Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study.

OBJECTIVES: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. METHODS: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. RESULTS: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). CONCLUSIONS: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.

Utility of Contrast-Enhanced Ultrasound for Early Therapeutic Evaluation of Hepatocellular Carcinoma After Transcatheter Arterial Chemoembolization.

OBJECTIVES: We aimed to investigate whether contrast-enhanced ultrasound (CEUS) could be useful for early evaluation of the treatment response to transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). METHODS: This study retrospectively selected HCCs in which homogeneous retention of iodized oil was confirmed on non-contrast-enhanced computed tomography performed immediately after TACE. Therapeutic responses of HCCs were evaluated by CEUS 1 to 2 days after TACE and by contrast-enhanced computed tomography (CECT) approximately 4 weeks after TACE. We investigated the noninferiority of CEUS 1 to 2 days after TACE to CECT approximately 4 weeks after TACE in terms of the diagnostic accuracy of the therapeutic response to TACE on HCC. RESULTS: Eighty-nine HCCs were enrolled in this study between April 2014 and June 2016. A complete response was observed in 57 of 89 nodules (64.0%), and an incomplete response was observed in the remaining 32 nodules (36.0%). The accuracy rates for CEUS 1 to 2 days after TACE and CECT approximately 4 weeks after TACE in the therapeutic effect of TACE on HCCs were 83.1% (95% confidence interval, 73.7%-90.2%) and 83.1% (95% confidence interval, 73.7%-90.2%), respectively. The difference in diagnostic accuracy between methods was 0%, which was below the predetermined noninferiority limit of 15%, and CEUS 1 to 2 days after TACE was noninferior to CECT approximately 4 weeks after TACE. CONCLUSIONS: Our results suggest that CEUS is a useful modality for early therapeutic evaluation of TACE for HCC, and we can thus plan the next treatment strategies for HCC within a few days after TACE.

Renal vein dilation predicts poor outcome in patients with refractory cirrhotic ascites.

AIM: Renal venous hypertension is known to be associated with worsening of renal function in patients with decompensated heart failure. Intra-abdominal hypertension including cirrhotic ascites also leads to renal venous hypertension. We aimed to clarify the effect of renal venous hypertension on cirrhotic ascites. METHODS: Two hepatologists measured the left renal vein diameter in 142 consecutive patients with refractory cirrhotic ascites using non-contrast computed tomography. The renal vein diameter was measured at the renal vein main trunk and upstream of the confluence of collateral veins. RESULTS: The inter-observer agreements were high for the measurements of the left renal vein (r = 0.918, P < 0.001). The median overall survival for patients with renal vein diameter ≥11 mm was less than that for patients with renal vein diameter <11 mm (P < 0.001; 2.5 vs. 32.0 months). One-year survival rates were 15.3% versus 66.4%. Multivariate analysis revealed renal vein diameter ≥11 mm (hazard ratio, 2.94; P < 0.001; 95% confidence interval, 1.67-5.20) and a high Model for End-stage Liver Disease score combined with serum sodium level (MELD-Na) (hazard ratio, 3.39; P < 0.001; 95% confidence interval, 2.00-5.74) were significant independent predictors of mortality. CONCLUSIONS: Renal vein dilation is a risk factor of mortality in patients with refractory cirrhotic ascites, independent of the MELD-Na score.

Solitary Variceal Rupture in the Small Intestine.

A 70-year-old man was referred to our hospital to undergo treatment for hepatocellular carcinoma. In hospital, he complained of hematochezia and a laboratory analysis revealed a decreased level of hemoglobin. Abdominal computed tomography revealed a tumor in the small intestine, with slow enhancement of the dorsal region. Double-balloon enteroscopy revealed a submucosal tumor with a depression in the jejunum. Partial enterectomy was performed and a pathological examination demonstrated the presence of a solitary varix. Solitary varix in the small intestine has not been reported previously. We herein report an extremely rare case of solitary varix in the jejunum.

Contrast-enhanced ultrasonographic findings of serum amyloid A-positive hepatocellular neoplasm: Does hepatocellular adenoma arise in cirrhotic liver?

