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  1. Article ; Online: 7-T MRI of explanted liver and ex-vivo pancreatic specimens

    Rosa Cervelli / Matteo Cencini / Guido Buonincontri / Francesco Campana / Andrea Cacciato Insilla / Giacomo Aringhieri / Paolo De Simone / Ugo Boggi / Daniela Campani / Michela Tosetti / Laura Crocetti

    European Radiology Experimental, Vol 4, Iss 1, Pp 1-

    prospective study protocol of radiological-pathological correlation feasibility (the EXLIPSE project)

    2020  Volume 10

    Abstract: Abstract The study focuses on radiological-pathological correlation between imaging of ex vivo samples obtained by a 7-T scanner and histological examination. The specimens will be derived from native explanted cirrhotic livers, liver grafts excluded ... ...

    Abstract Abstract The study focuses on radiological-pathological correlation between imaging of ex vivo samples obtained by a 7-T scanner and histological examination. The specimens will be derived from native explanted cirrhotic livers, liver grafts excluded from donation because of severe steatosis, and primary pancreatic tumours. Magnetic resonance imaging (MRI) examinations will be performed within 24 h from liver or pancreatic lesion surgical removal. The MRI protocol will include morphological sequences, quantitative T1, T2, and fat-, water-fraction maps with Cartesian k-space acquisition, and multiparametric methods based on a transient-state “MRI fingerprinting”. Finally, the specimen will be fixed by formalin. Qualitative imaging analysis will be performed by two independent blinded radiologists to assess image consistency score. Quantitative analysis will be performed by drawing regions of interest on different tissue zones to measure T1 and T2 relaxation times as well as fat- and water-fraction. The same tissue areas will be analysed by the pathologists. This study will provide the possibility to improve our knowledge about qualitative and quantitative abdominal imaging assessment at 7 T, by correlating imaging characteristics and the corresponding histological composition of ex vivo specimens, in order to identify imaging biomarkers. Trial registration: ClinicalTrials.gov : 13646. Registered 9 July 2019—retrospectively registered
    Keywords Liver cirrhosis ; Liver steatosis ; Liver transplantation ; Magnetic resonance imaging ; Pancreatic neoplasms ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
    Subject code 610
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher SpringerOpen
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer

    Daniela Massihnia / Amir Avan / Niccola Funel / Mina Maftouh / Anne van Krieken / Carlotta Granchi / Rajiv Raktoe / Ugo Boggi / Babette Aicher / Filippo Minutolo / Antonio Russo / Leticia G. Leon / Godefridus J. Peters / Elisa Giovannetti

    Journal of Hematology & Oncology, Vol 10, Iss 1, Pp 1-

    2017  Volume 17

    Abstract: Abstract Background There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and ...

    Abstract Abstract Background There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. Methods Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs) with specimens tissue from radically-resected patients (n = 100). Data were analyzed by Fisher and log-rank test. In vitro studies were performed in 14 PDAC cells, including seven primary cultures, characterized for their Akt1 mRNA and phospho-Akt/Akt levels by quantitative-RT-PCR and immunocytochemistry. Growth inhibitory effects of Akt inhibitors and gemcitabine were evaluated by SRB assay, whereas modulation of Akt and phospho-Akt was investigated by Western blotting and ELISA. Cell cycle perturbation, apoptosis-induction, and anti-migratory behaviors were studied by flow cytometry, AnnexinV, membrane potential, and migration assay, while pharmacological interaction with gemcitabine was determined with combination index (CI) method. Results Immunohistochemistry of TMAs revealed a correlation between phospho-Akt expression and worse outcome, particularly in patients with the highest phospho-Akt levels, who had significantly shorter overall and progression-free-survival. Similar expression levels were detected in LPC028 primary cells, while LPC006 were characterized by low phospho-Akt. Remarkably, Akt inhibitors reduced cancer cell growth in monolayers and spheroids and synergistically enhanced the antiproliferative activity of gemcitabine in LPC028, while this combination was antagonistic in LPC006 cells. The synergistic effect was paralleled by a reduced expression of ribonucleotide reductase, potentially facilitating gemcitabine cytotoxicity. Inhibition of Akt decreased cell migration and invasion, which was additionally reduced by the combination with gemcitabine. This combination significantly increased apoptosis, associated with induction of caspase-3/6/8/9, PARP and BAD, and inhibition of Bcl-2 and NF-kB in LPC028, but not in LPC006 cells. However, targeting the key glucose transporter Glut1 resulted in similar apoptosis induction in LPC006 cells. Conclusions These data support the analysis of phospho-Akt expression as both a prognostic and a predictive biomarker, for the rational development of new combination therapies targeting the Akt pathway in PDAC. Finally, inhibition of Glut1 might overcome resistance to these therapies and warrants further studies.
    Keywords Pancreatic ductal adenocarcinoma ; Akt ; Synergism ; Gemcitabine ; Diseases of the blood and blood-forming organs ; RC633-647.5 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Subject code 610 ; 500
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Co-localization of acinar markers and insulin in pancreatic cells of subjects with type 2 diabetes.

