{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T07:01:54Z","timestamp":1762326114600,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoar"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Preoperative biliary stenting (PBS) is commonly used to manage obstructive jaundice in patients undergoing pylorus-preserving pancreaticoduodenectomy (PPPD). However, the impact of PBS on intestinal barrier function and perioperative complications remains controversial. This study aims to evaluate the effect of PBS on intestinal dysfunction and surgical outcomes, focusing on the influence of the stent duration. Materials and Methods: In this prospective cohort study, 235 patients undergoing PPPD for resectable pancreatic neoplasms at Timi\u0219oara Municipal Emergency Clinical Hospital (2016\u20132024) were analyzed. Patients were divided into two groups: those with PBS (n = 98) and without PBS (n = 137). Intestinal barrier function was assessed pre- and postoperatively using biomarkers such as zonulin, fecal calprotectin, and serum lipopolysaccharides (LPS). Perioperative outcomes, including pancreatic fistula, delayed gastric emptying (DGE), infections, and hospital stay, were compared. Additionally, outcomes were stratified based on stent duration (2\u20133 weeks vs. 3\u20134 weeks). Results: PBS was associated with significantly higher levels of zonulin, fecal calprotectin, and serum LPS postoperatively, indicating compromised intestinal barrier function. The stented group had a higher incidence of pancreatic fistulas (Grade B\/C: 27.5% vs. 13.1%, p &lt; 0.01), DGE (25.5% vs. 13.1%, p = 0.008), postoperative infections (34.7% vs. 17.5%, p = 0.002), and prolonged hospital stay (16.9 \u00b1 4.2 days vs. 14.5 \u00b1 3.7 days, p = 0.019). Prolonged stenting (3\u20134 weeks) was associated with worse outcomes compared to shorter stenting durations (2\u20133 weeks), including increased rates of infections, sepsis, and ICU stay (p &lt; 0.05 for all comparisons). Conclusions: Preoperative biliary stenting is associated with increased intestinal barrier dysfunction, systemic inflammation, and higher rates of perioperative complications following PPPD. Prolonged stenting durations (&gt;3 weeks) further exacerbate these risks. Limiting the PBS duration to 2\u20133 weeks, alongside optimized perioperative management, may help reduce postoperative morbidity and improve surgical outcomes.<\/jats:p>","DOI":"10.3390\/medicina61030391","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T10:04:28Z","timestamp":1740391468000},"page":"391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Preoperative Biliary Stenting on Intestinal Dysfunction and Perioperative Complications After Pylorus-Preserving Pancreaticoduodenectomy"],"prefix":"10.3390","volume":"61","author":[{"given":"Gelu Mihai","family":"Breaza","sequence":"first","affiliation":[{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"University Clinic of Surgery I, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florin Emil","family":"Hut","sequence":"additional","affiliation":[{"name":"University Clinic of Surgery I, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Center for Hepato-Bilio-Pancreatic Surgery, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Octavian","family":"Cretu","sequence":"additional","affiliation":[{"name":"University Clinic of Surgery I, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6793-5361","authenticated-orcid":false,"given":"Simona-Alina","family":"Abu-Awwad","sequence":"additional","affiliation":[{"name":"Ist Clinic of Obstetrics and Gynecology, \u201cPius Brinzeu\u201d County Clinical Emergency Hospital, 300723 Timisoara, Romania"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6185-0960","authenticated-orcid":false,"given":"Ahmed","family":"Abu-Awwad","sequence":"additional","affiliation":[{"name":"Department XV\u2014Discipline of Orthopedics\u2014Traumatology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"},{"name":"Research Center University Professor Doctor Teodor Sora, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2854-7449","authenticated-orcid":false,"given":"Laurentiu","family":"Sima","sequence":"additional","affiliation":[{"name":"University Clinic of Surgery I, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radu Gheorghe","family":"Dan","sequence":"additional","affiliation":[{"name":"University Clinic of Surgery I, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina Ana-Maria","family":"Dan","sequence":"additional","affiliation":[{"name":"University Clinic of Surgery I, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1397-1864","authenticated-orcid":false,"given":"Raluca Maria","family":"Closca","sequence":"additional","affiliation":[{"name":"Department of Pathology, Emergency City Hospital, 300254 Timisoara, Romania"},{"name":"Department of Microscopic Morphology, University of Medicine and Pharmacy \u201cVictor Babes\u201d, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5755-179X","authenticated-orcid":false,"given":"Flavia","family":"Zara","sequence":"additional","affiliation":[{"name":"Department of Pathology, Emergency City Hospital, 300254 Timisoara, Romania"},{"name":"Department of Microscopic Morphology, University of Medicine and Pharmacy \u201cVictor Babes\u201d, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.6004\/jnccn.2021.0017","article-title":"Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology","volume":"19","author":"Tempero","year":"2021","journal-title":"J. Natl. Compr. Canc. Netw."