Application of a medium-energy collimator for I-131 imaging after ablation treatment of differentiated thyroid cancer

Purpose

High-energy (HE) collimators are usually applied for I-131 imaging after ablation treatment of differentiated thyroid cancer (DTC). However, purchase of HE collimators has been avoided in many nuclear medicine departments because the HE collimators are more expensive than other collimators. In this study, we compared the I-131 imaging using HE- and medium-energy (ME) collimators, which is more versatile than HE collimators.

Materials and methods

To simulate DTC patients with extra-thyroid beds, a phantom of acrylic containers containing I-131 was used. To simulate patients with thyroid beds, four phantoms representing extra-thyroid beds were arranged around the phantom representing normal thyroid tissues. Patients administered 1.11 or 3.70 GBq NaI-131 were also evaluated. Whole-body imaging and SPECT imaging of the phantoms and patients performed using HE-general-purpose (HEGP) and ME-low-penetration (MELP) collimators, and full-width at half maximum (FWHM) and percent coefficient of variation (%CV) were measured.

Results

In the extra-thyroid beds, FWHM and %CV with MELP were negligibly different from those with HEGP in whole-body imaging. Although FWHM with MELP was a little different from that with HEGP in SPECT imaging, %CV with MELP was significantly higher than that with HEGP. In the thyroid beds, only an extra-thyroid bed including higher radioactivity was identified in whole-body imaging with both collimators. Although SPECT images with MELP could not clarify extra-thyroid beds with low radioactivity, HEGP could identify them. In patients, although some whole-body images with MELP could not detect extra-thyroid beds, whole-body imaging with HEGP and SPECT imaging with both collimators could detect them.

Conclusions

Although HEGP is the best collimator for I-131 imaging, MELP is applicable for not only whole-body imaging but also SPECT imaging.     

Changes in serum levels of hepatitis C virus genotype 1b monitored by real-time quantitative polymerase chain reaction as a predictor of long term response to interferon-alpha treatment

OBJECTIVE: The aim of this study was to find whether there is a relationship between the changes in the amounts of hepatitis C virus (HCV) at the start of interferon treatment and the long term response to therapy. METHODS: In 20 patients with HCV genotype 1b each given 880 MU of interferon-alpha, the changes in serum HCV RNA during the first 2 wk of therapy were monitored by real-time quantitative polymerase chain reaction (PCR). RESULTS: Real-time quantitative PCR detected HCV RNA at 10(1)-10(8) copies/ml. Serum HCV RNA decreased rapidly between 8 and 24 h after the first administration (first phase) and more slowly thereafter (second phase), with median exponential decays of 2.14 and 0.11 log10/day, respectively. Four patients had sustained virological responses, nine patients had transient responses, and seven patients had no responses. The differences in the rate of first-phase viral decline among the three groups were not significant (p = 0.34), but the differences in the rate of second-phase viral decline were significant (p = 0.0004); the median viral decline (interquartile range) in the second phase was 0.48 (0.42-0.50) log10/day in patients with sustained responses, 0.16 (0.10-0.19) log10/day in patients with transient responses, and 0.026 (0.017-0.040) log10/day in patients with no responses. CONCLUSIONS: Changes in serum levels of HCV genotype 1b in the first 2 wk of interferon-alpha treatment, monitored by real-time quantitative PCR, can be used for prediction of the long term therapeutic response.     

Liver-related events after direct-acting antiviral therapy in patients with hepatitis C virus-associated cirrhosis

Journal of Gastroenterology - Direct-acting antiviral (DAA) therapy enables a high rate of sustained virologic response (SVR) in patients with hepatitis C virus associated cirrhosis. However, the...     

Similar effects of recombinant interferon-alpha-2b and natural interferon-alpha when combined with intra-arterial 5-fluorouracil for the treatment of advanced hepatocellular carcinoma.

