CASE DESCRIPTION

A 49- year- old female was admitted to our hospital due to upper abdominal pain with lower back pain for half a month. The patient reported a 1 yearhistory of "duodenal ulcer" and was treated with conventional oral omeprazole. She had no family history of cancer. Physical examination onadmission revealed no positive signs. The laboratory findings were as follows: serum CA72- 4 was 11.32 U/mL (normal range ＜8.2 U/mL), and allother tumor markers were in the normal range. Computed tomography (CT) showed low density of the pancreatic tail with multiple liver metastases(Figure 1). The magnetic resonance imaging (MRI) showed a tumor of about 4.3 cm in the pancreatic tail, showing long T1 mixed T2 signal withmultiple liver metastases (Figure 2). The 18Fluorine- FDG PET- CT showed high metabolism in the pancreatic tail but without high metabolism in theliver metastases (Figure 3). Gastroscopy suggested chronic superficial gastritis and multiple ulcers in the duodenum. According to the results ofadditional serological examination, gastrin was ＞1,000 pg/mL (normal range 25- 100 pg/mL).

Palliative surgery (distal pancreatectomy, splenectomy, and partial hepatectomy) was performed on the 18th of September, 2015. Postoperativepathological results showed high proliferative activity of pancreatic tail neuroendocrine tumor (gastrinoma) with multiple liver metastases (Ki- 67,25%). Postoperative recovery was uneventful. She was discharged on the 8th day after surgery.

Postoperatively, the patient was treated with proton pump inhibitor (PPI). One month later, the repeat serum gastrin level was still ＞1,000pg/mL.

Considering the liver metastases had the ability to secrete gastrin, the patient started to receive lanreotide 120 mg every 2 weeks. On the other hand, the hepatic- directed therapies were considered to reduce tumor bulk and relieve symptoms of hormone hypersecretion. The patient wastreated with trans- arterial chemoembolization (TACE, intraoperative chemotherapy drugs was oxaliplatin 150 mg and epirubicin 40 mg) twice at 2months and 4 months after the surgery. Moreover, she was treated with radiofrequency ablation (RAF) once at 6 months after the surgery. After the15 months follow- up, her serum gastrin had dropped significantly to 104.1 pg/mL. The MRI showed the patient was currently in stable condition(Figure 4) ,and the gastroscopy results were all normal.

DISC SSION

Gastrinoma is a rare kind of functioning neuroendocrine tumor that is usually associated with Zollinger-Ellison syndrome, which presents asgastric hypersecretion, hyperacidity, and recurrent peptic ulcers. It was first reported by Zollinger and Ellison in 1955. 1 Typical symptoms ofgastrinoma include abdominal pain, secretory diarrhea, esophagitis and hypercalcemia.2 Abdominal pain is the most common symptom and isusually caused by peptic ulcers. In this case, the initial symptom was also abdominal pain.

The majority of gastrinomas are identified within the gastrinoma triangle, which consists of the duodenum, pancreatic head and hepatoduodenalligament.3 Metastasis of gastrinomas to distant organs can occur, and the most common metastatic sites are the peripheral lymph nodes and liver.In this case, gastrinoma was located in the tail of pancreas with synchronous liver metastasis.

According to the 2016 ENETS guidelines and 2016 NCCN guidelines version 2, primary tumor resection combined with debulking of liver metastasis

Authors Guang Yang, Jie Chen, Chenghao Shao

E- mail shaochenghao_czyy@163.com

Institute Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University

City/Nationality Shanghai, China

Category Upper GI Lower GI Pancreatobiliary tract Others

Title of Case

A case of gastrinoma with liver metastasis

can be considered in the functioning pNET.4,5 The purpose of the surgery is to reduce the tumor burden as much as possible and relieve the clinicalsymptoms caused by increased hormone secretion.

For postoperative treatment, it can be divided into two parts. One is systemic treatment, including somatostatin analogs (SSA), molecularly targetedtherapies, and cytotoxic chemotherapy. Based on the recommendation4,5 of the updated guidelines and the results from the CLARINET study andPROMID trial,6,7 lanreotide and octreotide are both appropriate options for gastrinomas with liver metastasis. If the clinical symptoms of hormonehypersecretion cannot be relieved by SSA and liver metastases grow rapidly, then molecularly targeted therapies and cytotoxic chemotherapy can betaken into consideration.

The other option is hepatic- directed therapies, which includes bland hepatic arterial embolization, radioembolization, and chemoembolization. Thehepatic- directed therapies in general are an effective approach for debulking the liver metastases.

In conclusion, the present study reported a case of a 49- year- old female patient diagnosed of gastrinoma with liver metastasis, who was treated bypalliative surgery (distal pancreatectomy, splenectomy, and partial hepatectomy). For functioning NET, primary tumor resection combined withdebulking of metastasis are effective approaches. Postoperative treatment is essential for the functioning NET metastases.

FIGURES

FIGURE 1

Preoperative multiphasic computed tomography (CT) showed low density of the pancreatic tail with multiple liver metastases. In the arterial phaseand portal phase, the primary site was not enhanced, while the liver metastases were significantly enhanced. The arrows point to the tumors.

FIGURE 2

Preoperative multiphasic magnetic resonance imaging (MRI) showed a tumor of about 4.3 cm in the pancreatic tail with multiple liver metastases. They both showed long T1 mixed T2 signal. The arrows point to the tumors.

FIGURE 3

Preoperative 18Fluorine- FDG PET- CT showed high metabolism (max standardized uptake walue = 5.3) in the pancreatic tail, while high metabolism was not observed in the liver metastases. The arrows point to the pancreatic tail tumor.

FIGURE 4

Postoperative multiphasic magnetic resonance imaging (MRI) showed that the liver metastases are currently stable at 15 months.

REFERENCES

01 Zollinger RM and Ellison EH. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. 1955. CACancer J Clin 1989;39:231- 247.

02 Imamura M, Nakamoto Y, Uose S, et al. Diagnosis of functioning pancreaticoduodenal neuroendocrine tumors. J HepatobiliaryPancreat Sci 2015;22:602- 609.

03 Stabile BE, Morrow DJ and Passaro E Jr. The gastrinoma triangle: operative implications. Am J Surg 1984;147:25- 31.

04 Falconi M, Eriksson B, Kaltsas G, et al. ENETS consensus guidelines update for the management of patients with functional pancreaticneuroendocrine tumors and non- functional pancreatic neuroendocrine tumors. Neuroendocrinology 2016;103:153- 171.

05 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Neuroendocrine tumors, version 2. 2016.

06 Caplin ME, Pavel M, Cwikla JB, et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014;371:224-233.

07Rinke A, Müller HH, Schade- Brittinger C, et al. Placebo- controlled, double- blind, prospective, randomized study on the effect ofoctreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMIDStudy Group. J Clin Oncol 2009;27:4656- 4663.