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Background/Aim: Lenvatinib is available as a molecular target agent for hepatocellular carcinoma (HCC). In this study, we investigated the popping phenomena in patients with HCC who underwent radiofrequency ablation (RFA) after taking lenvatinib. Patients and Methods: Fifty-nine patients with HCC between 21-30 mm in diameter and no history of systemic treatment were enrolled in the study. The patients underwent RFA using a VIVA RFA SYSTEM with an ablation tip of 30 mm in length. For the initial lenvatinib administration, 16 patients had an adequate course of treatment and were treated with RFA as add-on therapy (combination group). The other 43 patients were treated by RFA monotherapy (monotherapy group). The popping frequency during RFA was recorded and compared. Results: Popping frequency in the combination group (RFA combined with lenvatinib) was significantly higher than that in the monotherapy group. There was no significant difference between the combination group and the monotherapy group in ablation time, maximum output level, tumour temperature after ablation, or initial resistance value. Conclusion: Popping frequency was significantly higher in the combination group. It is possible that the intra-tumour temperature increased rapidly during RFA in the combination group due to the inhibitory effect of lenvatinib on tumour angiogenesis, leading to the occurrence of popping. Further studies are needed to investigate popping after RFA, and precise protocols need to be developed.

Interventional radiology (IVR), including balloon-occluded retrograde transvenous obliteration (BRTO) and percutaneous transhepatic obliteration (PTO), is performed for patients with intractable hepatic encephalopathy (HE). However, information on the appropriate coil for endovascular coiling for preventing recanalization is lacking. This study aimed to compare the different types of coils for endovascular coiling used in BRTO and PTO for cases of intractable HE.This retrospective study included patients who underwent endovascular coiling with BRTO or PTO for HE caused by portosystemic shunts. The number of coils required for complete occlusion was compared among bare, fiber, and hydrogel-coated coils, and the expansion types that close the gap between and inside the hydrogel-coated coils were also compared.Of 38 patients (age range, 30-86 years), 16 and 22 underwent BRTO and PTO, respectively, using bare (19 patients), fiber (8 patients), and hydrogel-coated coils (10 patients; external expansion type, 4; internal expansion type, 6). No significant differences in the size of portosystemic shunts were observed according to the type of coil. The mean number of coils required for complete occlusion varied (bare coils, 19.32; fiber coils, 18.11; hydrogel-coated coils, 10.70). Significantly fewer coils were required for endovascular coiling with hydrogel-coated coils. In the internal expansion type, a mean of 8.5 coils was required for occlusion.In some patients who underwent portal vein embolization, complete occlusion was not achieved with the scheduled type of coil because of slight expansion of blood vessels due to coil pressure. The findings suggested that hydrogel-coated coils were effective in endovascular coiling for HE caused by a portosystemic shunt, and internal expansion-type hydrogel-coated coils may be effective for the first-line procedure.

The indications for TACE in the treatment of hepatocellular carcinoma have become more stringent with the development of systemic pharmacotherapy. Radical TACE is expected to be used only in situations such as for tumors with small volume which fulfill the “up-to-7”. Furthermore, a combination of molecular-targeted agents is expected to maximize the efficacy of TACE. In the intermediate stage, TACE and drug therapy play complementary roles, and it is important to select a treatment strategy that considers tumor status and hepatic reserve. However, no studies have investigated the various types of TACE in the treatment of such patients. Currently, TACE in Japan is broadly classified into conventional TACE, balloon occluded TACE (B-TACE), and drug-eluting beads TACE (DEB-TACE). This article outlines the evolution of B-TACE for hepatocellular carcinoma in the drug therapy era.

Objective Rifaximin has become available for treating hyperammonemia in patients with hepatic encephalopathy. This study analyzed the changes in the body composition and nutritional status after long-term rifaximin therapy. Methods Twenty-one patients who underwent rifaximin therapy at 1,200 mg/day for more than 24 weeks were evaluated for the changes in the controlling nutritional status (CONUT) scores for the nutritional assessment, albumin-bilirubin (ALBI) scores for the liver function assessment, and skeletal muscle index (SMI) for the body composition assessment. Results There were 17 men and 4 women, with a mean age of 67.14±8.32 years. Eleven cases had a portosystemic shunt (52.3%), and 10 had hepatocellular carcinoma (47.6%). The Child-Pugh class was A in 9 cases (42.9%), B in 9 cases (42.9%), and C in 3 cases (14.2%). The blood ammonia levels in the rifaximin group improved significantly upon rifaximin therapy, from 124.76±28.68 μg/dL at baseline to 47.00±14.43 μg/dL after 2 weeks (p

