A 69-year-old retired Chinese male was admitted into our hospital in September 2015, presenting with upper abdominal pain for the previous month and dark urine for the previous 2 days (Fig. 6). The patient had hypertension for more than 10 years and diabetes for more than 20 years, and he had smoked for more than 30 years. Physical examination of the abdomen showed no abnormalities. Serum studies indicated high alanine aminotransferase (ALT, 151 U/L, normal range 9-50), serum aspartate aminotransferase (AST, 68 U/L, normal range 15-40), total bilirubin (TB, 36.57 mumol/L, normal range 2.00-20.00), cancer antigen 19-9 (CA19-9, 160.46 U/ml, normally range 0.00-37.00).
Abdominal ultrasound revealed a solid liver mass, hypoechoic areas in the left branch of hepatic portal vein suggesting portal vein invasion by the liver mass, and dilation of the intrahepatic bile duct in the lateral segment of the left hepatic lobe suggesting obstruction of the bile duct. These findings suggested a diagnosis of liver cancer with portal vein invasion and obstruction of the bile duct.
Enhanced-CT revealed multiple lesions in the right and left hepatic lobes, and invasion of the lymph node in the portal triad (Fig. 7). Multiple masses were evident in the right hepatic lobe (Fig. 7a, b), a small and patchy shadow was evident in the left hepatic lobe (Fig. 7c), and an oval shadow (22 x 38 mm) was evident in the portal triad, indicating abnormal soft tissue density (Fig. 7d). Enhanced-CT also suggested an invasion of the left portal vein and mild dilation of the bile duct in the right hepatic lobe. In summary, enhanced-CT suggested the diagnosis of intrahepatic malignant tumors, lymph node metastasis in the portal triad, and invasion of the left portal vein.
During the hospital stay, the patient presented with yellow skin and sclera, as well as fever and rash, suggesting the possibility of autoimmune liver disease. However, pathological examination confirmed a diagnosis of NEC (Fig. 8 and Additional file 2: Figure S2). IHC staining indicated that the cells were positive for AE1/AE3, Syn, chromogranin A (CgA) and CD56; and the IHC measured a Ki-67 index of 95%. Thus, IHC examination of the liver biopsy excluded the possibility of autoimmune liver disease and confirmed the diagnosis of poorly differentiated NEC (grade 3), a type of small-cell carcinoma, of uncertain origin. To confirm the hepatic primary origin of NEC as opposed to hepatic metastases, we performed gastroscopy, colonoscopy, and PET-CT examinations, and failed to find NEC in other organs. Therefore, we diagnosed the patient with PHNEC.
To investigate the causes for the yellow hue of the skin and sclera, we examined liver biochemical factors, measurement of which confirmed obstructive jaundice, indicated by an elevated total bilirubin level (336.97 mumol/L, normal range 2.00-20.00) with an increased level of direct bilirubin (279.76 mumol/L, normal range 0.00-6.00) and a normal level of indirect bilirubin. Obstructive jaundice was also consistent with the dilation of the bile duct that had been revealed by enhanced-CT.
For treatment, we chose not to perform surgical resection, considering the poor physical condition of the patient and the extensive spread of the tumor. We further excluded TACE treatment, because of the extent of the tumor lesions in both the right and left hepatic lobes, as well as the left portal vein. While TACE stops tumor growth by interrupting the blood supply to the tumor, normal liver cells can continue to survive relying on the portal vein. Thus, portal vein invasion contraindicated use of TACE, which would have a high risk of inducing liver failure. We treated the patient with the somatostatin analogue octreotide intravenously for 24 h at the dose of 125 mug/h, with the goal of inhibiting the growth of the neuroendocrine tumor and extending the patient's survival. However, the patient developed itchy red rashes, which are characteristic of an allergic reaction to octreotide. Therefore, we discontinued this treatment immediately. At this point, treatment was limited to protecting the liver by a four-day course of supplementary intravenous human albumin 20% (20 g per l00 ml, 50 ml administered per day). The patient died 109 days after first admission (Fig. 6).