[18F]FB(ePEG12)12-exendin-4 noninvasive imaging of insulinoma negative for insulin immunostaining on specimen from endoscopic ultrasonography-guided fine needle aspiration: a case report with review of literature.

Insulinomas are the most common functional pancreatic neuroendocrine neoplasm; when treatment is delayed, they induce hyperinsulinemic hypoglycemia, which is life-threatening. As surgical resection is the only curative treatment for insulinoma, preoperative localization is crucial; however, localization based on conventional imaging modalities such as computed tomography (CT) and magnetic resonance imaging is often inconclusive. Somatostatin receptor-targeted imaging is another option for detecting pancreatic neuroendocrine neoplasms but has low sensitivity and is not specific for insulinoma. The clinical application of other localizing approaches such as selective arterial calcium stimulation and endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is limited by their being invasive and/or technically complex. Moreover, an EUS-FNA specimen of an insulinoma may be negative on insulin immunostaining. Thus, a noninvasive and clinically practical insulinoma-specific diagnostic tool to discriminate insulinomas with high accuracy is anticipated. Glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged in the effort to fulfill this need. We recently developed the novel fluorine-18-labeled exendin-4-based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4) for positron emission tomography (PET) imaging and reported its clinical benefit in a case of insulinoma in the pancreatic tail. We report here a case of insulinoma in the pancreatic head in which an EUS-FNA specimen was negative on insulin immunostaining while precise preoperative localization and conclusive evidence for curative enucleation was provided by 18F-exendin-4 PET/CT (Japan Registry of Clinical Trials; jRCTs051200156).

Anti-interleukin-6 receptor antibody treatment ameliorates postoperative adhesion formation.

Postoperative adhesion formation often ruins the quality of life or is an obstacle to illnesses with curative operation such as cancer. Previously we demonstrated that interferon-γ-promoted fibrin deposition drove postoperative adhesion formation. However, its underlying cellular and molecular mechanisms remain poorly understood. We found that myofibroblasts of the adhesion predominantly expressed signature molecules of mesothelial cells that line the serosa. Microarray analysis revealed IL-6 as a key underlying player, supported by elevated IL-6 levels in the peritoneal fluid of post-laparotomy human subjects. Injured serosa of cecum-cauterized mice also exhibited induction of Il6, which was followed by Tnf, concomitant with rapid accumulation of neutrophils, substantial population of which expressed TGF-ß1, a master regulator of fibrosis. Besides, neutrophil-ablated mice showed reduction in induction of the adhesion, suggesting that TGF-ß1+neutrophils triggered the adhesion. Human neutrophils expressed TGFB1 in response to TNF-α and TNF in response to IL-6. Moreover, anti-IL-6 receptor monoclonal antibody abrogated neutrophil recruitment and adhesion formation. Thus, IL-6 signaling represents a potential target for the prevention of postoperative adhesions.

The Effect of Daikenchuto, Japanese Herbal Medicine, on Adhesion Formation Induced by Cecum Cauterization and Cecum Abrasion in Mice.

Daikenchuto (DKT) has been widely used for the treatment of postsurgical ileus in Japan. However, its effect on postsurgical adhesion formation has been obscure. In this study, the effect of DKT on postsurgical adhesion formation induced by cecum cauterization or cecum abrasion in mice was investigated. First, the expression of adhesion-related molecules in damaged ceca was investigated by quantitative (q)RT-PCR. During 24 h after surgery, mRNA expressions of interferon-γ (IFN-γ), plasminogen activator inhibitor-1 (PAI-1), interleukin-17 (IL-17), and Substance P (SP) in cauterized ceca and those of PAI-1 and IL-17 in abraded ceca were significantly up-regulated. Next, the effect of DKT on adhesion formation macroscopically evaluated with adhesion scoring standards. DKT (22.5-67.5 mg/d) was administered orally for 7 d during the perioperative period, and DKT did not reduce adhesion scores in either the cauterization model (control : DKT 67.5 mg/d, 4.8 ± 0.2 : 4.8 ± 0.2) or in the abrasion model (control : DKT 67.5 mg/d, 4.9 ± 0.1 : 4.5 ± 0.3). Histologically, collagen deposition and leukocyte accumulation were found at the adhesion areas of control mice in both models, and DKT supplementation did not alleviate them. Last, effect of DKT on expression of proadhesion moleculs was evaluated. DKT also failed to down-regulate mRNA expression levels of them in damaged ceca of both models. In conclusion, PAI-1 and IL-17 may be key molecules of postsurgical adhesion formation. Collagen deposition and leukocytes accumulation are histological characteristic feature of post-surgical adhesion formation. DKT may not have any preventive effect on postsurgical adhesion formation in mice.

