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Activin A is an autocrine inhibitor of cell growth in the liver. The biological activity of activin A is mediated by a heteromeric receptor complex. Follistatin (FS) binds to activin and inhibits its biological effects, and acts as a negative regulator of muscle cells. The role of activin receptors during liver regeneration following a hepatectomy has not been fully assessed. This study investigates the mechanism underlying how activin receptors regulate hepatocyte growth, and the effects of intravenous administration of FS during liver regeneration.The expression of both activins and activin receptors in the liver after a 70% partial hepatectomy (HT) was assessed by RT-PCR and immunohistochemistry. FS 315 or 288 was infused for different periods of time based on changes in hepatocyte activin receptor expression after HT.Activin receptor expression peaked between 48 and 72 hours after HT. 72 hours after HT, an injection of FS 315 resulted in a more potent stimulation of DNA synthesis and produced a greater increase in body weight compared with the control rats.The expression of activin receptors after peak DNA synthesis might be a key component in the downregulation of DNA synthesis. Intravenous administration of FS 315 might promote liver regeneration and have anabolic actions.

During epithelial morphogenesis, adherens junctions (AJs) and tight junctions (TJs) undergo dynamic reorganization, whereas epithelial polarity is transiently lost and reestablished. Although ARF6-mediated endocytic recycling of E-cadherin has been characterized and implicated in the rapid remodeling of AJs, the molecular basis for the dynamic rearrangement of TJs remains elusive. Occludin and claudins are integral membrane proteins comprising TJ strands and are thought to be responsible for establishing and maintaining epithelial polarity. Here we investigated the intracellular transport of occludin and claudins to and from the cell surface. Using cell surface biotinylation and immunofluorescence, we found that a pool of occludin was continuously endocytosed and recycled back to the cell surface in both fibroblastic baby hamster kidney cells and epithelial MTD-1A cells. Biochemical endocytosis and recycling assays revealed that a Rab13 dominant active mutant (Rab13 Q67L) inhibited the postendocytic recycling of occludin, but not that of transferrin receptor and polymeric immunoglobulin receptor in MTD-1A cells. Double immunolabelings showed that a fraction of endocytosed occludin was colocalized with Rab13 in MTD-1A cells. These results suggest that Rab13 specifically mediates the continuous endocytic recycling of occludin to the cell surface in both fibroblastic and epithelial cells.

Tumor-associated angiogenesis is essential for tumor growth or metastasis, and consists of multiple and sequential steps regulated by proangiogenic and antiangiogenic factors. Vascular endothelial cell proliferation is involved in this process. We investigated the correlation of vascular endothelial cell proliferation with microvessel density (MVD) and expression of major proangiogenic molecules, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in hepatocellular carcinoma (HCC). Formalin-fixed paraffin-embedded specimens of surgically resected HCC from 67 patients were used. Proliferating endothelial cells were detected by immunofluorescence double staining for CD34 and proliferating cell nuclear antigen (PCNA). The proliferation activity of endothelial cells was determined by the rate of PCNA-positive endothelial cells, and evaluated at the periphery and center of the tumors and adjacent non-neoplastic livers. MVD and the expression of VEGF and bFGF in the tumors were also examined immunohistochemically. The proliferation activity of endothelial cells at the periphery of the tumors was significantly higher than that at the center of the tumors (35.8% vs. 12.7%, P

Spontaneous rupture is a major life-threatening complication of hepatocellular carcinoma(HCC). Ruptured HCC often causes hypovolemic shock and hepatic hypoperfusion. Patients with impaired liver function tend to lapse into liver failure, which is the main cause of death. To prevent liver failure, accurate diagnosis and adequate treatment for the restoration of the efficient liver perfusion are required. Emergent transarterial embolization (TAE) is the most effective and less-invasive treatment for hemostasis. On the other hand, emergent hepatic resection should be avoided because of the increased risk of postoperative liver failure and incomplete resection of the tumor. After achieving hemostasis, a second-stage therapeutic approach for HCC is required. Patients with acceptable liver function should undergo surgery. The prognosis of ruptured HCC treated with second-stage hepatectomy is considered to be comparable with that of nonruptured HCC. In conclusion, spontaneous rupture of HCC is considered to be a combination of acute and severe peritoneal hemorrhage with malignant disease. To improve the prognosis, adequate early treatment for the control of hemorrhage while preserving liver function is an important factor. TAE followed by elective hepatectomy is considered the most effective treatment.

