IPMN Surgical Management

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INTRODUCTION

IPMNs were first recognized in 1982 by Ohashi, but the term IPMN was not officially used until 1993. IPMNs are defined in the WHO Classification of Tumors of the Digestive System as an intraductal, grossly visible epithelial neoplasm of mucin-producing cells. Using imaging and histology, IPMNs can be classified into three types based on duct involvement:

1. Main-duct IPMN (approximately 25% of IPMNs): Segmental or diffuse dilation of the main pancreatic duct (>5 mm) in the absence of other causes of ductal obstruction.

2. Branch-duct IPMN (approximately 57% of IPMNs): Pancreatic cysts (>5 mm) that communicate with the main pancreatic duct.

3. Mixed type IPMN (approximately 18% of IPMNs): Meets criteria for both main and branch duct.

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Due to the asymptomatic nature of the disease, the overall incidence of IPMNs is difficult to define but is thought to account for approximately 3% to 5% of all pancreatic tumors. Most IPMNs are discovered as incidental lesions from the workup of an unrelated process by imaging or endoscopy. IPMNs are slightly more prevalent in males than in females, with a peak incidence of 60 to 70 years of age. Branch-duct IPMNs tend to occur in a slightly younger population and are less associated with malignancy compared with main-duct or mixed variants.

Because a majority of IPMNs are discovered incidentally, most are asymptomatic. When symptoms do occur, they tend to be nonspecific and include unexplained weight loss, anorexia, abdominal pain, and back pain. Jaundice can occur with mucin obstructing the ampulla or with an underlying invasive carcinoma. The obstruction of the pancreatic duct can also lead to pancreatitis. IPMNs may represent genomic instability of the entire pancreas. This concept, known as a “field defect,” has been described as a theoretical risk of developing a recurrent IPMN or pancreatic adenocarcinoma at a site remote from the original IPMN. The three different types of IPMNs, main duct, branch duct, and mixed duct, dictate different treatment algorithms.

MAIN DUCT IPMNs

Main-duct IPMNs should be resected in all patients unless the risks of existing comorbidities outweigh the benefits of resection. The goal of operative management of IPMNs is to remove all adenomatous or potentially malignant epithelium to minimize recurrence in the pancreas remnant. There are two theories on the pathophysiologic basis of IPMNs. The first groups IPMNs into a similar category as an adenocarcinoma, a localized process involving only a particular segment of the pancreas. The thought is that removal of the IPMN is the only treatment necessary. In contrast, some believe IPMNs to represent a field defect of the pancreas. All of the ductal epithelium remains at risk of malignant degeneration despite removal of the cyst. Ideally, a total pancreatectomy would eliminate all risk, but this is a radical procedure that is associated with metabolic derangements and exocrine insufficiency. Total pancreatectomy should be limited to the most fit patients, with a thorough preoperative assessment and proper risk stratification prior to undertaking this surgery. 

There is less uncertainty with treatment of main-duct IPMNs. The high incidence of underlying malignancy associated with the IPMNs warrants surgical resection. IPMNs localized to the body and tail (approximately 33%) can undergo a distal pancreatectomy with splenectomy. At the time of surgery, a frozen section of the proximal margin should be interpreted by a pathologist to rule out high-grade dysplasia. A prospective study identified a concordance rate of 94% between frozen section and final pathologic examination. If the margin is positive (high-grade dysplasia, invasion) additional margins may be resected from the pancreas until no evidence of disease is present. However, most surgeons will proceed to a total pancreatectomy after two subsequent margins demonstrate malignant changes. This more extensive procedure should be discussed with the patient prior to surgery, and the patient should be properly consented regarding the risks of a total pancreatectomy.

