Pancreatic neuroendocrine tumors are a rare group of pancreatic tumors, with an annual incidence of only 1 to 2/100,000, accounting for about 2% to 3% of pancreatic tumors, and a detection rate of 0.4% to 1.5% in autopsies. In the past, pancreatic neuroendocrine tumors were collectively called islet cell tumors, insulinoma, gastrinoma, pancreatic hyperglycemic tumor, VIP tumor, growth inhibitor tumor, pancreatic polypeptide tumor, growth hormone-releasing factor tumor, neurohypophyseal tumor, etc. are all neuroendocrine tumors. Pancreatic neuroendocrine tumors have the following biological characteristics.
They all originate from pluripotent stem cells in pancreatic ducts; the biological behavior and prognosis of malignant non-functional pancreatic neuroendocrine tumors are significantly better than those of highly malignant pancreatic ductal cell carcinoma. Pancreatic neuroendocrine tumors are tumors that develop from the proliferation of islet Langerhan cells.
They can be divided into two categories according to the presence or absence of secretory function. One category is tumors with secretory function, and the other category is tumors with normal serum hormone levels and no specific clinical manifestations, called nonfunctional pancreatic neuroendocrine tumors. The most common tumor in the first category is insulinoma, followed by gastrinoma, and more rarely, pancreatic hyperglycemia, vasoactive intestinal peptide tumor and growth inhibitor tumor, which mostly produce different clinical symptoms due to abnormal increase of specific hormone levels. Non-functioning pancreatic neuroendocrine tumors are mostly giant tumors of the pancreas, which can be diagnosed by imaging due to compression symptoms.
Insulinoma
I. Qualitative diagnosis
1. It is consistent with Whipple’s triad.
2.Serum insulin concentration≥36pmol/L, serum insulin level and blood glucose ratio>0.3, C-reactive peptide concentration≥200pmol/L, insulinogen≥5pmol/L.
3.If necessary, a starvation test extending to 72 hours can be performed under close supervision.
4.It is recommended to measure serum calcium, parathyroid hormone (PTH), gastrin, prolactin (PRL) and other hormone levels to exclude MEN.
Localization and diagnosis
1.B ultrasound of upper abdomen.
2.Slim CT or magnetic resonance imaging (MRI) scan with enhancement of the upper abdomen.
3.Endoscopic ultrasound pancreatic scan.
4.If non-invasive examination cannot be clearly localized, selective arterial calcium stimulated venous blood collection (ASVS) is recommended to determine insulin levels, and percutaneous transhepatic portal vein cannulation (PTPC) can also be performed to determine insulin levels.
Treatment After the qualitative diagnosis is clear, if there is an indication for surgical exploration, the localization should be as clear as possible. Pay attention to maintaining normal blood glucose level and electrolyte balance before surgery. Fasting blood glucose and insulin should be measured by blood sampling in the morning of surgery. Tumor removal is the main surgical procedure. After tumor removal, close monitoring of blood glucose is required intraoperatively and postoperatively to determine whether the tumor is completely removed and to promptly manage postoperative hyperglycemia.
Gastrinoma
I. Qualitative diagnosis
1.The possibility of gastrinoma should be suspected for peptic ulcers that recur even after regular drug or surgical treatment, peptic ulcers in rare sites and peptic ulcers with diarrhea.
2. Serum gastrin concentration >1000ng/L, gastric acid pH<2. 3. Tryptic stimulation test or calcium ion excitation test.
II. Localization diagnosis
1. Thin-section CTI or MRI plain scan plus enhancement scan of the upper abdomen.
2. Endoscopic ultrasound pancreatic scan.
3.Otriginous peptide isotope scan.
4.For cases that cannot be clearly localized by noninvasive examination, ASVS is recommended to determine gastrin levels. 5.Duodenoscopy is performed.
Treatment Surgical resection is preferred in disseminated cases, with open surgery being the mainstay, with different surgical options depending on the number of lesions and the site involved. All surgeries require clearance of lymphatic adipose tissue in the gastrin triangle. Proton pump inhibitors and medium- and long-acting growth inhibitors are indicated for patients who are inoperable or have recurrence after surgery.
Gastric hyperosmolar tumor
I. Qualitative diagnosis
1. The possibility of pancreatic hyperglycemia should be suspected in diabetic patients with necrotizing wandering erythema.
2.Serum glucagon concentration >800ng/L.
3. Skin biopsy at the erythema is recommended.
Localization diagnosis
1.Slim CTI or MRI scan plus enhancement of the upper abdomen.
2.Otrasound isotope scan.
Treatment The first choice is surgical excision. The surgical procedure is the same as that for insulinoma. Since most of the tumors are huge or malignant, open surgery is recommended. Other treatments include the application of medium- and long-acting growth inhibitors, azurenzolamide, chemotherapy or tumor embolization.
Pancreatic vasoactive intestinal peptide tumor (VIP tumor)
I. Qualitative diagnosis
VIP tumor should be suspected in patients with the triad of VIP tumor, i.e. watery diarrhea, low potassium and no (low) gastric acid.
2.Serum VIP concentration >200ng/L.
The local diagnosis is the same as that of pancreatic hyperglycemia.
Treatment The first choice is surgical resection. Preoperative potassium supplementation, correction of water, electrolyte and acid-base balance disorders. Inhibit the secretion of tumor hormones with medium and long-acting growth inhibitors. The surgical procedure is the same as that for pancreatic hyperglycemic tumor.
Non-functional pancreatic islet cell tumor
Diagnosis Generally, pancreatic tumors can be detected by imaging, and those with larger size can produce compression symptoms. For relatively long duration of disease, enhanced CT or MRI examination can show that most islet cell tumors are rich in blood supply and can be differentiated from pancreatic cancer.
Treatment Depending on the location, size and pathology of the tumor, local excision, pancreaticoduodenectomy or resection of the head of the pancreas with preservation of the duodenum can be performed. In case of poor local or systemic conditions, it is advisable to remove biliary and digestive tract obstruction through less invasive methods. Other treatments include the application of medium- and long-acting growth inhibitors and chemotherapy. Malignant islet cell tumors with liver metastases should be treated by removing the primary lesion, surrounding metastatic lymph nodes, and surface metastases from the liver as much as possible. Intrahepatic lesions can be treated with B-ultrasound-guided alcohol injection, radiofrequency ablation, and hepatic artery cannulation with chemotherapeutic agents such as streptomycin, fluorouracil, and adriamycin. Postoperative treatment is supplemented with growth inhibitors and similar drugs. In cases of postoperative recurrence of malignant islet cell tumors, they should be surgically resected again if they can be resected. For cases with limited primary lesions with extensive liver metastases and good general condition, primary lesion resection plus allogeneic liver transplantation can be considered after strict selection.
In conclusion, surgery is the treatment of choice for most pancreatic neuroendocrine tumors. Tumors on the surface of the pancreas or the tail of the pancreatic body can be operated via laparoscopic pathway. Even for malignant pancreatic neuroendocrine tumors, surgery should be actively performed to effectively prolong the survival of patients and improve the quality of life.