Transplantation After Successful Downstaging by Multimodal Treatments of American Joint Committee on Cancer Stage IIIB Hepatocellular Carcinoma With Portal Vein Thrombi: A Case Report.

The effective treatment for hepatocellular carcinoma (HCC) with American Joint Committee on Cancer stage IIIB remains controversial and challenging because of the high recurrence rate after resection and low survival rate. The median survival of those with macroscopic portal vein tumor thrombus (PVTT) is short. We reported such a case which received liver transplantation (LT) after successful consecutive downstaging therapies. A 40-year-old man with alcohol related liver cirrhosis and repeated esophageal varices bleeding had HCC with tumor thrombi in right main portal vein and the second portal branch of segment VI (stage IIIB). The received percutaneous alcohol injection, radiofrequency ablation, 8 sessions of transcatheter hepatic arterial chemoembolization, radiotherapy, and target therapy with sorafenib. Computed tomography (CT) scan and magnetic resonance imaging after treatments showed no viable fragments in the tumor and revealed both the right main portal vein and V1 branch were patent. One month later, the patient received a deceased LT. The perioperative course was rather smooth. After discharge, the interval follow-up CT studies of the chest and liver and whole body bone scan showed no tumor recurrence or metastasis up to 20 months postoperation.

Early Detection of a Hepatic Artery Pseudoaneurysm After Liver Transplantation Is the Determinant of Survival.

BACKGROUND: Hepatic artery pseudoaneurysm (PA) after liver transplantation (LT) is a rare but potentially fatal complication. Among a series of 50 patients of LT, we experienced 3 such cases. Some authors also have reported cases of PA, either intrahepatic or extrahepatic. The aim of this study was to investigate the important factors that affect the treatment outcome. METHODS: Three patients were presented. To analyze the factors, not only our patients but also the patients with PA reported in the literature (including 10 case series and 23 case reports) were enrolled for analysis. The possible factors probably affecting the survival were compared statistically, including age, sex, clinical manifestation as bleeding (including gastrointestinal bleeding, hemobilia, or intra-abdominal bleeding), treatment (with embolization or surgical exploration or stent), diagnosis establishment before or after bleeding, and so forth. RESULTS: From univariate analysis, the significant factors that affect survival are sex (female) (P = .036), stent treatment (P = .006), and early detection (P = .036), whereas age (P = .493) and presentation with hemorrhage (P = .877) are not significant factors. However, according to multivariate analysis, stent treatment has a borderline significance (P = .056). CONCLUSIONS: Early detection of such a life-threatening complication is a key determinant of survival. "Early" does not refer to early postoperative days but means the detection prior to the rupture of the pseudoaneurysm. Postoperative imaging studies such as computed tomographic scan or magnetic resonance cholangiopancreatography early and periodically to follow up the graft status is recommended, especially for those who had received other interventions before or after the liver transplantation.

Early incarcerated diaphragmatic hernia following right donor hepatectomy: a case report.

Right diaphragmatic hernia after donor hepatectomy is extremely rare. The occurrence is usually late. We present a case with early occurrence complicated with small bowel strangulation. Early detection and emergency surgical repair relieved the problem quickly. Predisposing factors are discussed. To avoid such a complication is very important.

Repeated introperative cholangiography is helpful for donor safety in the procurement of right liver graft with supraportal right bile duct variants in living-donor liver transplantation.

BACKGROUND: Despite recent advances in preoperative diagnostic imaging and operative techniques, biliary variation of the donor still remains a challenge in the procurement of graft. The supraportal right bile duct (BD) variant including presentation as trifurcation is a potential trap for injuring the remnant bile duct of donor. METHODS: Before living/related-donor liver transplantation (LRLT), cholangiogram with magnetic resonance images of each donor was performed as a routine. After exploration of the donor before hilar dissection, intraoperative chloangiography (IOC) was routinely performed. Among the supraportal right bile duct variants, if the preoperative cholangiography showed a suspected trifurcation of the bile duct, we then performed 3 sessions of IOC during liver graft procurement, including prior to hilar dissection, before the division of bile ducts and after the division. We reviewed the cholangiogram and the postoperative laboratory data of a consecutive series of 25 donors of LRLT. RESULTS: There was no division injury of the remnant bile duct of all of the donors. CONCLUSIONS: Repeated IOC is suggested as a routine for variants of supraportal right bile ducts especially trifurcation pattern in graft procurement to avoid the injury of donor remnant bile ducts.

