Continuing Education Activity

Intraductal papillary mucinous neoplasms (IPMNs) are cystic neoplasms of the pancreas that grow within the pancreatic ducts and produce mucin. They have the potential to become malignant, so it is important to diagnose and manage them early and appropriately. This activity reviews the evaluation and management of intraductal papillary mucinous neoplasms and highlights the role of the interprofessional team in the care of affected patients.

Objectives:

• Review the epidemiology of intraductal papillary mucinous neoplasms.

• Identify the types of intraductal papillary mucinous neoplasms.

• Summarize the diagnosis and management of intraductal papillary mucinous neoplasms.

• Explain the importance of collaboration and coordination among the interprofessional team to optimize outcomes for patients with intraductal papillary mucinous neoplasms.

Introduction

Intraductal papillary mucinous neoplasms (IPMN) are cystic neoplasms of the pancreas that grow within the pancreatic ducts and produce mucin. They have the potential to become malignant, for that reason; diagnostic criteria have been published to identify which patients will require surgical resection. The criteria usually involve anatomic identification based on imaging including the size of the cyst, the presence of a nodule, architectural changes, obstruction of the main duct, and presence of symptoms.[1][2]

Etiology

The risk factors of IPMNs are not clear. A few conditions have been identified as possible risk factors for the development of IPMNs and include diabetes (especially patients on insulin), chronic pancreatitis, and a family history of pancreatic ductal adenocarcinoma.[3] Smoking is an identified risk factor for pancreatic cancer [1] and has been associated with IPMNs as well.[4]

Epidemiology

The true incidence of IPMNs is unknown as most of them are small and asymptomatic. Studies that evaluated cross-sectional images of patients without a history of pancreatic lesions have shown that approximately 2.6 - 13.5% of adults have pancreatic cysts and the incidence correlated with increasing age.[5][6] The age of presentation is typically between the 5th and 7th decades.[7]

Pathophysiology

IPMNs are thought to progress from benign neoplasms to invasive cancers through DNA damage/mutation. The damaged DNA loses protective factors and undergoes malignant degeneration leading to uncontrolled growth and convalescence. KRAS and/or GNAS mutations have been identified in IPMNs.[8] IPMNs can involve the main pancreatic duct, a branch duct or sometimes it can involve both and is considered a mixed duct type. In all cases of main branch duct type involvement, surgical resection is recommended. Branch duct-type cases may be observed. Branch duct type IPMNs are generally believed to carry less risk of malignancy compared to main duct IPMNs [9].

Histopathology

IPMNs originate from stem cells of the epithelium of the pancreatic ducts which can differentiate into different phenotypes. They can have different subtypes based on their differentiation including intestinal, pancreaticobiliary, oncocytic, and gastric types.[10] IPMNs usually progress from benign neoplasms to invasive cancers. This progression is graded based on the degree of dysplasia as low-grade dysplasia (adenoma), moderate dysplasia (borderline), high-grade dysplasia (carcinoma in situ), and finally invasive carcinoma. The progression from adenoma to carcinoma has been estimated to take 5-6 years to happen and it depends on the subtype of the IPMN.[10]

When IPMNs become invasive, two different subtypes of carcinoma have been identified; tubular type, which usually arises from the pancreatobiliary IPMN and is morphologically similar to pancreatic ductal adenocarcinoma and colloid (mucinous) type, which usually arises from intestinal IPMNs and is morphologically characterized by extensive pools of mucin similar to cancers of other exocrine glands.[10] Colloid carcinomas have a better prognosis than tubular carcinomas [11].

History and Physical

IPMNs can come to clinical attention in a variety of different ways. They can be asymptomatic and detected incidentally on imaging. However; when symptoms are present, they are usually nonspecific including abdominal pain, back pain, nausea, vomiting, anorexia, and weight loss. They can also present with jaundice caused by obstruction of the bile ducts due to external compression or invasion or pancreatitis-like symptoms due to obstruction of the main pancreatic duct by mucin.[12]

Evaluation

The evaluation of IPMNs usually starts with imaging to evaluate the characteristics of the cyst, involvement of adjacent structures, and evidence of distant metastasis. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is first line. Computed tomography (CT) with pancreatic protocol is an alternative in patients whom MRIs are contraindicated. Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) should be used to assess cysts with malignant features, including large size, dilation of the main pancreatic duct, and/or presence of a solid component. Cystic fluid cytology can be assessed to look for atypical or malignant cells. Fluid markers, especially carcinoembryonic antigen (CEA), can help with the diagnosis as well. Cysts with a solid component and a dilated pancreatic duct or have malignant features on EUS and FNA should undergo surgical resection. Cysts with no concerning features should be monitored with MRIs.[13][14]