We report two cases that underwent extended left hepatic lobectomy combined with resection of the caudate lobe and extrahepatic bile duct only from the left side approach for hilar cholangiocarcinoma. The first case was a 54-year-old man and the second one was a 63-year-old man. Both patients had hilar cholangiocarcinoma with predominant left hepatic duct involvement and required resection and reconstruction of the right hepatic artery as well as left hepatic lobectomy. In both cases, the right hepatic lobe was never mobilized to protect the mechanical damage in the remnant liver and keep co-lateral blood supply route to the remnant liver from the diaphragm or retroperitoneum. Although arterial blood flow to the remnant right hepatic lobe was unfortunately insufficient after reconstruction of the right hepatic artery, the postoperative course was uneventful. The postoperative angiography showed co-lateral arterial blood supply to the right lobe via the subdiaphragmatic artery. In case of extended left hepatic lobectomy combined with resection of the caudate lobe and right hepatic artery, ipsilateral approach (approach only from the left side) is recommended.

Background. Hepatocellular carcinoma is likely to accompany liver cirrhosis in which the portal pressure increases with portasystemic shunt. When portal tumor thrombus is present in the primary bifurcation, blood flow differs between the thrombolic lobe and the non-thrombolic lobe. In those cases, it is difficult to evaluate exactly residual liver function by conventional test. Therefore, the following studies were performed. Materials and Methods. Adult mongrel dogs are divided into a control group (C group), group undergoing ligation of theleftportalbranch(PLgroup),groupundergoingportacaval anastomosis (PCS group) and group undergoing both ligation of the left portal branch and portacaval anastomosis (PL+PCSgroup)(n=5). ICG-R15 and MEGX15 in peripheral venous blood and right hepatic venous blood were determined. Mitchondrial metabolic capacity (adenosine triphosphate level, energy charge) was measured by high-performance liquid chromatography using liver biopsied specimens. Results. The MEGX ratio (right hepatic venous blood MEGX15/peripheral venous blood MEGX 15) positively correlated with energy charge in the right hepatic lobe. Conclusions. In evaluating liver function of the right hepatic lobe during portacaval shunt and the left portal branch ligation, the MEGX ratio may sensitively reflect the mitochondrial function. J. Med. Invest. 51 : 84-95, February, 2004

The study investigated the possibility of pharmacologically modulating hepatic allograft function from non-heart-beating donors (NHBDs) using male Lewis rats. The donors were divided into 4 groups: Group 1 in which the vehicle was administered, Group 2 in which FK506 (tacrolimus; a powerful immunosuppressive agent) was administered, Group 3 in which OKY046 (a specific thromboxane synthetase inhibitor) was administered and Group 4 in which FK506 and OKY046 were administered. The recipients received orthotopic liver transplantation. The survival rates differed significantly between the recipients that had received liver transplantation from Groups 1 and 4. The serum liver enzyme and inflammatory cytokine concentrations of the recipients which had received liver transplantation from Groups 2, 3 and 4 were significantly lower than those of the recipients that had received liver transplantation from Group 1. Although there was no significant difference, all parameters were better in the recipients that had received transplantation from Group 4 than those that had received transplantation from Groups 2 and 3. The action mechanisms of FK506 and OKY046 are completely different. Therefore, concomitant use of FK506 and OKY046 might have additive effects on liver transplantation from NHBDs. In conclusion, we demonstrated that pretreatment of NHBDs using FK506 and OKY046 ameliorated graft viability.

Pancreatic cancer is one of the major causes of cancer-related deaths in industrialized countries. It is known that pancreatic cancer is resistant to chemotherapy and that cancer cells are surrounded by extracellular matrix (ECM) proteins including collagen I, collagen IV, fibronectin, and laminin.To examine the role of ECM proteins in acquired resistance to anticancer drugs and proliferation regulation in pancreatic cancers.We used an in vitro model of ECM-induced chemoresistance and cell proliferation of cancer cell lines (MIA PaCa-2, PANC-1, and Capan-1) with 3 different malignancy grades and found that resistance to cytotoxic drugs and proliferation regulation was dependent on ECM proteins. Pancreatic cancer cell lines, especially MIA PaCa-2 cells, adhering to any of the ECM proteins showed decreased cytotoxicity of anticancer drugs, except for gemcitabine. PANC-1 and Capan-1 cells adhering to fibronectin, collagen I, and collagen IV proliferated more than the controls.ECM proteins have important roles in acquired resistance to anticancer drugs and cell proliferation regulation of pancreatic cancer cells. Therefore, the expression of ECM proteins in pancreatic cancer specimens could provide valuable information to aid anticancer drug cytotoxicity, and gemcitabine would be useful for treatment of patients with pancreatic cancer.

