The Differential Diagnosis and Management of Pancreatic Cystic Neoplasms

Background: The prevalence of pancreatic cyst lesions in the general population worldwide is 16%. The majority of these cysts are intraductal papillary mucinous neoplasms (IPMN), which are associated with a risk of developing pancreatic cancer. In this article, we summarize the current knowledge of the differential diagnosis and management of cystic pancreatic neoplasms.

Methods: This narrative review is based on a selective search for pertinent literature (1 January 2014 to 9 January 2025).

Results: Most cysts are less than 10 mm in diameter and have practically no potential for malignant transformation. If a small cyst remains unchanged in the absence of risk factors, monitoring can be ended five years after initial detection. Magnetic resonance imaging (MRI) is the best method of characterizing and following up such lesions. If the diagnosis is unclear, endosonography should be performed. For IPMN, the most common type of pancreatic cystic neoplasm, the international Kyoto guideline 2024 contains a revised management algorithm based on risk factors. IPMN with high-grade dysplasia is an ideal indication for surgical resection. Serous cystic adenomas should generally not be operated on, and mucinous cystic neoplasia or a cystic neuroendocrine tumor of the pancreas should be operated on only if it has reached a certain size. Minimally invasive and parenchyma-sparing techniques are now being increasingly used in pancreatic surgery.

Conclusion: Oncological criteria as well as potential surgical risks and long-term sequelae must enter into the decision whether a pancreatic lesion should be resected. Exocrine and endocrine insufficiency are relevant and sometimes irreversible complications.

Cite this as Schmitz D, Stenzinger A, Grützmann R, Esposito I, Raatschen HJ, Seufferlein TTW: The differential diagnosis and management of pancreatic cystic neoplasms. Dtsch Arztebl Int 2025; 122: 617–22. DOI: 10.3238/arztebl.m2025.0151

Most cystic lesions of the pancreas are nowadays identified as incidental findings on cross-sectional imaging (1). Some of these cysts are mucin-producing neoplasms, such as intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs); these cysts are associated with a risk of malignant transformation into pancreatic cancer (2). In 2024, the Kyoto guidelines were published (3), in which the risk factors for malignant transformation were modified in terms of known high-risk stigmata (HRS) and worrisome features (WFs). The aim of this narrative review is to summarize and evaluate the new insights gained in recent years regarding the differential diagnosis and management of pancreatic cystic neoplasms in an interdisciplinary discourse.

Methods

This review is based on a selective search in PubMed, Web of Science, ScienceDirect, EBSCO, and Google Scholar performed by a qualified librarian. The following MeSH search terms were used: “pancreatic cyst“ OR “pancreatic cyst lesion“ OR “pancreatic pseudocyst“ OR “serous cystadenoma“ OR “mucinous cyst neoplasm“ OR “pancreatic intraductal neoplasms“. The search was limited to studies, case reports, reviews, and guideline publications in German and English and retrieved 2594 publications (1 January 2014 to 9 January 2025). A further selection of publications was made with a focus on topics of relevance to clinical practice.

Results

Prevalence of pancreatic cystic lesions

A recently published meta-analysis of 15 studies with a total of 65 607 participants found a global prevalence of magnetic resonance imaging-detected pancreatic cystic lesions in the general population of 16% (95% confidence interval: [13%; 18%]) (1). Multiple lesions with 3.9 [3.2; 4.5] cysts per individual on average are the most common presentation of the condition (4). The prevalence of pancreatic cystic lesions does not differ significantly between the sexes. Among individuals under 50 years of age, the prevalence was found to be significantly lower (2%) and increased by 2.2 times among those aged 50 to 59 and by 13.8 times among those aged 80 and older (1). The vast majority of pancreatic cystic lesions measured less than 10 mm in diameter and the associated risk of malignant transformation was very low (5).