Immunohistochemical characterization of cancer-associated fibroblasts at the primary sites and in the metastatic lymph nodes of human intrahepatic cholangiocarcinoma.

Cancer-associated fibroblasts (CAFs) are an important constituent of the cancer stroma. In intrahepatic cholangiocarcinoma (ICC), the features of CAFs at the primary site and in the metastatic lymph nodes (Met-LNs) and their origin have been unclear. In the present study, we characterized CAFs at the primary site (n = 42) and in the Met-LNs (n = 10) of human ICC by immunohistochemistry using potential molecular markers of CAFs, portal fibroblasts (PFs), hepatic stellate cells (HSCs), and bone marrow-derived fibrocytes (BMDFs). At the primary site, the stroma was strongly positive for α-smooth muscle actin (α-SMA; marker for CAFs), platelet-derived growth factor receptor-ß (PDGFR-ß) (common marker for HSCs and PFs), fibulin-2, and thymus cell antigen-1 (Thy-1; PF marker), whereas immunoreactivity for fascin (HSC marker) was scarce. Most of the α-SMA-positive cells were found to express PDGFR-ß, Thy-1, and fibulin-2 by double immunostaining. A small population of BMDF marker-positive (α-SMA+CD45+CD34+) cells was found by triple immunostaining. In the micro-Met-LNs, α-SMA-positive cells were absent in cancer aggregates of the LN sinus, whereas they were present in the invasion area of cancer cells from the LN sinus to the LN parenchyma. In the macro-Met-LNs, there were abundant α-SMA-positive cells that were also positive for PDGFR-ß and Thy-1 but negative for fibulin-2 and fascin. Thus, regarding the expression of molecular markers, CAFs at the primary site of ICC are similar to PFs and different from those of HSCs or CAFs in the Met-LNs. CAFs at the primary sites and in the Met-LN are thought to be derived from PFs/BMDFs and resident cells of LNs, respectively.

Is Noncurative Hepatic Resection Justified for Advanced Hepatocellular Carcinoma?

It has been obscure whether or not noncurative hepatic resection (Hx) has a favorable impact on the clinical course in patients with advanced hepatocellular carcinoma (HCC). The aim of this study is to clarify the significance of noncurative Hx for advanced HCC. Among 666 consecutive patients undergoing Hx for HCC in our department, 79 patients underwent noncurative Hx. These patients were classified as Group A (presence of macrovascular invasion [MVI]; n = 29), Group B (residual tumors in the remnant liver; n = 37), Group C (residual tumors in the remnant liver with MVI; n = 7), or Group D (residual tumors in the remnant liver with distant metastasis [with or without MVI]; n = 6). The three-year survival rates were 49.6 per cent in Group A, 30.3 per cent in Group B, 14.3 per cent in Group C, and 0.0 per cent in Group D, respectively (Groups A and B vs Group D, P < 0.05). Moreover, the survival rate was significantly higher in patients with ≤3 tumors than in those with ≥4 tumors (P < 0.05), when Group B was divided into subgroups according to the number of residual tumors in the remnant liver. In conclusion, noncurative Hx might be acceptable for advanced HCC with MVI or ≤3 residual tumors in the remnant liver.

Short- and long-term outcomes of the Frey procedure for chronic pancreatitis: a single-center experience and summary of outcomes in Japan.

PURPOSE: To evaluate the short- and long-term outcomes of the Frey procedure for chronic pancreatitis (CP). METHODS: The subjects of this study were 12 patients who underwent the Frey procedure for CP between January, 2000 and December, 2016. We assessed pain relief, weight gain, and exocrine/endocrine insufficiency during follow-up. RESULTS: The study population comprised 11 men and 1 woman (91.7% vs. 8.3%; mean age, 50.3 ± 6.8 years; range 39-61 years). Pancreatitis was caused by alcohol in 9 (75%) patients and was idiopathic in 3 (25%) patients. The mean follow-up period was 82.5 ± 46.5 months (range 16.9-152.1 months). There was no operative mortality, but three patients (25%) suffered postoperative morbidity. All patients were pain-free at the time of discharge. There was no case of new-onset diabetes mellitus after surgery, although one patient (8.3%) suffered exocrine insufficiency. The body weight and body mass index of all patients improved during follow-up. Only one patient continued to suffer pain in the long term. CONCLUSION: The findings of this long-term follow-up of patients who underwent the Frey procedure suggest that it offers effective pain relief and is a safe technique for the management of CP.