Objective: Lenvatinib is considered the first-line treatment for unresectable advanced hepatocellular carcinoma (HCC); however, in some clinical cases, discontinuation of lenvatinib is unavoidable. It is important to elucidate if transcatheter arterial infusion (TAI) with drug-eluting beads transarterial chemoembolization (DEB-TACE) is a feasible second-line treatment after discontinuing lenvatinib. In this study, we aimed to evaluate the efficacy, hepatic function and nutritional status associated with TAI with DEB-TACE for patients who previously discontinued lenvatinib. Materials and Methods: We included 35 patients who were prescribed lenvatinib for unresectable HCC between July 2018 and December 2019, of whom 12 discontinued lenvatinib during the study. The changes in the albumin-bilirubin (ALBI) score and the controlling nutritional status (CONUT) score before and after discontinuing lenvatinib were examined. Furthermore, the tolerability and survival of patients treated using TAI with DEB-TACE as a second-line treatment were analysed. Results: The ALBI and CONUT scores were significantly worse when lenvatinib was started and stopped (p

Mac-2-binding protein glycosylation isomer (M2BPGi), a novel noninvasive biomarker for fibrosis, is a prognostic factor for liver disease; however, its relationship with hepatic function reserve and nutritional status remains unclear. Furthermore, the cut-off value of this marker varies with the underlying liver disease. This study aims to clarify that M2BPGi can be clinically used as a hepatic function reserve marker and nutritional index without pushing the search for alternative markers to the forefront in clinical practice as an important biomarker.Seven hundred and forty-three outpatients with chronic liver disease (CLD) were enrolled. We evaluated the relationship among M2BPGi, albumin-bilirubin (ALBI) grade, and Controlling Nutritional Status (CONUT) score as nutritional status markers. Diagnostic performance of M2BPGi values in distinguishing different modified ALBI (mALBI) grade and CONUT score were compared using receiver operating characteristic (ROC) curve analysis.The M2BPGi level increased with ALBI and mALBI grades. The correlation coefficient (r2) between M2BPGi and ALBI grade was 0.40 (r=0.63), indicating a positive correlation between M2BPGi and ALBI grade. The cut-off for M2BPGi to predict mALBI G1 vs. G2-G3 was 1.07, G1-2a vs. G2b-3 was 1.73, and mALBI G1-2 vs. G3 was 5.83 under the ROC curves. The cut-off for M2BPGi to predict CONUT score normal vs. light-severe was 1.60, normal-light vs. moderate-severe was 1.74, and normal-moderate vs. severe was 5.83 under the ROC curves. M2BPGi correlates with ALBI grade and is useful for diagnosing ROC analysis results, especially G2 and above. M2BPGi also correlates with the CONUT score and is useful for diagnosing ROC analysis results, especially moderate or higher. These results showed similar diagnostic performance regardless of the etiology of the background liver disease.Although the predictive cut-off value varied with the type of liver disease, M2BPGi was found to be a single predict biomarker of ALBI and CONUT, and thus, is an effective indicator of CLD status. Further investigation is warranted to determine the clinical utility of this marker.

Introduction Transjugular liver biopsy (TJLB) is indicated for patients in whom percutaneous liver biopsy is contraindicated, such as those with hematological diseases complicated by liver dysfunction. However, the clinical utility of TJLB in this group of patients has not been thoroughly investigated. The objective of this study is to evaluate the clinical efficacy of TJLB in patients with hematological diseases complicated by liver dysfunction. Methods We analyzed the data of patients who developed liver disorders during treatment for hematological diseases at our hospital and required tissue diagnosis via TJLB. The clinical features of patients were analyzed. Results Twenty-seven patients (mean age, 60.07 years; 12 men, 15 women) requiring tissue diagnoses via TJLB after developing liver disorders while undergoing treatment for hematological diseases were enrolled. One patient with autoimmune hemolytic anemia was diagnosed with drug-induced liver injury; two patients with amyloidosis had nonalcoholic steatohepatitis; one patient with acute promyelocytic leukemia had a drug-induced liver injury; one patient with chronic myelomonocytic leukemia had liver infiltration caused by an underlying disease; three patients with idiopathic thrombocytopenic purpura had autoimmune hepatitis; four patients with malignant lymphoma had liver infiltration by the underlying disease, and one patient with multiple myeloma had liver disorder caused by disseminated intravascular coagulation. Moreover, one patient had hepatitis B reactivation, another had hepatitis E, and six patients had a drug-induced liver injury. The treatment regimen was altered in cases of liver infiltration caused by the underlying disease, and the drug was changed for patients with drug-induced liver injury. Conclusion The etiology of liver disorders in patients with hematological diseases varies widely. Therefore, histological diagnosis using TJLB is useful to determine an appropriate therapeutic strategy for underlying hematological diseases.

Background/Aim: Tumor biopsy are needed frequency for accurate diagnosis. However, percutaneous liver tumor biopsy presents a risk of complications such as bleeding and tumor seeding. We investigated the feasibility of liver tumor biopsy, followed by cauterization with expandable radiofrequency ablation. Patients and Methods: Tumor biopsies using a co-access needle were performed in 102 patients. Expandable radiofrequency ablation was used to ensure cauterization and hemostasis of the puncture route. We evaluated the clinical background and complications. Results: The average (±standard deviation) tumor diameter was 56.87±39.45 mm. Pathological diagnosis was possible in all cases. In 20 patients, the postoperative pathological diagnosis differed from the preoperative diagnosis. No significant anemia progression was observed in any patients after biopsy, and no peritoneal seeding was observed during a mean follow-up observation period of 18.5 months. Conclusion: Liver tumor biopsy, followed by cauterization with expandable radiofrequency ablation via a co-access needle, is safe and useful for obtaining reliable diagnoses.