The prognosis for pancreatic cancer is still not satisfactory, even in patients who are operable. Liver metastasis and local recurrence occur in over 80% of cases of cancer recurrence. We performed intraoperative radiation therapy with resection of the pancreas to reduce local recurrence.

Surgical treatment for advanced gallbladder cancer has generally had a poor outcome; however, some recent studies have reported the possibility of an improved prognosis following extensive surgery.1–4 We performed an extended right lobectomy with resection of the extrahepatic bile duct and lymphadenectomy for advanced mucinous gallbladder cancer with invasion to the liver and greater omentum, and the patient had a good prognosis.

In Japan, because more than 90% of patients with hepatocellular carcinoma (HCC) are infected with the hepatitis C or B virus (HCV and HBV, respectively), their liver function is often poor. There have been some types of procedures for hepatic resection developed, such as lobectomy, seg-mentectomy, subsegmentectomy, and partial resection. Liver segmentectomy refers to resection of Couinaud’s sector and subsegmentectomy refers to resection of Couinaud’s segments. The choice between performing liver segmentectomy or larger and smaller resections is made on the basis of the patient’s liver function or the type of hepatitis virus with which the patient is infected. Because recurrence occurs from the primary tumor in patients with hepatitis B, larger systemic resection should be offered to those patients. In contrast, it has been reported that because synchronous or metachronous multicentric occurrence of the tumor is dominant in patients with hepatitis C, limited resection according to Glisson’s structures should be performed.1

Hepatocellular carcinoma (HCC) with extension into the right atrium has been regarded as beyond the realm of surgical resection. Most patients have died within a few months of pulmonary embolism, heart failure, or cancer progression.

Patients with chronic pancreatitis should be considered for surgery if recurrent or persistent pain has not been relieved by conservative treatment. The more common indication for decompression of the pancreatic duct by anastomosis to the jejunum is chronic pancreatitis with dilatation and stenosis of the whole pancreatic duct due to diffuse inflammatory changes. Frey’s operation was performed for the present patient because of multiple calcified stones in the branches as well as in the main pancreatic duct in the head of the pancreas as estimated by preoperative examination.

Commonly performed surgical treatment for hilar cholangiocarcinoma includes bile duct resection and various types of hepatectomy with caudate lobectomy. Central two segmentectomy with caudal lobectomy produces a wide sectional surface of the remaining liver and complicated bile duct reconstruction. However, central two segmentectomy preserves a larger volume of remaining liver compared with extended right or left hepatic lobectomy (Table 1). We indicated central two segmentectomy for a case that was expected to have poor remaining liver function.

The outflow for the main blood flow of hepatocellular carcinoma (HCC) is not through the hepatic vein but through the portal vein system. The abundant blood vessel networks that drain into the portal vein are located on both the inside and outside of the tumor capsule, and tumor progress via the portal vein occurs from an early stage. Therefore, it is not difficult for a tumor thrombus to form in the portal vein. Almost all patients with a tumor thrombus in the main branches of the portal vein die due to esophageal bleeding, intractable ascites, or liver failure within several months. Furthermore, conventional therapies, such as percutaneous ethanol injection, microwave coagulation therapy, and tran-scatheter arterial embolization, are generally not indicated for such patients owing to a lack of efficacy and because of possible complications. Therefore, we perform hepatic resection with the tumor thrombus. Extended right hepatic lobectomy with extirpation of the portal tumor thrombus extending to the main trunk and left branch of the portal vein was performed under ultrasound (US) in a patient with advanced hepatocellular carcinoma (HCC).

Drainage of the pancreatic duct by anastomosis to the jejunum may be indicated for symptomatic chronic calcific pancreatitis if the symptoms have not been relieved by conservative treatment.

Carcinoma arising at the confluence of the hepatic duct with predominant right hepatic duct involvement often demands extended right hepatic lobectomy combined with caudal lobectomy. To avoid postoperative hepatic failure, we always adopt right portal vein embolization, preserving the upper part of the medial segment (SIVb), and freeing the caudate lobe only from the right side (never mobilizing the lateral segment) for patients who undergo extended right hepatic lobectomy.

We report a rare case of carcinoma of the cystic duct (CCD) associated with pancreaticobiliary maljunction (PBM).

