A 69-year-old man was diagnosed with GBC with hepatic invasion after a 2-year follow-up for right breast cancer surgery, during which his serum carcinoembryonic antigen (CEA) level was elevated. He was referred to our hospital in Jun. 2007.
Preoperatively, abdominal ultrasonography and computed tomography (CT) scan revealed a tumor (37 × 30 mm in diameter), involving the liver bed from the neck of the gallbladder (Fig. 1). Endoscopic ultrasonography did not reveal any cystic duct invasion; however, metastasis to the lymph node near the common bile duct was suspected on CT scan. Distant metastasis, including to the liver, was not observed. The results of a blood test on admission indicated that liver and kidney functions were normal. The levels of tumor markers were as follows: CEA, 10.3 ng/mL and carbohydrate antigen (CA) 19-9, 785.24 U/mL.
Cholecystectomy with hepatectomy of S4a and S5, lymph node dissection of the hepatoduodenal ligament, resection of the extrahepatic bile duct, and Roux-en-Y choledochojejunostomy were performed in Jul. 2007. R0 resection was accomplished. The postoperative course was uneventful.
According to the seventh edition of the Tumor Nodes and Metastasis (TNM) Classification of the International Union Against Cancer, the postoperative pathological diagnosis was moderately differentiated adenocarcinoma of the gallbladder, T3, N0, M0, stage IIIA (Fig. 2).
The patient’s clinical course and associated changes in tumor markers are illustrated in Fig. 3. Adjuvant chemotherapy was administered (gemcitabine [GEM], 1000 mg/m2, biweekly). After 8 cycles of chemotherapy, the patient’s CA 19-9 level had increased to 210.51 U/mL and metastases to the common hepatic artery lymph nodes and para-aortic lymph nodes were detected in Oct. 2007 (3 months post-surgery) on CT scan. Therefore, the chemotherapy regimen was changed to GEM (1000 mg/m2, days 1 and 8) and TS-1 (a combination capsules of tegafur, gimeracil, and oteracil potassium, 60 mg/m2, daily, 2 weeks on/1 week off). GEM and TS-1 were discontinued when the patient developed thrombopenia accompanied by elevation of CA 19-9 to 801 U/mL in Jan. 2008. A CT scan revealed that the common hepatic artery lymph node and para-aortic lymph node metastases had increased in size by surrounding the common and proper hepatic arteries; the metastases reached the portal vein bifurcation (Fig. 4).
In Mar. 2008 (8 months post-surgery), a CT scan revealed an enlargement of the lymph node metastasis with invasion into the portal vein, celiac artery, superior mesenteric artery, duodenum, pancreas, and inferior vena cava. A combination of low-dose cisplatin (CDDP, 6 mg/body, daily) and X-ray radiation consisting of 50 Gy/25 fr was administered. After chemotherapy and radiation were completed in Jun. 2008 (11 months post-surgery), CA 19-9 levels had decreased to 22.53 U/mL.
After the decrease in CA 19-9 levels, GEM (1000 mg/m2) and CDDP (15 mg/m2) were re-administered on days 1 and 8 (2 weeks on/1 week off). CA 19-9 decreased to normal levels after three courses of treatment. GEM and CDDP were continued, and stable disease was maintained according to the Response Evaluation Criteria in Solid Tumor (RECIST). In Dec. 2009 (2 years and 5 months post-surgery), after 28 courses of treatment had been administered in total, a new metastatic lesion was detected near the colon of the hepatic flexure on a CT scan and was diagnosed as a peritoneal metastasis.
Owing to the discovery of the additional metastasis, the chemotherapy regimen was changed to uracil and tegafur (UFT, 300 mg/body) and leucovorin (25 mg/body), which were administered daily (4 weeks on/1 week off), in Jan. 2010 (2 years and 6 months post-surgery). X-ray radiation of 40 Gy/20 fr was also administered. After treatment, the levels of tumor markers decreased to normal, and a CT scan revealed reduced tumor size of the peritoneal metastasis (Fig. 5).
In Apr. 2011 (3 years and 9 months post-surgery), after 16 courses of UFT and leucovorin treatment, the levels of tumor markers had once again increased and the size of the peritoneal metastasis had increased. Radiotherapy treatment was no longer possible because the patient had reached the maximum dose allowable and because of the risk for adverse gastrointestinal effects. Multiple imaging modalities including CT, magnetic resonance imaging (MRI), and positron emission tomography (PET/CT) revealed that the peritoneal metastasis was isolated. Also, the lymph node metastases of hepatoduodenal ligament and para-aorta maintained stable disease and did not show any viability. Therefore, the peritoneal metastasis was resected in Apr. 2011. Open laparotomy findings did not reveal any peritoneal dissemination except the isolated peritoneal metastasis. The metastatic mass was 18 × 15 mm in size and was resected without a residual tumor. The postoperative pathological diagnosis was a metastatic adenocarcinoma. The effect of radiotherapy was also observed, and its effect was evaluated as grade 1b (about half of tumor cells showed highly change).
After resection, chemotherapy was discontinued because the tumor marker levels were within normal limits. PET/CT scan obtained in Nov. 2011 did not reveal any tumors.
At the time of reporting, 7.6 months have passed since the primary tumor was removed, and 3 years and 9 months have passed since the peritoneal metastasis was resected. At this time, the levels of tumor markers are within normal limits and tumor recurrences have not been detected on CT scan.