    Matilde Masini / Lorella Marselli / Eddy Himpe / Luisa Martino / Marco Bugliani / Mara Suleiman / Ugo Boggi / Franco Filipponi / Margherita Occhipinti / Luc Bouwens / Vincenzo De Tata / Piero Marchetti

    PLoS ONE, Vol 12, Iss 6, p e

    2017  Volume 0179398

    Abstract: To search for clues suggesting that beta cells may generate by transdifferentiation in humans, we assessed the presence of cells double positive for exocrine (amylase, carboxypeptidase A) and endocrine (insulin) markers in the pancreas of non-diabetic ... ...

    Abstract To search for clues suggesting that beta cells may generate by transdifferentiation in humans, we assessed the presence of cells double positive for exocrine (amylase, carboxypeptidase A) and endocrine (insulin) markers in the pancreas of non-diabetic individuals (ND) and patients with type 2 diabetes (T2D). Samples from twelve ND and twelve matched T2D multiorgan donors were studied by electron microscopy, including amylase and insulin immunogold labeling; carboxypeptidase A immunofluorescence light microscopy assessment was also performed. In the pancreas from four T2D donors, cells containing both zymogen-like and insulin-like granules were observed, scattered in the exocrine compartment. Nature of granules was confirmed by immunogold labeling for amylase and insulin. Double positive cells ranged from 0.82 to 1.74 per mm2, corresponding to 0.26±0.045% of the counted exocrine cells. Intriguingly, cells of the innate immune systems (mast cells and/or macrophages) were adjacent to 33.3±13.6% of these hybrid cells. No cells showing co-localization of amylase and insulin were found in ND samples by electron microscopy. Similarly, cells containing both carboxypeptidase A and insulin were more frequently observed in the diabetic pancreata. These results demonstrate more abundant presence of cells containing both acinar markers and insulin in the pancreas of T2D subjects, which suggests possible conversion from one cellular type to the other and specific association with the diseased condition.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571 ; 610
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Simultaneous Penile and Signet Ring Cell Bladder Carcinoma in Renal Transplant Recipient

    Francesca Manassero / Gianluca Giannarini / Davide Paperini / Andrea Mogorovich / Greta Alí / Ugo Boggi / Cesare Selli

    The Scientific World Journal, Vol 9, Pp 920-

    A First Case

    2009  Volume 923

    Abstract: The incidence and prevalence of cancer increase with time after transplantation. Therefore, a risk-adapted screening process is very important in order to identify low-grade malignancies early in their development. This provides the opportunity to ... ...

    Abstract The incidence and prevalence of cancer increase with time after transplantation. Therefore, a risk-adapted screening process is very important in order to identify low-grade malignancies early in their development. This provides the opportunity to initiate appropriate immunosuppressive regimens depending on the tumor type and stage of development. The first case presented is one of a 65-year-old patient with a double genitourinary carcinoma (penis and bladder). The patient received kidney transplantation 7 years prior to this event. After adequate surgical treatment (partial amputation of the penis for squamous cell carcinoma and complete transurethral resection of bladder adenocarcinoma), the patient was noted to be free of tumor recurrence and had functioning renal graft with a 2-year follow-up.
    Keywords Technology ; T ; Medicine ; R ; Science ; Q
    Language English
    Publishing date 2009-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Human Gyrovirus DNA in Human Blood, Italy

    Fabrizio Maggi / Lisa Macera / Daniele Focosi / Maria Linda Vatteroni / Ugo Boggi / Guido Antonelli / Marc Eloit / Mauro Pistello

    Emerging Infectious Diseases, Vol 18, Iss 6, Pp 956-

    2012  Volume 959

    Abstract: Human gyrovirus (HGyV) is a recent addition to the list of agents found in humans. Prevalence, biologic properties, and clinical associations of this novel virus are still incompletely understood. We used qualitative PCRs to detect HGyV in blood samples ... ...