Blood transfusion, splenectomy, and partial splenic embolization (PSE) are generally performed for thrombocytopenia in patients with cirrhosis. Recently, thrombopoietin (TPO) agonists have become available, and investigations of patients who would benefit from them are necessary. Therefore, it is important to understand the fluctuations in cytokine levels associated with PSE. Therefore, fluctuations in platelet-associated immunoglobulin G (PAIgG), interleukin 6 (IL-6), and TPO levels with PSE were analyzed in this study. The study included 110 patients with liver cirrhosis and thrombocytopenia, with the aim of improving platelet counts. Fluctuations in PAIgG, IL-6, and TPO levels were investigated. The average splenic embolization ratio was 58.0% in patients with PSE. The platelet count rose significantly from 6.95 [5.40, 8.60] × 104/mL to 14.05 [10.43, 18.05] × 104/mL (P .01), IL-6 rose significantly from 3.56 [2.53, 7.33] pg/mL to 18.90 [9.17, 32.95] pg/mL (P .01), TPO rose significantly from 0.82 [0.52, 1.21] fmol/mL to 1.58 [0.97, 2.26] fmol/mL (P .01), and PAIgG decreased significantly from 64.20 [38.33, 118.75] ng/107 cells to 37.50 [22.25, 70.00] ng/107 cells (P .01). On multivariate analysis of factors related to the rate of platelet increase with PSE, primary biliary cholangitis (B = 0.475, P .01), splenic embolization ratio (B = 0.75, P .01), IL-6 change ratio (B = 0.019, P .01), and PAIgG change ratio (B = -0.325, P .01) were significant. When attempting to improve thrombocytopenia with PSE, adequate splenic embolization needs to be obtained together with improvements in IL-6, PAIgG, and TPO levels. With unsatisfactory improvement in thrombocytopenia, TPO agonist administration was considered.

A 62-year-old man initially underwent transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma (HCC). One year after the initial treatment, he developed anemia. Upper gastrointestinal endoscopy revealed irregularly elevated tumors in the lower anterior gastric body, which were diagnosed to be metastasis from HCC. Left gastric artery coil embolization was performed to prevent sustained bleeding, and his anemia partially improved. In addition to direct invasion, hematogenous metastasis to the stomach from HCC is possible and therefore should be considered during treatment. Transcatheter arterial embolization for gastric metastasis is an effective treatment method which achieves a good degree of hemostasis in patients without any surgical indications.

Listeria monocytogenes is a common bacterium that can trigger an episode of amphixenosis from the consumption of contaminated food. It survives in the host as an intracellular parasite and can get reactivated when the host's immune system is compromised. The use of anti-tumor necrosis factor-α (TNF-α) blockers is reported to increase the risk of L. monocytogenes infections. In the field of gastroenterology, the use of TNF-α blockers is on the rise due to remarkable efficacy in select patients with inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease and the rise in the incidence and prevalence of IBDs. There are few case reports on this topic, despite the rapid development of novel TNF-α blockers. Here, we report two cases of septicemic listeriosis encountered during treatment with the more recent TNF-α blockers, namely, adalimumab and golimumab, in ulcerative colitis and review the published literature on the topic.

Background and aim Eosinophilic esophagitis (EoE) is a Th2-mediated allergic disease of the esophageal epithelium, associated with antigen. We previously reported a case series for eosinophilic esophageal myositis (EoEM)-a novel eosinophilic gastrointestinal disorder defined as eosinophilic infiltration localized in the esophageal muscle layer-and diagnosed it by peroral endoscopic muscle biopsy. Here, we investigated the immunopathology of EoEM to differentiate it from EoE. Methods Histological analysis was performed for three cases of EoEM and EoE, respectively. The results were compared with those of two control samples (non-eosinophilic gastrointestinal disorder full-layer esophagus). Using immunofluorescence, we analyzed the expression of the chemokine receptor CCR3 and its ligands eotaxin-1 and eotaxin-3 to investigate the eosinophilic reaction. Additionally, we determined the expression patterns of desmoglein-1 in the esophageal epithelium, which shows dysregulated expression in EoE. Results Eosinophil infiltration was observed in the muscle layer (maximum number, 30, 36, 73/high-power field) and the epithelium (50, 44, 40/high-power field) for EoEM and EoE, respectively. In EoE esophageal epithelium, the number of eotaxin-3-positive epithelial cells was significantly increased together with CCR3-positive infiltrating cells. However, in EoEM, a number of eotaxin-1-positive and eotaxin-3-positive myocytes and vascular endothelial cells were increased in the esophageal muscle layer. A significant loss of desmoglein-1 expression was only observed in EoE, not in EoEM. Conclusions Eotaxin-1 and eotaxin-3 expression on the smooth muscle and vessels plays a role in the pathogenesis of EoEM, while EoE shows an epithelial eotaxin-3-dominant immunoreaction. Thus, the EoEM immunological pattern displays clear differences from that of EoE.

