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Cystic tumors of the pancreas: Opportunities and risks

World Journal of Gastrointestinal Pathophysiology 2015年第2期6卷 29-32页

作者： marco del chiaro Caroline Verbeke Pancreatic Surgery Unit Division of Surgery Department of Clinical Science Intervention and Technology (CLINTEC) Karolinska Institute at Center for Digestive Diseases Karolinska University Hospital Department of Pathology Institute of Clinical Medicine University of Oslo Department of Pathology Karolinska Institute

Pancreatic cystic neoplasms(PCNs) are a high prevalence disease. It is estimated that about 20% of the general population is affected by PCNs. Some of those lesions can progress till cancer, while others behave in a benign fashion. In particular intraductal papillary mucinousneoplasms of the pancreas can be considered as the pancreatic analogon to colonic polyps. Treatment of these precursor lesions at an early stage can potentially reduce pancreas cancer mortality and introduce a new "era" of preemptive pancreatic surgery. However, only few of those lesions have an aggressive behavior. The accuracy of preoperative diagnosis, i.e., the distinction between the various PCNs is around 60%, and the ability to predict the future outcome is also less accurate. For this reason, a significant number of patients are currently over-treated with an unnecessary, high-risk surgery. Furthermore, the majority of patients with PCN are on life-long follow-up with imaging modality, which has huge cost implications for the Health Care System for limited benefits considering that a significant proportion of PCNs are or behave like benign lesions. The current guidelines for the diagnosis and management of PCNs are more based on expert opinion than on evidence. For all those reasons, the management of cystic tumors of the pancreas remains a controversial area of pancreatology. On one hand, the detection of PCNs and the surgical treatment of pre-cancerous neoplasms can be considered a big opportunity to reduce pancreatic cancer related mortality. On the other hand, PCNs are associated with a considerable risk of under- or over- treatment of patients and incur high costs for the Health Care System.

关键词： Pancreatic cystic neoplasms Mucinous cystic neoplasia Preemptive pancreatic surgery Pancreas Intraductal papillary mucinous neoplasia

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Tissue microarray-chip featuring computerized immunophenotypical characterization more accurately subtypes ampullary adenocarcinoma than routine histology

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World Journal of Gastroenterology 2020年第43期26卷 6822-6836页

作者： Matteo Palmeri Niccola Funel Gregorio Di Franco Niccolo Furbetta Desiree Gianardi Simone Guadagni Matteo Bianchini Luca E Pollina Claudio Ricci marco del chiaro Giulio Di Candio Luca Morelli General Surgery Unit Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisa 56124Italy Division of Surgical Pathology University-Hospital of PisaPisa 56124Italy Department of Surgical MedicalMolecular Pathology and Critical AreaUniversity of PisaPisa 56124Italy Department of Surgery University of ColoradoDenverCO 80045United States

BACKGROUND Ampullary adenocarcinomas(AACs)are heterogeneous tumors currently classified into three important sub-classes(SC):Intestinal(INT),Pancreato-Biliary(PB)and Mixed-Type(MT).The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative ***,they respond differently to chemotherapy and have different prognostic *** SC are often difficult to identify with conventional histology *** clinical outcome of all three remains unclear,particularly for *** To identify two main subtypes of AACs,using an immunohistochemical(IHC)score based on CDX2,CK7 and *** Tissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2,CK7 and CK *** IHC score was obtained for each marker by counting the number of positive cells(0=no stained cells;150%)and their intensity(1=weak;2=moderate and 3=strong).A global score(GS)was then obtained by summation of the IHC scores of each *** MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype,obtaining only two AACs *** overall survival in INT and PB patients was obtained by Kaplan-Meier *** Histological parameters defined the AACs subtypes as follows:15%INT,45%PB and 40%*** IHC expression and the GS,75%and 25%of MT samples were assigned to either the INT or the PB *** mean value of the GS was 9.5(range 4-16).All INT samples had a GS above the average,distinct from the PB samples which had a GS score significantly below the average(P=0.0011).The INT samples were identified by high expression of CDX2 and CK20,whereas PB samples exhibited high expression of CK7 and no expression of CK20(P=0.0008).The INT group had a statistically significant higher overall survival than in the PB group(85.7 mo vs 20.3 mo,HR:8.39;95%CI:1.38 to 18.90;P=0.0152).CONCLUSION The combination of histopathological a

关键词： Ampullary adenocarcinoma Histo-molecular phenotype Prognostic CK7 CK20 CDX2

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Early detection and prevention of pancreatic cancer:Is it really possible today?

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World Journal of Gastroenterology 2014年第34期20卷 12118-12131页

作者： marco del chiaro Ralf Segersvrd Matthias Lohr Caroline Verbeke Division of Surgery Department of Clinical ScienceIntervention and Technology (CLINTEC)Karolinska Institute141 86 StockholmSweden Division of Pathology Department of Laboratory MedicineKarolinska Institute141 86 StockholmSweden

