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Consensus & Guidelines

The International Study Group of Pancreatic Surgery (ISGPS) is an international panel of pancreatic surgeons from high-volume centers that develops standardized definitions and consensus statements to improve the consistency, comparability, and quality of pancreatic surgery research and clinical practice. Since its establishment in 2006, the ISGPS has focused on creating objective, universally accepted definitions for postoperative complications, surgical techniques, and disease classifications, particularly for pancreatic surgery. Below is an overview of key ISGPS definitions and consensus statements based on available information:

Key ISGPS Definitions and Consensus Statements

Postoperative Pancreatic Fistula (POPF)

  • Original Definition (2005): The ISGPS (initially ISGPF) defined POPF as an abnormal communication between the pancreatic ductal epithelium and another epithelial surface, with fluid output of any measurable volume via a drain, having amylase activity greater than three times the upper normal serum value. This replaced 26 inconsistent definitions, enabling standardized reporting.
  • 2016 Update: The ISGPS revised the POPF definition to address limitations:
    • Biochemical Leak (BL): Previously “Grade A POPF,” redefined as a biochemical leak with no clinical impact, no longer considered a true fistula.
    • Grade B and C: Clarified to better distinguish severity. Grade B requires significant changes in clinical management (e.g., prolonged drainage, antibiotics), while Grade C involves major invasive interventions (e.g., reoperation) or organ failure. Ambiguities around invasive procedures (e.g., percutaneous drainage) were resolved.
    • Impact: The update improved clinical relevance and consistency in reporting, addressing issues like misclassification of mild cases or discharge with drains in situ. POPF occurs in 10–34% of pancreatic resections in high-volume centers.
  • Adoption: Over 320,000 patients globally have been evaluated using the ISGPF/ISGPS criteria, with 84–98% of studies from 2010 onward compliant. However, Grade A fistulas (now BL) are often underreported due to their lack of clinical significance.

Postpancreatectomy Hemorrhage (PPH)

  • Definition (2007): PPH is defined by three parameters: onset (early: ≤24 hours post-surgery; late: >24 hours), location (intraluminal or extraluminal), and severity (mild or severe). It is graded as:
    • Grade A: Mild, no significant clinical impact.
    • Grade B: Requires significant management changes (e.g., transfusion, endoscopy).
    • Grade C: Severe, requiring major interventions (e.g., angiography, reoperation) or causing life-threatening conditions.
  • Issues and Validation: The definition is widely applicable but may overestimate mild (Grade A) cases due to reliance on surrogate markers like transfusion needs, which can be influenced by other factors. Studies suggest a minor modification to reduce false positives for mild PPH. Incidence is reported at ~29%, with 4.8% Grade A, 15.2% Grade B, and 9.2% Grade C in some cohorts.
  • Risk Factors: Early PPH is linked to preoperative anemia and multivisceral resection, while late PPH correlates with advanced age, chronic renal insufficiency, high blood loss, and long operative times.

Delayed Gastric Emptying (DGE)

  • Definition (2007): DGE is defined as the inability to return to a standard diet by the end of the first postoperative week, often requiring prolonged nasogastric intubation. It is graded as:
    • Grade A: Mild, minimal clinical impact.
    • Grade B: Requires significant management changes.
    • Grade C: Severe, with prolonged nasogastric drainage or major interventions.
  • Impact: DGE incidence is ~14.3–20.7% in pancreaticoduodenectomy, with the ISGPS definition adopted in most studies post-2010. Pyloric ring resection is suggested to reduce DGE rates. The definition correlates well with ICU stay, hospital stay, and total length of stay.
  • Challenges: Variability in definitions before ISGPS made comparisons difficult. The standardized definition enables better outcome analysis across centers.

Post-Pancreatectomy Acute Pancreatitis (PPAP)

  • Definition (2021): PPAP is a newer consensus definition, addressing a controversial complication. It is diagnosed based on postoperative hyperamylasemia, radiologic features consistent with acute pancreatitis, and clinical deterioration within 48 hours post-surgery.
  • Validation: A 2024 prospective international study validated PPAP’s clinical and financial implications, emphasizing routine screening after pancreaticoduodenectomy. It is graded for severity, though specific grades are not detailed in the provided references. Further large-scale validation is needed.
  • Significance: PPAP is recognized as a distinct complication, with the ISGPS definition aiding in its identification and management.

Chyle Leak

  • Definition (2017): Defined as milky-colored fluid output from a drain, drain site, or wound on or after postoperative day 3, with triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Graded based on clinical impact:
    • Grade A: No significant management change.
    • Grade B: Requires nutritional or medical management.
    • Grade C: Needs invasive intervention.
  • Context: Chyle leak complicates up to 10% of pancreatic resections. The ISGPS definition facilitates standardized reporting and comparison of prevention/treatment strategies.

Pancreatectomy Without Histologic Confirmation

  • Consensus (2014): Provides guidance on when to perform pancreatectomy without preoperative histologic confirmation of malignancy, addressing scenarios where biopsy is inconclusive or risky. Emphasizes clinical and imaging criteria to justify resection.

Borderline Resectable Pancreatic Cancer (BRPC)

  • Consensus (2014): The ISGPS supports the National Comprehensive Cancer Network (NCCN) criteria for BRPC, defining it based on tumor-vessel involvement. Key points:
    • Operative exploration and resection are supported for mesentericoportal venous axis involvement, with a new classification for venous resections (e.g., tangential resection, segmental resection with anastomosis or graft).
    • Arterial resections are not recommended except in exceptional cases under experimental protocols.
    • Preoperative diagnostics include CT-based evaluation and biomarkers like CA19-9, neutrophil/lymphocyte ratio, and modified Glasgow Prognostic Score.
  • Impact: The consensus enables standardized reporting and treatment planning for BRPC, with evidence supporting portomesenteric venous resection for improved survival compared to non-surgical approaches.

Extended Pancreatectomy

  • Definition (2014): Defined as pancreatic resection with additional organ resection (e.g., colon, stomach, or vascular structures) to achieve macroscopic (R1) or microscopic (R0) tumor clearance in locally advanced pancreatic ductal adenocarcinoma (PDAC).
  • Consensus: Feasible in selected patients at high-volume centers, despite increased morbidity (e.g., longer operative time, blood loss, ICU stay). Long-term survival is comparable to standard resections and better than bypass surgery or palliative treatments. No clear prognostic criteria were identified for specific additional organs resected.
  • Use Case: Particularly relevant for complex pancreatic tumors beyond PDAC, where extended resection is critical for oncologic outcomes.