Intrahepatic segmental portal vein thrombosis after living-related donor liver transplantation.

BACKGROUND: Intrahepatic segmental portal vein thrombosis after living-related liver transplantation (LRLT) is uncommon. The cause remains unclear. METHODS: After providing written informed consent, 25 recipients receiving LRLT at our institution from January 2011 to September 2013 were enrolled in this study. We performed triphase computerized tomographic (CT) study of the liver graft of each recipient 1 month after LRLT. The patencies of hepatic artery, portal vein, and hepatic vein were evaluated in detail. The triphase CT scans of the liver of each donor before transplantation also were reviewed. Thrombosis of the intrahepatic segmental portal vein was defined as the occlusion site of the portal vein being intrahepatic. Extrahepatic portal vein thrombosis was excluded in this study. RESULTS: Among the 25 patients, 2 (8%) developed thrombosis of intrahepatic segmental portal vein. One 47-year-old man received LRLT for hepatitis B viral infection-related liver cirrhosis (Child-Pugh class C) with 3 hepatocellular carcinomas (total tumor volume <8 cm). Another 53-year-old man received LRLT for alcoholic liver cirrhosis (Child-Pugh class C). Both had developed progressive jaundice and cholangitis 1 month after surgery. Intrahepatic biliary stricture was found on the follow-up magnetic resonance images. However, liver triphase CT study demonstrated occlusion of intrahepatic portal vein of segment 8 in each patient. Radiologic interventions and balloon dilatation therapy via percutaneous transhepatic biliary drainage route improved the symptoms and signs of cholangitis and obstructive jaundice for both. CONCLUSIONS: Thrombosis of intrahepatic segmental portal vein is not common but is usually associated with complications of intrahepatic bile duct. Early detection is important, and follow-up CT study of liver is suggested.

Loss of speech after living-related donor liver transplantation: detection of the lesion by diffusion tensor image.

INTRODUCTION: Loss of speech after living-related liver transplantation is uncommon. Either immunosuppressive agents, related sequelae, or a neurological event may cause it. CASE REPORT: A 46-year-old man developed dysarthria and dysphagia on the 10th day after living-related donor liver transplantation for alcoholic cirrhosis with Child-Pugh class C. Brain magnetic resonance images and electroencephalograms could not detect any lesion, but the diffusion tensor image showed a subacute lacunar infarction at right midbrain. The patient's speech improved 1 month after rehabilitation. CONCLUSIONS: Some unexpected neurological events, such as loss of speech, may occur after liver transplantation. The differential diagnosis becomes very important before active treatment. Magnetic resonance imaging supplemented with diffusion tensor imaging is an effective imaging study in establishing the diagnosis.

Case report: maximum-intensity projection and minimum-intensity projection of computed tomography are helpful in the diagnosis of Budd-Chiari syndrome in complicated liver cirrhosis.

BACKGROUND: Early detection of Budd-Chiari syndrome (BCS) to give the appropriate therapy in time is crucial. Angiography remains the golden standard to diagnose BCS. However, to establish the diagnosis of BCS in complicated cirrhotic patients remains a challenge. We used maximum intensity projection (Max IP) and minimum intensity projection (Min IP) from computed tomographic (CT) images to detect this syndrome in such a patient. CASE REPORT: A 55-year-old man with a history of chronic hepatitis B infection and alcoholism had undergone previously a left lateral segmentectomy for hepatic epitheloid angiomyolipoma (4.6 × 3.5 × 3.3 cm) with a concomitant splenectomy. Liver decompensation with intractable ascites and jaundice occurred 4 months later. The reformed images of the venous phase of enhanced CT images with Max IP and Min IP showed middle hepatic vein thrombosis. He then underwent a living-related donor liver transplantation with a right liver graft from his daughter. Intraoperatively, we noted thrombosis of his middle hepatic vein protruding into inferior vena cava. The postoperative course was unevenful. Microscopic findings revealed micronodular cirrhosis with mixed inflammation in the portal areas. Some liver lobules exhibited congestion and sinusoidal dilation compatible with venous occlusion clinically. CONCLUSIONS: We recommend Max IP and Min IP of CT images as simple and effective techniques to establish the diagnosis of BCS, especially in complicated cirrhotic patients, thereby avoiding invasive interventional procedures.

