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Gastric varices (GV) carry a high risk of massive hemorrhage because of potential rupture. To reduce the risk associated with GV, patients need to undergo hemostatic and preventive treatment. The objective of this retrospective study was to evaluate the usefulness of a new method, direct forward-viewing endoscopic ultrasonography (DFV-EUS) for the treatment of GV. We performed endoscopic injection sclerotherapy with histoacryl (EIS-HA) using DFV-EUS for GV in four patients. The paracentesis success rate was 75% (3/4). DFV-EUS has a significant advantage for the treatment of GV in that it can show physicians endoscopic and ultrasound views in real time during the delivery of the sclerosant into the GV. However, the proper use of the ultrasound view must be elucidated through further research for safer and more effective therapy. In the presence of distance between the mucosal surface and vascular lumen or when the blood flow site requires puncture as an additional treatment, DFV-EUS might be a good candidate for the treatment of GV. Altogether, EIS-HA with DFV-EUS might be a new therapeutic option for patients with GV.

Ectopic hepatocellular carcinoma (HCC) is a rare malignancy, which manifests similar morphology and immunohistochemistry to intrahepatic HCC. Herein, we report a case of ectopic HCC in a 73-year-old male. The patient presented to our hospital with gradually progressing right lower abdominal pain, and enhanced computed tomography revealed multiple nodules in the peritoneum without intrahepatic mass. A diagnostic laparoscopy was performed, and the final pathology result confirmed that it was HCC. Additional laboratory tests showed elevated serum alpha-fetoprotein and protein induced by vitamin K absence-II (PIVKA-II) levels, suggesting our diagnosis. The patient received sorafenib, a tyrosine kinase inhibitor (TKI), for unresectable ectopic HCC. However, the tumor progressed, and because of tarry stools and hemorrhagic anemia, sorafenib was ceased after 7 months of therapy. One month after the cessation of sorafenib, the PIVKA-II level increased abruptly, and the patient died 1 year after diagnosis. The effective treatment for unresectable ectopic HCC is still unknown. Additional cases should be accumulated to determine the effect of TKI on ectopic HCC.

Biliary atresia (BA) is the most common indication for liver transplantation (LT) in pediatric population. This study analyzed the comprehensive factors that might influence the outcomes of patients with BAwho undergo living donor LTby evaluating the largest cohort with the longest follow‐up in the world. Between November 1989 and December 2015, 2,085 BApatients underwent LDLTin Japan. There were 763 male and 1,322 female recipients with a mean age of 5.9 years and body weight of 18.6 kg. The 1‐, 5‐, 10‐, 15‐, and 20‐year graft survival rates for the BApatients undergoing LDLTwere 90.5%, 90.4%, 84.6%, 82.0%, and 79.9%, respectively. The donor body mass index, ABOincompatibility, graft type, recipient age, center experience, and transplant era were found to be significant predictors of the overall graft survival. Adolescent age (12 to <18 years) was associated with a significantly worse long‐term graft survival rate than younger or older ages. We conclude that LDLTfor BAis a safe and effective treatment modality that does not compromise living donors. The optimum timing for LTis crucial for a successful outcome, and early referral to transplantation center can improve the short‐term outcomes of LTfor BA. Further investigation of the major cause of death in liver transplanted recipients with BAin the long‐term is essential, especially among adolescents This study analyzes the factors that might influence the outcomes of patients with biliary atresia who undergo living donor liver transplantation and demonstrates that donor body mass index, blood type incompatibility, graft type, recipient age, center experience, transplant era, and adolescent age are significant predictors of overall graft survival.

Biliary atresia (BA) is the most common indication for liver transplantation (LT) in pediatric population. This study analyzed the comprehensive factors that might influence the outcomes of patients with BA who undergo living donor LT by evaluating the largest cohort with the longest follow-up in the world. Between November 1989 and December 2015, 2,085 BA patients underwent LDLT in Japan. There were 763 male and 1,322 female recipients with a mean age of 5.9 years and body weight of 18.6 kg. The 1-, 5-, 10-, 15-, and 20-year graft survival rates for the BA patients undergoing LDLT were 90.5%, 90.4%, 84.6%, 82.0%, and 79.9%, respectively. The donor body mass index, ABO incompatibility, graft type, recipient age, center experience, and transplant era were found to be significant predictors of the overall graft survival. Adolescent age (12 to <18 years) was associated with a significantly worse long-term graft survival rate than younger or older ages. We conclude that LDLT for BA is a safe and effective treatment modality that does not compromise living donors. The optimum timing for LT is crucial for a successful outcome, and early referral to transplantation center can improve the short-term outcomes of LT for BA. Further investigation of the major cause of death in liver transplanted recipients with BA in the long-term is essential, especially among adolescents