    Abstract Human gyrovirus (HGyV) is a recent addition to the list of agents found in humans. Prevalence, biologic properties, and clinical associations of this novel virus are still incompletely understood. We used qualitative PCRs to detect HGyV in blood samples of 301 persons from Italy. HGyV genome was detected in 3 of 100 solid organ transplant recipients and in 1 HIV-infected person. The virus was not detected in plasma samples from healthy persons. Furthermore, during observation, persons for whom longitudinal plasma samples were obtained had transient and scattered presence of circulating HGyV. Sequencing of a 138-bp fragment showed nucleotide identity among all the HGyV isolates. These results show that HGyV can be present in the blood of infected persons. Additional studies are needed to investigate possible clinical implications.
    Keywords human gyrovirus ; HGyV DNA ; transplantation ; HIV ; real-time PCR ; sequencing ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Subject code 610
    Language English
    Publishing date 2012-06-01T00:00:00Z
    Publisher Centers for Disease Control and Prevention
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women

    Giulia Peduzzi / Livia Archibugi / Verena Katzke / Manuel Gentiluomo / Gabriele Capurso / Anna Caterina Milanetto / Maria Gazouli / Mara Goetz / Hermann Brenner / Roel C. H. Vermeulen / Renata Talar-Wojnarowska / Giuseppe Vanella / Francesca Tavano / Maurizio Lucchesi / Beatrice Mohelnikova-Duchonova / Xuechen Chen / Vytautas Kiudelis / Péter Hegyi / Martin Oliverius /
    Hannah Stocker / Caterina Stornello / Ludmila Vodickova / Pavel Souček / John P. Neoptolemos / Sabrina Gloria Giulia Testoni / Luca Morelli / Rita T. Lawlor / Daniela Basso / Jakob R. Izbicki / Stefano Ermini / Juozas Kupcinskas / Raffaele Pezzilli / Ugo Boggi / Hanneke W. M. van Laarhoven / Andrea Szentesi / Bálint Erőss / Giovanni Capretti / Ben Schöttker / Jurgita Skieceviciene / Mateus Nóbrega Aoki / Casper H. J. van Eijck / Giulia Martina Cavestro / Federico Canzian / Daniele Campa

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 8

    Abstract: Abstract The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could ... ...

    Abstract Abstract The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P < 0.05). In the replication none of the findings were validated. In addition, a gene-based analysis was performed on the 208 selected genes. Four genes (NR5A2, MED1, NCOA2 and RUNX1) were associated with PDAC risk, but only NR5A2 showed an association (P = 4.08 × 10−5) below the Bonferroni-corrected threshold of statistical significance. In conclusion, despite differences in incidence between males and females, our study did not identify an effect of common polymorphisms in the oestrogen and pregnenolone pathways in relation to PDAC susceptibility. However, we validated the previously reported association between NR5A2 gene variants and PDAC risk.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Persistent or Transient Human β Cell Dysfunction Induced by Metabolic Stress

    Lorella Marselli / Anthony Piron / Mara Suleiman / Maikel L. Colli / Xiaoyan Yi / Amna Khamis / Gaelle R. Carrat / Guy A. Rutter / Marco Bugliani / Laura Giusti / Maurizio Ronci / Mark Ibberson / Jean-Valery Turatsinze / Ugo Boggi / Paolo De Simone / Vincenzo De Tata / Miguel Lopes / Daniela Nasteska / Carmela De Luca /
    Marta Tesi / Emanuele Bosi / Pratibha Singh / Daniela Campani / Anke M. Schulte / Michele Solimena / Peter Hecht / Brian Rady / Ivona Bakaj / Alessandro Pocai / Lisa Norquay / Bernard Thorens / Mickaël Canouil / Philippe Froguel / Decio L. Eizirik / Miriam Cnop / Piero Marchetti

    Cell Reports, Vol 33, Iss 9, Pp 108466- (2020)

    Specific Signatures and Shared Gene Expression with Type 2 Diabetes

    2020  

    Abstract: Summary: Pancreatic β cell failure is key to type 2 diabetes (T2D) onset and progression. Here, we assess whether human β cell dysfunction induced by metabolic stress is reversible, evaluate the molecular pathways underlying persistent or transient ... ...