Types and prevalences of pancreatic cystic neoplasms

The prevalence rates of the various cystic entities in the general population can only be estimated, as confirmation of the exact diagnosis can only be obtained through histological examination of the surgical specimen, and the diagnostic accuracy of cross-sectional imaging techniques, such as endoscopic ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI), or a combination of these techniques, reaches at most 84% concordance with the surgical histology findings (6). Histological examination of small pancreatic cysts measuring 1–27 mm in diameter in autopsied elderly patients found normal cystic epithelium in 40.9% and 47.5% of cases (7, 8) and changes typically seen with IPMN of the branch duct type in 49.2% of cases; thus, it is reasonable to assume that a significant proportion of the lesions incidentally discovered in cross-sectional imaging have no or only a very low potential for malignant transformation. In a sample of surgical patients with pancreatic cystic neoplasms of a high-volume hospital for pancreatic surgery, the leading diagnoses were main duct and branch-duct IPMNs, found in 61% of the surgical specimens, followed by MCN and serous cystadenoma (SCA) (each with 10%,) cystic pancreatic neuroendocrine tumor (pNET) (9%), and the rare solid pseudopapillary neoplasm of the pancreas (SPN) (4%) (9). For reasons of space, this review article cannot discuss very rare pancreatic cystic lesions in detail, but only make reference to them. Examples of these uncommon lesions include intraductal tubulopapillary neoplasm (ITPN) with little mucin formation und usually favorable tumor biology, which was first described only 20 years ago and has to be distinguished from main-duct IPMN, as well as acinar cell cystadenoma and lymphangioma (10).

Definitions of pathological terms

For the histopathological classification of the grade of dysplasia of an IPMN, the terms low-grade dysplasia (LGD), which now also includes intermediate grade dysplasia (= borderline dysplasia), high-grade dysplasia (HGD) and invasive carcinoma (IC) should be used (3). IPMNs are classified into three morphological subtypes of prognostic significance: gastric, intestinal and pancreatobiliary (3, 11). The rare, so-called oncocytic subtype is no longer classified as an IPMN, but as intraductal oncocytic papillary neoplasm (IOPN) (12). If an IPMN is present alongside a pancreatic carcinoma, then it is either a pancreatic carcinoma that has developed from the IPMN or a concomitant carcinoma. The latter seems to be associated with a ductal field effect of IPMN which is not yet fully understood and which may involve the entire pancreas. Histologically, IPMN-associated carcinoma is again differentiated into a tubular type with a less favorable prognosis and a colloidal type with a more favorable prognosis. Cytopathologic reporting of specimens typically obtained by endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) should follow the updated recommendations of the World Health Organization, introducing a seven-tiered system of diagnostic categories (eTable 1; cytology examples in eFigure 1) (13). More invasive sampling techniques, such as fine needle biopsy (EUS-FNB) or microforceps biopsy can be useful for diagnosis, in particular in the case of larger cysts, while taking into account an increased risk of complications.

eFigure 1

Typical (Papanicolaou-stained) cytology images of a gastric IPMN, low-grade (category 4), a high-grade mucinous cystic neoplasm (category 5), a cytology suspicious of malignancy (category 6), and a pancreatic ductal adenocarcinoma (category 7). The cytology images were created with kind assistance from Dr. Gerlinde Schumann (Institute of Pathology at the Heinrich Heine University Düsseldorf).

eTable 1

Current WHO recommendation (13) on pancreaticobiliary cytopathology reporting

Pancreatic cystic neoplasms and potential of malignant transformation

It is considered well established that serous cystadenoma hardly ever undergo malignant transformation (0.1%) and are usually only operated on if the preoperative diagnosis could not be confirmed or if patients experience SCA-related symptoms (14). MCNs occur almost exclusively in middle-aged women and are typically located in the body or tail of the pancreas. According to a meta-analysis of 52 observational studies with a total of 2050 patients, the proportion of persons with HGD or invasive carcinoma in resected small MCNs, measuring less than 4 cm in diameter, was only 0.03% (15); consequently, the 2018 European Guideline already recommended to monitor MCNs smaller than 4 cm in size without signs of invasive growth or HGD instead of treating them surgically (16).

For branch-duct IPMN, the presumably most common neoplastic pancreatic cyst entity, a meta-analysis of observational studies found for cysts without risk factors a cumulative incidence of invasive carcinomas of 0.02%, 1.40% and 7.77% after one year, three years and ten years, respectively. In the presence of risk factors, the incidence rates of invasive carcinoma were significantly higher, with 1.95%, 5.69% and 24.68% after one year, three years and ten years, respectively (17).

