Abstract

Multiple endocrine neoplasia type 1 (MEN-1) is an uncommon, autosomal dominant inherited condition with estimated frequency of 1:30,000 across the general population. Between 35% and 75% of patients with MEN-1 ultimately develop neuroendocrine tumors of pancreas, which present the most significant threat to long-term survival. Pancreatectomy remains the only curative therapy for such patients and has become increasingly safe over the past few decades. Here we present the case of a young woman with MEN-1 who was found to have a 3.5cm well-differentiated pancreatic neuroendocrine tumor in the head of the pancreas. We outline the natural history, preoperative care, intraoperative technique, and postoperative considerations.

Case Overview

Typical Clinical Presentation

Our patient is a 26 year-old female with a known history of MEN-1 in immediate family members. She had been in great health until development of headache and lactation without any abdominal pain or discomfort, weight loss, or symptoms of hypoglycemia. Work-up revealed a pituitary adenoma which was ultimately treated with cabergoline with a resolution of symptoms. Subsequent work-up for additional MEN-1 related tumors included an MRI and CT studies that revealed a 3.5cm mass in the head of the pancreas. Endoscopic ultrasound and needle biopsy showed a well-differentiated neuroendocrine tumor, positive for chromogranin and CD 56. KI-67 index was 3-4%. Our patient then presented for surgical evaluation of pancreatic head neuroendocrine tumor.

She has no prior medical or abdominal surgical history. Her only medication at time of presentation is cabergoline and only drinks an occasional glass of wine. Her family history is notable for MEN-1in maternal grandmother with pancreatic tumor s/p whipple procedure at age 50. Her father and two uncles have pancreatic and parathyroid tumors.

Physical exam revealed a healthy-appearing young lady, pulse: 80 bpm, blood pressure: 110/80. She has no scleral icterus, no cervical, supraclavicular lymphadenopathy. No palpable masses in the thyroid. Lungs are clear to auscultation bilaterally, heart has regular rate and rhythm without murmur. Abdomen is soft, non-tender, nondistended, and without any palpable masses, splenomegaly, hepatomegaly, or ascites. Skin and extremities exam are also without any focal abnormalities.

Imaging Studies

Our patient underwent a CT abdomen with arterial-phase contrast that showed a 3.5-cm, enhancing lesion in the head of the pancreas. Subsequent EUS with biopsy confirmed well-differentiated neuroendocrine tumor. Additional pathology evaluation found tumor cells to be positive for chromogranin and CD 56 but with a low KI-67 index of 3-4%, suggesting well-differentiated neuroendocrine tumor.

Patients often present to their surgeon having already undergone an array of radiologic studies. The most important imaging modality is a three-phase abdominal CT scan without contrast, with arterial-phase contrast, and with portal-venous phase contrast. Abdominal MRI can also provide useful information to differentiate between tumors of unclear etiology. However, pancreatic neuroendocrine tumors (PNETs) have very characteristic features on CT that, coupled with patients history and physical, can often provide adequate information for surgical recommendations.^1,2

PNETs are typically isodense with pancreatic parenchyma on pre-contrast images. However, the tumors have marked enhancement on arterial phase imaging with a minority of tumors also being evident on portal venous phase. On rare occasions, PNETS can be either hypovascular or cystic in nature, which diminishes ability to discriminate between other lesions via CT alone. Increasingly, endoscopic ultrasound with biopsy is being used to localize particularly small lesions. Though highly sensitive for smaller lesions, EUS is also highly operator-dependent.

Natural History

MEN-1 syndrome is an autosomal dominant inherited syndrome related to inactivating mutations in the tumor-suppressor protein menin. The clinical manifestations of the syndrome include parathyroid and pituitary adenomas as well as pancreatic neuroendocrine tumors (PNETs). Although PNET’s account for less than 3% of all pancreatic neoplasms in the general population, between 30% and 80% of patients with MEN-1 will develop evidence of neuroendocrine tumor.^3-5 Approximately half of all deaths in patients with MEN-1 can be attributed to malignant endocrine neoplasms.

Options for Treatment

Patients with lesions in the head of the pancreas will most likely require a pancreaticoduodenectomy to obtain adequate oncologic resection. Multiple variations in reconstruction including pylorus preservation, antecolic vs. retrocolic duodenojejunostomy (or gastrojejunostomy), and method of pancreaticojejunostomy have been described with little variation in immediate and long-term outcomes.^6-8 Lesions in the body or tail of pancreas can undergo a middle or distal pancreatectomy, respectively. Regardless of the procedure performed, regular surveillance with axial imaging is required given ongoing risk of developing additional PNET in remaining pancreas.

Discussion

Here we present the case of a 26 year-old female with MEN-1 and a nonfunctioning pancreatic neuroendocrine tumor at the head of the pancreas. She underwent an uncomplicated pylorus-preserving pancreaticoduodenectomy and has recovered without any additional complications. Final pathology revealed well-differentiated neuroendocrine tumor with 0 of 12 lymph nodes positive for malignancy.

The Whipple procedure remains the only option for curative treatment of pancreatic head malignancies, including neuroendocrine tumors. Mortality from the procedure has improved markedly over the past few decades, now with perioperative death rates of less than 2% at high-volume centers.¹¹ However, morbidity rates upwards of 40% continue to plague the surgery. Pancreatic fistulas occur in approximately 10-15% of cases. Recent work suggests that external pancreatic duct stents can help reduce clinically significant fistula in high-risk patients (soft gland and small pancreatic duct).¹² Although there has been considerable debate about the role of closed-suction drainage after the Whipple procedure, a recent randomized controlled trial showed that routine drainage also reduces the frequency and severity of postoperative complications. Multiple studies are underway to identify strategies to reduce the frequency of surgical site infections, presently standing between 8% and 10%. Increasing data suggest that the standard preoperative prophylactic antibiotics may not be adequately covering biliary flora, frequently present after preoperative instrumentation of biliary tract (ERCP, sphincterotomies, stents, etc.).¹³ Preliminary reports suggest that surgeons might consider tailoring antibiotic choices to microorganisms most frequently seen in their respective populations. Delayed gastric emptying also occurs between 25% and 30% of patients following pancreaticoduodenectomy with no clear association between pylorus-preservation versus classical Whipple or antecolic versus retrocolic duodenojejunostomy (or gastrojejunostomy).¹⁴

Equipment

Bookwalter retractor
Pediatric feeding tube – 3-5 French
Dilators
Argon Beam coagulator (optional)

Disclosures

None

Statement of Consent

Consent for the use of clinical history, radiology, and intraoperative video was obtained from the patient and providers involved in compilation of this case report and filming.