Previous clinical trials for the detection and treatment of small pancreatic carcinoma have demonstrated the possibility of improved prognosis.1 Segmental pancreatectomy is one of a number of minimally invasive procedures for neoplasms located in the body of the pancreas. We performed segmental pancreatectomy for small pancreatic cancer and the patient had a good prognosis.

Duodenum-preserving pancreatic head resection (DPPHR) has been performed for benign pancreatic head diseases. However, preservation of arterial blood supply to the duodenum and common bile duct during duodenum-preserving total resection of the pancreatic head is a major problem. Complete resection of the pancreatic head with preservation of the common bile duct and duodenum sometimes causes common bile duct or duodenal necrosis due to ischemia. We describe herein a safe procedure for complete resection of the pancreatic head with segmental duodenectomy to prevent complications.

Right posterior segmentectomy and total caudal lobectomy was performed by the diagonal approach for hepatocellular carcinoma (HCC) located in segments VII–I.

Although many treatments are performed for metastatic liver cancer, the results of most treatments are not as good as the results obtained following liver resection. In many patients with metastatic liver cancer, liver function is usually quite good without chronic liver disease, unlike the case in hepatocellular carcinoma. Therefore, as our basic policy we perform aggressive surgical resection for synchronous or metachronous metastasis to the liver, especially from colorectal cancer, estimating the possibility of liver resection generally. Simultaneously extended right lobectomy with combined resection of Couinaud’s segments IVb and II and low anterior resection with lymph node dissection (D2) were performed in a patient with multiple liver metastases from rectal cancer. The patient survived for 7 years and 1 month after surgery.

For a pancreatic body or tail tumor, distal pancreatectomy with splenectomy (DPS) is a standard operation. Spleen-preserving distal pancreatectomy (SPDP) was introduced in order to preserve the organ and, thus, provide the patient with a better quality of life.1 In contrast, despite the fact that intraductal papillary mucinous tumors (IPMTs) have a low but well-documented malignant rate of progression, an aggressive surgical approach is recommended. In addition, these tumors, even when malignant, are often resectable and have a more favorable prognosis than ductal adenocarcinoma and classic mucinous cystadenocarcinoma of the pancreas. These characteristics support limited surgical resection in cases of IPMTs.2 Thus, SPDP is considered as one of the options for the treatment of IPMTs of the body or tail of the pancreas. Here, we report a case of noninvasive intraductal papillary mucinous carcinoma that was treated with SPDP.

Surgical treatment for advanced gallbladder cancer has generally had a poor outcome. However, some recent studies have reported the possibility of improved prognosis by extensive surgery.1–3 However, high mortality and morbidity rates after aggressive surgical approaches, especially after hepatopancreatoduodenectomy (HPD), have also been reported.4 We performed a central bisegmentectomy of the liver with pylorus-preserving pancreatoduodenectomy (PpPD) for advanced gallbladder cancer and the patient had a good prognosis.

Experience and advances in hepatic transplantation have opened the possibility of bench surgery for liver disease. Pichlmayr et al.1 performed the first ex situ liver operation in February, 1998, on a patient to remove large metastases from a leiomyosarcoma of the stomach. We performed an ex situ operation on the liver of a 59-year-old man to remove a large cholangioma with involvement of the inferior vena cava (IVC) and invasion of the right hepatic vein, which otherwise had been assessed as truly unresectable.

The main indication for right anterior hepatic lobectomy preserving major hepatic veins is hepatocellular carcinoma (HCC) localized in the anterior segment. In cases where the tumor extends to segment VII, the right hepatic vein is unable to be preserved and right hepatic lobectomy is then needed. However, in patients in whom an inferior right hepatic vein (IRHV) can be demonstrated preoperatively, segment VI can be preserved. This operation is effective for postoperative functional reserve and complete resection of the affected segment.

Recently, improvements in techniques and instruments for hepatic resection have made massive hepatectomy safe. Patients with hilar cholangiocarcinoma often require hepatic lobectomy combined with resection of the caudate lobe, as well as resection of the extrahepatic bile duct, to remove cancerous lesions completely.1–3 In cases of left hepatic lobectomy combined with caudate lobectomy, we mobilize the caudate lobe from the left side only. Although sometimes both hepatic lobes are mobilized for complete resection of the caudate lobe, we do not mobilize the right lobe in cases of extended left hepatic lobectomy in order to decrease damage to the remnant liver. This technique is very beneficial for the formation of collateral arterial supply to the right hepatic lobe, as well as for protection against mechanical damage to the right hepatic lobe. In particular, when the right hepatic artery has to be resected and, unfortunately, reconstruction of the artery is unsuccessful in cases of left hepatic lobectomy, collateral arterial flow to the residual right hepatic lobe is very important for a good postoperative prognosis.