Pancreatic cancer is the 4th leading cause of cancerrelated death in Western *** the low incidence of pancreatic cancer,population-based screening is not ***,the existence of a group of individuals with an increased risk to develop pancreatic cancer has been well *** particular,individuals suffering from a somatic or genetic condition associated with an increased relative risk of more than 5-to 10-fold seem to be suitable for enrollment in a surveillance program for prevention or early detection of pancreatic *** aim of such a program is to reduce pancreatic cancer mortality through early or preemptive *** the risk associated with pancreatic surgery,the concept of preemptive surgery cannot consist of a prophylactic removal of the pancreas in high-risk healthy individuals,but must instead aim at treating precancerous lesions such as intraductal papillary mucinous neoplasms or pancreatic intraepithelial neoplasms,or early ***,results from clinical trials do not convincingly demonstrate the efficacy of this approach in terms of identification of precancerous lesions,nor do they define the outcome of the surgical treatment of these *** this reason,surveillance programs for individuals at risk of pancreatic cancer are thus far generally limited to the setting of a clinical ***,the acquisition of a deeper understanding of this complex area,together with the increasing request for screening and treatment by individuals at risk,will usher pancreatologists into a new era of preemptive pancreatic *** with the growing demand to treat individuals with precancerous lesions,the need for low-risk investigation,lowmorbidity operation and a minimally invasive approach becomes increasingly *** of these considerations are reasons for preemptive pancreatic surgery programs to be undertaken in specialized centers only.

关键词： Preemptive pancreatic surgery Cystic tumors of the

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Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals

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World Journal of Gastrointestinal Endoscopy 2015年第9期7卷 833-842页

作者： Gabriele Capurso Marianna Signoretti Roberto Valente Urban Arnelo Matthias Lohr Jan-Werner Poley Gianfranco delle Fave marco del chiaro Digestive and Liver Disease Unit S.Andrea HospitalUniversity Sapienza Departments of Gastroenterology and Hepatology Erasmus MCUniversity Medical Center Pancreatic Surgery Unit Division of SurgeryCLINTECKarolinska Institutet at Karolinska University Hospital

Pancreatic ductal adenocarcinoma(PDAC) is a lethal neoplasia, for which secondary prevention(i.e., screening) is advisable for high-risk individuals with "familiar pancreatic cancer" and with other specific genetic syndromes(Peutz-Jeghers, p16, BRCA2, PALB and mismatch repair gene mutation carriers). There is limited evidence regarding the accuracy of screening tests, their acceptability, costs and availability, and agreement on whom to treat. Successful target of screening are small resectable PDAC, intraductal papillary mucinous neoplasms with high-grade dysplasia and advanced pancreatic intraepithelial neoplasia. Both magnetic resonance imaging(MRI) and endoscopic ultrasound(EUS) are employed for screening, and the overall yield for pre-malignant or malignant pancreatic lesions is of about 20% with EUS and 14% with MRI/magnetic resonance colangiopancreatography. EUS performs better for solid and MRI for cystic lesions. However, only 2% of these detected lesions can be considered a successful target, and there are insufficient data demonstrating that resection of benign or low grade lesions improves survival. Many patients in the published studies therefore seemed to have received an overtreatment by undergoing surgery. It is crucial to better stratify the risk of malignancy individually, and to better define optimal screening intervals and methods either with computerized tools or molecular biomarkers, possibly in large multicentre studies. At the moment, screening should be carefully performed within research protocols at experienced centres, offering involved individuals medical and psychological advice.

关键词： Endoscopic ultrasound Pancreatic cancer Screening High-risk individuals Magnetic resonance

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Dose escalation of adalimumab as a strategy to overcome anti-drug antibodies:A case report of infantile-onset inflammatory bowel disease

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World Journal of Gastroenterology 2023年第38期29卷 5428-5434页

作者： Silvana Ancona Sara Signa Chiara Longo Giuliana Cangemi Roberta Carfora Enrico Drago Alessandro La Rosa marco Crocco Andrea chiaro Paolo Gandullia Serena Arrigo Dipartimento di Neuroscienze RiabilitazioneOftalmologiaGenetica e Scienze Materno-Infantili(DINOGMI)Universitàdegli Studi di GenovaGenova 16126Italy Pediatric Gastroenterology and Endoscopy Unit IRCCS Istituto Giannina GasliniGenova 16147Italy Chromatography and Mass Spectrometry Section Central Laboratory of AnalysisIRCCS Istituto Giannina GasliniGenova 16147Italy

BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for *** loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic *** present a case of IO-IBD treated with therapeutic drug monitoring(TDM)-guided high-dose anti-tumor necrosis factor therapy,in which dose escalation monitoring was used as a strategy to overcome anti-drug *** SUMMARY A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life,as well as relapsing perianal abscess and growth ***,anemia,and elevated inflammatory markers were also *** assessment revealed skip lesions with deep colic ulcerations,inflammatory anal sub-stenosis,and deep fissures with persistent abscess.A diagnosis of IO-IBD Crohn-like was *** patient was initially treated with oral steroids and *** the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of *** and biochemical steroid-free remission was achieved with good trough *** 3 mo,antibodies to ADA(ATA)were found with undetectable trough levels;therefore,we optimized the therapy schedule,first administering 10 mg weekly and subsequently up to 20 mg weekly(2.8 mg/kg/dose).After 2 mo of high-dose treatment,ATA disappeared,with concomitant high trough levels and stable clinical and biochemical remission of the *** TDM-guided high-dose ADA treatment as a monotherapy overcame ATA *** strategy could be a good alternative to combination therapy,especially in very young patients.

关键词： Infantile-onset inflammatory bowel disease Adalimumab Loss of response Dose escalation Anti-drug antibodies Case report

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