For this reason, the current recommendations of the Kyoto guideline from 2024 (3) further specified risk factors for malign transformation to select precisely those patients with IPMN and a high risk of HGD or early invasive carcinoma who should undergo surgery (Figure 1). The immediate recommendation for surgery for persons with IPMN and a main duct dilation of 5 mm or more is (still) largely undisputed, as in 49%–59% of cases invasive carcinomas or HGD were detected (16). The risks of malignant transformation and the respective recommendations for surgical treatment for cystic pNET and SPN can be found in Table 1.

Figure 1

Algorithm of the international evidence-based Kyoto guideline 2024 for the management of (presumed) intraductal papillary mucinous neoplasms (IPMN) of the pancreas. CA 19–9, tumor marker carbohydrate antigen 19–9

Table 1

Pancreatic cystic neoplasms with respective risk of malignant transformation and recommendation on surgery

Diagnosis

The gold standard of non-invasive diagnosis of pancreatic cystic neoplasms is MRI because of its excellent contrast resolution for soft tissue and fluid detection on T2-weighted images (3, 16). Endoscopic ultrasound offers the advantage of superior image resolution, but this is partly offset by the examiner dependence of the method and, above all, by the need for sedation of the patient during the examination. CT follow-up examinations should be avoided for reasons of radiation protection; for simple cysts, abdominal ultrasound can be used for surveillance. Branch-duct IPMN or main-duct IPMN is always suspected if the cyst communicates with a branch duct or in the presence of main pancreatic duct dilatation ≥ 5 mm in the absence of a mechanical obstruction (3). Of particular clinical significance in the differential diagnosis is the distinction between of a pancreatic cystic neoplasm and a pseudocyst or main pancreatic duct dilation as a result of pancreatitis. If the diagnosis of the cystic entity remains uncertain based on MRI findings or if IPMN-associated risk characteristics cannot be reliably ruled out in imaging (Figure 1), it is advisable to perform an endoscopic ultrasound, which can also be combined with the administration of a contrast agent or fine needle aspiration of the cyst or duct fluid (20). In addition to the cytological/histological analysis of the aspirate, which is often unusable due to the low content of viable cells, cystic fluid biomarkers (eMethods) can be used to identify the cystic entity. However, DNA sequencing analysis suitable for this purpose is currently only offered in Germany in the setting of studies (22, 26). Table 2 shows the characteristics of the four types of cysts of greatest differential diagnostic relevance in clinical practice (image examples in eFigure 2).

Table 2

Differential diagnostic characteristics of the four most common pancreatic cystic lesions with cystic fluid analysis

eFigure 2

Typical imaging findings of the four most common cystic pancreatic lesions from Table 1 (Institute of Radiology, Helios Kliniken Schwerin). a) Multifocal branch-duct IPMN (intraductal papillary mucinous neoplasm) in magnetic resonance cholangiopancreatography (MRCP); b) Post-pancreatic pseudocyst in the transverse image of computed tomography; c) Oligocystic serous cystadenoma in T2-weighted transverse image of magnetic resonance imaging; d) Mucinous cystic neoplasm (arrow) with eggshell calcification (triangle) in transverse image of computed tomography

Surveillance versus surgery

While the recommendations for the management of pancreatic cystic neoplasms not classified as IPMN can be formulated simply and clearly (Table 1), the management of IPMN in general and in particular of branch-duct IPMN remains complex. We now know that in the majority of branch-duct IPMNs, patients can be managed with surveillance alone. A multicenter study involving 3844 patients found that in patients with presumed branch-duct IPMN who had not developed risk features after five years of surveillance, the risk of developing pancreatic cancer was almost identical to that in the general population. Therefore, surveillance discontinuation may be considered in patients older than 75 years with cysts <30 mm and in patients 65 years or older who have cysts ≤ 15 mm if they have not developed risk factors (27).