When performing partial splenic arterial embolization (PSE), it can be difficult to determine the embolization ratio based on 2-dimensional digital subtraction angiography (DSA) image diagnosis alone. Therefore, at our department, we conduct computed tomography (CT) imaging intraoperatively and postoperatively to determine whether the planned embolization has been achieved. In recent years, developments in interventional radiology devices have enabled diagnostic imaging using cone beam CT. Here, we investigated whether the embolization ratio could be predicted from volume measurement with cone beam CT in PSE. We investigated correlations between volume measurement with conventional CT angiography (CTA) and volume measurement with cone beam CTA in 11 cases that underwent PSE with cone beam CT guidance (Allura Clarity FD20; Phillips, Amsterdam, The Netherlands) between December 2013 and May 2018. The mean subject age was 65.0 ± 5.8 years (6 men, 5 women). The subjects had underlying liver disorders of hepatitis C virus infection (4 cases), nonalcoholic steatohepatitis (4 cases), and alcohol-related disease (3 cases). A positive correlation was noted between conventional CTA and cone beam CTA, with infarction rates of 61.28 ± 9.31% and 64.04 ± 9.24%, respectively. The correlation coefficient between the 2 variables was .772. Because blood washout occurs rapidly in the spleen, contrast medium had to be continuously injected during imaging to enable dual-phase imaging with cone beam CT. However, we successfully performed imaging up to the second phase and volume measurement for the embolization ratio by inserting a catheter into the splenic artery and confirming the cone beam CT arrival time from the DSA images. The results were almost identical to those obtained from volume measurement with conventional CT based on CTA imaging. Thus, our results suggest that the splenic embolization ratio measurement obtained via cone beam CTA can be used to assess PSE treatment endpoints.

A 76-year-old female was referred to our hospital because of liver dysfunction. Abdominal contrasted computed tomography (CT) revealed a tumor of 7.5cm in the hepatic hilar area. Based on the biopsy, the tumor was diagnosed by as combined hepatocellular-cholangiocellular carcinoma (with stem-cell features). The tumor was considered unresectable;hence, the patient underwent transcatheter arterial chemoembolization (TACE). However, a CT scan revealed the treatment to be ineffective. Subsequently, systemic gemcitabine (GEM) chemotherapy was administered and tumor shrinkage was observed with reperfusion of the umbilical portion of the left portal vein. The patient's condition is currently stable 17 months after diagnosis, with no tumor regrowth on account of repeated TACE and GEM therapy. The present case of unresectable combined hepatocellular-cholangiocellular carcinoma was successfully treated using TACE and systemic GEM chemotherapy.

Percutaneous transhepatic obliteration (PTO) and percutaneous transhepatic sclerotherapy (PTS) are widely performed as an emergency measure in cases of variceal hemorrhage and intractable hepatic encephalopathy. The PTO/PTS technique is capable of directly blocking the blood supply in cases in which balloon-occluded retrograde transvenous obliteration (B-RTO) is not effective, or in cases with complicated collateral flow. Although PTO/PTS is not currently the first choice due to the invasiveness of transhepatic puncture, this procedure can modify the blood flow in an antegrade manner. The present study examined the changes in hepatic function reserve following PTO/PTS for intractable hepatic encephalopathy and/or gastric varices. In total, the study included 37 patients (mean age, 61.75±12.77 years; age range, 32–88 years; male to female ratio, 23:14) with a variety of gastrorenal shunts, or B-RTO-intractable hepatic encephalopathy and gastric varices without gastrorenal shunts. The patients underwent PTO/PTS by embolizing a microcoil or injection of a sclerosing agent (5% ethanolamine oleate iopamidol). Alterations in hepatic function reserve prior to and following the procedure were compared. The patients were treated for hepatic encephalopathy in 11 patients, gastric varices in 19 patients, and both conditions in 7 patients. The results indicated that the blood ammonia level improved from 135.76±75.23 mg/dl to 88.00±42.16 and 61.81±33.75 mg/dl at 3 and 6 months after therapy, respectively. In addition, the Child-Pugh score improved from 8.48±2.01 prior to therapy to 7.70±1.84 and 7.22±2.01 at 3 and 6 months after the procedure, respectively. Although there was a concern that PTO/PTS may cause complications due to an increase in portal venous pressure (PVP) arising from shunt occlusion, no severe complications were observed. In conclusion, for patients with various gastrorenal shunts or those with B-RTO-intractable hepatic encephalopathy and gastric varices without gastrorenal shunts, PTO/PTS can improve the antegrade blood flow to the liver, as demonstrated by improvement in the hepatic function reserve.