AIM: Intra-arterial 5-fluorouracil (5-FU) plus interferon (IFN) combination therapy is effective against advanced hepatocellular carcinoma (HCC) with portal vein tumour thrombosis. In this study, we compared the efficiency and safety of recombinant IFN-alpha-2b with natural IFN-alpha as components of the combination therapy. METHODS: Consecutive HCC patients (n=31) with portal vein tumour thrombosis were enrolled in this prospective study. They received combination therapy of 5-FU and either recombinant IFN-alpha-2b (R group, n=15) or natural IFN-alpha (N group, n=16). We compared the two groups for the early response rate, adverse reactions, time to progression (TTP) and survival rates. In addition, we assessed the cost-effectiveness of each protocol. RESULTS: The early response rate (R: 26.7%, N: 31.2%), median TTP (R: 5.8 months, N: 5.6 months) and median survival time (R: 7.5 months, N: 6.5 months) were not significantly different between the R and N groups. There were no differences in adverse reactions between the two groups. The estimated cost-effectiveness ratio of recombinant IFN-alpha-2b was better than natural IFN-alpha. CONCLUSIONS: In our protocol of combination therapy, there were no significant differences between recombinant IFN-alpha-2b and natural IFN-alpha with regard to early response to therapy, adverse effects, TTP and survival rates. 5-FU could be combined with either recombinant IFN-alpha-2b or natural IFN-alpha, although the cost-effectiveness of the former warrants its use clinically.     

Prognostic value of cardiovascular magnetic resonance derived right ventricular function in patients with interstitial lung disease

Background

Cardiovascular magnetic resonance (CMR) provides non-invasive and more accurate assessment of right ventricular (RV) function in comparison to echocardiography. Recent study demonstrated that assessment of RV function by echocardiography was an independent predictor for mortality in patients with interstitial lung disease (ILD). The purpose of this study was to determine the prognostic significance of CMR derived RV ejection fraction (RVEF) in ILD patients.

Methods

We enrolled 76 patients with ILD and 24 controls in the current study. By using 1.5 T CMR scanner equipped with 32 channel cardiac coils, we performed steady-state free precession cine CMR to assess the RVEF. RV systolic dysfunction (RVSD) was defined as RVEF ≤45.0% calculated by long axis slices. Pulmonary hypertension (PH) was defined as mean pulmonary artery pressure (mPAP) of more than 25 mmHg at rest in the setting of pulmonary capillary wedge pressure ≤15 mmHg.

Results

The median RVEF was 59.2% in controls (n = 24), 53.8% in ILD patients without PH (n = 42) and 43.1% in ILD patients with PH (n = 13) (p < 0.001 by one-way ANOVA). During a mean follow-up of 386 days, 18 patients with RVSD had 11 severe events (3 deaths, 3 right heart failure, 3 exacerbation of dyspnea requiring oxygen, 2 pneumonia requiring hospitalization). In contrast, only 2 exacerbation of dyspnea requiring oxygen were observed in 58 patients without RVSD. Multivariate Cox regression analysis showed that RVEF independently predicted future events, after adjusting for age, sex and RVFAC by echocardiography (hazard ratio: 0.889, 95% confidence interval: 0.809 – 0.976, p = 0.014).

Conclusions

The current study demonstrated that RVSD in ILD patients can be clearly detected by cine CMR. Importantly, low prevalence of PH (17%) indicated that population included many mild ILD patients. CMR derived RVEF might be useful for the risk stratification and clinical management of ILD patients.     

Optimal duration of additional therapy after biochemical and virological responses to lamivudine in patients with HBeAg-negative chronic hepatitis B: a randomized trial

Aim:  The endpoint of treatment with nucleoside analogs remains unclear for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We report the results of a randomized trial to determine the optimal duration of additional therapy after response to lamivudine in HBeAg-negative patients.
Methods:  Twenty-two patients with HBeAg-negative chronic hepatitis B who exhibited biochemical and virological responses to lamivudine were enrolled. When patients responded to treatment, they were randomly assigned to receive 12 more months of therapy (Group A, 11 patients) or 24 more months of therapy (Group B, 11 patients).
Results:  The baseline characteristics of the patients were similar in the two groups. Biochemical and virological responses were obtained in all patients within 6 months. Drug resistance developed in one patient in Group A during month 7 of additional therapy, and in five patients in Group B from months 13–23 of additional therapy. Ten patients in Group A and six in Group B completed the protocol and were included in analysis. Eight of the 10 patients in Group A experienced relapse between months 2 and 14 after the discontinuation of therapy, while three of the six patients in Group B experienced relapse between months 2 and 24. There was no difference in cumulative relapse rate between the groups ( P  = 0.275).
Conclusion:  Additional therapy with lamivudine for longer than 12 months after biochemical and virological responses in patients with HBeAg-negative chronic hepatitis B could increase the risk of drug resistance, but did not reduce the rate of relapse.     

