Pancreatic Tumors

Welcome to Today’s Episode!

In this episode, we’re diving into pancreatic tumors—covering the risk factors, symptoms, and treatment options for both pancreatic cancer and neuroendocrine tumors. We’ll explore key causes, from lifestyle factors to genetic syndromes, and break down the latest diagnostic tools and therapies.

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Transcript

Welcome to Today’s Episode!

Today, we’re exploring pancreatic cancer, one of the leading causes of cancer deaths in the United States, primarily affecting individuals over 60. Understanding the risk factors is essential. These include smoking, chronic pancreatitis, alcohol use, diabetes, obesity, and occupational exposure to chemicals found in the dry cleaning and metal industries. Interestingly for patients with diabetes, metformin use and possibly aspirin may slightly reduce the risk of pancreatic cancer. However, insulin use and GLP-1 therapies, such as sitagliptin, may increase the risk.

Pancreatic cancer can also occur as part of hereditary syndromes, including familial breast cancer, hereditary pancreatitis, familial atypical multiple mole melanoma, Peutz-Jeghers syndrome, ataxia-telangiectasia, and Lynch syndrome. Now, let’s talk about pancreatic neuroendocrine tumors. These include insulinomas, gastrinomas, vasoactive intestinal peptide producing tumors, and glucagonomas. Insulinomas typically present with recurrent hypoglycemia and elevated C-peptide levels. Gastrinomas may lead to refractory peptic ulcer disease, reflux disease, diarrhea, and other features of multiple endocrine neoplasia, or MEN syndrome. VIPomas often present with watery diarrhea, hypokalemia, and achlorhydria. Glucagonomas classically present with necrotic migratory erythema, weight loss, hypoalbuminemia, and impaired glucose tolerance. Genetic testing for multiple endocrine neoplasia type 1 is recommended for all young patients with gastrinomas or insulinomas.

Moving on to clinical features of pancreatic cancer, they often resemble chronic pancreatitis. Patients typically report vague, diffuse pain in the epigastrium or, in the left upper quadrant, if the lesion is in the tail of the pancreas. This pain can radiate to the back. Diarrhea may occur as an early symptom. Significant weight loss is common and can be associated with depression. Nausea, diarrhea, and jaundice may also present due to obstruction of extrahepatic biliary drainage, which can lead to an enlarged gallbladder. When an enlarged, non-tender gallbladder is present along with jaundice, we call this Courvoisier's sign. Other symptoms may include pale stools, dark urine, and pruritus due to increased conjugated bilirubin. New-onset diabetes and features of hypercoagulability, such as venous thromboembolism, may also appear. Migratory thrombophlebitis is a rare sign, and in advanced cases, a hard periumbilical nodule known as a Sister Mary Joseph nodule may be palpable. If there’s occult blood in the stool, it can suggest carcinoma of the ampulla of Vater. This condition may cause the stools to have a distinctive silver appearance due to the combination of biliary obstruction and bleeding.

Laboratory findings may include mild anemia, glycosuria, hyperglycemia, impaired glucose tolerance, or diabetes mellitus. Tumor markers like CA 19,9 and CEA are not recommended for diagnosis or screening but serve as prognostic markers. Serum lipase or amylase levels might be occasionally elevated, and liver biochemical tests may suggest obstructive jaundice. Elevated plasma chromogranin A levels are indicative of pancreatic neuroendocrine tumors.

For imaging we start with an abdominal ultrasound, though this can be unreliable due to interference from intestinal gas. If there’s a high clinical suspicion, we perform a pancreas protocol CT of the abdomen and pelvis with IV contrast. CT is the initial diagnostic procedure used to identify metastases, delineate the extent of the tumor, and enable percutaneous Fine Needle Aspiration for cytologic studies and tumor markers. MRI serves as an alternative to CT. PET scans are sensitive for detecting pancreatic cancer and metastases, but PET-CT is not typically used as a routine staging procedure. Endoscopic ultrasound or EUS, is more sensitive than CT for detecting pancreatic cancer and is comparable to CT for determining nodal involvement and resectability. A normal EUS can effectively exclude pancreatic cancer, and it may also guide FNA or biopsy for tissue diagnosis, tumor markers, and DNA analysis. ERCP, or endoscopic retrograde cholangiopancreatography, may clarify ambiguous CT or MRI studies by delineating the pancreatic duct system or confirming an ampullary or biliary neoplasm.