Hepatocellular adenoma (HCA) was recently classified into four pathological subtypes. There have been few studies describing the findings of contrast-enhanced ultrasonography (CEUS) of each type. Our case concerns a 78-year-old man who had undergone routine medical check-ups for hepatitis C for 11 years. Abdominal ultrasonography showed a 28 mm, hypo-echoic mass in the segment 4 of the liver. His integrating amount of drinking was 670 kg convert into ethanol. CEUS with Sonazoid demonstrated mild uniform hypo-enhancement with inflow of microbubbles from the periphery of the tumor in the arterial phase, and heterogeneously hypo-enhancement in the post vascular phase. Because the mass increased in size within 3 mo, a well differentiated hepatocellular carcinoma was suspected, and hepatic resection was performed. Microscopic findings showed homogeneous cell proliferation with low grade atypia, infiltration of inflammatory cells, ductular reactions, fatty deposit in part, and sinusoidal dilation. Immunohistochemistry revealed geographic positive for serum amyloid A (SAA), focal positive for glutamine synthetase, diffuse and strong positive for C-reactive protein, and positive for liver-type fatty acid binding protein. These pathological features corresponded to that of an inflammatory HCA. However, we could not make a clear diagnosis, because HCAs were defined as not to arise in cirrhotic liver. Finally, this tumor was diagnosed as a SAA positive hepatocellular neoplasm.

Clinical and structural remission rates increased annually and radiographic progression was continuously inhibited during a 3-year administration of tocilizumab in patients with rheumatoid arthritis: A multi-center, prospective cohort study by the Michinoku Tocilizumab Study Group.

OBJECTIVE: To evaluate the clinical and structural efficacy of tocilizumab (TCZ) during its long-term administration in patients with rheumatoid arthritis (RA). METHODS: In total, 693 patients with RA who started TCZ therapy were followed for 3 years. Clinical efficacy was evaluated by DAS28-ESR and Boolean remission rates in 544 patients. Joint damage was assessed by calculating the modified total Sharp score (mTSS) in 50 patients. RESULTS: When the reason for discontinuation was limited to inadequate response or adverse events, the 1-, 2-, and 3-year continuation rates were 84.0%, 76.8%, and 72.2%, respectively. The mean DAS28-ESR was initially 5.1 and decreased to 2.5 at 6 months and to 2.2 at 36 months. The Boolean remission rate was initially 0.9% and increased to 21.7% at 6 months and to 32.2% at 36 months. The structural remission rates (ΔmTSS/year ≤ 0.5) were 68.8%, 78.6%, and 88.9% within the first, second, and third years, respectively. The structural remission rate at 3 years (ΔmTSS ≤ 1.5) was 66.0%, and earlier achievement of swollen joint count (SJC) of 1 or less resulted in better outcomes. CONCLUSIONS: TCZ was highly efficacious, and bone destruction was strongly prevented. SJC was an easy-to-use indicator of joint destruction.

A case of miriplatin-induced lung injury.

A 69-year-old man with an 8-year history of hepatocellular carcinoma (HCC) was hospitalized for treatment of recurrent tumour. In 2010, the first transcatheter arterial chemoembolization (TACE) using miriplatin with agents (Lipiodol Ultra-Fluid) was performed and did not occur any adverse events. In 2014, since his HCC recurred, the TACE using miriplatin with agents was performed. Following this therapy, pyrexia occurred on day 3, followed by respiratory failure with cough and dyspnea on day 5. Chest radiography revealed scattered infiltration in the right upper lung fields, and chest computed tomography revealed ground grass attenuations, indicating fibrotic non-specific interstitial pneumonia. These findings progressively deteriorated, and a diagnosis of miriplatin-induced lung injury was made. His respiratory failure also progressively deteriorated. Treatment with pulse methylprednisolone therapy resulted in a dramatic improvement in both patient symptoms and radiological abnormalities.

Efficacy of a microballoon catheter in transarterial chemoembolization of hepatocellular carcinoma using miriplatin, a lipophilic anticancer drug: Short-term results.

AIM: The goal of the study was to evaluate the efficacy and safety of balloon-occluded transarterial chemoembolization (B-TACE) of hepatocellular carcinoma (HCC) using miriplatin (a lipophilic anticancer drug) and gelatin particles. METHODS: B-TACE was performed for 62 HCC nodules in 33 patients who could not be treated by surgical resection or radiofrequency ablation. All 33 patients had a history of transarterial chemoembolization (TACE) treatment prior to B-TACE. As a historical comparison, we investigated 40 nodules in 28 patients treated by TACE using a conventional microcatheter (C-TACE), miriplatin and gelatin particles. The therapeutic effect per tumor was compared between the groups based on the Response Evaluation Criteria in Cancer Study Group of Japan (RECICL) and side-effects were compared based on the Common Terminology Criteria for Adverse Events (ver. 4.0). RESULTS: The therapeutic efficacy after 4-12 weeks was evaluated in 59 nodules in the B-TACE group and in 37 nodules in the C-TACE group. Of these nodules, TE4 occurred in 29 (49.2%) in the B-TACE group and in 10 (27%) in the C-TACE group. Local efficacy was significantly higher in nodules treated by B-TACE than by C-TACE. The side-effects on hepatic function were similar in the two groups. CONCLUSION: Our results suggest that B-TACE with miriplatin is a useful treatment for hepatocellular carcinoma.