Multifocal Mass Lesions in Autoimmune Pancreatitis.

A 59-year-old male patient with jaundice was referred to our hospital because of mass lesions in the pancreatic head and tail. An immunological examination revealed an elevated serum IgG4 level. Computed tomography showed two clear boundary mass lesions in the pancreatic head and tail. Magnetic resonance imaging showed that the mass lesions exhibited low intensity on T1-weighted images and iso-intensity on T2-weighted images. Magnetic resonance cholangiopancreatography showed an obstruction of the main pancreatic duct in the pancreatic head and tail. The possibility of malignant tumors could not be ruled out; therefore, we performed total pancreatectomy. A histopathological examination of the nodular lesions revealed severe lymphoplasmacytic infiltration and inflammatory change around the pancreatic ducts. Immunohistochemistry revealed diffuse infiltration of IgG4-positive plasma cells in the nodules. According to these pathological findings, we diagnosed the patient with IgG4-related multifocal mass lesions of autoimmune pancreatitis (AIP). It is difficult to distinguish between focal type AIP and pancreatic cancer. We herein report a rare case of multifocal mass lesions in AIP and include bibliographical comments.

Laparoscopic Resection of an Epithelial Cyst in an Intrapancreatic Accessory Spleen.

An epithelial cyst in an intrapancreatic accessory spleen (ECIAS) is rare. We herein report a case of a patient with ECIAS who underwent laparoscopic surgery. A 57-year-old woman was referred to our hospital because of a pancreatic tail tumor. She was asymptomatic, and a physical examination revealed no remarkable abnormalities. The levels of the tumor marker carbohydrate antigen 19-9 (CA19-9) and s-pancreas-1 antigen (SPan-1) were elevated. Ultrasonography showed a well-defined homogeneous cystic tumor. Computed tomography showed a well-demarcated cystic tumor in the pancreatic tail. Magnetic resonance imaging showed that the cystic tumor exhibited low intensity on T1-weighted images and high intensity on T2-weighted images. The cystic tumor was diagnosed as mucinous cystic neoplasm preoperatively. The patient underwent laparoscopic spleen-preserving distal pancreatectomy. A histopathological examination revealed the cyst wall to be lined by stratified squamous epithelium within splenic parenchyma, and the ultimate diagnosis was ECIAS. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. ECIAS is very difficult to diagnose preoperatively. Laparoscopic surgery is a safe and minimally invasive procedure for patients with difficult-to-diagnose pancreatic tail tumor suspected of having low-grade malignancy.

Synchronous double cancers of primary hepatocellular carcinoma and cholangiolocellular carcinoma: a case report.

Synchronous double cancers consisting of hepatocellular carcinoma (HCC) and cholangiolocellular carcinoma (CoCC) are extremely rare. We herein report a surgical case of synchronous double cancers in a patient with primary HCC and CoCC. A 45-year-old man with hepatitis B was admitted to our hospital with hepatic tumors. The level of protein induced by vitamin K antagonist (PIVKA-II) was found to be elevated. Computed tomography (CT) revealed a 23-mm tumor with early-phase enhancement and late-phase washout in the 6th segment of the liver, and a 10-mm tumor with slight early-phase enhancement and late-phase washout in the 7th segment of the liver. Magnetic resonance imaging (MRI) revealed that the two tumors in the 6th and 7th segments showed low intensity on T1-weighted images and high intensity on T2-weighted images. Based on those preoperative examinations, the liver tumors were diagnosed as multiple primary hepatocellular carcinomas. The patient underwent a posterior segmentectomy. A histopathological examination revealed that the tumor of the 6th segment of the liver was moderately differentiated HCC, and that the tumor of the 7th segment of the liver was CoCC. The postoperative course was uneventful. However, lymph node recurrence was observed 6 months later and the patient died 20 months after surgery. There are only six reported surgical cases of synchronous double primary liver cancers consisting of HCC and CoCC. We are of the opinion that curative resection may be an effective treatment for double cancer consisting of HCC and CoCC, and that it may provide long-term survival.

Hepatic Pseudolymphoma with Fluorodeoxyglucose Uptake on Positron Emission Tomography.

