On December 07, 2014, a 73-year-old man presented to our hospital with right abdominal pain for 3 days. On physical examination, he presented with mild tenderness in the right upper quadrant of the abdomen and positive for Murphy’s sign. The patient had no family history of cancer. Tumor markers showed alpha-fetoprotein (AFP), 1.61 IU/L (normal, 0-5.8 IU/L); carcinoembryonic antigen (CEA), 115.8 IU/ml (normal, 0–5 ng/ml); carbohydrate antigen19-9 (CA19-9), > 1000 IU/ml (normal, 0–27 IU/L); CA12-5, 112.3 IU/ml (normal, 0–35 IU/L). Abdominal magnetic resonance imaging (MRI) indicated that gallbladder cancer with multiple hepatic metastases and peritoneal metastases (Fig. 1). 18F-FDG PET/CT showed that gallbladder cancer with multiple hepatic metastases, the invasion of adjacent peritoneum, and multiple lymph node metastases of the right supraclavicular fossa, the right inner mammary area, the right frontal portion of diaphragm, and the peri pancreas (Fig. 2). Subsequently, the patient underwent a fine needle aspiration biopsy of the intrahepatic metastases and the pathological examination indicated adenocarcinoma (Fig. 3).
Based on all the above examinations, the patient was diagnosed with stage IV gallbladder cancer with multiple intrahepatic metastases and multiple lymph node metastases. We recommended that the patient initially went to the oncology department to receive adjuvant treatment. On March 25, 2015, the patient started receiving 7 cycles of chemotherapy of gemcitabine and oxaliplatin (GEMOX) and started receiving targeted therapy of cetuximab from the second cycle of chemotherapy. During the chemotherapy and targeted therapy, the patient suffered from biliary hemorrhage, and it was cured by arterial angiography and arterial embolization. The level of tumor markers gradually decreased during chemotherapy and targeted therapy (Fig. 4). After seven cycles of chemotherapy on August 6, 2015, abdominal MRI showed the malformation of the gallbladder, thickening of the cystic duct and common bile duct wall, and multiple intrahepatic metastases and the largest metastasis was approximately 37 mm⊆56 mm in size and located in the right liver (Fig. 5).
In October 2015, the patient underwent radioactive seed implantation in an outside hospital for further treatment. On January 2, 2016, the patient started receiving continuous immunotherapy of programmed death 1 (PD-1) inhibitor nivolumab and targeted therapy of cetuximab and apatinib. Due to the side effects of hypertension, apatinib was in turn replaced with nintedanib and regorafenib. On March 18, 2016, 18F-FDG PET/CT depicted: (1) some intrahepatic lesions were larger than the previous scans, and new lesions appeared in the left liver with increased 18F-FDG uptake; (2) some lesions of gallbladder were smaller than before; (3) lymph node metastases of the right supraclavicular fossa, the right inner mammary area and peri pancreas disappeared.
On February 06, 2018, the level of the patient’s tumor markers was CEA, 82.84 ng/ml; CA19-9, 54.60 IU/ml; CA12-5, 391.40 IU/ml. Abdominal computed tomography (CT) indicated an unclear gallbladder display, a left hepatic metastasis approximately 84 mm⊆59 mm in size, and multiple liver cysts (Fig. 6). 18F-FDG PET/CT showed that a left hepatic metastasis approximately 92 mm⊆60 mm in size, and the right hepatic metastasis was significantly smaller than before (Fig. 7). Since the distant lymph node metastasis had disappeared and the metastasis was mainly limited to the left liver, the patient was subsequently treated with radical surgery of left hepatectomy with partial diaphragmatic resection and radical lymphadenectomy (Fig. 8). We did not find the gallbladder in the surgical specimens, and we considered the gallbladder might have gradually disappeared during the adjuvant treatment. The postoperative pathological examination confirmed a moderately poorly differentiated cholangiocarcinoma of 90 mm⊆60 mm⊆60 mm in size in the left liver, perineural invasion, liver capsule invasion, diaphragm invasion, and negative for the liver resection margin. The postoperative immunohistochemical examination indicated ARGINASE-1 (-), CK19 (+), GPC-3 (partial +), hep-par (-), CEA (partial+), CK20 (-), CK7 (+) (Fig. 9).
Postoperatively, the patient still received regular immunotherapy therapy and targeted therapy. On October 24, 2019, the patient came to our hospital for a follow-up, the tumor markers have reversed to normal levels with CEA, 2.23 ng/ml; CA19-9, 21.45 IU/ml; CA12-5, 11.54 IU/ml. Abdominal CT showed no signs of tumor recurrence (Fig. 10). On June 12, 2020, the patient’s tumor markers remained in normal levels with CEA, 1.74 ng/ml; CA19-9, 22.32 IU/ml; CA12-5, 10.79 IU/ml. The patient's entire treatment process from being diagnosed with gallbladder cancer to the final surgery is shown (Fig. 11).
This study was approved by the Institutional Review Board of the First Affiliated Hospital of Dalian Medical University. Written informative consent was signed by this patient.