The updated Kyoto guideline 2024 provides detailed information on the recommended management of presumed IPMN with risk factors, which are further differentiated into “high-risk stigmata” and “worrisome features“ (Figure 1). Of particular note is that new onset or deterioration of diabetes mellitus is now considered a “worrisome feature.” According to a new multicenter study, a higher cut-off value of ≥ 133 kU/L should be chosen for the risk feature “increased serum tumor marker CA 19–9“ to avoid unnecessary surgery due to false positive results (28). In addition, it has now been shown that multiple worrisome features, compared to a single one, (eTable 2) result in an additive increase in the risk of malignant transformation (HGD/invasive carcinoma); thus, a stronger recommendation for surgery may be made in this case. In contrast to the absolute or relative resection recommendations of the European guideline (16), the international Kyoto guideline emphasizes that when determining the indication for surgery, the general condition, comorbidity, life expectancy of the often elderly patients, and patient preference should always be taken into account (3).

eTable 2

Sensitivity and specificity of high-risk stigmata and worrisome features of the international Kyoto guideline 2024 (3) with regard to the identification of advanced IPMNs (HGD or invasive carcinoma)

Surgical resection and possible consequences of surgery

In cases of cystic findings suspicious for malignancy or confirmed to be malignant, oncological resection with lymphadenectomy is performed, as in the treatment of pancreatic cancer. Parenchyma-sparing pancreatic resection techniques, such as enucleation, spleenpreserving distal left-sided pancreatic resection or duodenum-preserving pancreatic head resection, are used with the aim to preserve as much functional pancreatic tissue as possible, thereby conserving endocrine and exocrine function (37). In tumors located close to the main pancreatic duct, enucleation is associated with a markedly increased rate of pancreatic fistula formation and should thus be avoided. Only if at the time of resection, the probability of invasive carcinoma is low, a parenchyma-sparing resection should be performed (3). This usually applies to serous cystadenoma (which only requires pancreatic resection in very rare symptomatic cases), small cystic pancreatic neuroendocrine tumors, small MCNs, and occasionally also to solid pseudopapillary tumors (Table 2). IPMN with HGD would also be the ideal indication for parenchyma-sparing pancreatic resection (Figure 2), if it can achieve complete (R0) resection. However, this diagnosis is (as yet) difficult to establish preoperatively based on imaging studies alone and accounted for only 12.3% of resected IPMNs in a large retrospective surgical study, while 57.8% of patients diagnosed with IPMN with LGD according to the current definition may have undergone surgery too early or unnecessarily (38). If intraoperative frozen-section analysis finds LGD at the resection margin, no re-resection is required, in contrast to cases with HGD and invasive carcinoma (3). Multifocality of branch-duct IPMN is common and does not increase the risk of malignant transformation (3); in this situation, the high-risk lesion is resected, but total pancreatectomy should be avoided. In pancreatic surgery, the superiority of a minimally invasive (laparoscopic or robot-assisted) approach over an open approach has not yet been demonstrated with regard to oncological outcomes, yet meta-analyses and retrospective studies have shown advantages, such as reduced perioperative morbidity (39) and shorter lengths of hospital stay (40).

Figure 2

Branch-duct IPMN with high-grade dysplasia, measuring 50 mm in diameter, (*) located in the area of the uncinate process of pancreas. a): MRCP image; b): surgical resection specimen obtained by robot-assisted enucleation used for parenchyma-sparing resection; MRCP, magnetic resonance cholangiopancreatography

Apart from oncological criteria, potential functional long-term consequences of the procedure should be taken into account when making the decision to perform pancreatic resection. Both exocrine and endocrine insufficiency are relevant and sometimes irreversible complications of the operation; they depend on the extent of the resection and the volume of the residual pancreatic parenchyma. After oncological pancreatic head resection, new-onset diabetes and exocrine pancreatic insufficiency can be expected in 14.5–15.5% and 25.2–49.1% of patients who underwent the procedure, respectively (e1). Endocrine or exocrine pancreatic insufficiency is less likely to occur after parenchyma-sparing surgery. Complications such as pancreatic fistulas, secondary bleeding, wound healing disorders, or delayed gastric emptying account for most of the surgery-associated morbidity. In a 2018 study analyzing Germany-wide inpatient data, in-hospital mortality after major pancreatic resections was 6.1–7.5% in high-volume centers and thus significantly lower than in hospitals with a smaller number of cases (e2).