A 69-year-old woman with chronic hepatitis B was admitted to our hospital with a hepatic tumor. The levels of 2 tumor markers, carcinoembryonic antigen and carbohydrate antigen 19-9, were slightly elevated; however, the α-fetoprotein and protein levels induced by vitamin K antagonist II were within the normal limits. Abdominal ultrasonography showed a well-defined peripheral hypoechoic mass that was isoechoic and homogeneous on the inside. Computed tomography showed a poorly enhanced tumor of 13 mm in diameter in the 5th segment of the liver. Fluorodeoxyglucose positron emission tomography showed a slight uptake (maximum standard uptake value 3.4) by the hepatic tumor. These findings suggested cholangiocellular carcinoma, and we performed anterior segmentectomy of the liver. A histopathological examination showed a hepatic pseudolymphoma. The patient's postoperative course was uneventful, and she remains alive without recurrence 5 months after undergoing surgery. In most cases, hepatic pseudolymphoma is preoperatively diagnosed as a malignant tumor and a definite diagnosis is made after resection. It is therefore necessary to consider hepatic pseudolymphoma as a differential diagnosis in patients with hepatic tumors.

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.

Analysis of unique liver volume restoration after laparoscopic fenestration of liver cysts.

INTRODUCTION: Laparoscopic fenestration is a standard procedure for the treatment of non-parasitic liver cysts. After fenestration, the remnant liver often restores its volume. However, no systematic analysis of the phenomenon exists. In the present study, the pattern of liver volume restoration after laparoscopic fenestration of liver cysts was analyzed, and the mechanism for the unique restoration was investigated. METHODS: Seven patients with giant non-parasitic liver cysts underwent laparoscopic fenestration. Liver volume restoration in each section and changes in the diameter of the portal branch were analyzed after fenestration with CT or MRI. In two patients, regional liver volume restoration was assessed in detail using region-growing software, and change in portal flow distribution was estimated using computational fluid dynamics. Then, the regional liver volume restoration rate was compared with the portal hemodynamic changes. RESULTS: Liver volume restoration after fenestration was dependent on the size and position of the cysts; it not uniform throughout the remnant liver. The liver volume restoration in sections that had been compressed by giant cysts was significantly greater than in other areas after fenestration. This volume restoration was accompanied by an increase in the diameters of the portal branches in these sections. In addition, a strong correlation between the regional liver volume restoration rate and the changes in portal flow distribution existed in the computationally analyzed cases. CONCLUSION: Liver volume restoration after the fenestration of giant liver cysts non-uniformly occurs in the remnant liver. Improved portal vein circulation in the hepatic area adjacent to the excised giant liver cysts most likely regulates the greater regional volume restoration rate in the area.

Regional hepatic regeneration after liver resection correlates well with preceding changes in the regional portal circulation in humans.

BACKGROUND AND AIMS: While portal hemodynamics largely affects the liver regeneration after partial hepatectomy, whether the remnant liver homogeneously regenerates is unclear, especially in humans. We hypothesized that change in flow distribution varies in each remnant portal branch after liver resection in humans and the liver consequently regenerates heterogeneously. METHODS: Twenty-two patients who underwent anatomical hepatic resection preserving intact drainage veins were analyzed. Based on perioperative contrast-enhanced computed tomography, the regional hepatic regeneration in each segment was analyzed using a region growing software. The perioperative change in the distribution of blood flow in each portal branch was assessed using the computational flow dynamics technique. The correlation between the change in the portal flow distribution and the later regional hepatic regeneration was investigated. RESULTS: The distribution of portal blood flow in each remnant branch largely changed at 2 weeks (71-389 %). Each remnant segment also heterogeneously regenerated at 3 months (85-204 %). Meanwhile, a good correlation between the regional regeneration rate at 3 months and the relative change in the flow distribution in each circulating portal branch at 2 weeks was detected in each patient (r = 0.74-0.99). CONCLUSIONS: After partial hepatectomy, the change in blood flow varies in each remnant portal branch and the liver heterogeneously regenerates in humans. The good correlation between the earlier change in the portal flow distribution and the later regional hepatic regeneration strongly suggests that the portal venous flow most likely regulates the non-uniform liver regeneration after hepatic resection in humans.

Angiogenesis is crucial for liver regeneration after partial hepatectomy.

