010年第6期16卷 732-739页

作者： lsabel Hostettler Inti Zlobec Luigi Terracciano alessandro Lugli Institute for Pathology University Hospital of Basel

AIM:To analyze the expression of 8 putative cancer stem cell(CSC) markers within colorectal cancer tumor buds and to determine their prognostic impact in patients with this disease. METHODS:Immunohistochemistry was performed on 101 colorectal cancer resections for CK22(to identify tumor buds) as well as CD133,CD166,CD24,CD44s,CD90,EpCAM,ALDH1,and ABCG5,and their expression within tumor buds was evaluated. RESULTS:CD90,CD44s,and CD133 expression in tumor buds was found in less than 5%of all cases. ALDH1,CD24,CD166 were expressed in 16.5%,16.2%,and 34%cases,respectively,while ABCG5 and EpCAM expression was more frequent and found in 35%and 69%of cases,*** the 8 markers studied,EpCAM and ABCG5 positivity in tumor buds were significantly associated with poor prognosis(P=0.023,P=0.038,respectively) in multivariable analysis with pT and pN classificationP=0.048;hazard ratio(HR) :2.64;95%ci:1.0-6.9,for EpCAM and P=0.029;HR:2.22;95%ci:1.0-4.5,for *** survival time was particularly striking for lymph node-negative patients with ABCG5-positive buds(Pciated with poor prognosis.

关键词： Colorectal cancer Cancer stem cells Tumor budding ABCG5 Prognosis

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Association between hepatocellular carcinoma and type 2 diabetes mellitus in Italy:Potential role of insulin

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World Journal of Gastroenterology 2008年第37期14卷 5695-5700页

作者： Valter Donadon Massimiliano Balbi Pietro Casarin alessandro Vario Alfredo Alberti Department of Medicine and Internal Medicine 3rd Pordenone HospitalPordenone 33170 Italy Department of Clinical and Experimental Medicine University of PadovaPadova 35100 Italy

AIM: To investigate the relationships between Type 2 diabetes mellitus (DM2) and the risk of hepatocellular carcinoma (HCC). METHODS: We studied the association between DM2 and HCC in a large case-control study that enrolled 465 consecutive Caucasian patients with HCC (78.3% males, mean age 68.5 ± 8.9 years) compared with an age and sex matched control group of 490 subjects. RESULTS: Prevalence of DM2 was significantly higher in HCC patients (31.2% vs 12.7%; OR = 3.12, 95% ci: 2.22-4.43) and in HCC cases with alcohol abuse. DM2 has been diagnosed before the appearance of HCC in 84.1% of diabetic HCC subjects with mean duration of 141.5 mo, higher in cases treated with insulin than in those with oral antidiabetic agents (171.5 vs 118.7 mo). Compared to controls, males DM2 with HCC were more frequently treated with insulin (38.1% vs 17.6%, P = 0.009) and with sulfonylurea with or without metformin than with diet with or without metformin (84% vs 68.3%, P = 0.049). CONCLUSION: DM2 in our patients is associated with a 3-fold increase risk of HCC. In most of our cases DM2 pre-existed to HCC. Patients with DM2 and chronic liver disease, particularly insulin treated males, should be considered for HCC close surveillance programs.

关键词： Hepatocellular carcinoma Type 2 diabetesmellitus Hepatitis virus B and C Insulin Antidiabetic therapy

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Physical activity support or weight loss counseling for nonalcoholic fatty liver disease?

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World Journal of Gastroenterology 2014年第29期20卷 10128-10136页

作者： Luca Montesi Chiara Caselli Elena Centis Chiara Nuccitelli Simona Moscatiello alessandro Suppini Giulio Marchesini Unit of Metabolic Diseases and Clinical Dietetics "Alma Mater Studiorum" University S. Orsola-Malpighi Hospital

AIM: To determine the clinical effectiveness of intense psychological support to physical activity (PA) in nonalcoholic fatty liver disease (NAFLD), compared with cognitive-behavioral treatment (CBT).

关键词： Nonalcoholic fatty liver disease Behavior treatment Physical activity Physical fitness Weight loss liver fat Liver enzymes

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The impact of extent of pancreatic and venous resection on survival for patients with pancreatic cancer

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Hepatobiliary & Pancreatic Diseases International 2019年第4期18卷 389-394页

作者： Matteo Serenari Giorgio Ercolani alessandro Cucchetti Matteo Zanello Enrico Prosperi Guido Fallani Michele Masetti Raffaele Lombardi Matteo Cescon Elio Jovine Department of Medical and Surgical Sciences S.Orsola-Malpighi HospitalAlma Mater Studiorum-University of BolognaBolognaItaly Department of General Surgery Maggiore Hospital-Bologna Local Health DistrictBolognaItaly