Follow-up care

Patients with IPMN with invasive carcinoma should receive the same follow-up care as patients with pancreatic cancer (3); however, this management strategy does not offer any proven survival advantage. The 5-year survival rates after resection of IPMN with LGD and HGD are 87.5% and 77.8%, respectively (e3). As the risk of developing a clinically relevant neoplastic lesion in the residual pancreas is 10% [0%; 21%], these patients should be offered lifelong follow-up (3).

Conclusions

While pancreatic cystic lesions are revealed by MRI in 16% of adults, only a small percentage of these have the potential for malignant transformation. The vast majority of the cysts are small dilated branch ducts, which are likely to largely represent neoplastic branch-duct IPMNs. Whether the clinical course of all patients with pancreatic cystic lesions should be monitored remains unclear. If a cyst without risk factors (as defined in the guideline) remains stable on imaging over a period of five years, surveillance can be stopped, depending on patient age and size of the cyst.

The gold standard for diagnosis is MRI using magnetic resonance cholangiopancreatography (MRCP). If the entity of the cyst or risk features are unclear, endoscopic ultrasound can be performed in addition; for this examination, however, the patient undergoing the scan needs to be sedated. The fluid obtained by endoscopic ultrasound–guided fine needle aspiration from the pancreatic cyst or pancreatic duct can be used to determine the entity of the cyst; however, the test is not (yet) included as a standard test in the diagnostic algorithm. The current international Kyoto guideline has further differentiated the recommendations on surveillance and resection of presumed IPMN, the by far most common type of pancreatic cystic neoplasm, to avoid over- or under-treatment. IPMN with HGD would be the ideal tumor stage for surgical resection; however, this condition can only rarely be diagnosed preoperatively as yet. In differential diagnostic workup, both pancreatitis-related pancreatic changes and pancreatic serous cystadenomas must be ruled out; these lesions usually do not require surgical treatment. MCN and cystic pancreatic NET should only be resected if they exceed a certain size. There is a clear recommendation on parenchyma-sparing pancreatic resections for all pancreatic cystic lesions with presumed LGD or HGD and no nodal involvement. In the case of invasive carcinoma, pancreatic cystic neoplasm is treated surgically in the same way as pancreatic cancer. Due to the advantages they offer with regard to perioperative morbidity and faster postoperative recovery, minimally invasive surgical techniques, such as laparoscopic or robot-assisted pancreatic resection, have become the new standard of care in pancreatic surgery. Perioperative morbidity and mortality should be communicated in a transparent way when making individual treatment decisions and in particular during discussions with patients to ensure a well-founded risk-benefit assessment.

Conflict of interest statement

IE received travel expense support from ESP, EPC and the International Academy of Pathology. She is a member of the advisory board ESP, EPC and the International Academy of Pathology DGP and contributes to the development of the Global IPMN Guidelines as well as the S3-level clinical practice guidelines Pancreatic Cancer.

The remaining authors declare no conflict of interest.

Manuscript received on 24 February 2025, revised version accepted on 18 August 2025

Translated from the original German by Ralf Thoene, M.D.

Corresponding author
Dr. med. Daniel Schmitz

References

1. Vilela A, Quingalahua E, Vargas A, et al.: Global prevalence of pancreatic cystic lesions in the general population on magnetic resonance imaging: A systematic review and meta-analysis. Clin Gastroenterol Hepatol 2024; 22: 1798–1809.e6.

2. Singhi AD, Koay EJ, Chari ST, Maitra A: Early detection of pancreatic cancer: Opportunities and challenges. Gastroenterology 2019; 156: 2024–40.

3. Ohtsuka T, Fernandez-Del Castillo C, Furukawa T, et al.: International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas. Pancreatology 2024; 24: 255–70.

4. Kromrey ML, Bülow R, Hübner J, et al.: Prospective study on the incidence, prevalence and 5-year pancreatic-related mortality of pancreatic cysts in a population-based study. Gut 2018; 67: 138–45.

5. Ciprani D, Weniger M, Qadan M, et al.: Risk of malignancy in small pancreatic cysts decreases over time. Pancreatology 2020; 20: 1213–7.

6. Jang DK, Song BJ, Ryu JK, et al.: Preoperative diagnosis of pancreatic cystic lesions: The accuracy of endoscopic ultrasound and cross-sectional imaging. Pancreas 2015; 44: 1329–33.

