{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:38:47Z","timestamp":1787027927148,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"autonomous non-profit organization Moscow Center for Innovative Technologies in Healthcare of the Moscow Healthcare Department","award":["2412-21\/22"],"award-info":[{"award-number":["2412-21\/22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Pancreatic fibrosis (PF) is a part of the pathogenesis in most pancreatic disorders and plays a crucial role in chronic pancreatitis development. The aim of our study was to investigate a relationship between PF grade and signs in resected pancreatic specimens, and the results of both multidetector computed tomography (MDCT) post-processing parameters and fibronectin (FN), hyaluronic acid (HA), matrix metalloproteinase (MMP)-1, and MMP-9 serum levels. The examination results of 74 patients were analyzed. The unenhanced pancreas density (UPD) value and contrast enhancement ratio (CER) showed statistically significant differences in groups with peri- and intralobular fibrosis grades, an integrative index of fibrosis, inflammation in pancreatic tissue, and pancreatic duct epithelium metaplasia, while the normalized contrast enhancement ratio in the venous phase (NCER VP) significantly differed with the perilobular fibrosis grade, integrative fibrosis index, and inflammation (p &lt; 0.05). The blood FN level showed a weak positive correlation with the intralobular fibrosis grade (rho = 0.32, p = 0.008). The blood level of HA positively correlated with the presence of prominent and enlarged peripheral nerves (rho = 0.28, p = 0.02) and negatively correlated with the unenhanced pancreas density value (rho = \u22120.42, p = 0.0001). MMP-1 and MMP-9 values\u2019 intergroup analysis and correlation did not show any statistical significance. The UPD value, NCER VP, and CER, as well as blood levels of FN and HA, could be used in non-invasive PF diagnosis.<\/jats:p>","DOI":"10.3390\/diagnostics13142435","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T01:08:11Z","timestamp":1690160891000},"page":"2435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Contrast-Enhanced Computed Tomography and Laboratory Parameters as Non-Invasive Diagnostic Markers of Pancreatic Fibrosis"],"prefix":"10.3390","volume":"13","author":[{"given":"Igor E.","family":"Khatkov","sequence":"first","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"},{"name":"Chair of Faculty Surgery No. 2, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-3992","authenticated-orcid":false,"given":"Dmitry S.","family":"Bordin","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"},{"name":"Chair of Faculty Surgery No. 2, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia"},{"name":"Chair of General Medical Practice and Family Medicine, Tver State Medical University, 170100 Tver, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-0172","authenticated-orcid":false,"given":"Konstantin A.","family":"Lesko","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena A.","family":"Dubtsova","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay S.","family":"Karnaukhov","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Kiriukova","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezhda V.","family":"Makarenko","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey S.","family":"Dorofeev","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina V.","family":"Savina","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9742-3955","authenticated-orcid":false,"given":"Diana A.","family":"Salimgereeva","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Shurygina","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila V.","family":"Vinokurova","sequence":"additional","affiliation":[{"name":"A.S. Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1177\/2050640616684695","article-title":"United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU)","volume":"5","author":"Rosendahl","year":"2017","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00535-022-01911-6","article-title":"Evidence-based clinical practice guidelines for chronic pancreatitis 2021","volume":"57","author":"Shimizu","year":"2022","journal-title":"J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.pan.2018.05.008","article-title":"International consensus statements on early chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with The International Association of Pancreatology, American Pancreatic Association, Japan Pancreas Society, PancreasFest Working Group and European Pancreatic Club","volume":"18","author":"Whitcomb","year":"2018","journal-title":"Pancreatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.5009\/gnl18491","article-title":"Detecting Early Pancreatic Cancer: Current Problems and Future Prospects","volume":"14","author":"Matsubayashi","year":"2019","journal-title":"Gut Liver"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41575-021-00457-x","article-title":"Pancreatic cancer epidemiology: Understanding the role of lifestyle and inherited risk