Preoperative diagnosis rate of pancreatic cancer has increased year by year. The prognosis of pancreatic cancer patients with unexpected liver metastasis found by intraoperative exploration is very poor, and there is no effective and unified treatment strategy.

To evaluate the therapeutic effect of radioactive ¹²⁵I seed implantation for pancreatic cancer patients with unexpected liver metastasis.

The demographics and perioperative outcomes of patients who underwent ¹²⁵I seed implantation to treat pancreatic cancer with unexpected liver metastasis between January 1, 2017 and June 1, 2019 were retrospectively analyzed. During the operation, ¹²⁵I seeds were implanted into the pancreatic tumor under the guidance of intraoperative ultrasound, with a spacing of 1.5 cm and a row spacing of 1.5 cm. For patients with obstructive jaundice and digestive tract obstruction, choledochojejunostomy and gastroenterostomy were performed simultaneously. After operation, the patients were divided into a non-chemotherapy group and a chemotherapy group that received gemcitabine combined with albumin-bound paclitaxel treatment.

Preoperative imaging evaluation of all patients in this study showed that the tumor was resectable without liver metastasis. There were 26 patients in this study, including 18 males and 8 females, aged 60.5 ± 9.7 years. The most common tumor site was the pancreatic head (17, 65.4%), followed by the pancreatic neck and body (6, 23.2%) and pancreatic tail (3, 11.4%). Fourteen patients (53.8%) underwent palliative surgery and postoperative pain relief occurred in 22 patients (84.6%). The estimated blood loss in operation was 148.3 ± 282.1 mL and one patient received blood transfusion. The postoperative hospital stay was 7.6 ± 2.8 d. One patient had biliary fistula, one had pancreatic fistula, and all recovered after conservative treatment. After operation, 7 patients received chemotherapy and 19 did not. The 1-year survival rate was significantly higher in patients who received chemotherapy than in those who did not (68.6% vs 15.8%, P = 0.012). The mean overall survival of patients in the chemotherapy group and non-chemotherapy group was 16.3 mo and 10 mo, respectively (χ² = 7.083, P = 0.008).

Radioactive ¹²⁵I seed implantation combined with postoperative chemotherapy can prolong the survival time and relieve pain of pancreatic cancer patients with unexpected liver metastasis.

In recent years, with the development of computer technology and imaging technology combined with the detection of serum tumor markers, the preoperative diagnosis rate of pancreatic cancer has increased year by year. Pancreatic cancer is characterized by insidious onset, rapid progress, and poor prognosis[1,2]. It is a common tumor in the digestive system, and patients usually lack of early symptoms. Most of patients are at the late stage of disease when diagnosed, and radical resection is the most effective treatment for pancreatic cancer[3]. Clinically, only 20% of patients have surgical conditions, while the rest can only receive palliative treatment[4-6].

Even if enhanced computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography/computed tomography (PET/CT) was performed before the operation, about 8% of the patients who planned to undergo radical resection still had liver metastasis found during the exploration. Liver metastasis is a sign of advanced stage of pancreatic cancer. Usually, surgeons only terminate the operation for such patients after pathology. If there is obstructive jaundice or digestive tract obstruction, palliative operations such as choledochojejunostomy and gastro-intestinal anastomosis can be performed.

The liver is the most common organ with metastasis of pancreatic cancer. The average survival time of pancreatic cancer patients with liver metastasis is only 3-6 mo[7]. There is no consensus on the treatment strategy for patients with pancreatic cancer and liver metastasis. There are simultaneous pancreatectomy combined with liver metastasis resection, first pancreatectomy followed by liver metastasis resection, resection of pancreatic cancer combined with radiofrequency ablation of liver metastasis, systemic chemotherapy combined with TACE treatment of liver metastasis, immunotherapy, and so on. None of the above treatments is satisfactory.

Since 1965, radioactive ¹²⁵I seeds began to be used in cancer treatment. It was initially used in the treatment of prostate cancer and achieved success[8]. A number of studies have shown that implantation of radioactive seeds in the treatment of pancreatic cancer can benefit the survival of patients, reduce pain, and improve the quality of their life[9-11]. The purpose of this study was to summarize a single center experience with ¹²⁵I seed implantation combined with postoperative chemotherapy in the treatment of pancreatic cancer patients with unexpected liver metastasis.

Pancreatic cancer often develops metastasis early because of the rapid growth of tumor cells, the rich blood vessels and lymphatic vessels around the pancreas, and the lack of a complete capsule. The liver is the most common target organ for metastasis of pancreatic cancer. The metastasis pathway of cancer locating in the pancreatic head is different from that of the pancreatic body and tail[12,13]. Cancer of the pancreas head often invades the common bile duct, duodenum, stomach, and celiac arteries, and its lymph node metastasis pathway is from the lymph nodes around the superior mesenteric artery and the lymph nodes around the aorta. However, cancer of the pancreas body and tail metastasizes to the lymph nodes of the upper pancreas and the hilum of the liver, and finally to the liver.

Liver metastasis of pancreatic cancer often has multiple focuses, which can occur in both left and right lobes of the liver. Patients often lose the chance of radical operation. For pancreatic cancer patients with liver metastasis, the treatment is limited and the total effect is not ideal. However, if the condition allows, active treatment such as surgery and interventional chemotherapy can still improve the quality of life and prolong the survival period of such patients. The biological behavior of pancreatic cancer itself is not sensitive to radiotherapy, and the radiation tolerance of its surrounding tissues is low. Therefore, it is difficult for conventional external radiotherapy to accurately locate the lesion area, so as to make enough therapeutic dose of radiation reach the target area, or even reach the tumor target area; it also causes great damage to the surrounding organs[14-16].

¹²⁵I seeds can continuously release a low dose of γ-ray when they are implanted into tumor tissue. It can damage the DNA of tumor cells and induce apoptosis of tumor cells, so as to kill the proliferative cancer cells[17,18]. The advantages of ¹²⁵I seeds in the treatment of pancreatic cancer are local adaptation and low dose continuous therapy[19-21]. Compared with radical resection, local implantation of ¹²⁵I seeds in pancreatic cancer has less trauma, faster postoperative recovery, less impact on patients’ immunity, shorter postoperative recovery period, and less impact on early postoperative chemotherapy.

Our results showed that patients with pancreatic cancer with unexpected liver metastasis experienced pain relief and quality of life was improved after implantation of radioactive ¹²⁵I seeds. The combination of postoperative chemotherapy is helpful to prolong the survival period of such patients. We suggest that all patients take biopsy of tumor tissue during operation, and if possible, we suggest that gene detection of biopsy samples of those patients be performed so as to choose a possible and effective scheme for further chemotherapy after operation.

In order to reduce the occurrence of pancreatic fistula and bleeding during and after radioactive seed implantation, our experience is that the puncture point is carefully sutured with 4/0 prolene suture after the puncture needle has been removed from each implantation site. During the operation, the needle channel should be carefully adjusted under the guidance of ultrasound to avoid the puncture into the blood vessel and the dilated pancreatic duct[22,23]. The postoperative complications such as seed displacement, local embolism, pain, liver dysfunction, and pancreatic fistula were all recovered after conservative treatment in this study. The main shortcoming of this study is that the case was selected from a single center. In the next step, we will combine more centers to do this study.

In conclusion, our experience showed that the survival time could be prolonged and the quality of life be improved in pancreatic cancer patients with unexpected liver metastasis by ¹²⁵I seed implantation combined with postoperative chemotherapy. More cases need to be accumulated in future studies to determine the effectiveness of this treatment strategy further.