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 involves 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.
The risk factors of IPMNs are not clear. A few coniditions have been identified as possible risk factors for the developement of IPMNs and include diabetes (especially patients on insulin), chronic pancreatitis and a family history of pancreatic ductal adenocarcinoma. Smoking is an identified risk factor for pancreatic cancer  and has been associated with IPMNs as well.
The true incidence of IPMNs is unknown as most of them are small and asymptomatic. Studies that evaluated cross-sectional images of patient without a history of pancreatic lesions have shown that approximately 2.6 - 13.5% of adults have pancreatic cysts and the inidence correlated with increasing age. The age of presentation is typically between the 5th and 7th decade.
IPMNs are thought to progress from benign neoplasms to invasive cancers through DNA damage/mutation. The damaged DNA lose protective factors and undergo malignant degeneration leading to uncontrolled growth and convalescence. KRAS and/or GNAS mutations have been identified in IPMNs. IPMNs can invovle the main pancreatic duct, a branch duct or sometimes it can involve both and is conisdered 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 .
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 type. IPMNs usually progress from benign neoplams 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.
When IPMNs become invasive, two different subtypes of carciomna 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. Colloid carcinomas have a better prognosis than tubular carcinomas .
IPMNs can come to clinical attention in a variety of different ways. They can be asymptomatic and detected incidently on imaing. Howver; 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.
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) are 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.
Surgery is inidcated 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 criteria for resection are typically followed with surveillance imaging .
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.
Differentials include pancreatic pseudocysts, serous cyst tumors, mucinous cyst neoplasms and solid pseudopapillary neoplasms. Imaging including MRI, MRCP and EUS with FNA helps in the differentiating IPMNs from other types of cysts.
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 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.
There is no role for radiation in the management of IPMNs.
No indication for chemotherapy for IPMN as it is considered a premalignant condition. Currently, surgery is the mainstay of therapy. If invasive cancer component identified after surgery then we need adjuvant chemotherapy. The chemotherapy would be Gemcitabine, or Gemcitabine plus Capecitabine or modified FOLFIRINOX for 6 months
Staging needs to be completed with CT of the chest, abdomen, and pelvis with intravenous contrast.
The 5-year survival for IPMNs is about 45% to 50% in comparison to pancreatic adenocarcinoma's 5-year survival of 30% .
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 analogues .
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 increase of drain output. If there is suspicion for a pancreatic fistula, fluid should be tested for amylase and lipase which are expected to be elevated.
Physical therapy, occupational therapy and nutritional consultations may be suggested.
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.
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.
Management of IPMNs require an interdisciplinary 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 V]
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