Because the right hepatic duct is short and the right hepatic artery runs just behind the right hepatic duct, tumors are more likely to invade the right hepatic artery. Resection and reconstruction of the right hepatic artery is often required in cases of extended left hepatic lobectomy for advanced hepatic hilar carcinoma that has invaded the right hepatic artery.

Although innovations have occurred in surgical and diagnostic techniques, the prognosis for advanced gallbladder carcinoma remains poor. Gallbladder cancer invades to the liver easily, either directly or by metastasizing in the gallbladder bed via the venous or lymphatic routes. The gallbladder veins drain into the intrahepatic portal vein, mostly at P4 and P5.1 We have reported that the lymphatic route is also important for hepatic metastasis from the gallbladder, especially metastasis to segments V and IVa.2 Furthermore, we have experienced recurrent tumor in segment V after resection of the gallbladder bed for gallbladder carcinoma with subserosal invasion (ss-cancer). Therefore, we have adopted hepatic segment V and segment IVa subsegmentec-tomy as the standard operative procedure for gallbladder carcinoma with subserosal or direct invasion into the liver extending for 2 cm or less.

Intrahepatic cholangiocellular carcinoma (CCC) has a tendency to spread extrahepatically, especially to the lymph nodes and the hilar bile duct. Consequently, results after hepatic resection are poor for advanced cancer. Small CCC without lymph node involvement is a good indication for hepatic resection. Extended left lobectomy, combined with resection of the caudate lobe and extrahepatic bile duct, and lymph node dissection was performed for small (2.5 cm diameter) CCC with invasion to the hilar bile duct, but without lymph node involvement. The patient is doing well 6 years after surgery without any evidence of recurrence.

Direct invasion to the inferior vena cava (IVC) from the tumor of hepatocellular carcinoma (HCC) is uncommon. Therefore, it is possible to dissect the tumor from the IVC in a number of cases HCC. However, in cases of HCC with direct invasion to the IVC, partial resection of the wall of the IVC with the tumor is necessary. If direct invasion to the IVC is extensive, resection of the hepatic IVC is necessary for curative surgery. In the present case, reconstruction of the IVC was performed without venovenous bypass or clamping of hepatic inflow. Vascular forceps were placed on the hepatic IVC just below the root of the left hepatic vein and above the root of the left renal vein. The IVC was reconstructed using an artificial vessel (Gore-tex, W.L. Gore & Assoc, Flagstaff, AZ, USA, without venovenous bypass or clamping of hepatic inflow.

Portal vein thrombus frequently develops in hepatocellular carcinoma (HCC), but is extremely rare in cholangiocellular carcinoma (CCC). If resection of a portal tumor thrombus is possible, portal hypertension caused by portal vein thrombosis can be alleviated and liver function may be improved by the restoration of portal blood flow. We performed right trisegmentectomy and resection of the extra-hepatic bile duct and portal vein with tumor thrombus extending to the main trunk and the opposite side branch of the portal vein using superior mesenteric vein (SMV)—left femoral vein (LFV) bypass.

Congenital dilatation of the bile duct (CDBD), also referred to as choledochal cyst, is mostly associated with pancreaticobiliary maljunction (PBM). Although previously CDBD was thought to be exclusively a childhood disease, recently it has been recognized to be present in both pediatric and adult populations. In adult patients, complicated clinical presentations and coexistent hepato-biliary-pancreatic diseases are encountered more frequently.1 Although radical excision of the cy stically dilated bile duct with reconstruction by end-to-side Roux-en-Y hepaticojejunostomy is performed as the standard procedure, it is often difficult in adult patients who have a history of long-lasting inflammation of the bile duct.2 In addition, biliary reconstruction for patients with intrahepatic biliary dilatation often leads to postoperative complications.3 In cases in whom the biliary stenosis is located at the orifice of the right or left hepatic ducts, resection from the hepatic hilus is required.4 We performed a radical operation with hepaticoplasty of the hepatic duct at the hilum for CDBD associated with PBM and the patient had a good prognosis.

