Randomized controlled study to examine the efficacy of hepatic arterial infusion chemotherapy with cisplatin before radiofrequency ablation for hepatocellular carcinoma.

AIM: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin is beneficial to patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. This study aimed to examine the effect of HAIC with cisplatin before radiofrequency ablation (RFA) in patients with HCC. METHODS: This was a multicenter, single-blinded, randomized controlled study (UMIN000007267). Early-stage HCC patients were randomly assigned (1:1) to receive HAIC with cisplatin before RFA therapy (HAIC group) or RFA monotherapy (non-HAIC group). The primary end-point was recurrence-free survival. Efficacy analysis and safety analysis followed the intention-to-treat principle. RESULTS: Between August 2012 and July 2016, 74 patients were recruited. A total of 70 eligible patients were randomly assigned to the HAIC group (n = 35) and non-HAIC group (n = 35). Recurrence-free survival rates at 1 (3) year in the HAIC group and non-HAIC group were 82.9% (54.3%) and 74.3% (34.3%), respectively (hazard ratio [HR], 0.597; 95% confidence interval [CI], 0.320-1.091; p = 0.094]. Subgroup analysis showed that the beneficial effect of HAIC was observed in patients with a single nodule and Child-Pugh score 5. Intrahepatic distant recurrence-free survival rate in the HAIC group was significantly better than that in the non-HAIC group (HR, 0.468; 95% CI, 0.235-0.896; p = 0.022). Adverse events were observed in just two patients in the HAIC group (6%) - grade 2 cholecystitis and grade 2 hyperkalemia. CONCLUSIONS: HAIC with cisplatin before RFA did not significantly decrease recurrence in patients with early-stage HCC. However, it might be effective in preventing intrahepatic distant recurrence.

[A Case of a Migrating Central Venous Catheter in the Internal Jugular Vein Diagnosed Using Ultrasonography in a Patient with Right-Sided NeckPain during Chemotherapy].

We report a case of a migrating central venous(CV)catheter with thrombosis in the internal jugular vein that was diagnosed using ultrasonography in a patient complaining of neck pain during chemotherapy. A 57-year-old man with distant metastasis at 1 year after laparoscopic Hartmann operation for rectal cancer was transported to the emergency department by ambulance complaining of severe right-sided neck pain. On that day, his 6th course of chemotherapy with modified FOLFOX6 (levofolinic acid, 5-fluorouracil[5-FU], oxaliplatin[L-OHP])and panitumumab was administered using a CV port that had been placed 3 months previously from the right subclavian vein in the superior vena cava, and verified using radiography. Cervical ultrasonography revealed line migration, with a surrounding low echoic area without a Doppler signal in the right internal jugular vein. This migration was also observed on the radiograph. These findings indicated migration of the CV catheter with thrombosis. After admission, the CV catheter was removed, a new one was inserted from the left subclavian vein in the superior vena cava, and a direct oral anticoagulant was administered to treat the thrombosis. Two days later, his neck pain, which was caused by phlebitis that was probably induced by L-OHP or continuous 5-FU, disappeared. We should consider the possibility of CV catheter issues, including migration or damage, when patients experience neck pain during chemotherapy. Additionally, the present case demonstrated the utility of cervical ultrasonography in diagnosing CV catheter migration, as well as thrombosis.

Mixed HCV Infection of Genotype 1B and Other Genotypes Influences Non-response during Daclatasvir + Asunaprevir Combination Therapy.