We investigated the expression of the αEβ7 integrin (CD103)-intestinal homing receptor of T-intraepithelial lymphocytes (IELs) in 130 cases of adult T-cell leukemia/lymphoma (ATLL). We detected CD103+lymphoma cells in 55% (31/56) of mainly gastrointestinal (GI)-involved ATLL cases. Among them, lymphoma cells of 18 cases located in other involved organs had similar CD103 expression patterns. Histologically, we found (a) increased reactive IELs in non-neoplastic mucosal layers in 28% (5/18) of surgical and mucosal resection cases, (b) preserved epithelial glands, and (c) numerous small intraepithelial ATLL nests in involved lesions in 36 (69%) and 21 (40%), respectively, of the 52 examined cases. These 3 patterns were common in intestinal type II enteropathy-associated T-cell lymphoma but were rare in intestinal EBV+nasal-type/like T/natural killer (NK)-cell lymphoma. We detected CD103+tumor cells in 41% (16/39) of lymph node–involved ATLL, in 31% (11/35) of skin-involved ATLL, in 68% (21/31) of type II CD4−enteropathy-associated T-cell lymphoma cases, in 36% (8/22) of primary gastric T/NK-cell lymphomas, and in 77% (7/9) of CD8+epidermotropic mycosis fungoides. CD103+ATLL prefers involving the GI tract over the skin (P<0.05). CD103 expression in GI-involved and/or total ATLL cases was significantly higher than in other 9 T/NK-cell lymphoma groups (P<0.05 or 0.01). Only ATLL cases were commonly CD103+in CD4+T/NK-cell lymphoma groups (P<0.05 or 0.01). Human T-lymphotropic virus-1–infected CD103+T-IELs and mucosal T cells may be important sources of ATLL.

The present study aimed to investigate the therapeutic efficacy and safety of the insertion technique of 3 bipolar electrodes in patients with hepatocellular carcinoma (HCC), using C-arm type X-ray fluoroscopy-assisted ultrasonography (US) in guiding a multipolar radiofrequency ablation (RFA) system. Seventy-three patients with HCC treated with a multipolar RFA system (1 electrode, n = 2; 2 electrodes, n = 56; 3 electrodes, n = 17) were enrolled in this retrospective cohort study. To analyze their therapeutic outcome in this study, we divided among 17 patients using 3 electrodes into 2 subgroups: the C-arm type X-ray fluoroscopy-assisted (n = 7) and the US-guided alone groups (n = 10). Therapeutic efficacy and safety were analyzed between the 2 groups. Multipolar RFA treatment was performed safely in all cases, and no severe adverse events occurred. Comparing the patient background of the group treated using 1 or 2 electrodes with that treated using 3 electrodes, larger-sized HCC was treated using 3 electrodes (P < .001). The differences in overall and recurrence-free survival rates between the 1- or 2-electrode and the 3-electrode groups were not significantly different (P = .843 and P = .891). Comparing the C-arm type X-ray fluoroscopy-assisted and the US-guided alone groups among patients treated using 3 electrodes, technical factors such as total ablation time and the number of sessions were not significantly different between the 2 groups. The local tumor progression rate was not significantly different between the 2 groups (P = .942). Multipolar RFA treatment was effective for the treating HCC; using 3 electrodes was suitable for larger-sized HCCs. The technical approach with C-arm type X-ray fluoroscopy assistance using 3 electrodes was useful for operators to perform safe and appropriate insertion techniques by synchronizing the US and X-ray fluoroscopy images.

