Setsuo Okada

Effect of preoperative portal vein embolization on major hepatectomy for advanced-stage hepatocellular carcinomas in injured livers: A preliminary report

With the aim of minimizing postoperative liver dysfunction and promoting increased resectability, we employed portal vein embolization (PVE). In this study, the effect of PVE on major hepatic resection for advanced-stage hepatocellular carcinoma (HCC) in injured livers was evaluated. PVE was performed prior to hepatectomy in 13 patients with stage III and IV HCCs. Following PVE, right trisegmentectomy was performed in 3 patients, extended right lobectomy in 3 and right lobectomy in 7. To evaluate the effect of PVE, the changes in liver functional capacity and estimated remnant liver volume (ERLV), determined by computed tomography, were examined before and after PVE. The operative morbility, mortality, and survival rates after hepatectomy were also assessed. By 2 weeks after PVE, ERLV had increased in all patients, by an average of 28%, and the mean resection rates had decreased from 70.0% to 62.2%. Postoperatively, the 30-day mortality rate was 15.3%, and the 1- and 2-year survival rates were 69% and 46%, respectively. The results of this study indicate that resectability can be increased, and major hepatectomy can be made safer by employing PVE preoperatively, in view of the fact that major hepatectomy was not considered feasible without PVE in these patients.

Measurement of Serum Hyaluronate as a Predictor of Human Liver Failure after Major Hepatectomy

Serum hyaluronate can be used as an index of hepatic sinusoidal endothelial cell function. This study was designed to evaluate its application as a predictor of liver failure after major hepatectomy. Thirty-six patients who underwent right liver lobectomy after percutaneous transhepatic right branch portal vein embolization were divided into two groups based on their postoperative clinical course (groups 1 and 2, with and without postoperative liver failure, n= 6 and n= 30, respectively). We serially measured serum hyaluronate levels using a sandwich binding protein assay system before and after hepatectomy and determined relations with progression of the underlying chronic liver disorder, portal venous pressure, and liver growth of the left lobe after portal embolization. Serum hyaluronate levels were significantly elevated, in line with the degree of severity of the underlying chronic liver disorder, and correlated well with the portal venous pressure and the hypertrophic ratio of the left lobe subsequent to portal embolization. Serum hyaluronate levels in group 1 were significantly higher than those in group 2 before surgery and increased steeply during the early period after hepatectomy. These results suggest that the serum hyaluronate reflects the hepatic functional reserve, and serial measurement of this parameter after hepatectomy can serve as a simple indicator for early detection of posthepatectomy liver failure.

PREDICTION OF THE EARLY PROGNOSIS OF THE HEPATECTOMIZED PATIENT WITH HEPATOCELLULAR CARCINOMA WITH A NEURAL NETWORK

The early prognosis of the hepatectomized patients with hepatocellular carcinoma was determined preoperatively with a perceptron-type neural network. The neural network was trained with the preoperative data of 54 example cases with the early prognosis, successful or died of hepatic dysfunction, as teaching signals. After learning these examples, the neural network came to give a precise prediction to the example data except for one case. With the learned neural network, the outcomes of the hepatectomy of 11 patients (10 successful; 1 died) were predicted prospectively with 100% precision. The usefulness of the neural network for the prediction was determined.

Reduced expression of cell cycle regulator p18INK4C in human hepatocellular carcinoma

Cyclins, cyclin‐dependent kinases (Cdks), and Cdk inhibitors (CdkIs) are frequently altered in human cancer. p18INK4C, a member of the INK4 family of CdkIs, is a potential tumor‐suppressor gene product. However, the expression of p18INK4C in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to examine the expression of p18INK4C in various liver diseases including HCC and to assess its clinical significance in HCC. To that end, we examined the expression of p18INK4C by immunohistochemistry in various liver diseases, including 51 HCCs, and also studied the relationship between p18INK4C expression, the phosphorylation of retinoblastoma protein (pRb), and the activity level of Cdk4 and Cdk6. Immunohistochemical analysis revealed the frequent loss of p18INK4C expression in HCC, especially in poorly differentiated HCC. The loss of p18INK4C expression was shown to be associated with a poor prognosis compared with that associated with p18INK4C‐ positivity. Further, the kinase activity of Cdk4 was found to be higher in p18INK4C‐negative HCCs than in p18INK4C‐ positive HCCs. However, the level of Cdk6 activity was similar in the 2 groups of HCCs. In p18INK4C‐ positive HCCs, p18INK4C dominantly interacted with Cdk4 rather than with Cdk6. pRb phosphorylated at serine(Ser) 780 was detected more frequently in p18INK4C ‐ negative than in p18INK4C ‐ positive HCCs. In conclusion, the loss of p18INK4C expression may play a role in the differentiation and development of HCC through the up‐regulation of Cdk4 activity. (HEPATOLOGY 2004;40:677–686.)

Castleman disease of the pararenal retroperitoneum: report of a case.

We describe herein the case of a 21-year-old woman in whom Castleman disease of the pararenal retroperitoneum was successfully resected. The patient was referred to our hospital from another hospital for investigation of a retroperitoneal mass in the right middle abdomen. Ultrasonography, computed tomography, and magnetic resonance imaging demonstrated a large retroperitoneal mass with heterogeneous imaging characteristics. An aortogram showed arterial feeding to this mass from a few lumbar arteries. Although a definitive preoperative diagnosis could not be made, surgical excision was performed and histopathological examination confirmed a diagnosis of the hyaline type of Castleman disease. The patient had an uneventful postoperative course and was discharged 14 days after her operation. She now leads an active social life without any signs of sequelae or recurrence 14 months later. To the best of our knowledge, only 2% (6/315) of all reported cases of Castleman disease have been located in the pararenal and retroperitoneal area.