Use of RNA interference to modulate liver adenoma development in a murine model transgenic for hepatitis B virus.

Chronic hepatitis B virus (HBV) infection is closely related to the development of severe liver complications, including hepatocellular carcinoma. In previous studies, we reported that in vivo long-term HBV suppression in transgenic mice can be achieved without apparent toxicity by short hairpin RNA sequentially delivered using adeno-associated viral (AAV) vectors of different serotypes. Our goal herein was to address the clinical utility of this delivery system and, in particular, to determine whether RNA interference (RNAi) and its ability to induce long-term HBV suppression will modulate the development of HBV-associated liver pathology. As a model system, we used a unique HBV transgenic mouse model, containing a 1.3 times over length of the HBV genome, on the ICR mouse background. These transgenic mice produce high serum HBV titers comparable with human chronic HBV patients, and, importantly, manifest characteristic HBV-associated pathology, including progressive hepatocellular injury and the development of hepatocellular adenoma. Using this system, we injected animals with AAV vectors expressing either HBV-specific or a control luciferase-specific short hairpin RNA and followed animals for a total of 18 months. We report herein that AAV-mediated RNAi therapy profoundly inhibits HBV replication and gene expression, with a significant reduction in hepatic regeneration, liver enzymes and, importantly, the appearance of liver adenomas. Indeed, the therapeutic effect of RNAi correlated with the reduction in HBV titers. Our data demonstrate that appropriately designed RNAi therapy has the potential to prevent formation of HBV-associated hepatocellular adenoma.

Enhancement of fermentation process in Pu-erh tea by tea-leaf extract.

Pu-erh tea is known as a fermented tea and longer storage enhances its flavor and taste. Recently, Aspergillus, Blastobotrys, and Streptomyces are found to play important roles in nutritional enhancement of Pu-erh tea by fermentation. Since water and temperature affect the microbial growth, we therefore explored the factors that might enhance the Pu-erh tea fermentation. The results showed that the addition of fresh tea-leaf extract (TLE) enhanced the withered tea fermentation (at 37 degrees C, 80 to 85% RH) as compared with the water only. Contents of statin, GABA, gallic acid, DPPH scavenging and polyphenol oxidase (PPO) activities were increased, whereas polyphenols and caffeine were decreased over 6 mo. TLE dose-dependently enhanced some of the qualities (that is, statin, PPO) of Pu-erh tea significantly as compared with the water only. The effect was related to the increase population of A. niger and A. carbonarius at 6 mo (from 7.6 +/- 1.2 x 10(1) and 3.2 +/- 1.3 x 10(1) to 3.1 +/- 1.2 x 10(6) and 2.4 +/- 1.1 x 10(5) colony forming units [CFU]/g, respectively). After drying process (90 degrees C, 30 min), the total microbial count from these samples returned to background level (3 +/- 0.5 x 10(2) CFU/g). None of ochratoxin and fumonisin, toxins from Aspergillus, was detected in the final products. The flavor and taste were also enhanced by treatment with TLE. The inoculation with S. cinereus Y11 with 2% TLE further enhanced these functional contents (about 2-fold increase of statin level) in the experimental Pu-erh tea. Therefore, this result may add a new process for Pu-erh tea manufacture.

YC-1 attenuates LPS-induced proinflammatory responses and activation of nuclear factor-kappaB in microglia.

