EBGH commenta la review: “Surgical indications and management of pancreatic cystic neoplasms” (Best Practice & Research Clinical Gastroenterology, Vol. 81), che propone una lettura critica delle linee guida internazionali sulle PCN e del loro impatto nella pratica clinica quotidiana. Il lavoro del gruppo di Padova integra fattori di rischio oncologico (mural nodules, dilatazione del dotto principale, dimensioni della cisti), comorbidità e fragilità del paziente per definire la “finestra terapeutica” ottimale, riducendo sia il rischio di mancata resezione di lesioni ad alto rischio sia l’overtreatment di cisti benigne. Una sintesi estremamente utile per team multidisciplinari (gastroenterologi, radiologi, chirurghi, oncologi) chiamati a decidere tra sorveglianza strutturata e chirurgia pancreatica maggiore in un setting di crescente incidenza di cisti incidentali.

A cura di: Riccardo Pellegrini, Giampaolo Perri, Giovanni Marchegiani

#EBGH #BestPractice #Pancreas #CistiPancreatiche #ChirurgiaPancreatica #Gastroenterologia #EvidenceBased

Riccardo Pellegrini, Giampaolo Perri, Giovanni Marchegiani

NDR: SI TRATTA DI UN MAGNIFICO NUMERO DI BEST PRACTICE. MERITO DEI NUOVI EDITOR, FACCIORUSSO E MACHICADO. GRAZIE ANTONIO!

https://www.sciencedirect.com/journal/best-practice-and-research-clinical-gastroenterology/vol/81/suppl/C

Abstract

In recent years, the detection of pancreatic cystic neoplasms (PCNs) has significantly increased, revealing a spectrum of biologically distinct entities with widely variable malignant potential. In this complex and heterogeneous landscape, a multidisciplinary approach is essential not only to correctly identify lesions at risk of malignancy, but also to determine their appropriate therapeutic window, avoiding unnecessary resections of benign cysts while ensuring timely intervention before progression to invasive cancer. Despite the development of several guidelines worldwide, the rates of misdiagnosis and overtreatment remain high across all cysts subtypes, raising concerns about the appropriateness of current surgical indications. This is particularly relevant in the context of incidental detection of small cysts due to the widespread use of cross-sectional imaging. This review critically examines the current evidence and limitations in the surgical management of PCNs, highlighting the need for improved risk stratification tools and more individualized treatment strategies.

1. Introduction

With the widespread use of cross-sectional imaging, pancreatic cystic neoplasms (PCNs)—once regarded as rare lesions—are now increasingly recognized as common incidental findings [1]. Their estimated prevalence ranges from 16 % to 49 % in the general population and increases markedly with age, especially after the fifth decade of life [2]. This growing detection rate has raised several important questions about optimal management strategies, as—despite being grouped under the same diagnostic family—these entities display distinct biological behaviors with significant clinical implications. Although more than 20 types of epithelial and non-epithelial pancreatic cysts have been identified, in clinical practice the vast majority falls into four main histologic categories: intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), serous cystic neoplasms (SCNs), and solid pseudopapillary neoplasms (SPNs) [3].

IPMNs and MCNs account for approximately 90 % of incidentally discovered PCNs and are particularly relevant due to their well-established malignant potential [4]. Therefore, surgical resection with negative margins—ideally performed prior to progression to invasive carcinoma—has long been considered the only effective strategy to prevent pancreatic ductal adenocarcinoma (PDAC). This paradigm historically supported a liberal approach to surgical management [5,6]. However, mounting evidence has shown that most mucinous cysts follow an indolent course, prompting a shift toward surveillance strategies in appropriately selected patients[[7], [8], [9]]. In contrast, SCNs are considered almost universally benign and do not require surgery unless truly symptomatic [10], while SPNs are defined by the 2019 World Health Organization (WHO) classification [3] as low-grade malignant tumors, for which surgical resection is to date always recommended, regardless of size or symptoms [7].

Given these significant differences in malignant potential, accurate preoperative characterization is essential to guide individualized clinical decision-making. Yet, despite advancements in imaging and diagnostics, preoperative accuracy remains limited—even in high-volume centers—with overtreatment rates up to 30 % of cases [11]. In this review, we critically examine the current evidence and ongoing limitations in the surgical management of the four most common cystic neoplasms of the pancreas.

2. Intraductal Papillary Mucinous Neoplasms (IPMNs)

IPMNs are the most common cystic lesions of the pancreas, accounting for approximately 82 % of all incidentally discovered PCNs [12]. From a morphological standpoint, these lesions can be classified according to the involvement of the main pancreatic duct (MPD) into three subtypes: main duct IPMNs (MD-IPMNs), when confined to the MPD; branch duct IPMNs (BD-IPMNs), when limited to the secondary pancreatic ducts; and mixed-type IPMNs (MT-IPMNs), when both the MPD and secondary ducts are affected. This distinction is crucial not only from an anatomical perspective but also because it strongly correlates with the risk of malignant transformation.

Historically, the difficulty in distinguishing benign from malignant lesions led to a cautious approach favoring liberal surgical resection [5,6], with early surgical series reporting malignancy rates up to 47 % [13,14]. More recently, observational studies—including conservatively managed cohorts, thereby reducing surgical selection bias—have shown that most incidentally detected cysts are BD-IPMNs with an indolent biological behavior. Their overall malignancy rate is about 2.7 %, with a pooled annual incidence of invasive cancer of 0.49 %, dropping to 0.26 % after five years of stable surveillance [15,16]. In contrast, MD-IPMN and MT-IPMN carry a substantially higher risk, with malignancy rates around 60–70 % [17], linked to more aggressive epithelial subtypes (intestinal or pancreatobiliary) compared to the typically indolent gastric-foveolar subtype of BD-IPMNs [18].

Despite these insights, IPMNs remain a persistent therapeutic challenge, particularly regarding the timing of progression from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or invasive carcinoma (IC). In this context, the concept of “timely intervention” has emerged: surgery is considered “timely” when HGD is present, “too early” with LGD, and “too late” if IC has already developed [19]. Ideally, resection should target the HGD stage to maximize oncologic benefit while avoiding unnecessary risks. Overly aggressive strategies may lead to significant perioperative morbidity and impaired long-term quality of life [20,21], while overly conservative approaches may allow malignant transformation to occur, with a significant reduction in survival, regardless of resection margin status [22,23]. However, in clinical practice, a wide range of patient-specific factors influence decision-making, making it particularly difficult to balance the risks of pancreatic surgery against its potential oncologic benefit [24]. The challenge for the surgeon is therefore to identify, in each individual case, the most appropriate timing for resection—carefully weighing disease biology, patient characteristics, and operative risk to achieve the best long-term outcomes.

Fig. 1. Risk stratification and current management algorithm for intraductal papillary mucinous neoplasms (IPMNs). AI: absolute indication; HRS: high-risk stigmata; RI: relative indication; WF: worrisome features; EUS: Endoscopic Ultrasound.

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Surgical indications and management of pancreatic cystic neoplasm