Treatment of recurrent hepatocellular carcinoma by hepatectomy with right and middle hepatic vein reconstruction using total vascular exclusion with extracorporeal bypass and hypothermic hepatic perfusion: report of a case.

We report herein the case of a patient who had previously undergone a lateral segmentectomy for hepatocellular carcinoma (HCC) in whom recurrent HCC invading the trunk of the right and middle hepatic veins in a damaged liver was treated by reconstruction of both hepatic veins, using total vascular exclusion with extracorporeal bypass and hypothermic hepatic perfusion. Reconstruction was performed using a graft taken from the left external iliac vein and divided into two pieces. Hepatic ischemia lasted for 91 min during the procedure and the intrahepatic temperature, as monitored by inserting a needle-type thermometer, was decreased to 11 degrees C throughout the procedure. The peak levels of serum glutamic pyruvic transaminase, lactate dehydrogenase, and total bilirubin were 363 IU/l, 1198 IU/ml, and 2.8 mg/dl, respectively, on postoperative day (POD) 2. The patients postoperative course was uneventful except for mild, temporary swelling of the left leg. Postoperative computed tomography and magnetic resonance imaging examinations disclosed no obstruction of either graft, and the patient was discharged on POD 40.

Increase in portal blood interleukin-6 soon after the commencement of digestive surgery

To determine whether cytokines produced in the operative field during digestive surgery selectively spill over into the portal blood, the changes in interleukin-6 (IL-6) levels in portal and peripheral venous blood were assayed at several points in time from the commencement of surgery until 14 days later, in 11 patients. Similar changes in the IL-6 levels were observed in the portal and peripheral blood samples; however, the IL-6 levels in the portal blood reached a maximum 6–12 h after the commencement of surgery, being earlier than in the peripheral venous blood. In fact, between 3 and 12 h after the commencement of surgery, the IL-6 levels were higher in the portal blood by 33–81 pg/ml. By 24 h or more after the commencement of surgery, the IL-6 levels did not differ significantly in the two types of blood samples. Moreover, the C-reactive protein levels 2 days after surgery were even more closely correlated to the maximum IL-6 levels in the portal blood than to those in the peripheral venous blood. These results suggest that IL-6 produced during intraabdominal digestive surgery initially enters the portal blood, being trapped by IL-6 receptors in the liver, where it may regulate the synthesis of acute-phase proteins as a hepatocyte-stimulating factor.

Surgical treatment of an enormous aneurysmal portahepatic venous fistula: Report of a case

We report herein the case of a 20-year-old woman in whom an enormous aneurysmal portahepatic venous fistula was found. The portal aneurysm developed in the anterior inferior segment of the right hepatic lobe, and communicated with the right portal vein and the right hepatic vein. Due to the enormous size of the shunt, and because the patients venous blood ammonia level increased by about twofold after eating, a right lobectomy of the liver was performed. A review of the available literature and a discussion of the most appropriate treatment follows the presentation of this case.

Extrapancreatic lymphoepithelial cyst of the pancreas

A lymphoepithelial cyst is reported. A 68-year-old man consulted a surgeon, presenting with a sense of abdominal fullness. Ultrasonography and computed tomography revealed a large tumor, 10 cm in diameter, behind the head of the pancreas. Celiac arteriography at our hospital showed feeding arteries from the dorsal pancreatic artery and the pancreatic arcades. CA19-9 was elevated to 178 U/ml. Laparotomy was performed. The tumor was well demarcated from the surrounding tissue by a fibrous capsule and there was no continuity to the pancreatic parenchyma. Simple tumorectomy and distal gastrectomy for peptic gastric ulcer disease were performed. The cut surface revealed a multicystic lesion containing atheromatous substances. Histopathologically, the internal surface of the cyst was lined with stratified squamous epithelium containing mucin-producing cells; many germinal centers were observed in the cyst wall.

Resection of the head of the pancreas in three patients with anomalous arrangement or occlusive diseases of the major abdominal visceral arteries

We resected the head of the pancreas in three patients with occlusive diseases or anomalous arrangement of the abdominal visceral arteries. The first patient who was diagnosed with cancer of the head of the pancreas; pancreatoduodenectomy (PD) was performed. Preoperative celiac angiography showed no significant occlusion of the celiac axis, while superior mesenteric arteriography visualized the common hepatic artery, with delayed retrograde filling. At the completion of the PD, an unsuspected atherosclerotic celiac occlusion was identified. Celiac reconstruction was performed. The second patient was diagnosed with cystadenoma of the head of the pancreas and had congenital ostial occlusion of the superior mesenteric artery (SMA), with dilated pancreaticoduodenal (PD) arcades as a celiacomesenteric collateral pathway. Duodenum-preserving resection of the head of the pancreas was performed, with preservation of the PD arcades. The third patient was diagnosed with cancer of the common bile duct, and exhibited a replaced common hepatic artery that arose from the SMA and formed PD arcades. PD was performed, with revascularization of the common hepatic artery. Following surgery, the three patients have done well for 18, 27, and 9 months, respectively. Careful preoperative investigation to identify abnormalities of the visceral arteries is necessary before resection of the head of the pancreas is performed.