factors","volume":"18","author":"Klein","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_6","unstructured":"International Agency for Research on Cancer, and World Health Organization (2023, March 11). Global Cancer Observatory 2018. Available online: https:\/\/gco.iarc.fr\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5851","DOI":"10.3748\/wjg.v27.i35.5851","article-title":"Pancreatic cancer in 2021: What you need to know to win","volume":"27","author":"Tonini","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.3748\/wjg.v24.i43.4846","article-title":"Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes","volume":"24","author":"McGuigan","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"322","DOI":"10.14309\/ajg.0000000000000535","article-title":"ACG Clinical Guideline: Chronic Pancreatitis","volume":"115","author":"Gardner","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"233","DOI":"10.2147\/IJGM.S337455","article-title":"Retrospective Analysis of the Value of Enhanced CT Radiomics Analysis in the Differential Diagnosis Between Pancreatic Cancer and Chronic Pancreatitis","volume":"15","author":"Ma","year":"2022","journal-title":"Int. J. Gen. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Huang, C.-T., Lin, C.-K., Lee, T.-H., and Liang, Y.-J. (2020). Pancreatic Fibrosis and Chronic Pancreatitis: Mini-Review of Non-Histologic Diagnosis for Clinical Applications. Diagnostics, 10.","DOI":"10.3390\/diagnostics10020087"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1007\/s11605-017-3660-2","article-title":"Association Between the Incidence of Pancreatic Fistula After Pancreaticoduodenectomy and the Degree of Pancreatic Fibrosis","volume":"22","author":"Deng","year":"2018","journal-title":"J. Gastrointest. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e597","DOI":"10.1097\/SLA.0000000000004855","article-title":"A Simple Classification of Pancreatic Duct Size and Texture Predicts Postoperative Pancreatic Fistula: A classification of the International Study Group of Pancreatic Surgery","volume":"277","author":"Schuh","year":"2021","journal-title":"Ann. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s00330-014-3526-x","article-title":"Abdominal CT predictors of fibrosis in patients with chronic pancreatitis undergoing surgery","volume":"25","author":"Sinha","year":"2014","journal-title":"Eur. Radiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1136\/gutjnl-2016-312432","article-title":"Metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis","volume":"67","author":"Mayerle","year":"2017","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/s12967-019-2058-1","article-title":"The role of collagen in cancer: From bench to bedside","volume":"17","author":"Xu","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0925-4439(00)00051-X","article-title":"Pancreatic carcinoma is characterized by elevated content of hyaluronan and chondroitin sulfate with altered disaccharide composition","volume":"1502","author":"Theocharis","year":"2000","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s12291-010-0103-1","article-title":"Role of Plasma MMP 9 levels in the Pathogenesis of Chronic Pancreatitis","volume":"26","author":"Venkateshwari","year":"2011","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1006\/jsre.2002.6403","article-title":"Pancreatic Stellate Cell Activation and MMP Production in Experimental Pancreatic Fibrosis","volume":"104","author":"Yokota","year":"2002","journal-title":"J. Surg. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/S1499-3872(14)60261-7","article-title":"Role of MMP-2 and MMP-9 and their natural inhibitors in liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases","volume":"13","author":"Kurzepa","year":"2014","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.lfs.2018.07.049","article-title":"Inhibiting autophagy promotes collagen degradation by regulating matrix metalloproteinases in pancreatic stellate cells","volume":"208","author":"Li","year":"2018","journal-title":"Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"947133","DOI":"10.3389\/fonc.2022.947133","article-title":"Methods of a New Chronic Pancreatitis and Spontaneous Pancreatic Cancer Mouse Model Using Retrograde Pancreatic Duct Injection of Dibutyltin Dichloride","volume":"12","author":"Zhang","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"451","DOI":"10.18388\/abp.2016_1443","article-title":"The role of serum hyaluronic acid determination in the diagnosis of liver fibrosis","volume":"64","author":"Cylwik","year":"2017","journal-title":"Acta Biochim. Pol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"264","DOI":"10.32098\/mltj.04.2015.02","article-title":"Hyaluronic acid and tendon lesions","volume":"5","author":"Kaux","year":"2016","journal-title":"Muscle Ligaments Tendons J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e62645","DOI":"10.7554\/eLife.62645","article-title":"Hyaluronic acid fuels pancreatic cancer cell growth","volume":"10","author":"Kim","year":"2021","journal-title":"eLife"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.canlet.2015.12.027","article-title":"Matrix control of