AbstractWe report two cases of Budd-Chiari syndrome. Case 1: A 57-year-old man presented with leg edema and esophageal varices. Cavography showed obstruction of the inferior vena cava with antiphospholipid syndrome. Further, the patient showed positive serology for hepatitis C virus and consumed large quantities of alcohol. Percutaneous transluminal angioplasty was performed on this patient and anticoagulants administered; leg edema and esophageal varices were ameliorated although liver biopsy showed cirrhosis without evident congestion. More than 9 months since the diagnosis, restenosis of the inferior vena cava has not occurred. Case 2: A 73-year-old woman presented abdominal pain but no edema or varices. Cavography showed membranous obstruction of the inferior vena cava which required no therapy. Manifestation of portal hypertension was not present and liver function was maintained although liver biopsy showed obvious congestion. These cases showed untypical features against histopathology, and careful observation will be required for emergence of hepatocellular carcinoma.Copyright © 2008 S. Karger AG, Basel

Abstract Intestinal lymphangiectasia (IL) is a rare disease requiring oral fat restriction. The aim of this study was to evaluate the efficacy of enteral nutrition compared to that of total parenteral nutrition (TPN). We retrospectively reviewed nine patients with IL presenting with protein-losing enteropathy. Of these, seven patients not responding to a low-fat diet were treated with elemental diet (ED), polymeric diet (PD) containing medium-chain triglycerides, or TPN. Improvement in serum total protein was observed in two of three on ED and in one of two on PD, compared with three of three on TPN. Enteric protein loss was improved in two of two on ED, one of two on PD, and two of two on TPN. Outpatients who continued to receive enteral nutrition maintained a total protein level. Enteral nutirition appears to be as effective as TPN for patients with IL, and it may provide a valid and safe alternative therapy.

Recurrence of peptic ulcer after successful eradication of Helicobacter pyloriis closely associated with reinfection. The aim of this study was to examine the recurrence of peptic ulcer and reinfection with H. pyloriafter successful eradication. To eradicate H. pyloriinfection, patients with active peptic ulcer disease were assigned to two treatment groups depending on the year of their enrollment AM group and OAMR group. Patients in the AM group received 400 mg of cimetidine twice per day, 300 mg of amoxicillin three times per day, and 250 mg of metronidazole three times per day for 2 weeks. Patients in the OAMR group received 20 mg of omeprazole once per day, 500 mg of amoxicillin granules three times per day, 250 mg of metronidazole three times per day, and 150 mg of roxithromycin twice per day for 1 week. After endoscopy verified ulcer scarring and successful eradication of H. pyloriinfection, study patients were followed up monthly and did not undergo acidsuppressive therapy. Endoscopy was performed at 6month intervals for the 1st year. After the 1st year, followup endoscopies were performed annually. In total, 107 patients with peptic ulcer duodenal ulcer DU, 65 gastric ulcer GU, 42 were followed up for a mean period of approximately 2 years. Recurrence of infection occurred in 10 9.3 of 107 patients AM group, 9 OAMR group, 1 after 210 patientyears of followup the recurrence rate was 4.8 per patientyear. Recurrence of H. pyloriinfection was significantly higher in the AM group 23.1 than in the OAMR group 1.5. H. pyloriinfection recurred in two patients 6 months after eradication therapy, in seven 1 year after, and in one 2 years after. Thereafter, no further cases of H. pylorirecurrence were observed. During followup periods, seven cases of ulcer recurrence were observed DU, 4 GU, 3. The rate of peptic ulcer recurrence within 2 years after eradication therapy was significantly higher than that after more than 2 years. Four cases of ulcer recurrence DU, 3 GU, 1 also had recurrence of H. pyloriinfection. One recurrent case of DU without reinfection was associated with nonsteroidal antiinflammatory drugs. The remaining two cases of GU recurred without H. pylorireinfection. In conclusion, peptic ulcer recurrence rarely occurred 3 2.9 of 103 in patients cured of H. pyloriinfection. Reinfection after apparent successful eradication was rarely noted when a powerful therapeutic regimen in eradication was used. Therefore, to eradicate H. pylori, a highly effective therapeutic regimen should always be used.