Quantitative sonographic image analysis for hepatic nodules: a pilot study.

PURPOSE: The aim of this study was to investigate the feasibility of quantitative image analysis to differentiate hepatic nodules on gray-scale sonographic images. METHODS: We retrospectively evaluated 35 nodules from 31 patients with hepatocellular carcinoma (HCC), 60 nodules from 58 patients with liver hemangioma, and 22 nodules from 22 patients with liver metastasis. Gray-scale sonographic images were evaluated with subjective judgment and image analysis using ImageJ software. Reviewers classified the shape of nodules as irregular or round, and the surface of nodules as rough or smooth. RESULTS: Circularity values were lower in the irregular group than in the round group (median 0.823, 0.892; range 0.641-0.915, 0.784-0.932, respectively; P = 3.21 × 10(-10)). Solidity values were lower in the rough group than in the smooth group (median 0.957, 0.968; range 0.894-0.986, 0.933-0.988, respectively; P = 1.53 × 10(-4)). The HCC group had higher circularity and solidity values than the hemangioma group. The HCC and liver metastasis groups had lower median, mean, modal, and minimum gray values than the hemangioma group. Multivariate analysis showed circularity [standardized odds ratio (OR), 2.077; 95 % confidential interval (CI) = 1.295-3.331; P = 0.002] and minimum gray value (OR 0.482; 95 % CI = 0.956-0.990; P = 0.001) as factors predictive of malignancy. The combination of subjective judgment and image analysis provided 58.3 % sensitivity and 89.5 % specificity with AUC = 0.739, representing an improvement over subjective judgment alone (68.4 % sensitivity, 75.0 % specificity, AUC = 0.701) (P = 0.008). CONCLUSION: Quantitative image analysis for ultrasonic images of hepatic nodules may correlate with subjective judgment in predicting malignancy.

B-flow imaging of vascular structure for the diagnosis of liver tumor.

PURPOSE: B-flow is a non-Doppler-based technology for visualizing blood flow and has a high spatial resolution. The aim of this study is to evaluate the blood flow information of liver tumors using B-flow in comparison with color Doppler sonography (CDS). METHODS: Seventy-nine patients with 82 hepatic nodules were studied using B-flow and CDS. The study group included 45 HCC nodules, 23 liver metastasis nodules, four intrahepatic cholangiocarcinomas (ICC), and 13 hemangiomas. The visualized vascularity and morphological findings of the hepatic tumor vessel were evaluated. RESULTS: B-flow showed multiple vessels in 48 nodules (58.5 %) and a single vessel in 13 nodules (15.9 %). CDS showed multiple vessels in 44 nodules (53.7 %) and a single vessel in 23 nodules (28.0 %). Multivariate analysis showed basket pattern was significant for HCC (OR 49.263; p = 0.0002), and penetrating vessel was significant for liver metastasis or ICC (OR 14.545; p < 0.0001). CONCLUSION: B-flow detects hepatic tumor blood flow with sensitivity as high as that of CDS. Vascular structure information obtained using B-flow could be potentially used to diagnose liver tumors.

[Peculiar "chestnuts in burrs" formation in MGIT cultures of pulmonary Mycobacterium xenopi cases].

We report 3 patients whose sputum and bronchoalveolar lavage fluid (BALF) cultures for acid fast bacteria in MGIT liquid media grew colonies of Mycobacterium xenopi (M. xenopi) with a characteristic chestnut burr like appearance. Patients I, II, and III were a 74-year-old man, 47-year-old woman, and 62-year-old woman, respectively. Chest X ray showed a pulmonary cavity in each case. Patient I had a history of pulmonary and renal tuberculosis. The past medical history of patient II was unremarkable. Patient III had a history of lung cancer. Eight sputum samples and 4 BALF samples from patient I, 3 sputum samples and 1 BALF sample from patient II, and 4 sputum samples from patient III were positive for acid fast bacteria, and the organism was identified as M. xenopi in 9 samples. Smears of these MGIT-positive cultures were stained by the Ziehl Neelsen method, and examined under a microscope. Large and small, spherical shaped, 15-100 microm clusters of thin, elongated bacteria, with a chestnut burr-like or spherical moss like and partly budding appearance, were scattered throughout the smear preparation. Although only 34 cases of M. xenopi infection were reported in Japan between 1984 and 2005, the number of reported cases has been on the increase in recent years. Since no report from Japan, Europe, or the United States have noted the characteristic appearance of M. xenopi in cultures, we consider that the feature described in this communication is useful to presumptively identify M. xenopi.

