Article

Does neoadjuvant therapy reduce pancreatic fistula after pancreatoduodenectomy and distal pancreatectomy?—a systematic review and meta-analysis

Sandro HügliDepartment of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, SwitzerlandVíctor López‐LópezDepartment of General, Visceral and Transplantation Surgery, Clinic and University Hospital Virgen de la Arrixaca, IMIB-ARRIXACA, Murcia, SpainSarvar AbdurakhmonovClinic for Surgery, Department of Internal Diseases, Faculty of Medicine, Karshi State University, Karshi, UzbekistanJan Philipp JonasDepartment of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, SwitzerlandElena RangelovaDepartment of Surgery, The Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenLuana GenovaDepartment of Surgery, The Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenMalleo GiuseppeUnit of General and Pancreatic Surgery, Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, Verona, ItalyRyan K. SchmockerDepartment of Surgery, University of Tennessee Graduate School of Medicine, Knoxville, TN, USALea TimmermannDepartment of Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyThomas MalinkaDepartment of Surgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, GermanyScott HeltonSection of General, Thoracic and Vascular Surgery, Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USARalph FritschDepartment of Hematology and Oncology, University Hospital Zurich and University of Zurich, Zurich, SwitzerlandFabian KaltDepartment of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, SwitzerlandCarol Ann TrachselDepartment of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, SwitzerlandFabian RösslerDepartment of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, SwitzerlandJohn Michael BryantDepartment of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USARussel PalmThe Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, OH, USASarah E. HoffeDepartment of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USACristiano GuidettiHepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, ItalyFabrizio Di BenedettoHepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, ItalyDaniel PietraszDepartment of Hepatogastroenterology and Gastrointestinal Oncology, Hôpital Européen Georges-Pompidou, AGEO (Association des Gastro-Enterologues Oncologues), Université de Paris, SIRIC CARPEM, Paris, FranceSameer H. PatelDivision of Surgical Oncology, The University of Cincinnati College of Medicine, Cincinnati, OH, USAGregory C. WilsonDivision of Surgical Oncology, The University of Cincinnati College of Medicine, Cincinnati, OH, USASyed A. AhmadDivision of Surgical Oncology, The University of Cincinnati College of Medicine, Cincinnati, OH, USAJin HeThe Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USAChanghoon YooDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of KoreaJulien. TaïebDepartment of Hepatogastroenterology and Gastrointestinal Oncology, Hôpital Européen Georges-Pompidou, AGEO (Association des Gastro-Enterologues Oncologues), Université de Paris, SIRIC CARPEM, Paris, FranceHenrik PetrowskyDepartment of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, SwitzerlandJuan LujanDepartment of General, Visceral and Transplantation Surgery, Clinic and University Hospital Virgen de la Arrixaca, IMIB-ARRIXACA, Murcia, SpainRicardo Robles-CamposDepartment of General, Visceral and Transplantation Surgery, Clinic and University Hospital Virgen de la Arrixaca, IMIB-ARRIXACA, Murcia, SpainSparrelid ErnestoDivision of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenJosé OberholzerDepartment of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Zurich, SwitzerlandDilmurodjon EshmuminovClinic for Surgery, Department of Internal Diseases, Faculty of Medicine, Karshi State University, Karshi, Uzbekistan

HepatoBiliary Surgery and Nutritionjournal2025en

ABI

Abstract

Background: Postoperative pancreatic fistula (POPF) is a major complication after pancreatic resection. This systematic review and meta-analysis investigated the impact of neoadjuvant therapy (NAT) on POPF rates after pancreatoduodenectomy (Whipple procedure) and distal pancreatectomy. Methods: A systematic search of PubMed/MEDLINE, Scopus, Embase, and Cochrane Central Register of Controlled Trials was conducted for studies published since 2016 using the updated International Study Group of Pancreatic Fistula (ISGPF) definition for POPF. Random-effects models were used to pool data. Results: Thirty studies (22,048 patients) were included. Of those, 24 were comparative studies between neoadjuvant and upfront surgery (UPS) groups, while 6 reported POPF rates only in the neoadjuvant group. NAT significantly reduced POPF rates after Whipple procedure [risk ratio (RR) 0.44, 95% confidence intervals (CI): 0.38-0.52, P<0.01]. A harder pancreatic texture was more common after NAT compared to UPS (RR 1.27, 95% CI: 1.23-1.32, P<0.001). There were no significant differences between the neoadjuvant and upfront surgery groups regarding pancreatic duct size or body mass index (BMI). Conclusions: NAT reduces POPF after Whipple procedure, likely by altering pancreatic texture. The exact mechanisms by which the pancreas becomes harder during neoadjuvant treatment remain unclear. This finding could be implemented to improve surgical outcomes in patients with a soft pancreas. However, accurately predicting tumor response to NAT is a prerequisite for such an approach to avoid potential disease progression. Advances in personalized medicine, where tumor response could be predicted, offer hope for tailoring treatment strategies and maximizing outcomes.

Topics

Pancreatic and Hepatic Oncology Research Pancreatitis Pathology and Treatment Cholangiocarcinoma and Gallbladder Cancer Studies

Identifiers

DOI: 10.21037/hbsn-2025-121

Citations and references

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