Standard Lymphadenectomy in PDAC

  • Consensus (2014): Defines a standard lymphadenectomy for pancreatic ductal adenocarcinoma to ensure consistent oncologic resection and reporting. It recommends specific lymph node stations to be removed during pancreaticoduodenectomy, addressing variability in surgical practice.
  • Impact: Standardizes surgical techniques, improving comparability of oncologic outcomes across centers.

Chronic Pancreatitis Surgery Reporting Standards

  • Consensus (2019): Provides a framework for reporting surgical outcomes in chronic pancreatitis, covering four domains:
    • Clinical Baseline: Preoperative patient characteristics (e.g., pain, comorbidities).
    • Morphology of Diseased Gland: Pancreatic head mass, ductal dilatation, or strictures.
    • Operative Terminology: Standardized terms for procedures (e.g., Frey, Beger, or Whipple).
    • Minimum Outcome Dataset: Key postoperative outcomes for comparison.
  • Purpose: Facilitates comparison across centers by addressing variability in reporting clinical baseline and pancreatic morphology, which impacts procedure choice and outcomes.

General Impact of ISGPS Definitions

  • Standardization: ISGPS definitions have been widely adopted, enabling consistent reporting of complications (e.g., POPF, PPH, DGE) and surgical outcomes across global centers. This has improved clinical trial comparability and meta-analyses.
  • Clinical Relevance: Definitions correlate with key outcomes like ICU stay, hospital length of stay, and mortality, aiding in risk stratification and management. For example, ISGPS grades for POPF and PPH predict clinical severity and resource use.
  • Challenges: Some definitions (e.g., mild PPH, Grade A POPF) have been criticized for overestimating complications or lacking clinical significance, prompting updates like the 2016 POPF revision.
  • Global Adoption: European studies show higher adoption (88%) of ISGPS criteria compared to Asian (77%) and North American (72%) studies, reflecting regional differences in uptake.

Critical Perspective

While ISGPS definitions are a significant step toward standardization, they are not without flaws. The reliance on surrogate markers (e.g., transfusion for PPH) can lead to false positives, and some definitions (e.g., Grade A complications) may lack clinical utility, as seen in the reclassification of Grade A POPF as a biochemical leak. Additionally, the focus on high-volume centers may limit generalizability to smaller institutions. The iterative updates (e.g., 2016 POPF revision) show responsiveness to clinical feedback, but ongoing validation and refinement are needed, particularly for newer definitions like PPAP

Conclusion

The ISGPS has profoundly influenced pancreatic surgery by providing standardized, evidence-based definitions for complications (POPF, PPH, DGE, PPAP, chyle leak), disease classifications (BRPC), and surgical techniques (extended pancreatectomy, lymphadenectomy). These consensus statements, developed through rigorous literature reviews and expert collaboration, enhance research comparability and clinical decision-making. However, ongoing refinements and broader validation are essential to address limitations and ensure applicability across diverse surgical settings. For further details, consult primary ISGPS publications on platforms like PubMed or ScienceDirect.
Postoperative pancreatic fistula: An international study group (ISGPF) definition.

Claudio Bassi, Christos Dervenis, Giovanni Butturini, Abe Fingerhut, Charles Yeo, Jakob Izbicki, John Neoptolemos, Michael Sarr, William Traverso, Marcus Buchler; International Study Group on Pancreatic Fistula Definition.
Surgery 138, 1, P8-13, 2005

Postpancreatectomy hemorrhage (PPH)–An International Study Group of Pancreatic Surgery (ISGPS) definition.

Moritz N. Wente, Johannes A. Veit, Claudio Bassi, Christos Dervenis, Abe Fingerhut, Dirk J. Gouma, Jakob R. Izbicki, John P. Neoptolemos, Robert T. Padbury, Michael G. Sarr, Charles J. Yeo, Markus W. Büchler.
Surgery 142, 1, P20-25, 2007

Delayed gastric emptying (DGE) after pancreatic surgery: A suggested definition by the International Study Group of Pancreatic Surgery (ISGPS).

Moritz N. Wente, Claudio Bassi, Christos Dervenis, Abe Fingerhut, Dirk J. Gouma, Jakob R. Izbicki, John P. Neoptolemos, Robert T. Padbury, Michael G. Sarr, L. William Traverso, Charles J. Yeo, Markus W. Büchler.
Surgery 142, 5, P761-768, 2007

Toward improving uniformity and standardization in the reporting of pancreatic anastomoses: A new classification system by the International Study Group of Pancreatic Surgery (ISGPS).

Parul J. Shukla, Savio G. Barreto, Abe Fingerhut, Claudio Bassi, Markus W. Büchler, Christos Dervenis, Dirk Gouma, Jakob R. Izbicki, John Neoptolemos, Robert Padbury, Michael G. Sarr, William Traverso, Charles J. Yeo, Moritz N. Wente.
Surgery 147, 1, P144-153, 2010

Extended pancreatectomy in pancreatic ductal adenocarcinoma: Definition and consensus of the International Study Group for Pancreatic Surgery (ISGPS).

Werner Hartwig, Charles M. Vollmer, Abe Fingerhut, Charles J. Yeo, John P. Neoptolemos, Mustapha Adham, Åke Andrén-Sandberg, Horacio J. Asbun, Claudio Bassi, Max Bockhorn, Richard Charnley, Kevin C. Conlon, Christos Dervenis, Laureano Fernandez-Cruz, Helmut Friess, Dirk J. Gouma, Clem W. Imrie, Keith D. Lillemoe, Miroslav N. Milićević, Marco Montorsi, Shailesh V. Shrikhande, Yogesh K. Vashist, Jakob R. Izbicki, Markus W. Büchler, for the International Study Group on Pancreatic Surgery.
Surgery 156, 1, P1-14, 2014

Borderline resectable pancreatic cancer: A consensus statement by the International Study Group of Pancreatic Surgery (ISGPS).

