Cytoglobin-expressing cells in the splenic cords contribute to splenic fibrosis in cirrhotic patients.

BACKGROUND AND AIM: Among several noninvasive evaluation methods of portal hypertension (PH), the measurement of spleen stiffness is a reliable method for predicting esophageal variceal bleeding; however, the underlying mechanisms for increased stiffness remain unclear. We attempted to elucidate the pathological changes to the spleen and the underlying mechanisms in patients with PH. METHODS: Histological examination was performed using splenic tissues from 42 patients with PH who underwent laparoscopic splenectomy, and the results were compared with those from patients without PH. RESULTS: In addition to splenic sinus congestion, diffuse fibrosis was detected in the splenic cords in the red pulp of patients with PH. The degree of the fibrosis was well correlated with severity in thrombocytopenia and splenomegaly. Cells expressing α-smooth muscle actin dramatically increased in the splenic cord. Cytoglobin (Cygb) expression was detected in human splenic cords as reported in animal reticular cells, and fluorescent double immunostaining revealed that these cells expressed α-smooth muscle actin in patients with PH, suggesting transformation of Cygb-expressing cells to myofibroblastic cells. Expression levels of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 2, nitrotyrosine, and transforming growth factor-ß were markedly upregulated in the red pulp of patients with PH, implying a significant role of oxidative stress in the mechanism for splenic fibrosis. CONCLUSION: Splenic fibrosis progresses along with advancement of PH. Cygb-expressing cells in the splenic cord possibly participate in this process through mechanisms including oxidative stress.

Bronchobiliary fistula caused after hepatectomy for hepatocellular carcinoma: a case report.

BACKGROUND: A bronchobiliary fistula, an intercommunication between the biliary tract and bronchial trees, is an extremely rare complication after hepatectomy. CASE PRESENTATION: A 70-year-old male underwent partial resection of the liver for recurrent hepatocellular carcinoma under a thoracoabdominal approach. The immediate postoperative clinical course was uneventful, but the patient was febrile and laboratory examinations revealed leukocytosis on the 15th postoperative day. An intraabdominal abscess was suspected based on the computed tomography findings, and percutaneous drainage was performed. Bile was drained, and fluoroscopy using a contrast medium from the drainage tube revealed a communication between the cavity and the common hepatic duct. Two weeks after drainage, bilioptysis was seen. Fistulography demonstrated the presence of the bronchus in the right lower lobe of the lung via the subphrenic space. Therefore, the patient was diagnosed to have a bronchobiliary fistula. Fistulography revealed closure of the communication with the bronchus about a month after drainage. However, the bile leakage and bilioptysis did not stop even after endoscopic nasogastric biliary drainage, and ethanol injection therapy were performed. Eventually, residual right bisectionectomy without resection of the fistulous tract and involved lung was performed to remedy the intractable bile leakage. The clinical course after the reoperation was good without bile leakage, bilioptysis, or pulmonary disorders, and the patient was discharged 40 days after reoperation. CONCLUSIONS: We experienced a rare case of bronchobiliary fistula that occurred after hepatectomy for hepatocellular carcinoma. Careful attention should be paid to prevent bile leakage during hepatectomy, since bile leakage has the potential to cause a bronchobiliary fistula.

Splenectomy attenuates murine liver fibrosis with hypersplenism stimulating hepatic accumulation of Ly-6C(lo) macrophages.

BACKGROUND & AIMS: Splenectomy in cirrhotic patients has been reported to improve liver function; however the underlying mechanism remains obscure. In the present study, we investigated the mechanism using a murine model, which represents well the compensated liver cirrhosis. METHODS: C57BL/6 male mice were allowed to drink water including thioacetamide (TAA: 300 mg/L) ad libitum for 32 weeks. After splenectomy at 32 weeks, mice were sacrificed on days one, seven, and 28, respectively, while TAA-administration was continued. Perioperative changes in peripheral blood and liver tissues were analyzed. RESULTS: TAA treatment of mice for 32 weeks reproducibly achieved advanced liver fibrosis with splenomegaly, thrombocytopenia, and leukocytopenia. After splenectomy, liver fibrosis was attenuated, and macrophages/monocytes were significantly increased in peripheral blood, as well as in the liver. Progenitor-like cells expressing CK-19, EpCAM, or CD-133 appeared in the liver after TAA treatment, and gradually disappeared after splenectomy. Macrophages/monocytes accumulated in the liver, most of which were negative for Ly-6C, were adjacent to the hepatic progenitor-like cells, and quantitative RT-PCR indicated increased canonical Wnt and decreased Notch signals. As a result, a significant amount of ß-catenin accumulated in the progenitor-like cells. Moreover, relatively small Ki67-positive hepatic cells were significantly increased. Protein expression of MMP-9, to which Ly-6G-positive neutrophils contributed, was also increased in the liver after splenectomy. CONCLUSIONS: The hepatic accumulation of macrophages/monocytes, most of which are Ly-6C(lo), the reduction of fibrosis, and the gradual disappearance of hepatic progenitor-like cells possibly play significant roles in the tissue remodeling process in cirrhotic livers after splenectomy.

Primary squamous cell carcinoma of the liver: an uncommon finding in contrast-enhanced ultrasonography imaging.

Primary squamous cell carcinoma (SCC) of the liver is rare tumor with an unfavorable prognosis. We report a case of advanced primary SCC of the liver arising adjacent to a nonparasitic liver cyst, invading into the right diaphragm and the right lung tissue. Contrast-enhanced ultrasonography (CE-US) demonstrated unique enhancement in the late vascular phase, which was incompatible with those observed in hepatocellular carcinoma, cholangiocellular carcinoma, or metastatic adenocarcinoma. The patient underwent surgical resection of the tumor followed by systemic chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP), while radiation chemotherapy was not applied because of relatively poor performance status. Although postoperative image analysis revealed no recurrence 4 months later, the patient died 13 months after the operation from recurrence. Immunohistological analysis of the resected specimen revealed that this SCC contained many capillary endothelial vessels expressing CD31 or CD34, possibly reflecting the unique imaging pattern in the late vascular phase of CE-US, which has been reported in choangiolocellular carcinoma. In addition, we reviewed which kind of treatment would be suitable for advanced hepatic primary SCC in the literature. From the review, it could be proposed that a combination of radiation therapy, systemic chemotherapy (5-FU and CDDP) and surgical resection, if possible, is appropriate for advanced primary SCC of the liver.