    Abstract Summary: Pancreatic β cell failure is key to type 2 diabetes (T2D) onset and progression. Here, we assess whether human β cell dysfunction induced by metabolic stress is reversible, evaluate the molecular pathways underlying persistent or transient damage, and explore the relationships with T2D islet traits. Twenty-six islet preparations are exposed to several lipotoxic/glucotoxic conditions, some of which impair insulin release, depending on stressor type, concentration, and combination. The reversal of dysfunction occurs after washout for some, although not all, of the lipoglucotoxic insults. Islet transcriptomes assessed by RNA sequencing and expression quantitative trait loci (eQTL) analysis identify specific pathways underlying β cell failure and recovery. Comparison of a large number of human T2D islet transcriptomes with those of persistent or reversible β cell lipoglucotoxicity show shared gene expression signatures. The identification of mechanisms associated with human β cell dysfunction and recovery and their overlap with T2D islet traits provide insights into T2D pathogenesis, fostering the development of improved β cell-targeted therapeutic strategies.
    Keywords type 2 diabetes ; lipoglucotoxicity ; glucolipotoxicity ; human pancreatic islets ; beta cells ; damage ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients.

    Abolfazl Avan / Amir Avan / Tessa Y S Le Large / Andrea Mambrini / Niccola Funel / Mina Maftouh / Majid Ghayour-Mobarhan / Maurizio Cantore / Ugo Boggi / Godefridus J Peters / Paola Pacetti / Elisa Giovannetti

    PLoS ONE, Vol 9, Iss 9, p e

    2014  Volume 108057

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) patients have the highest risk of developing cachexia, which is a direct cause of reduced quality of life and shorter survival. Novel biomarkers to identify patients at risk of cachexia are needed and might have a ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) patients have the highest risk of developing cachexia, which is a direct cause of reduced quality of life and shorter survival. Novel biomarkers to identify patients at risk of cachexia are needed and might have a substantial impact on clinical management. Here we investigated the prognostic value and association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia in PDAC. Genotyping was performed in DNA from blood samples of a test and validation cohorts of 151 and 152 chemo-naive locally-advanced/metastatic PDAC patients, respectively. The association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia as well as the correlation between cachexia and the candidate polymorphisms and overall survival were analyzed. Akt expression and phosphorylation in muscle biopsies were evaluated by specific ELISA assays. SELP-rs6136-AA and AKT1-rs1130233-AA/GA genotypes were associated with increased risk of developing cachexia in both cohorts (SELP: p = 0.011 and p = 0.045; AKT1: p = 0.004 and p = 0.019 for the first and second cohorts, respectively), while patients carrying AKT1-rs1130233-GG survived significantly longer (p = 0.002 and p = 0.004 for the first and second cohorts, respectively). In the multivariate analysis AKT1-rs1130233-AA/GA genotypes were significant predictors for shorter survival, with an increased risk of death of 1.7 (p = 0.002) and 1.6 (p = 0.004), in the first and second cohorts, respectively. This might be explained by the reduced phosphorylation of Akt1 in muscle biopsies from patients harboring AKT1-rs1130233-AA/GA (p = 0.003), favoring apoptosis induction. In conclusion, SELP and AKT1 polymorphisms may play a role in the risk of cachexia and death in PDAC patients, and should be further evaluated in larger prospective studies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes

    Bugliani, Marco / Bilal A. Omar / Bo Ahren / Decio L. Eizirik / Fabio Vistoli / Farooq Syed / Flavia M.M. Paula / Francesca Grano / Francesco Cardarelli / Franco Filipponi / Lorella Marselli / Mara Suleiman / Paolo De Simone / Piero Marchetti / Sandra Mossuto / Ugo Boggi / Vincenzo De Tata

    Molecular and cellular endocrinology. 2018 Sept. 15, v. 473

    2018  

    Abstract: It has been reported that the incretin system, including regulated GLP-1 secretion and locally expressed DPP-4, is present in pancreatic islets. In this study we comprehensively evaluated the expression and role of DPP-4 in islet alpha and beta cells ... ...