Maximilian Bockhorn, Faik G. Uzunoglu, Mustapha Adham, Clem Imrie, Miroslav Milicevic, Aken A. Sandberg, Horacio J. Asbun, Claudio Bassi, Markus Büchler, Richard M. Charnley, Kevin Conlon, Laureano Fernandez Cruz, Christos Dervenis, Abe Fingerhutt, Helmut Friess, Dirk J. Gouma, Werner Hartwig, Keith D. Lillemoe, Marco Montorsi, John P. Neoptolemos, Shailesh V. Shrikhande, Kyoichi Takaori, William Traverso, Yogesh K. Vashist, Charles Vollmer, Charles J. Yeo, Jakob R. Izbicki, for the International Study Group of Pancreatic Surgery.
Surgery 155, 6, P977-988, 2014

Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: A consensus statement by the International Study Group on Pancreatic Surgery (ISGPS).

Johanna A.M.G. Tol, Dirk J. Gouma, Claudio Bassi, Christos Dervenis, Marco Montorsi, Mustapha Adham, Ake Andrén-Sandberg, Horacio J. Asbun, Maximilian Bockhorn, Markus W. Büchler, Kevin C. Conlon, Laureano Fernández-Cruz, Abe Fingerhut, Helmut Friess, Werner Hartwig, Jakob R. Izbicki, Keith D. Lillemoe, Miroslav N. Milicevic, John P. Neoptolemos, Shailesh V. Shrikhande, Charles M. Vollmer, Charles J. Yeo, Richard M. Charnley, for the International Study Group on Pancreatic Surgery.
Surgery 156, 3, P591-600, 2014

When to perform a pancreatoduodenectomy in the absence of positive histology? A consensus statement by the International Study Group of Pancreatic Surgery.

Horacio J. Asbun, Kevin Conlon, Laureano Fernandez-Cruz, Helmut Friess, Shailesh V. Shrikhande, Mustapha Adham, Claudio Bassi, Maximilian Bockhorn, Markus Büchler, Richard M. Charnley, Christos Dervenis, Abe Fingerhutt, Dirk J. Gouma, Werner Hartwig, Clem Imrie, Jakob R. Izbicki, Keith D. Lillemoe, Miroslav Milicevic, Marco Montorsi, John P. Neoptolemos, Aken A. Sandberg, Michael Sarr, Charles Vollmer, Charles J. Yeo, L. William Traverso, for the International Study Group of Pancreatic Surgery.
Surgery 155, 5, P887-892, 2014

The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After.

Claudio Bassi, Giovanni Marchegiani, Christos Dervenis, Micheal Sarr, Mohammad Abu Hilal, Mustapha Adham, Peter Allen, Roland Andersson, Horacio J. Asbun, Marc G. Besselink, Kevin Conlon, Marco Del Chiaro, Massimo Falconi, Laureano Fernandez-Cruz, Carlos Fernandez-del Castillo, Abe Fingerhut, Helmut Friess, Dirk J Gouma, Thilo Hackert, Jakob Izbicki, Keith D. Lillemoe, John P. Neoptolemos, Attila Olah, Richard Schulick, Shailesh V. Shrikhande, Tadahiro Takada, Kyoichi Takaori, William Traverso, Charles Vollmer, Christopher L. Wolfgang, Charles J. Yeo, Roberto Salvia, Marcus Buchler, from the International Study Group on Pancreatic Surgery (ISGPS).
Surgery 161, 3, P584-591, 2017

Pancreatic anastomosis after pancreatoduodenectomy: A position statement by the International Study Group of Pancreatic Surgery (ISGPS).

Shailesh V. Shrikhande, Masillamany Sivasanker, Charles M. Vollmer, Helmut Friess, Marc G. Besselink, Abe Fingerhut, Charles J. Yeo, Carlos Fernandez-delCastillo, Christos Dervenis, Christoper Halloran, Dirk J. Gouma, Dejan Radenkovic, Horacio J. Asbun, John P. Neoptolemos, Jakob R. Izbicki, Keith D. Lillemoe, Kevin C. Conlon, Laureano Fernandez-Cruz, Marco Montorsi, Max Bockhorn, Mustapha Adham, Richard Charnley, Ross Carter, Thilo Hackert, Werner Hartwig, Yi Miao, Michael Sarr, Claudio Bassi, Markus W. Büchler, for the International Study Group of Pancreatic Surgery (ISGPS).
Surgery 161, 5, P1221-1234, 2017

Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery.

Marc G. Besselink, L. Bengt van Rijssen, Claudio Bassi, Christos Dervenis, Marco Montorsi, Mustapha Adham, Horacio J. Asbun, Maximillian Bockhorn, Oliver Strobel, Markus W. Büchler, Olivier R. Busch, Richard M. Charnley, Kevin C. Conlon, Laureano Fernández-Cruz, Abe Fingerhut, Helmut Friess, Jakob R. Izbicki, Keith D. Lillemoe, John P. Neoptolemos, Michael G. Sarr, Shailesh V. Shrikhande, Robert Sitarz, Charles M. Vollmer, Charles J. Yeo, Werner Hartwig, Christopher L. Wolfgang, Dirk J. Gouma, for the International Study Group on Pancreatic Surgery.
Surgery 161, 2, P365-372, 2017

Nutritional support and therapy in pancreatic surgery: A position paper of the International Study Group on Pancreatic Surgery (ISGPS).

Luca Gianotti, Marc G. Besselink, Marta Sandini, Thilo Hackert, Kevin Conlon, Arja Gerritsen, Oonagh Griffin, Abe Fingerhut, Pascal Probst, Mohammed Abu Hilal, Giovanni Marchegiani, Gennaro Nappo, Alessandro Zerbi, Antonio Amodio, Julie Perinel, Mustapha Adham, Massimo Raimondo, Horacio J. Asbun, Asahi Sato, Kyoichi Takaori, Shailesh V. Shrikhande, Marco Del Chiaro, Maximilian Bockhorn, Jakob R. Izbicki, Christos Dervenis, Richard M. Charnley, Marc E. Martignoni, Helmut Friess, Nicolò de Pretis, Dejan Radenkovic, Marco Montorsi, Michael G. Sarr, Charles M. Vollmer, Luca Frulloni, Markus W. Büchler, Claudio Bassi.
Surgery 164, 5, P1035-1048, 2018

Standards for reporting on surgery for chronic pancreatitis: a report from the International Study Group for Pancreatic Surgery (ISGPS).