An 18-year-old male adolescent diagnosed with ileocolitis-type Crohn’s disease received therapy involving an anti-tumor necrosis factor-α (TNF-α) blocker, which resulted in remission for 2 years. The patient presented with fever, stomatitis, and cough with respiratory distress. Chest radiography revealed bilateral hilar lymphadenopathy; bronchoalveolar lavage showed high lymphocyte level: 40.8% and CD4/8 value: 3.9. Transbronchial lung biopsy identified multiple non-caseating granulomas fused to each other with connective tissue septa, leading to the diagnosis of sarcoidosis. The sarcoidosis was defined as a paradoxical adverse event (PAE) due to the use of TNF-α blocker; therefore, cessation of TNF-α blocker administration was sufficient to induce remission. We report a rare case of PAE on Crohn’s disease. The characteristics and distinguishing histologies of PAE and Crohn’s disease are described. Biological agent therapy has been reported to cause several PAEs during the treatment of immune-mediated inflammatory disorders. PAEs are defined as pathological conditions that occur during biological agent therapy usually effective in treatment. The laboratory, radiography, and histological findings shown in this case are useful for differential diagnosis and management of PAE.

We describe a 52-year-old male who underwent endoscopic retrograde biliary drainage for acute cholangitis associated with common bile duct stones. Endoscopic papillary balloon dilatation was performed, and the stones were removed using a balloon catheter. Simultaneously, we initiated edoxaban for portal vein thrombosis. Approximately one month later, he visited our hospital complaining of tarry stools and dizziness. Contrast-enhanced computed tomography revealed a pseudoaneurysm in the hepatic artery (A7), and he was diagnosed with hemobilia from bile duct perforation associated with the hepatic arterial pseudoaneurysm. We performed an emergent transcatheter arterial embolization. Notably, re-bleeding has not occurred to date. Hepatic arterial pseudoaneurysms can occur after acute cholangitis;therefore, careful follow-up is essential.

BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory bowel disease, affecting the colon continuously from the rectum proximally. However, a clinical type with right-sided colitis sparing the anal side of the colon is also known. Mesalamine, which is generally used to treat UC, can rarely aggravate the disease. CASE REPORT A 56-year-old woman with no history of colonic diseases visited our hospital because of a positive fecal occult blood test. The first colonoscopy showed inflamed and edematous mucosa extending from the ascending colon to the right-half of the transverse colon. Colonic biopsy specimens demonstrated infiltrations of chronic inflammatory cells in the mucosa and crypt abscesses, but no epithelioid granulomas, compatible with UC. She was highly positive for PR3-ANCA, confirming the diagnosis of UC. After starting mesalamine, she had hypersensitivity reactions and aggravations of UC, which were confirmed endoscopically. CONCLUSIONS Right-sided colitis may be a subgroup of UC, and this is the first report of this type of disease complicated by aggravation due to mesalamine hypersensitivity.

The optimum retreatment strategy for chronic hepatitis C virus (HCV) patients who failed directly-acting antiviral agents (DAA)-based therapy is unknown. We herein report the outcomes of an HCV genotype (GT) 2a-infected patient with virologic failure following treatment with sofosbuvir plus ribavirin (SOF+RBV) who was successfully retreated with ombitasvir/paritaprevir/ritonavir plus ribavirin (OBV/PTV/r+RBV).

For refractory chronic hepatitis C, interferon (IFN)-based triple-agent combination therapy with second-generation direct-acting antivirals (DAAs) has been established as the standard treatment method. The rate of decrease in the viral load and the negative conversion of hepatitis C virus (HCV) RNA in the early phase following treatment initiation are considered important factors for predicting the therapeutic outcome. In the present study, the Roche Cobas AmpliPrep/COBAS TaqMan (CAP/CTM) HCV v2.0 assay and the AccuGENE m-HCV RNA quantitative assay [Abbott RealTime HCV (ART) assay] were analyzed for their clinical efficacy and ability to predict therapeutic outcomes in the early phase in patients with relapse following IFN-based second-generation DAA therapy. Of the 56 patients who received IFN-based second-generation DAA therapy since December 2013, 6 achieved an end-of-treatment response (ETR), but subsequently experienced relapse. In these 6 patients, fluctuations in viral loads in the early phase detected by the CAP/CTM and ART assays were compared. At 4 weeks after treatment initiation, 4 of the 6 patients were diagnosed as negative by the CAP/CTM assay, whereas 2 of these 4 patients were not identified as negative by the ART assay. Of the 2 patients, one was signal-positive with an HCV RNA load

Background and aims Helicobacter pylori (H. pylori) is recognized as a causative agent for unexplained iron-deficiency anemia (IDA). We evaluated many background factors influencing an iron-deficiency state in adult patients with various H. pylori-infected upper gastrointestinal tract diseases. Method Study 1: H. pylori-infected 121 patients (nodular gastritis (NG) (n = 19), duodenal ulcer (DU) (n = 30), or gastric ulcer (GU) (n = 47), or gastric hyperplastic polyp (GHP) (n = 25)) were enrolled. The RBC count and hemoglobin, iron, ferritin, pepsinogen (PG) I, PG II, gastrin, and anti-H. pylori antibody (Ab) levels in the serum were measured. Study 2: H. pylori-infected 105 patients (NG, n = 19; DU, n = 43; GU, n = 32; GHP, n = 11) and non-H. pylori-infected individuals (n = 35) were examined for the levels of prohepcidin, ferritin, and iron in the serum. In addition, we measured the data before and after the H. pylori eradication. Results In the patients with GHP and NG, hypoferritinemia was observed in comparison with the GU and DU patients. In the GHP patients, low levels of PG I, a decreased PG I/II ratio, and hypergastrinemia were observed. The levels of serum prohepcidin in the patients with H. pylori-associated disease were higher than those in the uninfected adults. In the patients with NG, the serum prohepcidin levels were higher than those in the other H. pylori-infected patient groups and decreased after the eradication. Conclusion H. pylori-related iron-deficiency state might be associated with several factors, such as hypochlorhydria and hepcidin, in patients with GHP or NG.

