A Selective Approach to the Resection of Cystic Lesions of the Pancreas: Results From 539 Consecutive Patients

To the Editor:

We read with interest the recent article by Allen et al on pancreatic cysts, which discusses the role of nonoperative management for the majority of these lesions. We fully agree with them that a selective approach is needed when evaluating a patient with a pancreatic cyst, particularly if it is an incidental finding, to avoid operations on benign neoplasms that may be associated with early and late complications.

However, we have some reservations about this study:

1. The term “cystic lesions of the pancreas” is too heterogeneous, and any decision regarding treatment needs to go several steps further by selective use of dedicated pancreatic imaging (computed tomography and/or magnetic resonance imaging resonance with cholangiopancreatography) and endoscopic ultrasound. Even assuming that a distinction between inflammatory and neoplastic cyst has been made (hopefully on the basis of a clinical correlate), merely dichotomizing neoplastic cysts into serous and mucinous may result in dangerous oversimplification, since not all mucinous cysts are equal.^1–7 It is important that both the radiologist and the clinician who is responsible for the patient make the effort to differentiate between a mucinous cystic neoplasm, a branch-duct intraductal papillary mucinous neoplasm (IPMN), or a main-duct IPMN. Dr. Allen and coworkers wrongly assume that main-duct IPMNs are unlikely to present as a cystic lesion in the pancreas. Several papers have highlighted that the radiologic presentation of main-duct IPMN can be that of an isolated cyst^8–10; and with a frequency of malignancy in main-duct IPMN of 70% and a rate of invasive carcinoma of 40%,^1,11 this is not a lesion that should be observed. Likewise, if the lesion is suspected to be a mucinous cystic neoplasm (because there is no connection to the ductal system of the pancreas, the patient is female, and the cyst is in the distal pancreas), the current recommendation is to proceed with resection and not to observe.¹¹ The radiologist and the clinician also need to keep in mind that there are other neoplastic cysts that are nonserous and nonmucinous. These include solid pseudopapillary neoplasm and cystic neuroendocrine tumors, both of which should be resected. Finally, other factors, such as a family history of pancreatic cancer or an elevated serum CA 19.9, should be considered in the decision-making.

2. An adenocarcinoma was found in 8 patients initially followed radiographically and, unfortunately, 5 of them had unresectable or metastatic disease when surgical intervention was finally taken. In 3 of them, the time between initial diagnosis and identification of a malignancy was more than 4 years. In these patients, the definitive histologic diagnosis is not known since their neoplasms were not resected (a biopsy showing adenocarcinoma cannot distinguish between ductal adenocarcinoma and adenocarcinoma arising in IPMN). The authors make the statement that “no patient with a malignant mucinous tumor underwent a delayed resection.” We challenge that assertion and propose that some or all of those 5 patients could have had a malignant mucinous neoplasm at the onset because it is extremely unlikely that ductal adenocarcinoma of the pancreas would progress so slowly (range, 57–84 months). In these cases, it is more likely that an adenocarcinoma arose in the background of an IPMN.

3. Among mucinous neoplasms, a nonoperative management should be proposed only for branch-duct IPMNs, as suggested by the International Association of Pancreatology guidelines.¹¹ These guidelines state that asymptomatic patients affected by branch-duct IPMN with a diameter less than 3 cm, with a nondilated (<5 mm) main pancreatic duct and without any malignancy-related parameters (presence of nodules and/or thick wall) can be considered for careful nonoperative follow-up with computed tomography or magnetic resonance imaging resonance with cholangiopancreatography every 6 months, at least initially.

4. The 3% malignancy risk in cysts <3 cm and without solid component may not be accurate because the denominator of 369 that the authors used included patients who had solid component, symptoms, or lesions >2.5 cm, but still were managed nonoperatively. It would be very useful to the reader to know what happened to the 25% of patients with solid components and the 37% who had symptoms but were not resected. Furthermore, the 3% may be falsely reassuring because the median follow-up was only 24 months, which is very short for malignant neoplasms with a less aggressive biology, such as IPMNs and neuroendocrine neoplasms.

We would like also to highlight that knowledge of the natural history of these neoplasms is incomplete; therefore, data from large series with longer follow-up are needed to confirm the proper application and safety of a surveillance approach. For this reason, follow-up should preferably be performed in referral centers by surgeons, radiologists, and gastroenterologists with expertise and interest in pancreatic diseases.

Stefano Crippa, MD
Carlos Fernández-del Castillo, MD
Department of Surgery
Massachusetts General Hospital
Boston, MA