Intrahepatic cholangiocellular carcinoma (CCC) is a rare malignancy that arises from the small intrahepatic bile ducts. It is usually an advanced cancer at the time of diagnosis because of the relatively low early detection rate in comparison with the detection rate of hepatocellular carcinoma, which has high risk factors, such as chronic hepatitis B or C virus infection. Another clinocopathologic characteristic of CCC is a tendency to disperse extrahepatically, especially to the lymph nodes. Right trisegmentectomy and partial resection of the caudal lobe and hepatoduodenal ligamentectomy (combined resection of the extrahepatic bile duct, the hepatic artery, and the portal vein) underwent for advanced CCC with strong lymph node metastasis in the hepatoduodenal ligament.

Carcinoma arising at the confluence of the right and left hepatic ducts is problematic because of the difficulty of resection and reconstruction. The bile duct is located in the right hepatic anterior aspect of the hepatoduodenal ligament, and the right hepatic artery and portal vein run across and behind the proximal bile duct. Therefore, when left-sided resection of the liver for advanced cancer is performed, occasionally the right hepatic artery and/or portal vein are resected in a radical operation. In this patient, the right hepatic artery was found to branch off from the superior mesenteric artery (SMA) by angiography and encasement of the right hepatic artery was not seen.

Selecting the right approach for resection of a large liver tumor is very important. This patient was diagnosed by other doctors with an unresectable hepatocellular carcinoma (HCC) because of too large a tumor mass. He approached our clinic requesting resection of his liver tumor. We used a J-Incision and thoracolaparotomy with division of the diaphragm that Makuuchi et al1 use generally to obtain a good operative field.

The prevalence of situs inversus in the general population has been estimated to be between 0.002% and 0.1%.1 Three anatomic variations have been described: situs inversus totalis (complete abdominal and thoracic situs inversus); abdominal situs inversus with levocardia; and partial situs inversus.2 Within each of these general classifications, variations of intestinal anatomy, solid-organ orientation, and vascular anatomy occur with considerable frequency, such that the precise anatomy in any given individual with situs inversus is difficult to predict.

Recently, liver resection for malignant liver tumor with invasion to the inferior vena cava (IVC) has become possible using the techniques of vascular surgery and liver transplant surgery.

Preoperative right portal vein embolization enhances remnant liver function following massive hepatectomy. Several studies have reported an increase in the volume of the left hepatic lobe after right portal vein embolization, but little information exists regarding heat shock protein induction in hepatocytes after right portal vein embolization. The objective of this study is to determine whether heat shock protein is induced in hepatocytes after right portal vein embolization in patients who underwent extended right hepatic lobectomy.Four patients with gallbladder cancer and one patient with intrahepatic cholangiocellular carcinoma who underwent extended right hepatic lobectomy combined with caudate lobectomy and resection of the extrahepatic bile duct after right portal vein embolization were enrolled in this study. Operation was performed 21-36 days after right portal vein embolization. At operation, small liver specimens were taken immediately after laparotomy from both the right anterior segment (embolized lobe) and lower part of the left medial segment (non-embolized lobe) and heat shock protein 70 was induction in these specimens was measured by Western blotting.Heat shock protein 70 was induced in the left lobe relative to the right lobe in four patients, three of whom had an uneventful postoperative course.This paper is the first report to show the induction of heat shock protein 70 in the non-embolized hepatic lobe after right portal vein embolization in the clinical cases.

Despite various treatment trials for unresectable pancreatic carcinoma with liver metastases, the outcome has not been satisfactory. This paper reports a case of pancreatic carcinoma with multiple liver metastases that responded well to arterial infusion chemotherapy.A 65-year-old male was diagnosed with multiple liver tumors, and needle biopsy revealed adenocarcinoma. With endoscopic ultrasonography, a tumor in the pancreatic head was detected, and pancreatic carcinoma with multiple liver metastases was diagnosed. He received arterial infusion chemotherapy: cisplatin at a dose of 10 mg/body/day and 500 mg/body/day of 5-fluorouracil After 14 days administration, liver metastases had decreased in number and size, but thereafter, because of hepatic arterial occlusion, the same dose of drugs was administered intravenously. The patient was discharged from the hospital and was given chemotherapy 3 days a week on an outpatient basis. Although the chemotherapy was effective, it was stopped because of severe general fatigue 5 months after discharge. His general status continued to gradually worsen, and he died 12 months after diagnosis.Prognosis of pancreatic carcinoma with liver metastases is poor; however, transarterial infusion chemotherapy may be effective to improve the prognosis and quality of life of the patients.

