Intraductal Papillary Mucinous Neoplasm—When to Resect?

Indications for resection

The most pressing—and probably most controversial—clinical question regarding the management of IPMNs is the indication for surgical resection. In general, the indications for resection in patients who have IPMNs are (1) cancer, (2) cancer prevention in patients at high risk for malignant transformation, and (3) management of symptoms. A diagnosis of cancer in IPMNs (ie, invasive IPMNs) is the strongest indication for surgical resection. A diagnosis of cancer in patients who have IPMNs should

Oncologic risk stratification

Before approaching this area of discussion, a firm grasp of terminology is important in making comparisons in the literature. The words “malignant” and “invasive” IPMN have been used interchangeably in some reports [14], [15], [16]. Others have used the term “malignant” to indicate the category of lesions with either carcinoma in situ (CIS) or invasive pathology, whereas CIS is specifically excluded from the invasive category. This latter distinction is used in this article. Another important

Diagnosis

Establishment of optimal and accurate oncologic risk stratification in patients depends on a diagnosis of IPMN. IPMNs are defined as mucin-producing papillary lesions in connection with the pancreatic ductal system (Fig. 1A). IPMNs may be diagnosed pathologically or clinically.

A pathologic diagnosis may be made at the time of surgical resection. Frozen and permanent sections are highly accurate for the establishment of the diagnosis, and sometimes gross pathology is sufficient if the

Type

The role of IPMN type in preoperative oncologic risk stratification and operative planning is paramount. In most surgical series, IPMN type is determined radiographically. Based on radiographic classification of IPMN type, patients with suspected main duct IPMN (Fig. 2A, C) involvement have a 35% to 80% (35% in the Indiana University series) incidence of invasive pancreatic cancer at the time of surgical resection [3], [4], [10], [29], [30]. Conversely, patients with side branch disease only

Size

The influence of size on oncologic risk of IPMN is unclear. Until recently, most series analyzed the influence of size on main and side branch IPMN collectively. In examining IPMN types collectively, size does predict malignancy and invasion [4]. Similarly, when examining IPMN collectively, main pancreatic duct diameter also predicts malignancy and invasion [4]. The reader must appreciate, however, that when looking at size, main duct IPMNs naturally have a larger length/size because of their

Topography (location, number, distribution)

IPMN topography plays an important role in preoperative oncologic risk stratification and operative planning. Head/uncinate location is the most common location for IPMNs. Several studies of patients who have IPMNs evaluated the association of the lesion location with oncologic risk. In our series, which looked specifically at side branch lesions, unifocal lesions in the body/tail of the pancreas showed malignant character (CIS, invasive cancer) in 22% of cases versus only 10% of cases with

Features

With the increasing use of different imaging modalities to diagnose and evaluate these lesions, the appearance of some differentiation with regard to the features of these lesions has been addressed in the literature. A wide variety of radiologic features has been described and compared with final pathology in an effort to further risk stratify these patients. The first and most accepted of these factors is the presence of a mural nodule or solid or mass component in or adjacent to the cystic

Cytopathology

Cytopathologic assessment is the single most important predictor of malignant IPMNs. Invasive cancer cannot be distinguished from CIS via cytopathology; however, positive cytopathology for high-grade atypia or adenocarcinoma indicates with near 100% certainty the presence of a malignant (ie, CIS or invasive) IPMN. On the contrary, the absence of positive cytopathology does not predict benign IPMNs. Pancreatic juice sampling by peroral pancreatoscopy has demonstrated a similar pattern with

Symptoms, signs, and conditions

Associated symptomatology is a critical set of data that should not be ignored when creating a treatment plan for patients who have IPMNs. It is significantly less important in patients who have main duct involvement based on imaging. In these patients, the risk of malignancy regardless of the presence of associated symptoms is high enough to consistently recommend surgical therapy in fit patients until better biomarkers of dysplasia are available. Two recent studies characterized the

Demographics and other factors

In main duct–involved IPMN, age has been significantly associated with malignancy [3], as has male gender [4]. No specific demographic factors have been associated with malignancy in side branch IPMN. Other factors that should be weighed in the decision to resect are need for prolonged surveillance, inability to adequately perform noninvasive surveillance (eg, contraindication to MRI), difficulty in surveillance (extensive diffuse multifocal disease), and patient tolerance of risk.

Operative strategy

After the decision has been made to offer an operative intervention to patients with IPMN, the next hurdle is the selection of an appropriate operative strategy. Before taking a patient to the operating room, preoperative studies to characterize the IPMN location and distribution should be current (ideally within 1–2 months of operation) and of optimal imaging quality.

Surveillance

The decision to resect or re-resect in patients undergoing surveillance is often a difficult decision. Surveillance of patients with IPMNs falls into two groups: primary surveillance for patients who have not undergone operative intervention and secondary surveillance for patients who require surveillance of the remnant pancreas after resection. These groups are further subdivided into patients with or without radiographically detectable IPMN. The optimal surveillance regimen is unknown [44],

Summary

Based on the experience to date with IPMNs, the approach to patients remains relatively complex. A meticulous and careful approach to diagnosis, oncologic risk assessment, operative planning, and surveillance is needed to adequately address these lesions. Indications for resection in patients with IPMN are (1) cancer, (2) cancer prevention in patients at high risk for malignant transformation, and (3) management of symptoms.

Differentiating patients who have IPMNs by type is an important initial