BACKGROUND: Recent studies of hepatic regeneration have mainly focused on the growth of parenchymal cells. However, remodeling of liver vessels seems to be crucial during hepatic regeneration. In this study, we investigated the influence of antiangiogenesis on hepatic regeneration using sFlt-1, a soluble receptor for vascular endothelial growth factor that acts as a dominant negative receptor, and the hepatocyte growth factor antagonist NK4. METHODS: A sFlt-1-expressing adenoviral vector, an NK4-expressing adenoviral vector, or both combined were infected into C57BL6 mice via the tail vein. A 70% partial hepatectomy was performed on all of the mice 48 hours after infection. The remnants of the liver were removed after the partial hepatectomy, and hepatic regeneration was assessed by measuring the remnant liver weight and hepatocyte mitosis, bromodeoxyuridine staining, immunohistochemical staining with anti-platelet endothelial cell adhesion molecule-1 antibodies, and real-time polymerase chain reaction studies for angiogenic factors. RESULTS: The immunohistochemical staining for CD31 showed suppression of sinusoidal endothelial cells growth in sFlt-1-expressing adenoviral vector-and NK4-expressing adenoviral vector-infected mice. Increases in the remnant hepatic weight were significantly lower in the sFlt-1-expressing adenoviral vector-infected mice. The bromodeoxyuridine index and mitotic cell results revealed a significant decrease in hepatic regeneration in the sFlt-1-expressing adenoviral vector-and NK4-expressing adenoviral vector-infected mice. The suppressive effects on hepatic regeneration were significantly enhanced by combined sFlt-1-expressing adenoviral vector and NK4-expressing adenoviral vector infection. Real-time polymerase chain reaction results revealed the significant suppression of angiogenic growth factor receptors Tie-1 and Tie-2. CONCLUSION: The angiogenesis inhibitor significantly suppressed hepatic regeneration. These results suggest that hepatic regeneration after hepatectomy closely correlates with angiogenesis.

Primary epithelioid hemangioendothelioma of the retroperitoneum: report of a case.

We herein report the case of a 48-year-old Japanese female with retroperitoneal epithelioid hemangioendothelioma (EHE), a rare malignant vascular tumor of intermediate grade. She was referred to our hospital because a retroperitoneal tumor was found during a medical checkup, in which strong accumulation of (18)F-fluorodeoxyglucose (FDG) was observed by (18)F-FDG-positron emission tomography (PET). A histological examination of the resected tumor revealed that it consisted of large epithelioid cells with vesicular nuclei, and clear cells with vacuolated cytoplasm and intracytoplasmic lumina. These cells expressed CD31 and vimentin, and the final pathological diagnosis was EHE. Postoperative surveillance with FDG-PET revealed distant metastasis in Virchow's lymph node 7 months after the operation. After dissection of the metastatic lymph node, the patient has been free from recurrence for 13 months. Close follow-up with FDG-PET seemed to be useful for surveillance of the recurrence of this tumor with unpredictable behavior, making an early treatment for the recurrent lesions possible.

Fascin, a novel marker of human hepatic stellate cells, may regulate their proliferation, migration, and collagen gene expression through the FAK-PI3K-Akt pathway.

Fascin is a component of actin bundles and may regulate various cellular events. The expression and function of fascin in human hepatic stellate cells (HSCs) has remained largely uncharacterized. Fascin expression in human liver tissue was studied using immunohistochemistry. To identify cells expressing fascin, double immunofluorescent staining with vimentin, α-smooth muscle actin (α-SMA), or fibulin-2 was performed and analyzed with confocal microscopy. In culture experiments, fascin expression and the phosphorylation of focal adhesion kinase (FAK) and Akt in LX-2 cells, a cell line of human HSCs, were investigated using western blot. Specific siRNAs were used to reduce the expression of fascin in LX-2 cells. Proliferation and migration were assayed with a CyQuant assay kit and a Matrigel-coated culture insert system, respectively. Levels of matrix metalloproteinase (MMP)-2 and collagen mRNAs were examined using quantitative RT-PCR. Immunohistochemistry revealed the expression of fascin along sinusoids and overlapping with vimentin and α-SMA in both non-fibrotic and fibrotic liver tissue, but it was almost absent in periportal myofibroblastic cells and did not colocalize with fibulin-2, a marker of portal myofibroblasts. In addition, fascin immunoreactivity was almost undetectable in septa of fibrotic human liver tissue. The expression of fascin in LX-2 cells was confirmed using western blot. Two different specific siRNAs against fascin significantly reduced the number of viable LX-2 cells to 65% compared with control cultures and downregulated the mRNAs levels of types I and III collagen and MMP-2 to 62%, 65%, and 70% of control levels, respectively. This condition also reduced the migration activity of LX-2 cells to 46% of control cells and the phosphorylation level of both FAK and Akt. Fascin may be an excellent novel marker of human HSCs that distinguishes HSCs from periportal myofibroblasts. Fascin may regulate functions of human HSCs through the FAK-phosphoinositide 3-kinase-Akt pathway.