Daclatasvir (DCV) + asunaprevir (ASV) combination therapy has become available for patients with hepatitis C virus (HCV) serogroup 1 infection. We studied the efficacy of this therapy by focusing on the factors associated with sustained virological responses (SVR) including resistance-associated variants (RAVs) and mixed infection of different HCV genotypes. We enrolled 951 HCV serogroup 1-positive patients who received this combination therapy at our hospital or affiliated hospitals. The presence of RAVs in non-structural (NS) regions 3 and 5A was analyzed by direct sequencing. HCV genotypes were determined by PCR with genotype-specific primers targeting HCV core and NS5B regions. SVR was achieved in 91.1% of patients. Female sex, age > 70 years, and RAVs were significantly associated with non-SVR (p<0.01 for all). Propensity score-matching results among the patients without RAVs regarding sex, age, and fibrosis revealed that mixed HCV infection determined by HCV NS5B genotyping showed significantly lower SVR rates than 1B-mono infection (p=0.02). Female sex and RAVs were significant factors associated with treatment failure of this combination therapy for patients with HCV serogroup 1 infection. Mixed HCV infection other than 1B-mono infection would be useful for predicting treatment failure.

[A case of Hamman's syndrome associated with acute-onset type 1 diabetes mellitus presenting with abdominal pain].

A 21-year-old female presented at an emergency department with abdominal pain and nausea. Computed tomography (CT) of the chest and abdomen revealed a small amount of mediastinal emphysema in the precardiac area, but the underlying cause could not be identified. On admission, her plasma glucose was 371 mg/dl, glycated hemoglobin (HbA1c) was 14.0%, and blood pH was 6.91. These findings supported a diagnosis of Hamman's syndrome associated with diabetic ketoacidosis. Her diabetic ketoacidosis was managed with insulin and fluid therapy, and the mediastinal emphysema disappeared spontaneously by the time of discharge. Presence of free air of the chest and abdominal cavity must warrant a differential diagnosis of gastrointestinal perforation; however, when the free air is accompanied by diabetic ketoacidosis, it is not necessary to perform urgent endoscopy.

[A case of ceftriaxone-associated pseudolithiasis in an adult patient that disappeared after the discontinuation of ceftriaxone].

We report a case of a 47-year-old female patient with ceftriaxone (CTRX)-associated pseudolithiasis. CTRX was administered at a dosage of 2g/day for 8 days because of colonic diverticulitis. A routine abdominal computed tomography (CT) scan was performed to investigate the diverticulitis. However, the CT scan demonstrated stones and sludge in the gallbladder, which had not been present before CTRX administration. Therefore, we diagnosed the patient with pseudolithiasis caused by CTRX and stopped CTRX administration. The stones and sludge disappeared 6 days after stopping CTRX administration. This underreported adverse effect of CTRX should be considered when treating both children and adult patients.

Serum interferon-gamma-inducible protein 10 level was increased in myocardial infarction patients, and negatively correlated with infarct size.

OBJECTIVES: We examined the serum levels of interferon-gamma-inducible protein 10 (IP-10), an inflammation-induced chemokine, in acute myocardial infarction (AMI). DESIGN AND METHODS: The subjects were 33 AMI patients, 20 stable angina pectoris patients (AP) and 20 normal subjects. In AMI patients, blood samples were collected before percutaneous coronary intervention (PCI) and on days 3, 7 and 28. RESULTS: Patients with AMI showed significantly higher serum IP-10 levels (137.5+/-79.8 pg/mL) than control subjects (91.2+/-40.1 pg/mL) and patients with AP (93.3+/-41.1 pg/mL). The serum IP-10 level before PCI was negatively correlated with infarct size, as indicated by cumulative release of creatine kinase (CK) and peak CK and its isoenzyme CK-MB. Stepwise multiple regression analysis revealed that the serum IP-10 level before PCI was an independent predictor of cumulative CK release. CONCLUSIONS: The serum IP-10 level was increased in AMI, and a higher level of serum IP-10 before PCI may be informative regarding infarct size.

Mutations in the hepatitis B virus preS2 region and abrogated receptor activity for polymerized human albumin.