Ajith K. Siriwardena, John Windsor, Nicholas Zyromski, Giovanni Marchegiani, Dejan Radenkovic, Catherine Morgan, Ioannis Passas, Attila Olah, Kevin C. Conlon, Martin Smith, Olivier Busch, Minas Baltatzis, Marc G. Besselink, Charles Vollmer, Carlos Fernandez-del Castillo, Helmut Friess, Giuseppe Garcea, Sean Burmeister, Thilo Hackert, Keith D. Lillemoe, Richard Schulick, Shailesh V. Shrikhande, Andrew Smith, Luca Gianotti, Massimo Falconi, David Adams, Mustapha Adham, Roland Andersson, Marco Del Chiaro, John Devar, Santhalingam Jegatheeswaran, Hjalmar van Santvoort, Igor Khatkov, Jakob Izbicki, Markus Büchler, John P. Neoptolemos, Claudio Bassi, Christos Dervenis.
Surgery 168, 1, P101-105, 2020

Management of the pancreatic transection plane after left (distal) pancreatectomy: Expert consensus guidelines by the International Study Group of Pancreatic Surgery (ISGPS).

Yi Miao, Zipeng Lu, Charles J. Yeo, Charles M. Vollmer, Carlos Fernandez-del Castillo, Paula Ghaneh, Christopher M. Halloran, Jörg Kleeff, Thijs de Rooij, Jens Werner, Massimo Falconi, Helmut Friess, Herbert J. Zeh, Jakob R. Izbicki, Jin He, Johanna Laukkarinen, Cees H. Dejong, Keith D. Lillemoe, Kevin Conlon, Kyoichi Takaori, Luca Gianotti, Marc G. Besselink, Marco Del Chiaro, Marco Montorsi, Masao Tanaka, Maximilian Bockhorn, Mustapha Adham, Attila Oláh, Roberto Salvia, Shailesh V. Shrikhande, Thilo Hackert, Tooru Shimosegawa, Amer H. Zureikat, Güralp O. Ceyhan, Yunpeng Peng, Guangfu Wang, Xumin Huang, Christos Dervenis, Claudio Bassi, John P. Neoptolemos, Markus W. Büchler, the International Study Group of Pancreatic Surgery (ISGPS).
Surgery 168, 1, P72-84, 2020

Evidence Map of Pancreatic Surgery – A living systematic review with meta-analyses by the International Study Group of Pancreatic Surgery (ISGPS).

Pascal Probst, Felix J. Hüttner, Ömer Meydan, Mohammed Abu Hilal, Mustapha Adham, Savio G. Barreto, Marc G. Besselink, Olivier R. Busch, Maximillian Bockhorn, Marco Del Chiaro, Kevin Conlon, Carlos Fernandez-del Castillo, Helmut Friess, Giuseppe Kito Fusai, Luca Gianotti, Thilo Hackert, Christopher Halloran, Jakob Izbicki, Eva Kalkum, Dezso Kelemen, Hannes G. Kenngott, Rüdiger Kretschmer, Vincent Landre, Keith D. Lillemoe, Yi Miao, Giovanni Marchegiani, Andre Mihaljevic, Dejan Radenkovic, Roberto Salvia, Marta Sandini, Alejandro Serrablo, Shailesh Shrikhande, Parul J. Shukla, Ajith K. Siriwardena, Oliver Strobel, Faik G. Uzunoglu, Charles Vollmer, Jürgen Weitz, Christopher L. Wolfgang, Alessandro Zerbi, Claudio Bassi, Christos Dervenis, John Neoptolemos, Markus W. Büchler, Markus K. Diener.
Surgery 170 (2021) 1517e1524

Post-pancreatectomy acute pancreatitis (PPAP): definition and grading from the International Study Group for Pancreatic Surgery (ISGPS).

Marchegiani, Giovanni; Barreto, Savio George; Bannone, Elisa; Sarr, Michael; Vollmer, Charles; Connor, Saxon; Falconi, Massimo|; Besselink, Marc G; Salvia, Roberto; Wolfgang, Christopher L.; Zyromski, Nicholas J.; Yeo, Charles J.; Adham, Mustapha; Siriwardena, Ajith K.; Takaori, Kyoichi; Hilal, Mohammad Abu; Loos, Martin; Probst, Pascal; Hackert, Thilo; Strobel, Oliver; Busch, Olivier R. C.; Lillemoe, Keith D.; Miao, Yi; Halloran, Christopher M.; Werner, Jens; Friess, Helmut; Izbicki, Jakob R.; Bockhorn, Maximillian; Vashist, Yogesh K.; Conlon, Kevin; Passas, Ioannis; Gianotti, Luca; Del Chiaro, Marco; Schulick, Richard D.; Montorsi, Marco; Oláh, Attila; Fusai, Giuseppe Kito; Serrablo, Alejandro; Zerbi, Alessandro; Fingerhut, Abe; Andersson, Roland; Padbury, Robert; Dervenis, Christos; Neoptolemos, John P.; Bassi, Claudio; Büchler, Markus W.; Shrikhande, Shailesh V.; on behalf of the International Study Group for Pancreatic Surgery.
Ann Surg 275(4):p 663-672, April 2022.

Complexity and Experience Grading to Guide Patient Selection for Minimally-invasive Pancreatoduodenectomy An ISGPS Consensus.

Barreto, S. George; Strobel, Oliver; Salvia, Roberto; Marchegiani, Giovanni; Wolfgang, Christopher L.; Werner, Jens; Ferrone, Cristina R.; Abu Hilal, Mohammed; Boggi, Ugo; Butturini, Giovanni; Falconi, Massimo; Fernandez-Del Castillo, Carlos; Friess, Helmut; Fusai, Giuseppe K.; Halloran, Christopher M.; Hogg, Melissa; Jang, Jin-Young; Kleeff, Jorg; Lillemoe, Keith D.; Miao, Yi; Nagakawa, Yuichi; Nakamura, Masafumi; Probst, Pascal; Satoi, Sohei; Siriwardena, Ajith K.; Vollmer, Charles M.; Zureikat, Amer; Zyromski, Nicholas J.; Asbun, Horacio J.; Dervenis, Christos; Neoptolemos, John P.; Büchler, Markus W.; Hackert, Thilo; Besselink, Marc G.; Shrikhande, Shailesh V.; for the International Study Group for Pancreatic Surgery.
Ann Surg 281(3):p 417-429

Prospective Validation of the Pancreatic Fistula Risk Classification by the International Study Group for Pancreatic Surgery (PARIS trial).