We report a rare case of adenomatous hyperplasia (AH) with malignant transformation, which was observed initially in the liver with chronic hepatitis C. A 47-year-old man was admitted to the hospital and chronic active hepatitis was diagnosed using fine needle biopsy, in addition abdominal computed tomography (CT) and ultrasonography showed multiple and hypovascular liver mass. Needle biopsy of the nodules showed AH. Despite transcatheter arterial embolization and percutaneous ethanol injection therapy (PEIT), the patient was readmitted due to enlargement of the nodules and elevation of alpha-fetoprotein 9 months later. On readmission, the nodules in the liver showed early-stage well-differentiated hepatocellular carcinoma (HCC) histopathologically, that were strongly stained on CT-arteriography and were stained less than the surrounding liver on CT-arterial portography, indicating arterial supply in the nodules and malignant transformation. Thereafter, the patient developed jaundice, and enhanced CT and magnetic resonance imaging showed multiple nodules, which occupied most of the liver, and needle biopsy revealed typical well-differentiated HCC. The patient died of hepatic failure 3 years after the initial admission. In this case, it was confirmed that AH transformed into HCC, which showed a multiple tumor on pathological diagnosis. It has been reported that borderline lesions are curable by less aggressive procedures such as enucleation and PEIT. However, such procedures may not be useful for this type of HCC, which rapidly developed from borderline lesions of the liver.

Pancreaticobiliary maljunction (PBM) is a congenital anomaly defined as a union of the pancreatic and biliary duct that is located outside the duodenal wall. The Japanese Study Group on Pancreaticobiliary Maljunction and the Committee for Registration enrolled and analyzed 1627 patients with PBM who had been diagnosed and treated from January 1, 1990 to December 31, 1999 at 141 hospitals throughout the country. There were 1239 patients with dilatation of the bile duct (group A) and 388 patients without dilatation (group B). The average age was 24 years in group A and 47 years in group B; the age was significantly higher in group B. The type of confluence between the terminal choledochus and the pancreatic duct has been classified into three types (type a, right-angle type; type b, acute-angle type; and type c, complex type). In group A, type a accounted for 57.9% and was significantly more frequent compared with the other types (type b, 32.4%; type c, 5.6%). In group B, type b accounted for 60.8%, being significantly more frequent compared with the other types (type a, 29.4%; type c, 7.2%). Subjective symptoms, preoperative complications (e.g., liver dysfunction and acute pancreatitis), pancreatic stone, and pancreatic duct morphological abnormality were significantly more frequent in group A. However, the amylase levels in the bile and gallbladder were significantly higher in group B, and the presence of gallstone and morphological abnormality of the gallbladder was significantly more frequent in group B. The occurrence rate of cancer in the biliary tract was 10.6% in group A and 37.9% in group B, being significantly higher in group B. In group A, cancer of the extrahepatic bile duct was seen in 33.6% and cancer of the gallbladder was seen in 64.9%, but gallbladder cancer was present significantly more frequently in the patients with diffuse or cylindrical dilatation, and bile duct cancer was present significantly more frequently in the patients with cystic dilatation. In group B, 93.2% of the patients had gallbladder cancer, and bile duct cancer was found in as few as 6.8%. Against this background Japanese surgeons regard cholecystectomy, resection of the extrahepatic bile duct, and hepaticojejunostomy as standard operations for PBM with dilatation of the bile duct. However, opinion on whether or not the bile duct should be removed in the treatment of PBM without dilatation of the bile duct has been divided among Japanese surgeons. A randomized controlled trial is necessary.

Background/Aims : A stress-inducible heat shock protein 70 (HSP70) is one of the best-known endogenous factors protecting cell injury under various pathological conditions. The aim of this study was to examine anti-apoptotic actions of a non-toxic HSP70 inducer, geranylgeranylacetone (GGA), on hepatocytes exposed to hydrogen peroxide (H 2 O 2 ) or ethanol. Methods : Primary cultures of rat hepatocytes were treated with different concentrations of GGA and exposed to 0.5 mM H 2 O 2 or 100 mM ethanol. The heat shock response was assessed by measuring the activation of heat shock factor 1 (HSF1), HSP70 mRNA expression, and accumulations of HSP70, HSP90, and HSP27. Apoptosis was evaluated by DNA fragmentation. Results : Pretreatment with 1 μ M GGA for 2 h enhanced nuclear translocation and phosphorylation of HSF1, HSF1-DNA binding, HSP70 mRNA expression, and its accumulation, when the cells were exposed to H 2 O 2 or ethanol. In association with this accelerated response, GGA suppressed the insult-induced activation of c-Jun N-terminal kinases, caspase 9, and caspase 3-like proteases, leading to significant inhibition of apoptosis. Conclusions : GGA exerted anti-apoptotic actions, at least in part, by priming hepatocytes for enhanced HSP70 induction. Our results suggest that GGA may have a potential benefit for the treatment of alcoholic and ischemia-reperfusion liver injuries.