    Abstract It has been reported that the incretin system, including regulated GLP-1 secretion and locally expressed DPP-4, is present in pancreatic islets. In this study we comprehensively evaluated the expression and role of DPP-4 in islet alpha and beta cells from non-diabetic (ND) and type 2 diabetic (T2D) individuals, including the effects of its inhibition on beta cell function and survival.Isolated islets were prepared from 25 ND and 18 T2D organ donors; studies were also performed with the human insulin-producing EndoC-βH1 cells. Morphological (including confocal microscopy), ultrastructural (electron microscopy, EM), functional (glucose-stimulated insulin secretion), survival (EM and nuclear dyes) and molecular (RNAseq, qPCR and western blot) studies were performed under several different experimental conditions.DPP-4 co-localized with glucagon and was also expressed in human islet insulin-containing cells. Furthermore, DPP-4 was expressed in EndoC-βH1 cells. The proportions of DPP-4 positive alpha and beta cells and DPP-4 gene expression were significantly lower in T2D islets. A DPP-4 inhibitor protected ND human beta cells and EndoC-βH1 cells against cytokine-induced toxicity, which was at least in part independent from GLP1 and associated with reduced NFKB1 expression. Finally, DPP-4 inhibition augmented glucose-stimulated insulin secretion, reduced apoptosis and improved ultrastructure in T2D beta cells.These results demonstrate the presence of DPP-4 in human islet alpha and beta cells, with reduced expression in T2D islets, and show that DPP-4 inhibition has beneficial effects on human ND and T2D beta cells. This suggests that DPP-4, besides playing a role in incretin effects, directly affects beta cell function and survival.
    Keywords apoptosis ; confocal microscopy ; dyes ; electron microscopy ; gene expression ; glucagon ; glucagon-like peptide 1 ; humans ; insulin secretion ; islets of Langerhans ; noninsulin-dependent diabetes mellitus ; quantitative polymerase chain reaction ; secretin ; toxicity ; ultrastructure ; Western blotting
    Language English
    Dates of publication 2018-0915
    Size p. 186-193.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2018.01.019
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA)

    Jony van Hilst / Maarten Korrel / Sanne Lof / Thijs de Rooij / Frederique Vissers / Bilal Al-Sarireh / Adnan Alseidi / Adrian C. Bateman / Bergthor Björnsson / Ugo Boggi / Svein Olav Bratlie / Olivier Busch / Giovanni Butturini / Riccardo Casadei / Frederike Dijk / Safi Dokmak / Bjorn Edwin / Casper van Eijck / Alessandro Esposito /
    Jean-Michel Fabre / Massimo Falconi / Giovanni Ferrari / David Fuks / Bas Groot Koerkamp / Thilo Hackert / Tobias Keck / Igor Khatkov / Ruben de Kleine / Arto Kokkola / David A. Kooby / Daan Lips / Misha Luyer / Ravi Marudanayagam / Krishna Menon / Quintus Molenaar / Matteo de Pastena / Andrea Pietrabissa / Rushda Rajak / Edoardo Rosso / Patricia Sanchez Velazquez / Olivier Saint Marc / Mihir Shah / Zahir Soonawalla / Ales Tomazic / Caroline Verbeke / Joanne Verheij / Steven White / Hanneke W. Wilmink / Alessandro Zerbi / Marcel G. Dijkgraaf

    Trials, Vol 22, Iss 1, Pp 1-

    study protocol for a randomized controlled trial

    2021  Volume 11

    Abstract: Abstract Background Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery ... ...

    Abstract Abstract Background Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP. Methods/design DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin ≥ 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-β), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, ...
    Keywords Minimally invasive ; Laparoscopic ; Robot-assisted ; Distal pancreatectomy ; Left pancreatectomy ; Pancreatic tail resection ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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