BACKGROUND AND PURPOSE: An inflammatory response in the central nervous system mediated by the activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. LPS has been reported to cause marked microglia activation. It is very important to develop drugs that can inhibit microglia activation and neuroinflammation. Here, we investigated the inhibitory effect of YC-1, a known activator of soluble guanylyl cyclase, against LPS-induced inflammatory responses in microglia. EXPERIMENTAL APPROACH: To understand the inhibitory effects of YC-1 on LPS-induced neuroinflammation, primary cultures of rat microglia and the microglia cell line BV-2 were used. To examine the mechanism of action of YC-1, LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, iNOS, COX-2 and cytokine expression were analyzed by Griess reaction, ELISA, Western blotting and RT-PCR, respectively. The effect of YC-1 on LPS-induced activation of nuclear factor kappa B (NF-kappaB) was studied by NF-kappaB reporter assay and immunofluorocytochemistry. KEY RESULTS: YC-1 inhibited LPS-induced production of NO and PGE2 in a concentration-dependent manner. The protein and mRNA expression of iNOS and COX-2 in response to LPS application were also decreased by YC-1. In addition, YC-1 effectively reduced LPS-induced expression of the mRNA for the proinflammatory cytokines, TNF-alpha and IL-1beta. Furthermore, YC-1 inhibited LPS-induced NF-kappaB activation in microglia. CONCLUSIONS AND IMPLICATIONS: YC-1 was able to inhibit LPS-induced iNOS and COX-2 expression and NF-kappaB activation, indicating that YC-1 may be developed as an anti-inflammatory neuroprotective agent.

Long-term inhibition of hepatitis B virus in transgenic mice by double-stranded adeno-associated virus 8-delivered short hairpin RNA.

RNA interference (RNAi) was reported to block hepatitis B virus (HBV) gene expression and replication in vitro and in vivo. However, it remains a technical challenge for RNAi-based therapy to achieve long-term and complete inhibition effects in chronic HBV infection, which presumably requires more extensive and uniform transduction of the whole infected hepatocytes. To increase the in vivo transfection efficiency in liver, we used a double-stranded adeno-associated virus 8-pseudotyped vector (dsAAV2/8) to deliver shRNA. HBV transgenic mice were used as an animal model to evaluate the inhibition effects of the RNAi-based gene therapy. A single administration of dsAAV2/8 vector, carrying HBV-specific shRNA, effectively suppressed the steady level of HBV protein, mRNA and replicative DNA in liver of HBV transgenic mice, leading to up to 2-3 log(10) decrease in HBV load in the circulation. Significant HBV suppression sustained for at least 120 days after vector administration. The therapeutic effect of shRNA was target sequence dependent and did not involve activation of interferon. These results underscore the potential for developing RNAi-based therapy by dsAAV2/8 vector to treat HBV chronic infection, and possibly other persistent liver infections as well.

Subcutaneous Rosai-Dorfman disease: is surgical excision justified?

Rosai-Dorfman disease in soft tissue without nodal disease has been recognized as a distinct clinicopathologic entity. It may represent a diagnostic challenge and the natural history and optimal treatment has not been well clarified. We investigated a patient in whom Rosai-Dorfman disease was confined to the subcutis of the abdominal wall and recurred after incomplete excision. Complete resolution was achieved by wide surgical excision with negative margins. Pathologic examination confirmed the diagnosis of extranodal Rosai-Dorfman disease. The patient is disease-free after 1 year of follow-up. Despite the possibility that spontaneous remission may occur, our results suggest that when anatomically feasible, complete excision can be a treatment option for persistence or recurrence of exclusively extranodal disease. Larger case series and longer follow-up are needed to assess the long-term efficacy in these patients.

Evaluation of non-point sources pollution impacts by integrated 3S information technologies and GWLF modelling.

Assessing the potential of non-point source pollution to assist in the planning of Best Management Practice (BMP) is significant for improving pollution prevention and control in a river basin. In many cases, however, the grid-based modelling analysis is prohibitively laborious and hindered because of insufficient information. This paper presents a new and fast methodology for catchment land-use identification and waste load estimation by properly integrating the skills of remote sensing (RS), geographic information system (GIS), global positioning system (GPS), and the Generalized Watershed Loading Functions (GWLF) model. In this analysis, eight types of land-use patterns in the watershed area of the Kao-Ping River Basin were classified with the aid of SPOT satellite images, Erdas Imagine image processing system, and ArcView GIS system. Hydrologic and geographical features were obtained or derived by the Digital Elevation Model (DEM) and GIS technique simultaneously. The GWLF model was used to estimate the waste loads of non-point sources in terms of the total phosphorus (TP) and total nitrogen (TN). It shows that the variations of TN and TP loadings are closely related to the amount of rainfall over seasons. Final managerial policy can be made with respect to the identified three impact levels of nutrient loadings in the Kao-Ping River Basin, southern Taiwan, which could eventually perform as part of the Total Maximum Daily Load (TMDL) study in this region.