AIM Hepatocellular carcinoma (HCC) is frequently complicated with cirrhosis, and it is not unusual for treatment options to be limited as a result of pancytopenia due to hypersplenism. Partial splenic embolization (PSE) has been performed for thrombocytopenia resulting from hypersplenism. We studied the efficacy in terms of hepatic functional reserve and safety in patients who underwent concurrent transcatheter arterial chemoembolization (TACE) with PSE for HCC. METHODS The study population consisted of 101 HCC patients with thrombocytopenia. Fifty-three patients were treated with concurrent TACE/PSE (PSE group), and the remaining 48 TACE patients without PSE (non-PSE group) were investigated hepatic functional reserve. RESULTS Platelet counts were significantly higher in the PSE group after 2 weeks, 2 months and 6 months after TACE than the non-PSE group. Child-Pugh score significantly deteriorated from 7.13 ± 1.16 to 7.60 ± 1.20 at 2 weeks, to 7.71 ± 1.25 at 2 months, and 7.71 ± 1.35 at 6 weeks after TACE in the non-PSE group. Hence, it worsened from 7.04 ± 1.05 to 7.21 ± 0.99 at 2 weeks temporally, but improved to 7.00 ± 1.17 after 2 months and 6.70 ± 1.16 at 6 weeks after TACE in the PSE group. CONCLUSION Thrombocytopenia has been improved and treatment continued using concurrent PSE. In addition, hepatic functional reserve could be maintained even after treatment for HCC. Concurrent TACE and PSE for HCC with thrombocytopenia can be expected to help maintain hepatic reserve, and may contribute to improving the prognosis of HCC.

OBJECTIVE Postsplenectomy sepsis (PSS) and overwhelming postsplenectomy infection (OPSI) following splenectomy or the development of hyposplenism are associated with a high mortality rate. The presence of Howell-Jolly bodies (HJBs) in peripheral erythrocytes is attracting attention as a parameter of hyposplenism. To date, whether HJBs appear following partial splenic embolization (PSE) has not been investigated. Therefore, we examined the prevalence of HJBs in patients who have undergone PSE. METHODS Whether HJBs were present in 95 patients who underwent PSE between November 2007 and August 2012 was assessed. RESULTS No serious complications occurred due to PSE; however, 17 of the 95 patients (17.89%) exhibited HJBs during the follow-up. The residual spleen volume and splenic infarction rate did not differ significantly compared to those observed in the HJB-negative group. CONCLUSION With the recent increase in the use of autoanalyzers, the opportunities to perform microscopic examinations have been decreasing. Therefore, the presence of HJBs, which can only be confirmed visually, may be overlooked, and the clinical significance of these bodies tends to be disregarded. However, the presence of HJBs is associated with a risk of PSS and OPSI due to hyposplenism. Because HJBs are common in the peripheral erythrocytes of patients who have undergone PSE, irrespective of the residual spleen volume or splenic infarction rate, the presence or absence of HJBs should be assessed visually. In HJB-positive patients, preventing serious infections, for example, by administering the pneumococcal vaccine, is important.

Eosinophilic esophagitis (EoE) is a Th2-mediated allergic disease of the esophageal epithelium, associated with antigen. We previously reported a case series for eosinophilic esophageal myositis (EoEM)-a novel eosinophilic gastrointestinal disorder defined as eosinophilic infiltration localized in the esophageal muscle layer-and diagnosed it by peroral endoscopic muscle biopsy. Here, we investigated the immunopathology of EoEM to differentiate it from EoE.Histological analysis was performed for three cases of EoEM and EoE, respectively. The results were compared with those of two control samples (non-eosinophilic gastrointestinal disorder full-layer esophagus). Using immunofluorescence, we analyzed the expression of the chemokine receptor CCR3 and its ligands eotaxin-1 and eotaxin-3 to investigate the eosinophilic reaction. Additionally, we determined the expression patterns of desmoglein-1 in the esophageal epithelium, which shows dysregulated expression in EoE.Eosinophil infiltration was observed in the muscle layer (maximum number, 30, 36, 73/high-power field) and the epithelium (50, 44, 40/high-power field) for EoEM and EoE, respectively. In EoE esophageal epithelium, the number of eotaxin-3-positive epithelial cells was significantly increased together with CCR3-positive infiltrating cells. However, in EoEM, a number of eotaxin-1-positive and eotaxin-3-positive myocytes and vascular endothelial cells were increased in the esophageal muscle layer. A significant loss of desmoglein-1 expression was only observed in EoE, not in EoEM.Eotaxin-1 and eotaxin-3 expression on the smooth muscle and vessels plays a role in the pathogenesis of EoEM, while EoE shows an epithelial eotaxin-3-dominant immunoreaction. Thus, the EoEM immunological pattern displays clear differences from that of EoE.