},{"key":"ref_2","first-page":"783","article-title":"Pylorus-preserving versus classical pancreaticoduodenectomy: A systematic review and meta-analysis of randomized controlled trials","volume":"401","author":"Klaiber","year":"2016","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.surg.2016.11.001","article-title":"Preoperative biliary stenting versus operation first in jaundiced patients due to malignant lesions in the pancreatic head: A meta-analysis of current literature","volume":"161","author":"Scheufele","year":"2017","journal-title":"Surgery"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1016\/j.hpb.2022.01.006","article-title":"Is preoperative biliary stenting associated with increased rate of postoperative complications for patients undergoing pancreatoduodenectomy? A review of national surgical quality improvement program data","volume":"24","author":"Olecki","year":"2022","journal-title":"HPB"},{"key":"ref_5","first-page":"399","article-title":"Isolated microorganisms in plastic biliary stents placed for benign and malignant diseases","volume":"27","author":"Basioukas","year":"2014","journal-title":"Ann. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106","DOI":"10.4291\/wjgp.v12.i6.106","article-title":"Bacterial translocation in patients undergoing major gastrointestinal surgery and its role in postoperative sepsis","volume":"12","author":"Doudakmanis","year":"2021","journal-title":"World J. Gastrointest. Pathophysiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.4240\/wjgs.v15.i7.1262","article-title":"Pathophysiological consequences and treatment strategy of obstructive jaundice","volume":"15","author":"Li","year":"2023","journal-title":"World J. Gastrointest. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Heidt, C., K\u00e4mmerer, U., Fobker, M., R\u00fcffer, A., Marquardt, T., and Reuss-Borst, M. (2023). Assessment of Intestinal Permeability and Inflammation Bio-Markers in Patients with Rheumatoid Arthritis. Nutrients, 15.","DOI":"10.3390\/nu15102386"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1097\/SLA.0000000000002838","article-title":"Preoperative biliary stenting and major morbidity after pancreatoduodenectomy: Does elapsed time matter? The FRAGERITA Study Group","volume":"268","author":"Sandini","year":"2018","journal-title":"Ann. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1148\/radiol.2018180628","article-title":"Pancreatic cancer CT: Prediction of resectability according to NCCN criteria","volume":"289","author":"Hong","year":"2018","journal-title":"Radiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.surg.2014.02.001","article-title":"Borderline resectable pancreatic cancer: A consensus statement by the International Study Group of Pancreatic Surgery (ISGPS)","volume":"155","author":"Bockhorn","year":"2014","journal-title":"Surgery"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Du, J., Gao, X., Zhang, H., Sun, B., and Yang, L. (2022). Stent selection in preoperative biliary drainage for patients with operable pancreatic cancer receiving neoadjuvant therapy: A meta-analysis and systematic review. Front. Surg., 9.","DOI":"10.3389\/fsurg.2022.875504"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1245\/s10434-023-14523-y","article-title":"Comparison between plastic and metallic biliary stent placement for preoperative patients with pancreatic head cancer: A systematic review and meta-analysis","volume":"31","author":"Endo","year":"2024","journal-title":"Ann. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1089\/lap.2018.0029","article-title":"Comparison of metal and plastic stents for preoperative biliary drainage in resectable and borderline resectable periampullary cancer: A meta-analysis and system review","volume":"28","author":"Liu","year":"2018","journal-title":"J. Laparoendosc. Adv. Surg. Tech. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1097\/01.sla.0000242711.74502.a9","article-title":"A systematic review and meta-analysis of pylorus-preserving versus classical pancreaticoduodenectomy for surgical treatment of periampullary and pancreatic carcinoma","volume":"245","author":"Diener","year":"2007","journal-title":"Ann. Surg."},{"key":"ref_16","first-page":"CD006053","article-title":"Pylorus-preserving pancreaticoduodenectomy (pp Whipple) versus pancreaticoduodenectomy (classic Whipple) for surgical treatment of periampullary and pancreatic carcinoma","volume":"2","author":"Fitzmaurice","year":"2016","journal-title":"Cochrane Database Syst Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1097\/01.sla.0000143248.71964.29","article-title":"Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure: A prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors","volume":"240","author":"Tran","year":"2004","journal-title":"Ann. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"593","DOI":"10.21037\/gs-22-648","article-title":"The role of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy in patients with obstructive jaundice","volume":"12","author":"Zhu","year":"2023","journal-title":"Gland Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1056\/NEJMoa0903230","article-title":"Preoperative biliary drainage for cancer of the head of the pancreas","volume":"362","author":"Rauws","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.cmet.2017.04.001","article-title":"Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease","volume":"25","author":"Loomba","year":"2017","journal-title":"Cell Metab."