Treatment / Management

Surgery is indicated in patients with IPMNs and high-grade dysplasia or IPMNs that have progressed to invasive carcinoma. Surgery is recommended for all mucinous neoplasms and main duct neoplasms. In cases of branch duct cysts, observation may be elected. For patients with invasive ductal adenocarcinoma of the pancreas, postresection adjuvant therapy improves survival, even in patients with positive margins or involved lymph nodes. There is controversy as to the best adjuvant strategy. Due to the significant morbidity and mortality associated with pancreaticoduodenectomy or distal pancreatectomy, the patient's and surgeon's decision to perform surgery should include factors such as the patient's age and general health, the malignant risk of the lesion, and the suspicion for malignancy. Cysts not meeting the criteria for resection are typically followed with surveillance imaging [15].

If the main duct is greater than or equal to 1.5 cm, suitable patients should undergo surgical resection. If the whole duct is affected, then total pancreatectomy is the treatment of choice. If the head of the pancreas is affected, then Whipple's procedure (pancreaticoduodenectomy) is the operation of choice. If the tail of the pancreas is affected, then distal pancreatectomy plus or minus splenectomy may be warranted.

Differential Diagnosis

Differentials include pancreatic pseudocysts, serous cyst tumors, mucinous cyst neoplasms, and solid pseudopapillary neoplasms. Imaging including MRI, MRCP, and EUS with FNA helps in differentiating IPMNs from other types of cysts.

Surgical Oncology

For operative technique, an upper midline incision is made, once, inside the abdomen, entrance to lesser sac is created with harmonic scalpel. Kocherization of the duodenum is performed. Once the pancreas is identified, the tissue is dissected where the IPMN is involved. As much as possible, the pancreatic parenchyma should be preserved to ameliorate the side effects of diabetes mellitus and exocrine insufficiency secondary to missing pancreatic tissue. One trick for intraoperative surgery is to palpate the duct of the pancreas. If it feels dilated, then it has to be resected as it needs to be assumed that it is dilated due to increased mucin production (abnormal). Confirm negative margins with a frozen section by sending to pathology.

Radiation Oncology

There is no role for radiation in the management of IPMNs.

Medical Oncology

There is no indication for chemotherapy for IPMN as it is considered a premalignant condition. Currently, surgery is the mainstay of therapy. If an invasive cancer component is identified after surgery then the patient needs adjuvant chemotherapy. The chemotherapy would be gemcitabine, or gemcitabine plus capecitabine or modified FOLFIRINOX for 6 months

Staging

Staging needs to be completed with CT of the chest, abdomen, and pelvis with intravenous contrast.

Prognosis

The 5-year survival for IPMNs is about 45 to 50% in comparison to pancreatic adenocarcinoma's 5-year survival of 8% [1].

Complications

After surgery, complications such as bleeding, anastomotic leak, abscess, or death can occur. Pancreatic enterocutaneous fistulas are a dreaded complication of pancreatic surgery for which to be aware. Typically, these are treated with total parenteral nutrition (TPN), nothing by mouth, and drainage and possibly somatostatin analogs [16].

Postoperative and Rehabilitation Care

Early ambulation is recommended postoperatively. Drain placed at surgery should be removed after the oral diet is advanced and the patient tolerates a regular diet without an increase of drain output. If there is suspicion of a pancreatic fistula, the fluid should be tested for amylase and lipase which are expected to be elevated. 

Consultations

Physical therapy, occupational therapy, and nutritional consultations may be suggested.

Deterrence and Patient Education

Patients need diabetes education. The patient needs to closely follow up with his primary care provider for diabetes management and prevention. Patients who smoke need to be given resources to quit smoking.

Pearls and Other Issues

Patients should undergo follow-up surveillance every 6 months for a year after the surgery with CT scans of the abdomen. If by 1 year nothing is seen, then patients can follow up annually and have imaging with MRCP to reduce radiation exposure.

Enhancing Healthcare Team Outcomes

Management of IPMNs requires an interprofessional team consisting of an oncology nurse, oncologist, surgeon, and pharmacist specializing in oncologic medications. The patient will require regular follow-ups by the team for best results. [Level 5]