Alendronate, a bisphosphonate compound, lowers serum calcium in patients with cancer-associated hypercalcemia through its inhibitory effect on bone resorption and as a result symptoms associated with hypercalcemia improve. This study was carried out to investigate the effects of alendronate in patients with hypercalcemia due to bone metastasis of hepatocellular carcinoma (HCC). Two patients were evaluated. Their corrected serum calcium and alpha-fetoprotein (AFP) levels and their computed tomography (CT), bone scintigraphy and magnetic resonance imaging (MRI) findings were evaluated before and during alendronate treatment. After treatment, not only the corrected serum calcium levels but also AFP levels and bone pain decreased; in addition, the regression of the metastatic focus was noted in the MRI analysis. These tumor inhibitory effects of alendronate have not been reported in HCC before; and alendronate might serve to prevent bone metastases in patients with HCC. In conclusion, two patients who developed hypercalcemia associated with bone metastasis after surgery for HCC were treated with alendronate and they experienced alleviation of the pain due to bone metastasis, improvement of their quality of life and a marked decrease in AFP levels with tumor regression.

We report a rare case of hepatocellular carcinoma (HCC) for which intravenous administration of cisplatin (CDDP) was effective. A 48-year-old woman with recurrent HCC was admitted to our hospital. She had undergone right hepatectomy 1 year previously. A large tumor in the liver and multiple lung metastases were found by computed tomography in June 1995. She was icteric, and titers of serum alpha-fetoprotein (AFP; 214 ng/ml) and protein induced vitamin K absence or antagonist-II (PIVKA-II; 80 AU/ml) were high. According to these findings, she was diagnosed as having nonresectable recurrent HCC with extrahepatic lesions. She was treated by intravenous administration of CDDP. The dose of CDDP was 50 mg and it was infused once a week. One kur of CDDP was 4 weeks, and a total of four kur were administered. We noted that the lung metastases and primary liver tumor resolved after 1 kur of chemotherapy. The levels of serum AFP and PIVKA-II decreased markedly, to 26 ng/ml and0.07 AU/ml, respectively. A complete response was obtained, and she maintained a good state of health for the next 6 months, until brain metastases occurred. She died 13 months after the initiation of treatment with CDDP. In general, intravenous CDDP cannot be recommended as a single agent for HCC therapy, but CDDP showed good antineoplastic activity in our patient.

530 Background: It has recently been suggested that the SDF-1/CXCR4 axis is involved in tumor progression, angiogenesis, metastasis, and survival in various cancer. In this study, we investigate the possible role of SDF-1/CXCR4 axis in colorectal liver metastasis. Methods: Both primary colorectal tumors and liver metastatic tumors were obtained from 12 patients with colorectal liver metastasis. Expression levels of CXCR4 and SDF-1 were determined using RT-PCR. In 4 patients with benign liver disease, the expression level of SDF-1 in normal liver tissues was also determined. We divided the 12 patients into two groups; high expression group (n=6) and low expression group (n=6) according to each expression level of SDF-1 and CXCR4, and compared the clinicopathological factors between the two groups. Results: 1. CXCR4 expression levels in primary tumor: The frequency of the peritoneal dissemination in the CXCR4 high expression group was higher than in the low expression group (p=0.07). Moreover, overall survival rate in the CXCR4 high expression group was significantly lower than that in the low expression group (3 year-survival rate: 67% vs. 100%, p Conclusions: The present data suggest that there is a significant association of the SDF-1/CXCR4 axis with enhanced liver metastasis and poor prognosis of the patients with colorectal liver metastasis. Furthermore, an enhanced expression of SDF-1 in non-tumor liver tissues may have an important role in the formation of liver metastasis.

We present an unusual case involving intracranial arteriovenous malformations in the anterior cranial fossa located symmetrically on both sides. A mixed pial and dural arteriovenous malformation, the nidus of which was localized in the brain parenchyma, was found on the right side and a pure dural arteriovenous malformation on the left side. Our case is felt to support the hypothesis of a congenital origin for dural arteriovenous malformation in the anterior cranial fossa, because the dural arteriovenous malformation coexisted with the mixed pial and dural arteriovenous malformation, which can be attributed to a disturbance of normal embryonic development.