Background & Aims:Wilson disease is a genetic disorder characterized by the accumulation of copper in the body as a result of a defect of copper excretion from hepatocytes. The intracellular localization of the Wilson disease gene product, ATP7B, was recently identified as the late endosomes. Various mutations have been documented in patients with Wilson disease. The clinical manifestations vary greatly among the patients; however, there is little information on the genotype-phenotype correlation. Methods:We investigated the distribution of a common ATP7B mutant His1069Gln and a mutant Asp1270Ser by expressing the mutants tagged with green fluorescent protein in Huh7 and HEK293 cells. Intracellular organelles were visualized by fluorescence microscopy. Results:Although the wild-type ATP7B and Asp1270Ser mutant localized in the late endosomes, His1069Gln mutant did not locate in the late endosomes and was degraded by the proteasomes in the cytoplasm. Furthermore, His1069Gln formed aggresomes composed of the degradates and intermediate filaments at the microtubule-organizing center. These aggresomes were similar to Mallory bodies on electron microscopy. Conclusions:The different protein properties of ATP7B mutants may explain the variety of clinical spectrums in patients with Wilson disease.

A 45-year-old woman with chronic hepatitis B underwent partial hepatectomy for hepatocellular carcinoma (HCC). However, the HCC recurred 2 months after surgery and rapid progression of the disease resulted in her death. Immunohistochemistry showed that transforming growth factor-α (TGFα) was barely expressed in the liver specimens obtained at hepatic resection, whereas autopsy specimens were strongly stained with anti-TGFα antibody in the cytoplasm of both non-tumourous and tumourous liver cells. A higher level of Ki67 expression, a proliferating marker, was observed in the recurrent HCC, similar to that of TGFα. Thus, we speculate that the partial hepatectomy increased the level of TGFα leading to recurrence and progression of HCC through an autocrine/paracrine mechanism.

Interferon (IFN) is widely used for patients with hepatitis C. Less than half of treated patients respond to IFN therapy, however, and increased resistance to IFN is particularly observed in genotype 1b patients. Recently, genotype 1b patients with the wild type sequence in the NS5A gene were shown to be resistant to therapy, suggesting that the NS5A protein may be involved to IFN resistance. Thus, we investigated the serum 2′,5′‐oligoadenylate synthetase (2′,5′‐OAS) levels before and during IFN treatment. In addition, other biochemical markers and NS5A mutations were also examined in 30 HCV genotype 1b‐positive patients. Before IFN treatment, 2′,5′‐OAS activity in sera was significantly lower in wild type patients than in mutant type patients. All patients were subsequently enrolled in IFN therapy, and 2′,5′‐OAS activity was elevated both in wild and mutant type patients, irrespective of the number of mutations in NS5A. Logistic regression analysis revealed that clearance of serum HCV RNA was independently related to the pretreatment viral load and NS5A mutations, but not to serum 2′,5′‐OAS activity. We concluded that the NS5A protein, that is associated with the outcome of IFN therapy, affects the kinetics of IFN‐induced molecules, such as 2′,5′‐OAS. 2′,5′‐OAS activity does not, however, seem to be related to long‐term virological response to IFN therapy. J. Med. Virol. 62:185–190, 2000. © 2000 Wiley‐Liss, Inc.

Wilson's disease is a genetic disorder characterized by the accumulation of copper in the body due to a defect of biliary copper excretion. However, the mechanism of biliary copper excretion has not been fully clarified. We examined the effect of copper on the intracellular localization of the Wilson disease gene product (ATP7B) and green fluorescent protein (GFP)-tagged ATP7B in a human hepatoma cell line (Huh7). The intracellular organelles were visualized by fluorescence microscopy. GFP-ATP7B colocalized with late endosome markers, but not with endoplasmic reticulum, Golgi, or lysosome markers in both the steady and copper-loaded states. ATP7B mainly localized at the perinuclear regions in both states. These results suggest that the main localization of ATP7B is in the late endosomes in both the steady and copper-loaded states. ATP7B seems to translocate copper from the cytosol to the late endosomal lumen, thus participating in biliary copper excretion via lysosomes.