The preS2 region of the hepatitis B virus (HBV) has been reported to have human polymerized albumin receptor (PAR) activity, which correlates with viral replication. Here, we studied the genomic sequence of the preS region from rare patients lacking PAR activity, despite active viral replication. PAR and DNA polymerase activity was identified in 178 HBe antigen-positive HBV carriers, and a significant correlation between 2 markers was shown, except in 2 hepatitis patients lacking PAR activity. Nucleotide sequences of the preS region of HBV from both patients were examined by direct sequencing of PCR products. In one patient, a 45-base deletion was found to overlap half of the putative polymerized human albumin binding site in the preS2 region. In the other patient, a point mutation at the first nucleotide of the start codon of the preS2 region of HBV was found. There was no such genomic change in the 3 control HBV sequences. These results indicate that the preS2 region is necessary for binding of polymerized human albumin, and this is the first report of naturally existing mutant virus with no or low PAR activity.

Regional radioactivity discrepancy between Tc-99m GSA and Tc-99m phytate liver scans in a patient with massive hepatic necrosis.

A 22-year-old woman with severe acute hepatitis underwent a Tc-99m galactosyl human serum albumin (GSA) scan. Intense accumulation was observed in the cephalic region of the right hepatic lobe, whereas the accumulation was reduced in the left lobe and the caudal region of the right lobe. A computed tomographic (CT) scan showed that the left lobe and the caudal region of the right posterior segment had atrophied and become hypodense, which were thought to represent postnecrotic scarring after massive hepatic necrosis. The relatively hyperdense region in the right lobe was slightly swollen and was thought to represent regenerating liver tissue or a "potato liver." Compared with the CT, the regions of elevated Tc-99m GSA accumulation correlated well with the areas of regenerating liver tissue, and the regions with reduced accumulation corresponded closely with the areas of postnecrotic scarring. On a Tc-99m phytate scan, unlike the Tc-99m GSA scan, the radiocolloid accumulation was intense in the left lobe and caudal region of the right lobe and reduced in the cephalic region of the right lobe. Together, the Tc-99m GSA scan and the Tc-99m phytate scan formed a set of exact "nega-posi" images. Biopsy specimens obtained during laparoscopy showed a few hepatocyte columns in the postnecrotic scarred left lobe. Severe disruption of the hepatocytes, prominent inflammatory cell infiltration, and obvious Kupffer cell hypertrophy and clustering were also observed.

Two cases of development of entecavir resistance during entecavir treatment for nucleoside-naive chronic hepatitis B.

BACKGROUND: Entecavir (ETV) is a potent nucleoside analogue against hepatitis B virus (HBV), and emergence of drug resistance is rare in nucleoside-naive patients because development of ETV resistance (ETVr) requires at least three amino acid substitutions in HBV reverse transcriptase. We observed two cases of genotypic ETVr with viral rebound and biochemical breakthrough during ETV treatment of nucleoside-naive patients with chronic hepatitis B (CHB). RESULTS: Case 1: A 44-year-old HBeAg-positive man received ETV 0.1 mg/day for 52 weeks and 0.5 mg/day for 96 weeks consecutively. HBV DNA was 10.0 log(10) copies/ml at baseline, declined to a nadir of 3.1 at week 100, and rebounded to 4.5 at week 124 and 6.7 at week 148. Alanine aminotransferase (ALT) level increased to 112 IU/l at week 148. Switching to a lamivudine (LVD)/adefovir-dipivoxil combination was effective in decreasing HBV DNA. Case 2: A 47-year-old HBeAg-positive man received ETV 0.5 mg/day for 188 weeks. HBV DNA was 8.2 log(10) copies/ml at baseline, declined to a nadir of 2.9 at week 124, and then rebounded to 4.7 at week 148 and 6.4 at week 160. ALT level increased to 72 IU/l at week 172. The ETVr-related substitution (S202G), along with LVD-resistance-related substitutions (L180M and M204V), was detected by sequence analysis at week 124 in both case 1 and case 2. CONCLUSIONS: ETVr emerged in two Japanese nucleoside-naive CHB patients after prolonged therapy and incomplete suppression and in one patient after <0.5 mg of dosing. ETV patients with detectable HBV DNA or breakthrough after extended therapy should be evaluated for compliance to therapy and potential emergence of resistance.