Preoperative estimation of asialoglycoprotein receptor expression in the remnant liver from CT/99mTc-GSA SPECT fusion images correlates well with postoperative liver function parameters.

BACKGROUND: Accurate preoperative estimation of remnant liver function is critically important for hepatic surgery, and the expression of asialoglycoprotein receptors (ASGPR) is associated with hepatic function. METHODS: Thirty-two patients with hepatocellular carcinoma who underwent surgical resection were studied. To estimate the expression of ASGPR in the remnant liver, simulated surgery was performed on fusion images that combined data from (99m)technetium-galactosyl human serum albumin ((99m)Tc-GSA)/single photon emission computed tomography (SPECT) and computed tomography (CT) scanning. The liver uptake ratio (LUR) of (99m)Tc-GSA and the functional liver volume (FLV) in the remnant liver were predicted and were compared with postoperative liver function parameters. RESULTS: The LUR of (99m)Tc-GSA was strongly correlated with the extent of hepatic ASGPR expression (r = 0.944, p = 5.01 x 10(-16)), being confirmed to be a reliable parameter for the evaluation of liver function. The estimated remnant LUR, but not the estimated remnant FLV, was significantly correlated with postoperative liver function parameters, such as serum total bilirubin (r = -0.430, p < 0.05), prothrombin activity (r = 0.515, p < 0.01), and serum cholinesterase activity (r = 0.546, p < 0.01) at 1 week. CONCLUSION: Preoperative estimation of the extent of ASGPR expression in the remnant liver on CT/GSA-SPECT fusion images correlated well with postoperative liver function parameters, suggesting its usefulness for surgical decisions.

[Efficacy and toxicity of transcatheter arterial chemoembolization with Cisplatin suspended in lipiodol for unresectable hepatocellular carcinoma].

In this study we evaluated the efficacy and toxicity of transcatheter arterial chemoembolization (TACE) with Cisplatin (CDDP)-Lipiodol (LIP) suspension in 24 patients with advanced hepatocellular carcinoma (HCC). Eligibility criteria were as follows; unresectable HCC, age <75 years, performance status (PS) 0-2, Child-Pugh A or B and adequate heart and renal function. When TACE was performed, the catheter was placed selectively in feeding arteries of the tumors, and CDDP-LIP suspension (20 mg/mL) was injected followed by gelatin sponge particles. The direct and total effect on tumors were evaluated 3 and 6 months after TACE, respectively. As for a direct effect, complete and partial response rates were 54.2% and 25%, respectively. As for a total effect, complete and partial response rates were 41.7% and 4.1%, respectively. Grade 3/4 drug-related toxicities were as follows: thrombocytopenia (13%), appetite loss (8%) and nausea (4%). These severe side effects disappeared within 10 days after TACE. No renal and hepatic dysfunction was encountered, and no drug-related deaths occurred. TACE with CDDP suspended in LIP may provide some clinical benefits with relatively tolerable toxicities.

Expression of somatostatin receptors in splanchnic blood vessels of normal and cirrhotic rats.

BACKGROUND/AIMS: Somatostatin has been used for over two decades to treat acute variceal bleeding. Although it is assumed that somatostatin lowers portal pressure by constriction of the splanchnic arteries, little is known about the expression of somatostatin receptors (SSTR) in splanchnic blood vessels. In this study we investigated SSTR expression in splanchnic blood vessels from normal and cirrhotic rats. METHODS/RESULTS: Cirrhosis was induced by intraperitoneal injection of 50 mg thioacetamide twice a week for 14 weeks. In portal vein, mesenteric artery and aorta of normal and cirrhotic rats, mRNA for the five known SSTR was measured by quantitative reverse transcriptase-polymerase chain reaction. SSTR subtypes 1, 2, 3 and 4 were expressed, but subtype 5 was undetectable. In the portal vein of cirrhotic animals, SSTR1 was significantly down-regulated as compared with controls. Otherwise, no major differences in receptor expression between normal and cirrhotic animals were observed. Using immunohistochemistry, we identified all five receptors, although the staining of receptor 5 was very weak. CONCLUSION: All five SSTR are expressed in splanchnic blood vessels. Our results suggest that cirrhosis reduces expression of SSTR1 in portal vein. In other vessels, no major differences between the normal and cirrhotic state were noted.