Aim: In patients with refractory genotype 1b chronic hepatitis C with high viral loads, we retrospectively compared the efficacy of standard of care treatment (SOC: combined PEG-IFN-α-2b/ribavirin for 48 weeks) and a regimen in which 2 weeks of SOC induction was replaced by twice-daily β-interferon alone (IFN-β induction therapy). Methods: Seventeen patients received the IFN-β induction therapy plus SOC (IFN-β induction group) and 13 patients received SOC alone (SOC group). Results: In the IFN-β induction group and SOC group, early virological response (EVR) rates were 88.2% and 53.8%, respectively. The end of treatment rates were 100.0% and 92.3%, and sustained virological response (SVR) rates were 70.6% and 53.8%, respectively. By induction with IFN-β, even in refractory cases, the high virus negative conversion rate in the early treatment phase and actions of pegylated IFN-α-2b and ribavirin in the maintenance treatment phase led to an additive effect. In the analysis of contributing factors, only the achievement of EVR was associated with a significant difference in SVR (P = 0.0011). The univariate logistic regression analysis showed that only IFN-β treatment was associated with a significant difference in EVR (P = 0.0492, odds ratio = 6.248, 95% confidence interval = 1.026–40.252), whereas no significant factors were found in the multivariate analysis due to small samples. Conclusion: IFN-β induction therapy with higher EVR might be beneficial for protease inhibitor-refractory chronic hepatitis C patients.

Objective To assess the ability to predict the local recurrence of hepatocellular carcinoma by analyzing tissues adhering to the radiofrequency ablation probe after complete ablation. Methods From May 2002 to March 2011, tissue specimens adhering to the radiofrequency ablation probe from 284 radiofrequency ablation sessions performed for hepatocellular carcinomas ≤3 cm in size were analyzed. The specimens were classified as either viable tumor tissue or complete necrosis, and the local recurrence rates were calculated using the Kaplan-Meier method. Results From the tumors ≤3 cm in size, viable tissue was present in 6 (2.1%) of 284 specimens, and the local recurrence rates after 1 and 2 years of follow-up were 6.7% and 11.2%, respectively. Local recurrence developed significantly earlier in the viable tissue group. The recurrence rate was not significantly different based on whether transcatheter arterial chemoembolization was performed. Conclusion The histopathology of the tissue adhering to the radiofrequency ablation probes used for hepatocellular carcinoma treatment can predict local recurrence. Additional aggressive treatment for patients with viable tissue can therefore improve the overall survival.

Background and study aims Although endoscopic papillary balloon dilation (EPBD) has appeared with the expectation of better preserving sphincter of Oddi function than endoscopic sphincterotomy (EST), whether it can more effectively prevent bacterial contamination of the biliary tract than EST is controversial. To address this issue, we investigated the bacterial flora in the bile after the two procedures. Patients and methods Eighty-six patients were alternately allocated to EPBD or EST. Blood-liver function tests, ultrasonography, and endoscopic retrograde cholangiopancreatography were performed 6 months and 2 years after EPBD or EST, and the bile was sampled for bacterial culture during endoscopic retrograde cholangiopancreatography. Bactobilia and late complications were prospectively compared between the two procedures. Results Overall, no significant difference was found in the incidence of bactobilia between EPBD and EST at the two examination points. Limiting stone diameter to 8 mm or less, there was a trend toward lower rate of bactobilia in the EPBD group 2 years later although the statistical significance disappeared after correction for multiple comparisons. The absence rate of late complications after EPBD was higher than that after EST, but there was no significant difference between the two procedures, both for the overall patients and for the patients with small stones. Conclusion EPBD has a possibility of suppressing bacterial contamination of the biliary tract compared with EST in patients with small stones. A large, long-term follow-up, randomized, controlled trial is necessary to clarify whether this benefit of EPBD reduces late complications.

The efficacy of double filtration plasmapheresis (DFPP) plus interferon (IFN)-β induction therapy was preliminarily investigated in re-treated patients with chronic genotype 1b hepatitis C and high viral load (patients with relapse or non-response to previous IFN therapies). In eight patients with chronic hepatitis C, DFPP was performed five times over 2 weeks during IFN-β therapy, and 3 MU of IFN-β was administered twice a day for 2 weeks. Combination therapies with ribavirin and pegylated IFN-α2b (PEG-IFN-α2b) or pegylated IFN-α2a (PEG-IFN-α2a) were subsequently used. After 4 weeks, hepatitis C virus (HCV)-RNA tended to be more greatly decreased with DFPP combination therapy than with previous IFN therapy (4.5 ± 2.0 log(10) IU/mL vs. 2.9 ± 1.2 log(10) IU/mL). Rates of both rapid virological response and complete early virological response were significantly higher with DFPP and IFN-β induction therapy than with previous IFN therapy. DFPP plus IFN-β induction therapy produced a great reduction of viral load during the early stage of treatment and achieved a high early virological response, suggesting that this combination therapy may be useful as a new treatment modality for chronic hepatitis C patients in difficult-to-treat states. This combination may contribute to sustained virological response (SVR). The effects of DFPP on SVR and its significance remain to be clarified.

