We discuss a patient who had poorly differentiated HCC with pyrexia and high CRP in laboratory data, which are not commonly observed in the usual HCC. A 50-year-old man with a history of liver dysfunction was admitted with a chief complaint of a prolonged fever and general fatigue. Preoperative diagnosis was HCC with portal vein tumor thrombus. Posterior segmentectomy of the liver and thrombectomy was performed. Rapid tumor recurrence occurred after surgery, and he died 79 days after the operation. Immunohistochemical stain of HCC in this patient revealed the production of proinflammatory cytokine, interleukin-8 (IL-8). IL-8 production may have contributed to the high fever, high inflammatory reaction, and poor prognosis in this case.
Hepatocellular carcinoma (HCC) is a common malignancy and is now one of the major causes of death in Asian countries [
Recently, increased production of proinflammatory cytokines and chemokines, such as interleukin-1
We herein discuss a case of HCC accompanied by prolonged spiking fevers, which disappeared after tumor resection. Immunohistochemical stain of HCC in this patient revealed the production of IL-8.
A 50-year-old man with a history of liver dysfunction was admitted to Iizuka Hospital with the chief complaint of a prolonged fever and general fatigue in October, 2005. The temperature was over 38°C. Hematological laboratory data on admission were as follows: WBC 9670/
Laboratory data in this patient. (normal range).
WBC | 9670/ | (3500–9500) |
71.8 | (40–74) | |
21.5 | (20–74) | |
Hb | 13.2 g/dl | (12.7–17.1) |
Plt | ( | |
PT | 77.6 | (86–130) |
APTT | 41.9 sec | (24.8–36.5) |
TP | 7.1 g/dl | (6.7–8.3) |
Alb | 2.6 g/dl | (4.0–5.0) |
T.Bil | 0.4 mg/dl | (0.3–1.2) |
D.Bil | 0.1 mg/dl | (0–0.4) |
AST | 38 U/l | (13–33) |
ALT | 23 U/l | (6–30) |
LDH | 330 U/l | (119–229) |
ALP | 552 U/l | (115–359) |
79 U/l | (10–47) | |
ChE | 30 U/l | (214–466) |
TC | 97 mg/dl | (128–219) |
TG | 48 mg/dl | (30–149) |
Amy | 111 U/l | (42–132) |
BUN | 11 mg/dl | (8–22) |
Cr | 0.6 mg/dl | (0.6–1.1) |
FBS | 103 mg/dl | (69–109) |
CRP | 16.7 mg/dl | ( |
ICGR15 | 11.5 | ( |
AFP | 11.1 ng/mL | ( |
PIVKA-II | 16 mAU/mL | ( |
CEA | 1.1 ng/mL | ( |
CA19-9 | 13.5 U/mL | ( |
HBs-Ag | HBe-Ag (+) | |
HBe-Ab | HCV-Ab |
(a) A Computed tomography (CT) showed a peripherally enhanced low density mass 7.5 cm in diameter, which located in segment 6 in the right lobe of the liver. (b) Tumor was accompanied with tumor thrombus to the posterior branch of portal vein. (c) Celiac angiography showed this lesion to be hypervascular. (d) Portal vein tumor thrombus in posterior segment was observed in portal phase of SMA angiography.
Biopsy was not done in this case because of danger of tumor seeding. Patients have chronic hepatitis B and then tumor was hypervascular and accompanied with portal thrombus, which is the feature of HCC, therefore a preoperative diagnosis was made as HCC with portal vein thrombus and nonsteroidal anti-inflammatory drugs were used to reduce the fever. Enough explanation was performed to the patient and informed consent for operation was obtained. Hepatic resection was conducted in November, 2005. The tumor was white and intrahepatic metastasis was observed (Figure
(a) Intraoperative findings revealed tumor was white and intrahepatic metastasis was observed. (b) On cut section, tumor was white and contained coagulation and necrosis. Portal vein tumor thrombus in segment 6 of the liver was observed (arrow heads).
(a) Histological findings revealed poorly differentiated HCC with trabecular pattern. Neutrophil infiltration in the tumor was observed. (b) Immunohistochemically, paraffin section of tumor tissue stained positive for IL-8 (arrow heads).
After the tumor resection, fever disappeared and CRP dropped gradually from 16.7 to 2.7, but the patient had recurrence with multiple liver metastasis and pleuritis carcinomatosa and died on February 2, 2006, 79 days after the operation.
In 1991, Okuda et al. [
It is well known that cancer cells produce humoral factors and cause the “paraneoplastic syndrome”. Among the clinical symptoms and laboratory data, fever and high CRP, which is not commonly observed in the patients with HCC, is suspected to be due to humoral factors, especially inflammatory cytokine. IL-8 is a proinflammatory cytokine whose principal role in infection and inflammation appears to be the recruitment and activation of circulating and tissue neutrophils to the site of tissue damage. It has been demonstrated that IL-8 is produced by a wide variety of cell types in vitro, including endothelium, monocytes, eosinophils, astrocytes and keratinocytes. In sepsis patients, for example, IL-8 concentrations have been reported as being markedly elevated at diagnosis and remaining high during the course of the illness [
In other cancer, Interleukin-8 Producing Malignant Fibrous Histiocytoma with Prolonged Fever was reported [
In many cancers such as esophageal cancer, gastric cancer and colorectal cancer, serum CRP was known as a prognostic indicator [
In this report we discussed a patient who had poorly differentiated HCC with pyrexia and high CRP. The patient had surgical resection, but rapid tumor recurrence occurred. IL-8 production was histologically revealed in this case and may have contributed to the high fever, high inflammatory reaction and poor prognosis.