pancreatic cancer: New insights into fibronectin signaling","volume":"381","author":"Topalovski","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7242","DOI":"10.3748\/wjg.v23.i40.7242","article-title":"Dachaihu decoction ameliorates pancreatic fibrosis by inhibiting macrophage infiltration in chronic pancreatitis","volume":"23","author":"Duan","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.pan.2020.04.009","article-title":"Guidelines on the histopathology of chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and the European Pancreatic Club","volume":"20","author":"Esposito","year":"2020","journal-title":"Pancreatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.ultrasmedbio.2018.02.016","article-title":"Ultrasound-Guided Percutaneous Core Needle Biopsy for the Diagnosis of Pancreatic Disease","volume":"44","author":"Huang","year":"2018","journal-title":"Ultrasound Med. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1001\/jama.2019.20967","article-title":"Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis: The ESCAPE Randomized Clinical Trial","volume":"323","author":"Issa","year":"2020","journal-title":"JAMA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00121","article-title":"Stromal Content Is Correlated With Tissue Site, Contrast Retention, and Survival in Pancreatic Adenocarcinoma","volume":"2","author":"Torphy","year":"2018","journal-title":"JCO Precis. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1007\/s11605-011-1687-3","article-title":"Dual-Phase Computed Tomography for Assessment of Pancreatic Fibrosis and Anastomotic Failure Risk Following Pancreatoduodenectomy","volume":"15","author":"Hashimoto","year":"2011","journal-title":"J. Gastrointest. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1097\/00006676-199105000-00003","article-title":"Pseudocysts in chronic pancreatitis: A morphological analysis of 57 resection specimens and 9 autopsy pancreata","volume":"6","author":"Maillet","year":"1991","journal-title":"Pancreas"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/01.rli.0000152833.35744.7f","article-title":"Contrast-Enhanced Computed Tomography and Ultrasound for the Evaluation of Tumor Blood Flow","volume":"40","author":"Broumas","year":"2005","journal-title":"Investig. Radiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.hpb.2019.05.008","article-title":"Pancreatic attenuation on computed tomography predicts pancreatic fistula after pancreaticoduodenectomy","volume":"22","author":"Ohgi","year":"2020","journal-title":"HPB"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/j.hpb.2022.03.008","article-title":"Histological pancreatic findings correlate with computed tomography attenuation and predict postoperative pancreatic fistula following pancreatoduodenectomy","volume":"24","author":"Sano","year":"2022","journal-title":"HPB"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"800516","DOI":"10.3389\/fphys.2021.800516","article-title":"Imaging of Fibrosis in Chronic Pancreatitis","volume":"12","author":"Yamashita","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1097\/01.LAB.0000073126.56932.46","article-title":"In Chronic Pancreatitis, Widespread Emergence of TRAIL Receptors in Epithelia Coincides with Neoexpression of TRAIL by Pancreatic Stellate Cells of Early Fibrotic Areas","volume":"83","author":"Hasel","year":"2003","journal-title":"Lab. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1089\/ars.2011.4079","article-title":"The Fibrosis of Chronic Pancreatitis: New Insights into the Role of Pancreatic Stellate Cells","volume":"15","author":"Pirola","year":"2011","journal-title":"Antioxidants Redox Signal."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Abatangelo, G., Vindigni, V., Avruscio, G., Pandis, L., and Brun, P. (2020). Hyaluronic Acid: Redefining Its Role. Cells, 9.","DOI":"10.3390\/cells9071743"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Pratt, R.L. (2021). Hyaluronan and the Fascial Frontier. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136845"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1136\/gut.52.2.275","article-title":"Rat pancreatic stellate cells secrete matrix metalloproteinases: Implications for extracellular matrix turnover","volume":"52","author":"Phillips","year":"2003","journal-title":"Gut"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1007\/s10528-013-9594-9","article-title":"Influence of Matrix Metalloproteinase-1 Gene \u22121607 (1G\/2G) (rs1799750) Promoter Polymorphism on Circulating Levels of MMP-1 in Chronic Pancreatitis","volume":"51","author":"Manjari","year":"2013","journal-title":"Biochem. Genet."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/14\/2435\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:16:17Z","timestamp":1760127377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/14\/2435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,21]]},"references-count":43,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["diagnostics13142435"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13142435","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,21]]}}}