BACKGROUND: The effectiveness of additional chemotherapy in preventing intrahepatic distant tumor recurrence of hepatocellular carcinoma (HCC) has not been fully established. The authors compared the efficacy of 2 platinum-based chemotherapeutic agents in combination with radical local treatment for preventing intrahepatic distant recurrence (IDR). METHODS: Seventy-eight patients with stage I/II HCC aged 45 to 85 years underwent transcatheter arterial chemoembolization and/or radiofrequency ablation after they received hepatic arterial infusion (HAI) of platinum compounds. The HAI consisted of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (carboplatin) in 25 patients and cis-diamminedichloroplatinum (II) (cisplatin) in 53 patients. Multivariate analysis was used to identify independent factors that were associated with IDR. RESULTS: Cumulative IDR rates at 1 year, 2 years, and 3 years were 21.7%, 52.2% and 75.7%, respectively, in the carboplatin group and 8.1%, 22.7%, and 36.9%, respectively, in the cisplatin group. The cisplatin group had a significantly lower IDR rate compared with the carboplatin group. The selection of a platinum agent was 1 of the independent factors for IDR in a multivariate Cox proportional hazards model. CONCLUSIONS: HAI chemotherapy with cisplatin before radical local treatment was effective in patients with HCC. The authors concluded that radical local treatment with concurrent HAI using cisplatin may contribute to a longer progression-free period, which could be predicted with intrahepatic imaging in patients with stage I/II HCC. Cancer 2011;. © 2011 American Cancer Society.

症例は83歳，女性．83歳から慢性腎不全のため，血液透析を導入．透析導入時の血液検査で，高ガンマグロブリン血症と抗核抗体320倍を認めたが，その他自己免疫疾患を示唆する所見は認めなかった．また，慢性腎不全の原疾患は不明であった．週3回の外来血液透析を継続中，平成20年6月末から水様性下痢（5～6行/日）が出現．整腸剤，塩酸ロペラミド，バンコマイシンなどの内服を行ったが，下痢は慢性再発性に出現を繰り返していた．下痢に伴う低アルブミン血症，浮腫を認めた．それまで服用していたランソプラゾールを塩酸ラニチジンに変更したが，下痢は出現を繰り返し，大腸内視鏡検査を行った．肉眼では異常所見を認めずほぼ正常の粘膜所見であり，横行結腸からの粘膜生検で粘膜表層部上皮直下にエオシン好性で，マッソントリクローム染色では25～35μm幅の沈着物を帯状に認め，粘膜固有層全層に小型リンパ球，形質細胞といった慢性炎症性細胞浸潤に加え，好酸球浸潤が目立ち，collagenous colitisと診断した．塩酸ラニチジンを中止後，下痢は消失し，低アルブミン血症も徐々に改善した．Collagenous colitisは1976年にLindstromによって報告され，慢性水様性下痢，肉眼的にほぼ正常な大腸所見，特徴的組織所見を有する臨床的症候群である．欧米では数百例の報告があり，慢性水様性下痢の原因として決して稀ではないと報告されている．本邦での報告例はまだ少ないが，年々増加傾向にある．病因は不明だが，自己免疫や薬剤の関与などが考えられている．本例も薬剤中止後に下痢が消失したことから，その関与が考えられた．透析患者での報告はまだないが，慢性下痢の鑑別疾患の一つとして念頭に置くことが必要と考え，報告した．

Paraneoplastic syndromes of hepatocellular carcinoma (HCC) are not uncommon. However, the prognosis is poor and follow-up and improvement of paraneoplastic syndromes with treatment have been reported rarely. We report a successful case in an aged man of a massive HCC with paraneoplastic syndrome, treated by combined intraarterial chemotherapy and hepatic resection. Paraneoplastic syndrome (erythrocytosis and hyperlipidemia) was monitored throughout the treatment and erythropoietin (EPO) mRNA also was analyzed in the resected liver. The hemoglobin level and serum levels of EPO and total cholesterol (T-cho) decreased dramatically with treatment, along with a decrease in serum levels of alpha-fetoprotein and protein induced by vitamin vitamin K absence II (PIVKA-II). Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) revealed that the residual cancer expressed EPO RNA but the nontumor tissue did not. This was a rare case of paraneoplastic syndrome of HCC that was treated successfully. This case indicates that paraneoplastic syndrome reflected tumor progression and that serum levels of both EPO and T-cho might be used as tumor markers.

Nutcracker esophagus and jackhammer esophagus are largely unknown motility disorders, also sometimes called hypertensive and hypercontractile peristalsis, respectively. There is currently no standardized diagnostic or management plan for these diseases. Here, we report on three patients with jackhammer/nutcracker esophagus who were treated with either peroral endoscopic myotomy or a systemic steroid regimen, focusing particularly on two novel presentations of nutcracker and jackhammer esophagus involving eosinophilic infiltration into the muscularis propria, and their responses to both interventions.