Are modified procedures significantly better than conventional procedures in percutaneous transhepatic treatment for complicated right hepatolithiasis with intrahepatic biliary strictures?

BACKGROUND: Conventional percutaneous procedures for treating patients with recurrent hepatolithiasis associated with complicated intrahepatic biliary strictures require multiple dilation sessions before stone extraction. We modified the approach, reducing the number of dilation sessions required and using newer lithotripsy and irrigation methods. We suggest that the modified procedures are superior to conventional management and demonstrate their utility in clearing hepatolithiasis. METHODS: Percutaneous transhepatic stricture dilation and cholangioscopic lithotripsy were performed to treat patients with right recurrent hepatolithiasis with complicated intrahepatic biliary strictures. Conventional methods were used in 40 patients (Group A). Modified methods, including simplification of tract establishment and stricture dilation and electrohydraulic lithotripsy (EHL) were used in 60 patients (Group B). RESULTS: Group B patients had fewer complications (massive hemobilia: 0% versus 15%, P = 0.0032, cholangitis: 0% versus 17.5%, P=0.0012), tolerated the procedures better (intolerable pain: 0% versus 12.5%, P=0.0087), had a higher rate of success (residual stones: 3.3% versus 20%, P=0.0132; remaining asymptomatic and stone-free: 81% versus 50%, P = 0.0021), a shorter hospital stay (17.8 +/- 4.4 days versus 36.2 +/- 5.5 days, P < 0.001) and lower overall expense (USD 2689 versus USD 3848) than Group A patients. CONCLUSION: We believe that the modified methods are superior to conventional treatment in that they effectively decrease procedural complications and cost, and significantly improve treatment results.

The benefits of a second transhepatic route in failed percutaneous management of difficult intrahepatic biliary strictures with recurrent hepatolithiasis.

Percutaneous stricture dilatation and cholangioscopic lithotomy has become a mainstay in the treatment of patients with recurrent hepatolithiasis associated with intrahepatic biliary strictures. In a consecutive series of 125 patients who underwent percutaneous management of recurrent hepatolithiasis from 1987 to 1999, there were 15 patients in whom the procedure failed to clear the stones. A second percutaneous transhepatic route was established for subsequent treatment. A reappraisal of its indications and efficacy was done. Treatment through a second route was helpful for patients with bilateral strictures, angulated duct, difficult strictures, large impacted stones, a subcutaneous jejunal limb, or hemobilia developing in the first route. Strictures remained impacted in 1 of the 15 patients (failure rate, 7%), with the remaining having complete clearance of stones. Cholangitis occurred in two patients; no other complications were encountered. A second percutaneous route is very helpful for the management of complicated hepatolithiasis and biliary stricture.

Dehydroepiandrosterone inhibits lipopolysaccharide-induced nitric oxide production in BV-2 microglia.

Levels of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) decline during aging and reach even lower levels in Alzheimer's disease (AD). DHEA is known to exhibit a variety of functional activities in the CNS, including an increase of memory and learning, neurotrophic and neuroprotective effects, and the reduction of risk of age-related neurodegenerative disorders. However, the influence of DHEA on the immune functions of glial cells is poorly understood. In this study, we investigated the effect of DHEA on activated glia. The production of inducible nitric oxide synthase (iNOS) was studied in lipopolysaccharide (LPS)-stimulated BV-2 microglia, as a model of glial activation. The results showed that DHEA but not DHEAS significantly inhibited the production of nitrite in the LPS-stimulated BV-2 cell cultures. Pretreatment of BV-2 cells with DHEA reduced the LPS-induced iNOS mRNA and protein levels in a dose-dependent manner. The LPS-induced iNOS activity in BV-2 cells was decreased by the exposure of 100 microM DHEA. Moreover, DHEA suppressed iNOS gene expression in LPS-stimulated BV-2 cells did not require de novo synthesis of new proteins or destabilize of iNOS mRNA. Since DHEA is biosynthesized by astrocytes and neurons, our findings suggest that it might have an important regulatory function on microglia.