Schuh, Fabian; Yildirim, Berk; Klotz, Rosa MD; Pianka, Frank MD; Boskovic, Andrea; Werba, Alexander; Fink, Matthias A. MD; Wild, Caroline MD; Schwab, Constantin MD; Eckert, Christoph MD; Feisst, Manuel PhD; Mihaljevic, André L.; Loos, Martin; Büchler, Markus; Probst, Pascal.
Ann Surg 2024

Pancreatic cystic neoplasms (PCNs) are fluid-filled lesions in the pancreas, increasingly detected due to widespread use of advanced imaging. They include various types with differing malignant potential, such as intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), serous cystic neoplasms (SCNs), and solid pseudopapillary neoplasms (SPNs). Management focuses on balancing cancer prevention with avoiding unnecessary surgery, guided by several consensus guidelines. Below is an overview of key guidelines, their recommendations, and areas of consensus or divergence, based on current evidence.

Key Guidelines for PCN Management
Several organizations have developed guidelines to standardize the diagnosis, surveillance, and treatment of PCNs. The most prominent include:

European Study Group on Cystic Tumours of the Pancreas (2018)

  • Scope: Covers all PCNs (IPMN, MCN, SCN, and rare cysts).
  • Formulation: Evidence-based, using GRADE methodology, involving multidisciplinary European and non-European experts.
  • Key Recommendations:
    • Diagnosis: Use a combination of CT, MRI/MRCP, and endoscopic ultrasound (EUS) with or without fine-needle aspiration (FNA) for accurate diagnosis. MRI/MRCP is preferred for assessing cyst-duct communication.
    • Surveillance: Lifelong surveillance for IPMNs and MCNs <40 mm without risk factors, as long as patients are fit for surgery. Surveillance intervals vary based on cyst size and features.
    • Surgical Indications:
      • Absolute: Main pancreatic duct (MPD) dilation ≥10 mm, enhancing mural nodules ≥5 mm, or positive cytology for malignancy.
      • Relative: Cyst size ≥40 mm, growth rate ≥5 mm/year, new-onset diabetes mellitus, acute pancreatitis, elevated serum CA 19-9, or enhancing mural nodules <5 mm.
    • MCN-Specific: Surgery for MCNs ≥40 mm, symptomatic MCNs, or those with high-risk features (e.g., mural nodules, MPD dilation).
    • SCN: Conservative management unless symptomatic, as malignancy risk is negligible.
  • Unique Aspects: First evidence-based guideline for all PCNs, emphasizes minimizing lifelong screening costs and patient burden.

International Association of Pancreatology (IAP) Fukuoka Guidelines (2017)

  • Scope: Focuses on IPMNs (main duct [MD-IPMN], branch duct [BD-IPMN], mixed-type) and MCNs.
  • Formulation: Consensus-based, updated from 2006 Sendai Guidelines, incorporating recent literature.
  • Key Recommendations:
    • Diagnosis: Pancreatic protocol CT or MRI/MRCP for cyst characterization. EUS-FNA recommended for worrisome features (e.g., mural nodules, MPD dilation).
    • Surveillance: BD-IPMNs without high-risk stigmata are monitored based on size: <1 cm (every 2–3 years), 1–2 cm (annually), 2–3 cm (every 6 months initially). Post-resection surveillance for IPMNs due to recurrence risk.
    • Surgical Indications:
      • MD-IPMN: Resection in surgically fit patients due to high malignancy risk (>60%).
      • BD-IPMN: Surgery for high-risk stigmata (e.g., obstructive jaundice, enhancing mural nodules ≥5 mm, MPD ≥10 mm) or worrisome features (e.g., cyst ≥3 cm, growth >5 mm/year, pancreatitis).
      • MCN: Resection for all MCNs in surgically fit patients, regardless of size, due to malignant potential.
  • Unique Aspects: More aggressive approach for MCNs compared to European guidelines; emphasizes size stratification for BD-IPMN surveillance.

American Gastroenterological Association (AGA) Guidelines (2015)

  • Scope: Focuses on asymptomatic neoplastic PCNs, excluding MD-IPMN, SPN, and cystic neuroendocrine tumors.
  • Formulation: Evidence-based, targeting low-risk lesions.
  • Key Recommendations:
    • Diagnosis: MRI/MRCP preferred for initial evaluation. EUS-FNA only if ≥2 high-risk features (e.g., cyst ≥3 cm, solid component, dilated MPD).
    • Surveillance: Cysts <3 cm without solid components or MPD dilation are monitored with MRI at 1 year, then every 2 years for 5 years. Surveillance may be discontinued if stable.
    • Surgical Indications: Surgery only for cysts with both MPD dilation (≥5 mm) and a solid component, or positive cytology for malignancy.
  • Unique Aspects: Most conservative, prioritizing minimal intervention for asymptomatic cysts. Does not address symptomatic cysts or high-risk lesions like MD-IPMN.

American College of Radiology (ACR) Guidelines (2017)

  • Scope: Focuses on incidental pancreatic cysts, emphasizing imaging-based management.
  • Formulation: Consensus-based, targeting radiologists.
  • Key Recommendations:
    • Diagnosis: MRI/MRCP for detailed cyst characterization, including MPD size, worrisome features, and growth.
    • Surveillance: Cysts <3 cm without worrisome features are followed with MRI every 1–2 years. Growth or high-risk stigmata prompt surgical referral.
    • Surgical Indications: Referral for cysts with interval growth, worrisome features (e.g., mural nodules, MPD dilation), or high-risk stigmata.
  • Unique Aspects: Tailored for radiologists, emphasizes standardized reporting of cyst features.

Hong Kong Consensus Recommendations (2022)

  • Scope: Covers all PCNs, with local adaptations for clinical practice in Hong Kong.
  • Formulation: Consensus-based, using Oxford Centre for Evidence-Based Medicine’s 2011 Levels of Evidence.
  • Key Recommendations:
    • Diagnosis: EUS with needle-based confocal laser endomicroscopy (nCLE) may improve diagnostic accuracy for high-grade dysplasia, though not widely used locally.
    • Surveillance: Lifelong for neoplastic PCNs in surgically fit patients, with intervals based on cyst size and features.
    • Surgical Indications: Worrisome features include cyst size ≥3 cm, MPD 5–9 mm, mural nodules <5 mm, rapid growth (≥5 mm/2 years), pancreatitis, new-onset diabetes, or elevated CA 19-9.
  • Unique Aspects: Highlights emerging technologies like EUS-nCLE, less commonly addressed in other guidelines.