For incidental pancreatic masses found during workup or screening, including incidentalomas, we recommend obtaining pancreas protocol imaging, either CT or MRI. Based on findings or if the diagnosis remains uncertain, advanced testing, such as EUS or MRCP, should be considered. Tissue sampling for histopathology is typically arranged for most patients.

When it comes to staging the tumor, thoracic imaging using CT or chest X-ray is essential. The TNM system is the commonly used classification for staging pancreatic cancer, which helps determine which patients should receive adjuvant or neoadjuvant therapy. Localized pancreatic cancer includes resectable, borderline resectable, and locally advanced (unresectable) disease.

Treatment is multimodal and depends on the stage of the cancer and its resectability. The only potentially curative treatment for pancreatic cancer is surgical resection, often in combination with other therapies. Neither chemotherapy nor radiation therapy can be curative without surgery. Radical pancreaticoduodenal, or Whipple resection is indicated for cancers strictly limited to the head of the pancreas, periampullary area, and duodenum.

Adjuvant chemotherapy may involve Gemcitabine with capecitabine or a modified FOLFIRINOX regimen, which includes 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin. Neoadjuvant chemotherapy, with or without radiation, is increasingly used to downstage patients with resectable cancer. When resection is not feasible, endoscopic stenting of the bile duct can be performed to relieve jaundice. Chemoradiation may be utilized for palliation of unresectable cancer confined to the pancreas. Additionally, celiac plexus nerve block can improve pain control.

For neuroendocrine tumors, surgical resection is the preferred treatment when feasible. Non-functioning lesions less than one centimeter in diameter and showing no evidence of local invasion or metastasis may be monitored expectantly. Metastatic disease can be managed with long-acting somatostatin analogs, interferon, chemotherapy, peptide-receptor radionuclide therapy, or chemoembolization.

Incidental pancreatic cysts may be monitored through imaging tests such as MRI every year for the first year, then every two years for five years, and possibly longer if no changes are observed. If a cyst enlarges to three centimeters or other high-risk features develop, such as a dilated main pancreatic duct or a solid component, EUS and FNA may be performed.

Surgical resection is indicated for mucinous cystic neoplasms, symptomatic serous cystadenomas, solid pseudopapillary tumors, and cystic tumors larger than two centimeters in diameter that remain undefined after helical CT, EUS, and diagnostic aspiration. All intraductal papillary mucinous neoplasms of the main pancreatic duct should be resected.

The recommended frequency for follow up is every three to six months for the first two years, then every six to twelve months afterward. CA 19,9 levels should be monitored if elevated at baseline, along with cross-sectional abdominal imaging, like a CT scan.

Finally, let’s discuss the prognosis. Carcinoma of the pancreas, particularly in the body or tail, has a poor prognosis. Obesity may negatively impact mortality. Tumors of the ampulla have a better prognosis, while jaundice and lymph node involvement are adverse prognostic factors. For individuals with a family history of pancreatic cancer, especially if there are at least two first-degree relatives affected or if there’s a genetic syndrome linked to increased risk, annual screening with EUS alternating with MRI should be considered. This generally begins at age 50, 40 for CDKN2A or PRSS1 pathogenic variant carriers, and 35 for those with Peutz-Jeghers syndrome. Alternatively, screening may start ten years before the age at which pancreatic cancer was first diagnosed in a family member.

That’s all for today’s episode. Thanks for listening to AudioBoards. Stay tuned for more educational content in our next episode!

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