Background:We investigated the clinical characteristics of hepatitis C virus (HCV) antibody‐positive hepatocellular carcinoma (HCC) patients who developed HCC at a relatively young age. Methods:Clinical characteristics of patients in their 40s were investigated and were compared with those of patients 50 years and older. The subjects were 648 HCC patients, 469 men (72%) and 179 women (28%), who were treated at our hospital between 1991 and 1997. Results:No patient was under 40 years of age. Eighteen patients (3%) were in their 40s, 137 patients (21%) were in their 50s, 338 patients (52%) were in their 60s, 143 patients (22%) were in their 70s, and 12 patients (2%) were in their 80s. Fifteen of the patients (83%) in their 40s were male. The proportion of men in their 40s was higher than that of all men. Eight of the 15 men in their 40s (53%) were heavy drinkers, and 2 (14%) were habitual drinkers. Three of the 15 men (20%) were HBV carriers, and these 3 HBV carriers were not drinkers. The proportion of heavy drinkers and HBV carriers was significantly higher among the patients in their 40s than in the 60 patients randomly sampled from the patients 50 years of age and older. The mean ages of male patients with HCC who were heavy drinkers, habitual drinkers, occasional drinkers, or nondrinkers were 52.3, 58.9, 62.0, and 61.7 years, respectively. HCC occurred significantly earlier in heavy drinkers than in the other 3 groups. We compared laboratory data of the patients in their 40s with data of all of the patients of 50 years and older. Serum total bilirubin, prothrombin time, and platelet counts were significantly worse in the patients in their 40s. Conclusions:Logistic regression analysis revealed that heavy drinking and presence of HBV infection were independently related to HCV antibody‐positive HCC development at a younger age.

Abstract: A 17-year-old woman with arterial and venous thrombosis of the leg diagnosed as antiphospholipid syndrome (APS) associated with systemic lupus erythematosus (SLE) is reported. Her serum C-reactive protein (CRP) was elevated and complement concentrations were normal. Symptoms of APS were improved with prednisolone, when the serum CRP concentration decreased, and low serum complement concentration and white blood cell count appeared. These are characteristic features of SLE. It is suggested that APS is a possible complication of SLE and may modify the clinical features of SLE.

A 17-year-old woman with arterial and venous thrombosis of the leg diagnosed as antiphospholipid syndrome (APS) associated with systemic lupus erythematosus (SLE) is reported. Her serum C-reactive protein (CRP) was elevated and complement concentrations were normal. Symptoms of APS were improved with prednisolone, when the serum CRP concentration decreased, and low serum complement concentration and white blood cell count appeared. These are characteristic features of SLE. It is suggested that APS is a possible complication of SLE and may modify the clinical features of SLE.

To investigate the effect of a thickened pericanalicular ectoplasm in tubulovesicular transport and biliary excretion, we examined the ultrastructure of the intracellular membranous system in rat hepatocytes with and without phalloidin treatment, by transmission electron microscopy and scanning electron microscopy combined with the Aldehyde prefix Osmium-Dimethyl Sulfoxide-Osmium method. Hepatocytes possessed elaborate networks of tubules around bile canaliculi, and some of them extended to the bile canaliculi in control rats. Vesicles were also present around the bile canaliculus. Treatment of rats with phalloidin produced a thick pericanalicular ectoplasm around the bile canaliculus visualized by transmission electron microscopy, and the density of vesicles (p<0.001) and tubules (p<0.001) within 0.5 μm around the bile canaliculus significantly decreased in phalloidin-treated rats. The number of lysosomes in hepatocytes apparently increased in phalloidin-treated rats; however, they were rarely observed around the bile canaliculus. The Aldehyde prefix Osmium-Dimethyl Sulfoxide-Osmium method produced an organelle-free space around the bile canaliculus by removing the thick pericanalicular ectoplasm in scanning electron microscopic examination, and the thickened pericanalicular ectoplasm inhibited the approach of intracellular membranes to the canalicular membrane in the transmission electron microscopic examination. In some pathological cholestatic conditions, the thickened pericanalicular ectoplasm may inhibit not only bile canalicular contraction but also biliary excretion of substances, which is mediated by the tubulovesicular transport system.