Areas of Consensus

  • High-Risk Features: All guidelines agree on key indicators of malignancy risk, including:
    • Presence of enhancing mural nodules (≥5 mm) or solid components.
    • MPD dilation (≥10 mm for absolute indication; 5–9.9 mm as relative).
    • Positive cytology for malignancy or high-grade dysplasia.
    • Cyst size ≥3–4 cm (threshold varies).
    • Rapid growth (≥5 mm/year).
    • Symptoms like jaundice, acute pancreatitis, or new-onset diabetes.
  • Imaging Modalities: MRI/MRCP is universally preferred for cyst characterization due to its accuracy in assessing cyst-duct communication. EUS-FNA is recommended for evaluating worrisome features.
  • Lifelong Surveillance: For IPMNs and MCNs without high-risk features, lifelong surveillance is advised in surgically fit patients, with intervals based on cyst size and risk.
  • MD-IPMN: High malignancy risk warrants resection in fit patients across all guidelines.
  • SCN: Conservative management is standard due to low malignant potential, unless symptomatic.

Areas of Divergence

  • MCN Management:
    • IAP (Fukuoka): Recommends resection for all MCNs in surgically fit patients, regardless of size, due to malignant potential.
    • European: Suggests conservative management for MCNs <40 mm without high-risk features, with surgery for ≥40 mm or symptomatic cases.
    • AGA/ACG: Aligns with European guidelines, recommending surveillance for MCNs <3 cm without high-risk features.
  • BD-IPMN Surveillance:
    • Fukuoka: Stratifies surveillance by cyst size (<1 cm, 1–2 cm, 2–3 cm) with frequent initial imaging (6–12 months).
    • AGA: Less frequent surveillance (every 2 years for stable cysts <3 cm) and potential discontinuation after 5 years if stable.
  • Surgical Thresholds:
    • AGA: Most conservative, requiring multiple high-risk features (e.g., MPD dilation and solid component) for surgery.
    • European/Fukuoka: Include relative indications like cyst size ≥3–4 cm or growth rate, lowering the surgical threshold.
  • Target Population:
    • AGA: Limited to asymptomatic cysts, excluding MD-IPMN and other high-risk lesions.
    • European/ACG: Broader, covering all PCN types and symptomatic cases.
  • Evidence Base:
    • European: Only guideline using GRADE methodology, emphasizing evidence-based recommendations.
    • Others: Largely consensus-based, with varying incorporation of recent literature.

Diagnostic Approach

  • Imaging: MRI/MRCP is the gold standard for initial evaluation, with CT as an alternative if MRI is contraindicated. EUS is critical for assessing worrisome features like mural nodules or cyst fluid analysis.
  • Cyst Fluid Analysis: EUS-FNA assesses carcinoembryonic antigen (CEA), amylase, and cytology. CEA >192 ng/mL suggests mucinous cysts (MCN/IPMN), though sensitivity for malignancy is low (27–48%).
  • Biomarkers: Serum CA 19-9 (>37 U/mL) may indicate malignancy in IPMNs, but no reliable blood biomarkers differentiate PCN subtypes.

Challenges and Future Directions

  • Guideline Variability: Differences in surgical thresholds and surveillance intervals create clinical confusion. For example, the AGA’s conservative approach may miss some cancers, while Fukuoka’s aggressive stance risks overtreatment.
  • Diagnostic Accuracy: Small cysts (<2 cm) are hard to characterize due to overlapping imaging features. EUS-nCLE shows promise but is not widely available.
  • Surveillance Burden: Lifelong imaging is costly and burdensome. Identifying patients who can safely discontinue surveillance is a research priority.
  • Standardized Terminology: Lack of uniform cytology terminology hinders diagnosis and guideline harmonization.
  • Future Goals: The European Study Group aims for global evidence-based guidelines to unify care and reduce conflicting recommendations.

Clinical Implications

  • Individualized Care: Management requires multidisciplinary teams (gastroenterologists, surgeons, radiologists) to tailor decisions based on cyst type, patient fitness, and guideline recommendations.
  • Risk Stratification: High-risk features (e.g., mural nodules, MPD dilation) prompt immediate action, while low-risk cysts (e.g., SCN, small BD-IPMN) may be monitored.
  • Patient Counseling: Discuss the balance between cancer prevention and surgical risks, especially for asymptomatic cysts with uncertain malignant potential.
International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.

Masao Tanaka, Suresh Chari, Volkan Adsay, Fernandez-Del Carlos Castillo, Massimo Falconi, Michio Shimizu, Koji Yamaguchi, Kenji Yamao, Seiki Matsuno.
Pancreatology. 2006;6(1-2):17-32

International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas.

Masao Tanaka, Carlos Fernández-del Castillo, Volkan Adsay, Suresh Chari, Massimo Falconi, Jin-Young Jang, Wataru Kimura, Philippe Levy, Martha Bishop Pitman, C. Max Schmidt, Michio Shimizu, Christopher L. Wolfgang, Koji Yamaguchi, Kenji Yamao.
Pancreatology. 2012 May-Jun;12(3):183-97

European experts consensus statement on cystic tumours of the pancreas.

Marco Del Chiaroa, Caroline Verbeke, Roberto Salvia, Gunter Klöppel, Jens Werner, Colin McKay, Helmut Friess, Riccardo Manfredi, Eric Van Cutsem, Matthias Löhr, Ralf Segersvärd, the European Study Group on Cystic Tumours of the Pancreas.
Digestive and Liver Disease 45 (2013) 703–711

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms.

Italian Association of Hospital Gastroenterologists and Endoscopists, AIGO Italian Association for the Study of the Pancreas, AISP.
Digestive and Liver Disease 46 (2014) 479–493

American Gastroenterological Association Institute Guideline on the Diagnosis and Management of Asymptomatic Neoplastic Pancreatic Cysts.

Santhi Swaroop Vege, Barry Ziring, Rajeev Jain, Paul Moayyedi, & the Clinical Guidelines Committee.
Gastroenterology 2015;148:819–822

Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas.