Selective expansion of donor‐derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome

IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engraftment and regimen‐related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor‐derived Tregs and disappearance of anti‐villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor‐derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.     

Diagnostic accuracy of the 13C-urea breath test for childhood Helicobacter pylori infection: a multicenter Japanese study

OBJECTIVES: In adults, the 13C-urea breath test (UBT) has been widely used as a noninvasive test of Helicobacter pylori infection because of its high sensitivity and specificity. However, this test is less well established in pediatric practice. The optimum cutoff value and test protocol of the 13C-UBT remains to be established in the pediatric population. The primary purpose of this study was to evaluate diagnostic accuracy of the 13C-UBT for children and to determine its optimum cutoff value. METHODS: A total of 220 Japanese children aged 2-16 yr (mean = 11.9) who underwent upper GI endoscopy and gastric biopsies were finally studied. Endoscopic diagnoses included gastritis (n = 131), gastric ulcer (n = 15), duodenal ulcer (n = 72), and combined ulcer (n = 2). H. pylori infection status was confirmed by biopsy tests including histology, urease test, and culture. With the 13C-UBT, breath samples were obtained at baseline and at 20 min after ingestion of 13C-urea without a test meal and were analyzed by isotope ratio mass spectrometry. Based on biopsy tests, a cutoff value was determined using a receiver operating characteristic curve. In 26 children (seven children infected and 19 noninfected), paired breath samples were also measured by nondispersive infrared spectometry (NDIRS). RESULTS: Biopsy tests demonstrated that 89 children (40%) were infected with H. pylori and 131 children were not infected. There were no statistical differences in mean delta 13C values at 20 min between male and female H. pylori-infected and noninfected patients. A receiver operating characteristic analysis defined the best cutoff value as 3.5 per thousand. The overall sensitivity and specificity at a cutoff value of 3.5 per thousand were 97.8% (95% CI = 92.1-99.7%) and 98.5% (95% CI = 96.4-100%), respectively: high sensitivity and specificity were demonstrated in all three age groups (< or =5, 6-10, and > or = 11 yr). There was a close correlation between the values with isotope ratio mass spectrometry and NDIRS methods (r = 0.998, p < 0.001). CONCLUSIONS: The 13C-UBT with a cutoff value of 3.5 per thousand is an accurate diagnostic method for active H. pylori infection. The test with the NDIRS method is inexpensive and might be widely applied in clinical practice.     

Effects of structural variations of APOBEC3A and APOBEC3B genes in chronic hepatitis B virus infection

Aim: Human APOBEC3 deaminases induce G to A hypermutation in nascent DNA strand of hepatitis B virus (HBV) genomes and seem to operate as part of the innate antiviral immune system. We analyzed the importance of APOBEC3A (A3A) and APOBEC3B (A3B) proteins, which are potent inhibitors of adeno‐associated‐virus and long terminal repeat (LTR)‐retrotransposons, in chronic HBV infection. Methods: We focused on the common deletion polymorphism that spans from the 3′ part of A3A gene to the 3′ portion of A3B gene. An association study was carried out in 724 HBV carriers and 469 healthy control subjects. We also analyzed hypermutated genomes detected in deletion and insertion (non‐deletion) homozygous patients to determine the effect of APOBEC3 gene deletion. Further, we performed functional analysis of A3A gene by transient transfection experiments. Results: The association study showed no significant association between deletion polymorphism and chronic HBV carrier state. Context analysis also showed a negligible effect for the deletion. Rather, mild liver fibrosis was associated with APOBEC gene deletion homozygosity, suggesting that A3B deletion is not responsible for chronic HBV infection. Functional analysis of A3A showed that overexpression of A3A induced hypermutation in HBV genome, although the levels of hypermutants were less than those introduced by A3G. However, overexpression of A3A did not decrease replicative intermediates of HBV. Conclusion: These results suggest that A3A and A3B play little role in HBV elimination through anti‐viral defense mechanisms. The significance of hypermutation induced by A3A should be investigated further.