7. Kimura W, Nagai H, Kuroda A, Muto T, Esaki Y: Analysis of small cystic lesions of the pancreas. Int J Pancreatol 1995; 18: 197–206.

8. Matsuda Y, Kimura W, Matsukawa M, et al.: Association between pancreatic cystic lesions and high-grade intraepithelial neoplasia and aging: An autopsy study. Pancreas 2019; 48: 1079–85.

9. Roldán J, Harrison JM, Qadan M, et al.: Evolving trends in pancreatic cystic tumors: A 3-decade single-center experience with 1290 resections. Ann Surg 2023; 277: 491–7.

10. Esposito I, Häberle L, Yavas A, Kraft A, Gaida MM: Intraduktale Pankreasneoplasien [Intraductal neoplasms of the pancreas]. Pathologe 2021; 42: 472–83.

11. Distler M, Kersting S, Niedergethmann M, et al.: Pathohistological subtype predicts survival in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg 2013; 258: 324–30.

12. Basturk O, Tan M, Bhanot U, et al.: The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes. Mod Pathol 2016; 29: 1058–69.

13. Pitman MB, Centeno BA, Reid MD, et al. The World Health Organization Reporting System for Pancreaticobiliary Cytopathology. Acta Cytol. 2023; 67: 304–320. doi:10.1159/000527912.

14. Jais B, Rebours V, Malleo G, et al.: Serous cystic neoplasm of the pancreas: A multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European study group on cystic tumors of the pancreas). Gut 2016; 65: 305–12.

15. Servin-Rojas M, Fong ZV, Fernandez-Del Castillo C, et al.: Identification of high-risk features in mucinous cystic neoplasms of the pancreas. Surgery 2023; 173: 1270–4.

16. European study group on cystic tumours of the pancreas. European evidence-based guidelines on pancreatic cystic neoplasms. Gut 2018; 67: 789–804.

17. Choi SH, Park SH, Kim KW, Lee JY, Lee SS: Progression of unresected intraductal papillary mucinous neoplasms of the pancreas to cancer: A systematic review and meta-analysis. Clin Gastroenterol Hepatol 2017; 15: 1509–20.e4.

18. Ventin M, Arya S, Cattaneo G, et al. Clinicopathological characteristics and long-term outcomes of cystic vs. solid pancreatic neuroendocrine tumors: a multi-institutional experience with 1727 patients. Ann Surg. Published online 9 January, 2025. doi:10.1097/SLA.0000000000006624

19. Liu Q, Dai M, Guo J, et al.: Long-term survival, quality of life, and molecular features of the patients with solid pseudopapillary neoplasm of the pancreas: A retrospective study of 454 cases. Ann Surg 2023; 278: 1009–17.

20. Kitano M, Yoshida T, Itonaga M, Tamura T, Hatamaru K, Yamashita Y: Impact of endoscopic ultrasonography on diagnosis of pancreatic cancer. J Gastroenterol 2019; 54: 19–32.

21. Singhi AD, McGrath K, Brand RE, et al.: Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia. Gut 2018; 67: 2131–41.

22. Schmitz D, Volckmar D, Stenzinger A, et al.: KRAS/GNAS-testing by highly sensitive deep targeted next generation sequencing improves the endoscopic ultrasound-guided workup of suspected mucinous neoplasms of the pancreas. Genes Chromosomes Cancer 2021; 60: 489–97.

23. Paniccia A, Polanco PM, Boone BA, et al.: Prospective, multi-institutional, real-time next-generation sequencing of pancreatic cyst fluid reveals diverse genomic alterations that improve the clinical management of pancreatic cysts. Gastroenterology 2023; 164: 117–133.e7.

24. Faias S, Cravo M, Chaves P, Pereira L: Comparative analysis of glucose and carcinoembryonic antigen in the diagnosis of pancreatic mucinous cysts: A systematic review and meta-analysis. Gastrointest Endosc 2021; 94: 235–47.

25. Pflüger MJ, Jamouss KT, Afghani E, et al.: Predictive ability of pancreatic cyst fluid biomarkers: A systematic review and meta-analysis. Pancreatology 2023; 23: 868–77.