Masao Tanaka, Carlos Fernández-del Castillo, Terumi Kamisawa, Jin Young Jang, Philippe Levy, Takao Ohtsuka, Roberto Salvia, Yasuhiro Shimizu, Minoru Tada, Christopher L. Wolfgang.
Pancreatology. 2017 Sep-Oct;17(5):738-753.

European evidence-based guidelines on pancreatic cystic neoplasms The European Study Group on Cystic Tumours of the Pancreas.

The European Study Group on Cystic Tumours of the Pancreas.
Gut 2018;67:789–804

ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts.

Elta, Grace H; Enestvedt, Brintha K; Sauer, Bryan G; Lennon, Anne Marie.
American Journal of Gastroenterology 113(4):p 464-479, April 2018.

International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas.

Takao Ohtsuka, Carlos Fernandez-del Castillo, Toru Furukawa, Susumu Hijioka, Jin-Young Jang, Anne Marie Lennon, Yoshihiro Miyasaka, Eizaburo Ohno, Roberto Salvia, Christopher L. Wolfgang, Laura D. Wood.
Pancreatology 24 (2024) 255e270

Natural History of the Remnant Pancreatic Duct after Pancreatoduodenectomy for Non-Invasive Intraductal Papillary Mucinous Neoplasm: Results from an International Consortium.

Rachel C Kim, Giampaolo Perri, Dario M Rocha Castellanos, Hyesol Jung, Michael J Kirsch, Greg D Sacks, Julie Perinel, Brian Goh, Max Heckler, Thilo Hackert, Mustapha Adham, Christopher Wolfgang, Marco Del-Chiaro, Richard Schulick, Jin-Young Jang, Carlos Fernandez Del Castillo, Roberto Salvia, Giovanni Marchegiani, Eugene P Ceppa, C Max Schmidt, Alex M Roch; <br>Verona EBM Study Group on IPMN.
Annals of Surgery:10.1097/SLA.0000000000006519, September 3, 2024 

Pancreatic Cysts.

Tamas A. Gonda, Djuna L. Cahen, & James J. Farrell.
N Engl J Med 2024;391:832-43.

Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors arising from the neuroendocrine cells of the pancreas. They are distinct from the more common pancreatic adenocarcinoma due to their origin, behavior, and management. Below is a comprehensive overview covering definitions, classifications, and current guidelines based on established medical consensus.

Definitions

  • Pancreatic Neuroendocrine Neoplasia (PanNEN): A broad term encompassing all neoplasms originating from the neuroendocrine cells of the pancreas. These cells are part of the diffuse endocrine system and produce hormones or peptides. PanNENs include both benign and malignant tumors.
  • Pancreatic Neuroendocrine Tumor (PanNET): A subset of PanNENs, specifically well-differentiated neoplasms with neuroendocrine features. PanNETs can be functional (hormone-secreting, causing clinical syndromes) or non-functional (not causing hormonal symptoms).
  • Pancreatic Neuroendocrine Carcinoma (PanNEC): Poorly differentiated, high-grade malignancies with aggressive behavior, often resembling small cell or large cell neuroendocrine carcinomas.

Classification

PanNENs are classified based on histological differentiation, grading, and functionality:
  1. Histological Differentiation (WHO 2022 Classification):
    • Well-differentiated PanNETs: Organized, resemble normal islet cells, and are graded based on proliferation.
    • Poorly differentiated PanNECs: Disorganized, aggressive, with high mitotic rates and necrosis.
  2. Grading (based on Ki-67 proliferation index and mitotic count):
    • G1: Ki-67 <3%, mitotic count <2/10 HPF (low grade).
    • G2: Ki-67 3–20%, mitotic count 2–20/10 HPF (intermediate grade).
    • G3: Ki-67 >20%, mitotic count >20/10 HPF (high grade, but still well-differentiated).
    • PanNEC: Ki-67 typically >20% (often >50%), poorly differentiated.
  3. Functionality:
    • Functional PanNETs: Secrete hormones (e.g., insulin, gastrin, glucagon, VIP) causing syndromes like hypoglycemia (insulinoma) or Zollinger-Ellison syndrome (gastrinoma).
    • Non-functional PanNETs: Do not secrete hormones or cause clinical syndromes; often detected incidentally or due to mass effects.
  4. Staging (AJCC/UICC 8th Edition):
    • Based on tumor size, lymph node involvement, and metastases (TNM system).
    • Common sites of metastasis include liver, lymph nodes, and bones.

Epidemiology

  • Incidence: ~0.8–1 per 100,000 people annually, though increasing due to improved imaging detection.
  • Age: Typically diagnosed in adults (median age ~50–60 years).
  • Associations: ~10–20% of PanNETs are linked to hereditary syndromes like Multiple Endocrine Neoplasia type 1 (MEN1), von Hippel-Lindau (VHL), or neurofibromatosis type 1 (NF1).

Clinical Presentation

  • Functional PanNETs: Symptoms depend on hormone secreted (e.g., insulinoma: hypoglycemia; gastrinoma: peptic ulcers; VIPoma: watery diarrhea).
  • Non-functional PanNETs: Often asymptomatic until large, causing mass effects (e.g., abdominal pain, jaundice, weight loss).
  • PanNECs: Present with aggressive symptoms, often metastatic at diagnosis.

Diagnosis

  1. Imaging:
    • CT/MRI: Preferred for detecting primary tumors and metastases.
    • Somatostatin receptor imaging (e.g., 68Ga-DOTATATE PET/CT): Highly sensitive for well-differentiated PanNETs expressing somatostatin receptors.
    • Endoscopic ultrasound (EUS): Useful for small tumors and biopsy.
  2. Biochemical Markers:
    • Chromogranin A (CgA): Elevated in most PanNENs, though non-specific.
    • Specific hormones (e.g., insulin, gastrin) for functional tumors.
  3. Histopathology:
    • Biopsy confirms diagnosis, assessing differentiation and Ki-67 index.
    • Immunohistochemistry: Positive for neuroendocrine markers (e.g., chromogranin, synaptophysin).

