Pancreatic somatostatinoma represents a rare group of neuroendocrine tumors, which was first reported by Ganda and Larsson in 1977. Less than 50 cases have been reported to the present. We treated a case of pancreatic somatostatinoma at our hospital.
A 44-year-old woman presented with iterative diarrhea which had been ignored for one year, followed by increasing abdominal girth, right upper-quadrant fullness, and a weight loss of more than 4 kg. At presentation, the serum alpha-fetoprotein (AFP) level and other tumor markers were normal. Cancer antigen 125 (CA-125) was 45.8 U/ml (normal, <35 U/ml), somatostatin 95.68 pg/ml (normal, <30 pg/ml), insulin 7.4 μIU/ml (normal, 2.1-30.8 μIU/ml), gastrin 52.22 pg/ml (normal, <108 pg/ml), and parathyrin 90.9 pg/ml (normal, 9.0-55.0 pg/ml). Percutaneous liver biopsy was positive for a neuroendocrine tumor without an exact diagnosis. No lesions were found ultrasonographically in the parathyroid glands. Abdominal computed tomography (CT) revealed poor visualization of the left branch of the portal vein, innumerable metastasis of the liver without thrombosis of the portal vein, an angioma in the right hepatic lobe, and a low density mass of 4 cm × 4 cm in the tail of the pancreas. Because of the size and multi-focal nature of the hepatic lesions (Figure 1), the patient was admitted to our center for possible liver transplantation.
The patient was considered to be suitable for liver transplantation and radical distal pancreatectomy. Since the results of liver function test were normal, radical distal pancreactectomy was performed first, followed by a total hepatectomy without the use of veno-venous bypass. The donor liver was procured by a rapid perfusion technique. Briefly, the terminal aorta and the inferior mesenteric vein were dissected to insert the aortic and portal perfusion cannulae. Cardiac arrest lasted for 2 minutes. The time for allograft liver procurement was 20 minutes. The time for warm and cold ischemia was 3 minutes and 5 hours, respectively. The allograft was implanted by end-to-end hepatic venous drainage from the recipient portal vein to the donor portal vein, the gastroduodenal artery of the donor to the recipient gastroduodenal artery, and biliary drainage with an end-to-end anastomosis of the common bile duct. The allograft functioned immediately. The duration of the procedure was 5 hours and the duration of the anhepatic phase was 50 minutes. The transfusion required 10 U red blood cells and 10 U plasma during the surgery.
The patient got well after the surgery. The diarrhea resolved and the levels of serum somatostatin and parathyroxin decreased from 95.68 pg/ml and 90.9 pg/ml to 28.69 pg/ml and 36.8 pg/ml, respectively. She was discharged from the hospital at the third postoperative week and given a maintenance immunosuppressive regimen with tacrolimus and prednisone (prednisone tapered off in 2 weeks). Follow-up CT scans showed negative results for any new growths 9 months after the surgery. Hepatic function improved or remained normal without evidence of tumor recurrence in 10 months of follow-up. The patient now is employed for a full-time work.
The native liver weighed 3800 g, and it was 30 cm × 25 cm × 12.5 cm in size. The capsular surface of the liver was markedly enlarged and distorted, with firm-to-rubbery in texture, and bulging masses (Figure 2). A solid tumor of 4 cm × 4 cm in the tail of the pancreas was palpated as an integral capsule (Figure 3). The surgical margins were free of the tumor and non-neoplastic portions of the liver showed neither portal fibrosis nor significant steatosis. The hilar nodes were free from the neoplastic involvement.
The tumor cells showed histological features common to all pancreatic endocrine tumors, with cells forming mastoid and acinar structures. They were mostly short spindles or polygonal like with abundant cytoplasm and round or ovoid nuclei. A loose, thin, fibrous septum and plentiful sinusoids were also observed. Immunohistochemical staining showed synaptophysin (Syn) (+), chromogranin A (CgA) (+), neuron-specific enolase (NSE) (+), somatostatin (SS) (++), CD56 (±), gastrin (-), pancreatic polypeptide (PP) (-), glucagon (-), insulin (-), and vasoactive intestinal peptide (VIP) (-) (Figure 4).