26. Haeberle L, Schramm M, Goering W, et al.: Molecular analysis of cyst fluids improves the diagnostic accuracy of pre-operative assessment of pancreatic cystic lesions. Sci Rep 2021; 11: 2901.

27. Marchegiani G, Pollini T, Burelli A, et al.: Surveillance for presumed BD-IPMN of the pancreas: Stability, size, and age identify targets for discontinuation. Gastroenterology 2023; 165: 1016–24.e5.

28. Levink IJM, Jaarsma SC, Koopmann BDM, et al.: The additive value of CA19.9 monitoring in a pancreatic cyst surveillance program. United European Gastroenterol J 2023; 11: 601–11.

29. Del Chiaro M, Beckman R, Ateeb Z, et al.: Main duct dilatation is the best predictor of high-grade dysplasia or invasion in intraductal papillary mucinous neoplasms of the pancreas. Ann Surg 2020; 272: 1118–24.

30. Xu JH, Ni CY, Zhuang YY, et al.: Acute pancreatitis in intraductal papillary mucinous neoplasm: A single-center retrospective cohort study with systematic review and meta-analysis. BMC Gastroenterol 2023; 23: 424.

31. Pergolini I, Schorn S, Jäger C, et al.: Diabetes mellitus in intraductal papillary mucinous neoplasms: A systematic review and meta-analysis. Surgery 2021; 169: 411–8.

32. Scheiman JM, Hwang JH, Moayyedi P: American gastroenterological association technical review on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015; 148: 824–48.e22.

33. Marchegiani G, Andrianello S, Borin A, et al.: Systematic review, meta-analysis, and a high-volume center experience supporting the new role of mural nodules proposed by the updated 2017 international guidelines on IPMN of the pancreas. Surgery 2018; 163: 1272–9.

34. Iwaya H, Hijioka S, Mizuno N, et al.: Usefulness of septal thickness measurement on endoscopic ultrasound as a predictor of malignancy of branched-duct and mixed-type intraductal papillary mucinous neoplasm of the pancreas. Dig Endosc 2019; 31: 672–81.

35. Zhao W, Liu S, Cong L, Zhao Y: Imaging features for predicting high-grade dysplasia or malignancy in branch duct type intraductal papillary mucinous neoplasm of the pancreas: A systematic review and meta-analysis. Ann Surg Oncol 2022; 29: 1297–312.

36. Akahoshi K, Ono H, Akasu M, et al.: Rapid growth speed of cysts can predict malignant intraductal mucinous papillary neoplasms. J Surg Res 2018; 231: 195–200.

37. Brunner M, Grützmann R: Zystische Pankreastumoren [Pancreatic cystic neoplasms]. Chirurgie (Heidelb) 2024; 95: 939–52.

38. Tjaden C, Sandini M, Mihaljevic AL, et al.: Risk of the watch-and-wait concept in surgical treatment of intraductal papillary mucinous neoplasm. JAMA Surg 2021; 156: 818–25.

39. Chen L, Xia N, Wang Z, Junjie X, Tian B. Minimally invasive versus open total pancreatectomy: a systematic review and meta-analysis. Int J Surg. 2023; 109: 2058–69. doi:10.1097/JS9.0000000000000392

40. Uijterwijk BA, Wei K, Kasai M, et al.: Minimally invasive versus open pancreatoduodenectomy for pancreatic ductal adenocarcinoma: Individual patient data meta-analysis of randomized trials. Eur J Surg Oncol 2023; 49: 1351–61.

e1. Beger HG, Poch B, Mayer B, Siech M: New onset of diabetes and pancreatic exocrine insufficiency after pancreaticoduodenectomy for benign and malignant tumors: A systematic review and meta-analysis of long-term results. Ann Surg 2018; 267: 259–70.

e2. Krautz C, Nimptsch U, Weber GF, Mansky T, Grützmann R: Effect of hospital volume on in-hospital morbidity and mortality following pancreatic surgery in Germany. Ann Surg 2018; 267: 411–17.

e3. Vaalavuo Y, Vornanen M, Ahola R, et al.: Long-term (10-year) outcomes and prognostic factors in resected intraductal papillary mucinous neoplasm tumors in Finland: A nationwide retrospective study. Surgery 2023; 174: 75–82.