Guidelines and Consensus

Several organizations provide evidence-based guidelines for PanNEN management, including the European Neuroendocrine Tumor Society (ENETS), North American Neuroendocrine Tumor Society (NANETS), and National Comprehensive Cancer Network (NCCN). Key points from the 2023–2025 guidelines:
  1. Diagnosis and Staging:
    • ENETS/NANETS recommend multiphase CT or MRI for initial evaluation, with 68Ga-DOTATATE PET/CT for somatostatin receptor status.
    • EUS-guided biopsy is standard for histological confirmation.
    • Staging follows AJCC/UICC TNM classification.
  2. Management of PanNETs:
    • Localized Disease:
      • Surgery is the primary treatment for resectable G1/G2 PanNETs. Options include enucleation (small tumors), distal pancreatectomy, or pancreaticoduodenectomy (Whipple procedure).
      • Observation may be considered for small (<2 cm), asymptomatic, low-grade non-functional PanNETs, per ENETS/NCCN.
    • Locally Advanced/Metastatic Disease:
      • Somatostatin analogs (SSAs): Lanreotide or octreotide for G1/G2 tumors with somatostatin receptor expression to control symptoms and tumor growth (CLARINET trial).
      • Targeted therapies: Everolimus (mTOR inhibitor) or sunitinib (tyrosine kinase inhibitor) for progressive G1/G2 PanNETs (RADIANT-3, SUNNET trials).
      • Peptide receptor radionuclide therapy (PRRT): 177Lu-DOTATATE for somatostatin receptor-positive, progressive G1/G2 tumors (NETTER-1 trial).
      • Chemotherapy: Limited role in G1/G2; used more in G3 PanNETs (e.g., capecitabine/temozolomide).
    • Liver-directed therapies: Embolization, ablation, or resection for liver metastases.
  3. Management of PanNECs:
    • Aggressive chemotherapy (e.g., cisplatin/etoposide or carboplatin-based regimens) is the mainstay.
    • Poor prognosis, with median survival <12 months.
  4. Functional Tumor Management:
    • SSAs for symptom control (e.g., octreotide for carcinoid syndrome).
    • Specific therapies (e.g., proton pump inhibitors for gastrinomas).
  5. Follow-Up:
    • ENETS/NCCN recommend lifelong surveillance for PanNETs due to recurrence risk, with imaging and biomarkers every 3–12 months based on grade and stage.
  6. Hereditary Syndromes:
    • Screening recommended for MEN1, VHL, etc., with annual imaging and biochemical tests starting in adolescence (ENETS).

Consensus Updates (2023–2025)

  • ENETS 2023 Guidelines: Emphasize risk stratification for small, non-functional PanNETs, supporting active surveillance for tumors <2 cm in low-risk patients.
  • NANETS 2024 Consensus: Highlights PRRT as a standard for progressive G1/G2 PanNETs and clarifies the role of adjuvant therapy post-resection (minimal benefit in G1/G2).
  • NCCN 2025 Guidelines: Updated to include capecitabine/temozolomide as a preferred regimen for G3 PanNETs based on recent trials showing improved response rates.
  • Molecular Profiling: Emerging role of genetic testing (e.g., DAXX/ATRX, MEN1 mutations) to guide prognosis and therapy, though not yet standard in routine practice.

Prognosis

  • PanNETs: 5-year survival varies widely: ~90% for G1, ~60–70% for G2, ~30–50% for G3.
  • PanNECs: Poor prognosis, with 5-year survival <10%.
  • Factors: Grade, stage, resection status, and somatostatin receptor expression.

Challenges and Future Directions

  • Limited data on optimal sequencing of therapies for metastatic PanNETs.
  • Ongoing trials exploring immunotherapy (e.g., PD-1 inhibitors) in PanNECs, though responses are limited.
  • Need for biomarkers to predict treatment response and guide personalized therapy.

For further details, refer to:

  • ENETS guidelines (www.enets.org) (www.enets.org)
  • NCCN guidelines (www.nccn.org) (www.nccn.org)
  • NANETS consensus (www.nanets.net) (www.nanets.net)
ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary.

Marianne Pavel; Eric Baudin; Anne Couvelard; Eric Krenning; Kjell Öberg; Thomas Steinmüller; Martin Anlauf; Bertram Wiedenmann; Ramon Salazar; all other Barcelona Consensus Conference participants.
Neuroendocrinology 2012;95:157–176

ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes.

Robert T. Jensen; Guillaume Cadiot; Maria L. Brandi; Wouter W. de Herder; Gregory Kaltsas; Paul Komminoth; Jean-Yves Scoazec; Ramon Salazar; Alain Sauvanet; Reza Kianmanesh; all other Barcelona Consensus Conference participants.
Neuroendocrinology 2012;95:98–119

ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors.

M. Falconi; B. Eriksson; G. Kaltsas; D.K. Bartsch; J. Capdevila; M. Caplin; B. Kos-Kudla; D. Kwekkeboom; G. Rindi; G. Klöppel; N. Reed; R. Kianmanesh; R.T. Jensen; all other Vienna Consensus Conference participants.
Neuroendocrinology 2016;103:153–171

Treatment of metastatic pancreatic neuroendocrine tumors: relevance of ENETS 2016 guidelines.

Margaux Foulfoin, Emmanuelle Graillot, Mustapha Adham, Pascal Rousset, Julien Forestier, Valérie Hervieu, Philip Robinson, Jean-Yves Scoazec,Catherine Lombard-Bohas & Thomas Walter.
Endocrine-Related Cancer (2017) 24, 71–81

European Neuroendocrine Tumour Society (ENETS) 2023 guidance paper for nonfunctioning pancreatic neuroendocrine tumours.

Beata Kos-Kudła, Justo P Castaño, Timm Denecke, Enrique Grande, Andreas Kjaer, Anna Koumarianou, Louis de Mestier, Stefano Partelli, Aurel Perren Stefan Stättner, Juan W Valle, Nicola Fazio.
J Neuroendocrinol. 2023;35:e13343.

Neoadjuvant 177Lu-DOTATATE for non-functioning pancreatic neuroendocrine tumours (NEOLUPANET): multicentre phase II study.

Stefano Partelli, Luca Landoni, Mirco Bartolomei, Alessandro Zerbi, Chiara Maria Grana, Ugo Boggi, Giovanni Butturini, Riccardo Casadei10, Roberto Salvia and Massimo Falconi.
BJS, 2024, Vol. 111, No. 9

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This page is designed only for learning support purposes.
It is not dedicated for any medical use or patient care.
HBPSurG makes no claims of the accuracy of the information contained herein.​

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