Correlation between severity of rheumatoid arthritis and manner and extent of cervical lesion.

Abstract To determine the proper management of treatment for rheumatoid cervical lesions, we investigated the clinical course of the cervical spine in rheumatoid arthritis (RA). The severity of RA was classified into three groups according to the disease subsets advocated by Ochi et al.: the less erosive subset (LES), the more erosive subset (MES), and mutilating disease (MUD). Then the following radiographic assessments were performed on cervical roentogenograms: atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS). One hundred and seventy-four patients were available for this study. The mean age of the patients was 60.9 years (19-85 years). The average duration from the onset of RA was 19.1 years (10-40 years). Eighty-seven patients were classified as LES, 69 were MES, and 18 were MUD. We found that few patients in the LES group had required an operation on the cervical spine. AAS was seen in about 60% of the MES patients, but few cases had VS or SAS, and most operations were atlantoaxial fusion. All patients in the MUD group had some cervical instabilities. Not only VS but also SAS were seen in more than half of these patients, and many patients had required occipitothoracic fusion.

New simple and rapid test for culture confirmation of Mycobacterium tuberculosis complex: a multicenter study.

Mycobacterial antigen MPB64 has been identified as a Mycobacterium tuberculoisis complex-specific secretory protein since 1984. Recently, a simple culture confirmation test for M. tuberculosis complex has been developed by using lateral flow immunochromatographic assay (ICA) to detect MPB64 with anti-MPB64 monoclonal antibody. The current multicenter study evaluated the performance of an ICA slide test for MPB64 antigen in the clinical setting. Primary positive cultures from clinical specimens, as well as stock cultures, were tested. Approximately 100 microl of positive liquid culture medium or suspension made from colonies on solid medium was placed into the test well of the plastic slide devise, and the test was read after 15 min. No processing or instrumentation was required. A total of 304 mycobacterial isolates consisting of M. tuberculosis complex (171 isolates) and mycobacteria other than M. tuberculosis (MOTT) complex (133 isolates) belonging to 18 different species were tested. Growth in liquid media (Mycobacteria Growth Indicator Tube [MGIT] and Radiometric 12B), as well as in solid (Löwenstein-Jensen and Middlebrook 7H10 agar) media, was evaluated. Results were compared with those obtained with nucleic acid-based and/or high-pressure liquid chromatography identification. All MOTT were found to be negative on the ICA slide with no cross-reaction. All M. tuberculosis and M. africanum cultures were found to be positive, whereas the results of M. bovis and M. bovis BCG cultures were variable since some of the BCG strains are known to lack MPB64 antigen production. The results did not change with prolonged storage of cultures. This low-tech rapid test with high sensitivity and specificity could provide an alternative to currently available identification methods, particularly for recently introduced nonradiometric liquid culture systems such as MGIT.

A longitudinal study of the relationship between osteo sono-assessment index and lifestyle in elderly female in nursing homes.

The aim of this study was to investigate the longitudinal effect of mobility and daily activity, in the form of exercise and everyday activities, on the bones of 102 elderly female nursing home residents who had physical disabilities as well as marked postmenopausal bone loss, using calcaneal ultrasound apparatus for bone evaluation.Of the 102 subjects initially measured, 74 (mean age, 83.5±6.55 years; range, 64-99 years) could be measured again approximately one year later. The osteo sono-assessment index (OSI) in this study was determined using an ultrasound bone evaluation device. This device measures the speed of sound (SOS) and transmission index (TI) as ultrasound passes through the calcaneus. The OSI is calculated by computer analysis (OSI=TI×SOS(2)). For mobility, the OSI decreased significantly by an average of 1.8% after 11.8 months in all of the residents who were using a wheelchair (n=41, p<0.01). In contrast, the OSI rose significantly by a mean of 1.9% in the ambulatory group (n=33, p<0.01).The OSI increased significantly in residents who exercised every day, were out of bed for at least seven hours per day, and walked on a regular basis, suggesting that exercise, mainly in the form of walking, may increase the calcaneal OSI.