Background:Borderline resectable pancreatic cancer may require extended resections in order to achieve tumor-free margins,especially in the case of up-front resections,but it is important to know the limits of surgical therapy in this *** study aimed to investigate the impact of extent of pancreatic and venous resection on short-and long-term outcomes in patients with pancreatic adenocarcinoma(PDAC).Methods:This was a retrospective study from a prospectively maintained database of pancreatic resections for ***-and long-term outcomes were analyzed in patients having borderline resectable PDAC submitted to up-front total pancreatectomy(TP)or pancreaticoduodenectomy(PD)with simultaneous portal vein(PV)and/or superior mesenteric vein(SMV)*** resections were carried out as tangential venous resection(TVR)or segmental venous resection(SVR).Patients were divided into 4 groups:(1)PD+TVR,(2)PD+SVR,(3)TP+TVR,(4)TP+***-and multivariate Cox regression analysis were performed to identify factors associated with ***:Ninety-nine patients were submitted to simultaneous pancreatic and venous resection for *** them,25 were submitted to PD+TVR(25.3%),12 to PD+SVR(12.1%),23 to TP+TVR(23.2%),and 39 to TP+SVR(39.4%).Overall,major morbidity(Clavien-Dindo grade≥IIIA)was 26.3%.Thirty-and 90-day mortality were 3%and 11.1%,*** were no significant differences among groups in terms of short-term *** overall survival of patients submitted to PD+TVR was significantly higher than those to TP+SVR(29.5 vs 7.9 months,P=0.001).Multivariate analysis identified TP(HR=2.11;95%ci:1.31–3.44;P=0.002)and SVR(HR=2.01;95%ci:1.27–3.15;P=0.003)as the only independent prognostic factors for overall ***:Up-front TP associated to SVR was predictive of worse survival in borderline resectable *** treatments in high-risk surgical groups may improve such poor outcomes.

关键词： Pancreatic resection Vascular resection Pancreatic cancer surgery

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Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

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World Journal of Gastroenterology 2010年第38期16卷 4823-4831页

作者： Inti Zlobec Francesca Molinari Vittoria Martin Luca Mazzucchelli Piercarlo Saletti Rosangela Trezzi Sara De Dosso Tatjana Vlajnic Milo Frattini alessandro Lugli Institute for Pathology University Hospital Basel Institute of Pathology Division of Medical Oncology Institute of Southern Switzerland

AIM:To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients. METHODS:Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and "high-grade" tumor budding was defi ned as 15 buds/high-power f ***: Tumor buds and K-RAS mutation both correctly classif ied 68% of patients. All patients with K-RAS mutation (n=7) or high-grade tumor budding (n=11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% ci): 2.8 (1.3-6.0, P=0.008)].CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting.

关键词： Anti-epidermal growth factor receptor therapy Colorectal cancer K-RAS Prognosis Tumor budding

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Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study

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World Journal of Gastroenterology 2019年第40期25卷 6094-6106页

作者： Gian Luca Colussi Debora Donnini Rosario Francesco Brizzi Silvia Maier Luca Valenti Cristiana Catena alessandro Cavarape Leonardo Alberto Sechi Giorgio Soardo Department of Medicine University of Udine

BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected ***,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well *** To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with *** Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern *** study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be *** The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%ci:15-136,Pci:0.025-0.194,Pcirrhosis(HR:0.521,Pcing SVR and protecting against HCC or death.A residual risk of HCC persi

关键词： Direct-acting antiviral agents Hepatitis C virus Mixed cryoglobulinemia Sustained virologic response cirrhosis Survival analysis

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Clinical significance of glycemic parameters on venous thromboembolism risk prediction in gastrointestinal cancer

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World Journal of Gastroenterology 2017年第28期23卷 5187-5195页

作者： Fiorella Guadagni Silvia Riondino Vincenzo Formica Girolamo Del Monte Anna Maria Morelli Jessica Lucchetti Antonella Spila Roberta D’alessandro David Della-Morte Patrizia Ferroni Mario Roselli San Raffaele Roma Open University Interinstitutional Multidisciplinary Biobank IRCCS San Raffaele Pisana Department of Systems Medicine Medical Oncology UnitTor Vergata Clinical CenterUniversity of Rome Tor Vergata Department of Palliative Care San Raffaele CassinoClinical Center Department of Systems Medicine University of Rome Tor Vergata

To investigate the possible predictive role of routinely used glycemic parameters for a first venous thromboembolism (VTE) episode in gastrointestinal (GI) cancer ambulatory patients - with or without clinically diagnosed type 2 diabetes (T2D) or obesity - treated with ***-treatment fasting blood glucose, insulin, glycated hemoglobin (HbA1c) and homeostasis model of risk assessment (HOMA) were retrospectively evaluated in a cohort study of 342 GI cancer patients. Surgery was performed in 142 (42%) patients with primary cancer, 30 (21%) and 112 (79%) of whom received neoadjuvant and adjuvant therapies, respectively. First-line chemotherapy was administered in 200 (58%) patients with metastatic disease. The study outcome was defined as the occurrence of a first symptomatic or asymptomatic VTE episode during active *** glucose tolerance (IGT) or T2D were diagnosed in 30% of GI cancer patients, while overweight/obesity had an incidence of 41%. VTE occurred in 9.4% of patients (7% of non-diabetic non-obese), especially in those with a high ECOG score (P = 0.025). No significant association was found between VTE incidence and T2D, obesity, different tumor types, metastatic disease, Khorana class of risk, or different anti-cancer drugs, although VTE rates were substantially higher in patients receiving bevacizumab (17% vs 8%, P = 0.044). Conversely, all glucose metabolic indexes were associated with increased VTE risk at ROC analysis. Multivariate Cox proportional analyses confirmed that HOMA index (HR = 4.13, 95%ci: 1.63-10.5) or fasting blood glucose (HR = 3.56, 95%ci: 1.51-8.39) were independent predictors of VTE occurrence during *** results here reported demonstrate that evaluating glucose metabolic asset may allow for VTE risk stratification in GI cancer, helping to identify chemotherapy-treated patients who might benefit from thromboprophylaxis. Further multicenter prospective studies involv

关键词： Gastrointestinal cancer Type 2 diabetes Venous thromboembolism Chemotherapy Insulin resistance

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