Coding exons of the MENI gene amplified by PCR from peripheral lymphyocyte genomic DNA were negative.
Pancreatic somatostatinoma has biological characteristics differing from those of other malignant tumors. Its clinical features are concealed but there is always a single lesion with a potentially lower malignancy and slower growth. The disease, from onset to death, spans several years. 'Inhibitory syndrome' as the main symptom of pancreatic somatostatinoma includes mild diabetes, cholelithiasis, steatorrhea, and weight loss. In this case, there was no definite diagnosis before surgery because of the absence of typical clinical manifestations as mentioned above. With the experiences from another 2 cases in China,1,2 we did serum somatostatin test in diagnosing the disease for those patients with a tumorous mass in the pancreas without elevation of serum CA-199 level. Octreoscan had a sensitivity of 67% and a specificity of 100%, but the diagnostic value needs to be tested further.3
The patients without liver metastasis should undergo radical resection of the primary lesion, which may include lymphadenectomy of para-aortic lymph nodes and retroperitoneal lymph nodes. The therapeutic approach to hepatic metastasis of pancreatic somatostatinomas is still controversial.4 Surgeons have to consider the risk-benefit ratio of liver transplantation to its alternatives. Radical resection gives a recovery rate of only 20% for the patients with the tumor;5 however, liver transplantation is a choice to cure otherwise unresectable liver lesions. Liver transplantaion is attempted for an oncologic cure because the biological behavior of neuroendocrine, liver metastases, and tumor recurrence are not the predominant issues. In the two patients mentioned above, one received radical treatment because of the absence of liver involvement.1 Abdominal metastasis was seen in another patient who was a non-candidate for liver transplantation.2 Our patient, however, had a chance of survival by undergoing radical resection for the primary lesion while receiving a simultaneous liver transplantation. The patient did well after the surgery and got a full employment. The 5- and 10-year survival rates were 75% and 50%, respectively, which were significantly higher than those in patients who did not undergo liver transplantation.6,7 Lang et al 6 reported a tumor bulk of less than 40%-50% in the explant in patients who had had no recurrence during follow-up. Thus, liver transplantation may be regarded as a curative treatment for patients with metastases of neuroendocrine tumor. Coppa et al5 proposed that patients with non-resectable disease were suitable for liver transplantation if they met the following criteria: (1) confirmed carcinoid histology (excluding non-carcinoid primary tumors); (2) primary tumor drained by the portal system (excluding tumors with systemic venous drainage); (3) 50% hepatic replacement by tumor metastases; (4) good response or stable disease during the pre-transplant period; and (5) absence of any extra-hepatic disease at the time of transplantation. In a group of 9 patients who underwent liver transplantation based on these criteria, the 5-year survival rate was 70% and the 5-year disease-free survival rate was 53%. Pancreatic somatostatinoma is sometimes associated with multiple endocrine neoplasia type I (MEN I). The positive results of MENI gene analysis are an indicator for a high recurrence rate and poor prognosis of the disease.
Furthermore, there is no direct evidence as to whether post-transplant immunosuppression stimulates the growth of tumor cells. Because the indication for liver transplantation is strictly controlled, tumor recurrence is associated with a rational choice and maintenance of an immunosuppressant. Since tumor recurrence is related to lower immunity, a rationale regimen of immunosuppressants should be chosen to control rejection and overgrowth of tumor cells. The regimen including adrenolcortical hormones with FK506 or Neoral has been adopted for post-transplant immunosuppression with lower levels of FK506 and cyclosporin A in blood and early cessation of prednisone.
Octreotide, a somatostatin analogue, is definitely effective in localizing and managing somatostatinoma. Octreotide can reduce the levels of serum somatostatin. 8 However, it is not effective in patients with liver metastasis. Although the level of serum somatostatin may drop to normal limits after hepatectomy or liver transplantation, periodic test of serum somatostatin is imperative. The regular administration of octreotide helps to prevent tumor recurrence after radical excision or liver transplantation.
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