Background:Endothelin (ET) is known as a vasoconstrictive substance. The receptors for ET have been shown in various organs. However, little is known about the endothelin-1 (ET-1) binding sites in the liver. The aim of this study was to examine ET-1 binding sites in the liver. Methods:ET-1 binding sites in rat liver were studied in vivo by light- and electron-microscopic autoradiography using 125I-ET-1. Results:Light-microscopic autoradiographic observation revealed strong localization of grains in the sinusoidal lining cells of the hepatic lobule and a small number of grains in the luminal space of the portal vein and central vein. In the hepatic lobule, more grains were located in the periportal region, and the quantity tended to decrease from the midzonal to the pericentral region. Electron-microscopic autoradiographic observation revealed grains in Ito cells and in the endothelial cells of the portal vein, central vein, and hepatic sinusoids. Conclusions:These results suggest that ET-1 acts on Ito cells and on endothelial cells of the hepatic sinusoids, portal vein, and central vein and that its action is related to hemodynamics of the liver, particularly regulation of the microcirculation of the hepatic sinusoids.

Patients with autoimmune hepatitis (AIH) may sometimes have concomitant idiopathic thrombocytopenic purpura (ITP). Severe thrombocytopenia in ITP interferes with percutaneous liver biopsy for pathological diagnosis of AIH. Here, we report a case of AIH with ITP in a 63-year-old woman. The patient presented to our hospital with liver dysfunction and thrombocytopenia. For histological examination, transjugular liver biopsy (TJLB) was performed, leading to a diagnosis of AIH. Corticosteroids treatment led to an improvement in her liver enzyme levels and platelet count. In conclusion, patients with AIH may sometimes have concomitant ITP. TJLB was effective for making the diagnosis of AIH with severe thrombocytopenia due to ITP.

The aortitis syndrome is a chronic inflammatory process that affects the aorta and its primary branches. Patients with aortitis syndrome exhibit various ocular changes. We present a patient in whom cataract was the initial objective finding. The serum concentration of vascular endothelial growth factor, a cytokine that affects neovascularization, and vasopermeability, was elevated before the initiation of prednisolone treatment. Cataract should be considered as a possible characteristic initial finding in patients with aortitis syndrome. Vascular endothelial growth factor may be involved in the progression of aortitis syndrome. Masaru Harada, Second Department of Medicine, Kurume University School of Medicine, Asahi-Machi 67, Kurume 830, Japan

OBJECTIVE: Recent studies have reported that duodenal heterotopic gastric mucosa (HGM) has been observed in 8.9% of patients who undergo esophagogastroduodenoscopy. However, there are few reports concerning the endoscopic and endoscopic ultrasound characteristics of submucosal tumour-like HGM in the duodenum.METHODS: Endoscopic, endoscopic ultrasound (EUS) and histological findings were analyzed in six patients with submucosal tumour-like HGM, which were confirmed by pathological examination of biopsy or endoscopic polypectomy specimens.RESULTS: Endoscopically, the lesions appeared as a solitary, sessile submucosal tumour-like mass with a depression at the top. In four of six patients, small granular structures were found in the depressed area of the mass. On EUS, all masses demonstrated a heterogeneous pattern, among which four patients presented anechoic areas while two patients showed no anechoic areas. All lesions were localized within the mucosa and submucosa on EUS. Histologically, they consisted of gastric glands and some dilated glands, and were covered with normal duodenal epithelium. In four of six lesions, the tumours were composed of gastric-type foveolar epithelium showing papillary growth, fundic glands and pyloric glands, while the others consisted of gastric-type foveolar epithelium and pyloric glands.CONCLUSION: A heterogeneous pattern on EUS and small granular structures on esophagogastroduodenoscopy represent valuable diagnostic features of submucosal tumour-like HGM.

The ultrastructure of the intracellular membranous system in rat hepatocytes was observed three dimensionally with a scanning electron microscope using the aldehyde prefix osmium-dimethyl sulfoxide-osmium method. Intracellular organelles were clearly observed in three dimensions, and direct connection of tubular structures with the bile canalicular membrane was clearly seen. The transcellular pathway of asialoglycoproteins in isolated cultured rat hepatocytes was also investigated, by affinity cytochemistry, using gold-conjugated asialofetuin, under a transmission electron microscope. Gold particles were clearly seen not only in vesicles, endosomes and lysosomes, but also in the tubular structures. These results suggest that the tubular structures in rat hepatocytes directly participate in the transcellular transport of macromolecules. In addition, the frequent connections of tubular structures with the bile canalicular membrane indicate that these structures around the bile canaliculus may supply membrane components to the bile canalicular membrane.