IPMNs localized to the head or uncinate process of the pancreas should undergo a pancreaticoduodenectomy. A frozen section of the distal margin should be analyzed by pathology for evidence of disease. As mentioned before, after two additional margins reveal malignant changes, a total pancreatectomy is usually indicated (approximately 5%). The absence of abnormal changes in frozen sections does not equate to negative disease throughout the pancreas remnant. Rather, skip lesions involving the remainder of the pancreas can exist and thus patients ultimately still require imaging surveillance after successful resection. A prophylactic total pancreatectomy is rarely performed because the subsequent pancreatic endocrine (diabetes mellitus) and exocrine deficits (malnutrition) carry an increased morbidity.

BRANCH DUCT IPMNs

Localized branch-duct IPMN can be treated with a formal anatomic pancreatectomy, pancreaticoduodenectomy, or distal pancreatectomy, depending on the location of the lesion. However, guidelines were established that allow for nonoperative management with certain branch- type IPMN characteristics.

These include asymptomatic patients with a cyst size less than 3 cm and lack of mural nodules. The data to support this demonstrate a very low incidence of malignancy (approximately 2%) in this patient group. Which nearly matches the anticipated mortality of undergoing a formal anatomic resection. In approximately 20% to 30% of patients with branch- duct IPMNs, there is evidence of multifocality. The additional IPMNs can be visualized on high-resolution CT or MRI imaging. Ideally, patients with multifocal branch-duct IPMNs should undergo a total pancreatectomy. However, as previously mentioned, the increased morbidity and lifestyle alterations associated with a total pancreatectomy allows for a more conservative approach. This would include removing the most suspicious or dominant of the lesions in an anatomic resection and follow-up imaging surveillance of the remaining pancreas remnant. If subsequent imaging demonstrates malignant charac- teristics, a completion pancreatectomy is usually indicated.

RECURRENCE RATES

Recurrence rates with IPMNs are variable. An anatomic resection of a branch-duct IPMN with negative margins has been shown to be curative. The recurrence of a main- duct IPMN in the remnant gland is anywhere from 0% to 10% if the margins are negative and there is no evidence of invasion. Most case series cite a 5-year survival rate of at least 70% after resection of noninvasive IPMNs. In contrast, evidence of invasive disease, despite negative margins, decreases 5-year survival to 30% to 50%. The recurrence rate in either the pancreatic remnant or distant sites approaches 50% to 90% in these patients. Histopathologic subtype of the IPMN is correlated with survival. The aggressive tubular subtype has a 5-year survival ranging from 37% to 55% following surgical resection, whereas the colloid subtype has 5-year survival ranging from 61% to 87% post resection. Factors associated with decreased survival include tubular subtype, lymph node metastases, vascular invasion, and positive margins. IPMNs with evidence of invasion should be treated similar to pancreatic adenocarcinomas. Studies show that IPMNs tend to have better survival than pancreatic adenocarcinoma. This survival benefit may be secondary to the less aggressive tumor biology or the earlier diagnosis of IPMNs.

SURVEILLANCE

All patients who have a resected IPMN should undergo imaging surveillance. There is continual survival benefit with further resection if an IPMN does recur. International Consensus Guidelines published in 2017 offer recom- mendations for the frequency and modality of imaging surveillance after resection. Routine serum measurement of CEA and CA 19-9 has a limited role for detection of an IPMN recurrence. Of note, a new pancreatic lesion discovered on imaging after resection could represent a postoperative pseudocyst, a recurrence of the IPMN from inadequate resection, a new IPMN, or an unrelated new neoplastic process. IPMNs may also be associated with extrapancreatic neoplasms (stomach, colon, rectum, lung, breast) and pancreatic ductal adenocarcinoma. It is unclear if this represents a true genetic syndrome. However, patients with IPMNs should have a discussion about the implications of their disease with their physician and are encouraged to undergo colonoscopy to exclude a synchronous neoplastic process.

The incidence of PANCREATIC CYSTIC LESIONS will continue to increase as imaging technology improves. EUS, cytology, and molecular panels have made differentiating the type of PCN less problematic. The importance of an accurate preoperative diagnosis ensures that operative management is selectively offered to those with high-risk lesions. Management beyond surgery, including adjuvant therapy and surveillance, continue to be active areas of research.

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