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Parada Venegas, D., De la Fuente, M.K., Landskron, G., Gonz\u00e1lez, M.J., Quera, R., Dijkstra, G., Harmsen, H.J.M., Faber, K.N., and Hermoso, M.A. (2019). Short-chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00277"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13073-016-0307-y","article-title":"The healthy human microbiome","volume":"8","author":"Huttenhower","year":"2016","journal-title":"Genome Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1749-6632.2012.06538.x","article-title":"Zonulin, regulation of tight junctions, and autoimmune diseases","volume":"1258","author":"Fasano","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_24","unstructured":"Kopylov, U., and Seidman, E.G. (2013). Role of fecal calprotectin in pediatric inflammatory bowel disease. Front. Pediatr., 1."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic endotoxemia initiates obesity and insulin resistance","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Scheffler, L., Crane, A., Heyne, H., T\u00f6njes, A., Schleinitz, D., Ihling, C.H., Stumvoll, M., Freire, R., Fiorentino, M., and Fasano, A. (2018). Widely used commercial ELISA does not detect precursor of haptoglobin2, but recognizes properdin as a potential second member of the zonulin family. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00022"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41575-022-00605-x","article-title":"The gut microbiome as a modulator of healthy ageing","volume":"19","author":"Ghosh","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/j.1651-2227.2005.tb01904.x","article-title":"Tight junctions, leaky intestines, and pediatric diseases","volume":"94","author":"Liu","year":"2005","journal-title":"Acta Paediatr."},{"key":"ref_29","first-page":"212563","article-title":"Activation of Toll-like receptor 4 by lipopolysaccharide induces systemic inflammatory cascade","volume":"2010","author":"Kim","year":"2010","journal-title":"J. Immunol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3748\/wjg.v24.i1.112","article-title":"Characterization of biofilms in biliary stents and potential factors involved in occlusion","volume":"24","author":"Vaishnavi","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zaborina, O., Lepine, F., Xiao, G., Valuckaite, V., Chen, Y., Li, T., Ciancio, M., Petroff, E., Turner, J.R., and Rahme, L.G. (2007). Dynorphin activates quorum sensing quinolone signaling in Pseudomonas aeruginosa. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030035"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s00534-012-0572-0","article-title":"TG13 antimicrobial therapy for acute cholangitis and cholecystitis","volume":"20","author":"Gomi","year":"2013","journal-title":"J. Hepatobiliary Pancreat. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101791","DOI":"10.1016\/j.suronc.2022.101791","article-title":"Systemic inflammation response index (SIRI) as predictor of anastomotic leakage after total gastrectomy for gastric cancer","volume":"43","author":"Schietroma","year":"2022","journal-title":"Surg. Oncol."},{"key":"ref_34","first-page":"435","article-title":"Serum albumin and C-reactive protein predict in-stent restenosis after percutaneous coronary intervention","volume":"68","author":"Zhong","year":"2017","journal-title":"Angiology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Li, L., Zhu, X., Zhang, X., Wang, T., and Wu, Z. (2021). The C-reactive protein to albumin ratio predicts mortality and adverse outcomes in patients with chronic total coronary occlusion undergoing percutaneous coronary intervention. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.731261"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1089\/sur.2015.184","article-title":"Persistent Inflammation, Immunosuppression, and Catabolism: Evolution of Multiple Organ Dysfunction","volume":"17","author":"Rosenthal","year":"2016","journal-title":"Surg. Infect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/bjs.7305","article-title":"Nutritional predictors of postoperative outcome in pancreatic cancer","volume":"98","author":"Kanda","year":"2011","journal-title":"Br. J. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1007\/s10151-014-1210-4","article-title":"The influence of preoperative nutritional status on the outcomes of an enhanced recovery after surgery (ERAS) programme for colorectal cancer surgery","volume":"18","author":"Lohsiriwat","year":"2014","journal-title":"Tech. Coloproctol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e22714","DOI":"10.1097\/MD.0000000000022714","article-title":"The effect of preoperative biliary stents on outcomes after pancreaticoduodenectomy: A meta-analysis","volume":"99","author":"Gong","year":"2020","journal-title":"Medicine"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gavazzi, F., Ridolfi, C., Capretti, G., Angiolini, M.R., Morelli, P., Casari, E., Montorsi, M., and Zerbi, A. (2016). Role of preoperative biliary stents, bile contamination and antibiotic prophylaxis in surgical site infections after pancreaticoduodenectomy. BMC Gastroenterol., 16.","DOI":"10.1186\/s12876-016-0460-1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"212","DOI":"10.14701\/ahbps.2017.21.4.212","article-title":"Effect of preoperative biliary stenting on post-operative infectious complications in pancreaticoduodenectomy","volume":"21","author":"Ng","year":"2017","journal-title":"Ann. Hepatobiliary Pancreat. Surg."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/3\/391\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:41:20Z","timestamp":1760028080000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/3\/391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,24]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["medicina61030391"],"URL":"https:\/\/doi.org\/10.3390\/medicina61030391","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2025,2,24]]}}}