Treatment Outcomes in Global Systematic Review and Patient Meta-Analysis of Children with Extensively Drug-Resistant Tuberculosis.

Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and outcomes for 37 children (<15 years of age) with bacteriologically confirmed XDR TB in 11 countries. These patients were managed during 1999-2013. For the 37 children, median age was 11 years, 32 (87%) had pulmonary TB, and 29 had a recorded HIV status; 7 (24%) were infected with HIV. Median treatment duration was 7.0 months for the intensive phase and 12.2 months for the continuation phase. Thirty (81%) children had favorable treatment outcomes. Four (11%) died, 1 (3%) failed treatment, and 2 (5%) did not complete treatment. We found a high proportion of favorable treatment outcomes among children, with mortality rates markedly lower than for adults. Regimens and duration of treatment varied considerably. Evaluation of new regimens in children is required.

Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis.

BACKGROUND: An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children. METHODS AND FINDINGS: To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged <15 years) who were treated for bacteriologically confirmed or clinically diagnosed MDR-TB, and if treatment outcomes were reported. The search yielded 2,772 reports; after review, 33 studies were eligible for inclusion, with IPD provided for 28 of these. All data were from published or unpublished observational cohorts. We analyzed demographic, clinical, and treatment factors as predictors of treatment outcome. In order to obtain adjusted estimates, we used a random-effects multivariable logistic regression (random intercept and random slope, unless specified otherwise) adjusted for the following covariates: age, sex, HIV infection, malnutrition, severe extrapulmonary disease, or the presence of severe disease on chest radiograph. We analyzed data from 975 children from 18 countries; 731 (75%) had bacteriologically confirmed and 244 (25%) had clinically diagnosed MDR-TB. The median age was 7.1 years. Of 910 (93%) children with documented HIV status, 359 (39%) were infected with HIV. When compared to clinically diagnosed patients, children with confirmed MDR-TB were more likely to be older, to be infected with HIV, to be malnourished, and to have severe tuberculosis (TB) on chest radiograph (p < 0.001 for all characteristics). Overall, 764 of 975 (78%) had a successful treatment outcome at the conclusion of therapy: 548/731 (75%) of confirmed and 216/244 (89%) of clinically diagnosed children (absolute difference 14%, 95% confidence interval [CI] 8%-19%, p < 0.001). Treatment was successful in only 56% of children with bacteriologically confirmed TB who were infected with HIV who did not receive any antiretroviral treatment (ART) during MDR-TB therapy, compared to 82% in children infected with HIV who received ART during MDR-TB therapy (absolute difference 26%, 95% CI 5%-48%, p = 0.006). In children with confirmed MDR-TB, the use of second-line injectable agents and high-dose isoniazid (15-20 mg/kg/day) were associated with treatment success (adjusted odds ratio [aOR] 2.9, 95% CI 1.0-8.3, p = 0.041 and aOR 5.9, 95% CI 1.7-20.5, p = 0.007, respectively). These findings for high-dose isoniazid may have been affected by site effect, as the majority of patients came from Cape Town. Limitations of this study include the difficulty of estimating the treatment effects of individual drugs within multidrug regimens, only observational cohort studies were available for inclusion, and treatment decisions were based on the clinician's perception of illness, with resulting potential for bias. CONCLUSIONS: This study suggests that children respond favorably to MDR-TB treatment. The low success rate in children infected with HIV who did not receive ART during their MDR-TB treatment highlights the need for ART in these children. Our findings of individual drug effects on treatment outcome should be further evaluated.

Diagnostic Accuracy of 68Ga-PSMA-11 PET/MRI Compared with Multiparametric MRI in the Detection of Prostate Cancer.

Purpose To compare the diagnostic accuracy of gallium 68 (68Ga)-labeled prostate-specific membrane antigen (PSMA)-11 PET/MRI with that of multiparametric MRI in the detection of prostate cancer. Materials and Methods The authors performed a retrospective study of men with biopsy-proven prostate cancer who underwent simultaneous 68Ga-PSMA-11 PET/MRI before radical prostatectomy between December 2015 and June 2017. The reference standard was whole-mount pathologic examination. Readers were blinded to radiologic and pathologic findings. Tumor localization was based on 30 anatomic regions. Region-specific sensitivity and specificity were calculated for PET/MRI and multiparametric MRI by using raw stringent and alternative neighboring approaches. Maximum standardized uptake value (SUVmax) in the tumor and Prostate Imaging Reporting and Data System (PI-RADS) version 2 grade were compared with tumor Gleason score. Generalized estimating equations were used to estimate population-averaged sensitivity and specificity and to determine the association between tumor characteristics and SUVmax or PI-RADS score. Results Thirty-two men (median age, 68 years; interquartile range: 62-71 years) were imaged. The region-specific sensitivities of PET/MRI and multiparametric MRI were 74% (95% confidence interval [CI]: 70%, 77%) and 50% (95% CI: 45%, 0.54%), respectively, with the alternative neighboring approach (P < .001 for both) and 73% (95% CI: 68%, 79%) and 69% (95% CI: 62%, 75%), respectively, with the population-averaged generalized estimating equation (P = .04). Region-specific specificity of PET/MRI was similar to that of multiparametric MRI with the alternative neighboring approach (88% [95% CI: 85%, 91%] vs 90% [95% CI: 87%, 92%], P = .99) and in population-averaged estimates (70% [95% CI: 64%, 76%] vs 70% [95% CI: 64%, 75%], P = .99). SUVmax was associated with a Gleason score of 7 and higher (odds ratio: 1.71 [95% CI: 1.27, 2.31], P < .001). Conclusion The sensitivity of gallium 68-labeled prostate-specific membrane antigen-11 PET/MRI in the detection of prostate cancer is better than that of multiparametric MRI. © RSNA, 2018 See also the editorial by Civelek in this issue.

Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10-year intention-to-treat analysis.

In a long-term (10-year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post-LT tumor recurrence, and long-term intention-to-treat, disease-specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand-alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow-up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor-specific waiting list dropout rates, post-LT tumor recurrence, and 10-year post-LT and intention-to-treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post-LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence-free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention-to-treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively. CONCLUSION: RFA as a first-line stand-alone bridge therapy to LT achieves excellent long-term overall and tumor-specific survivals, with a low dropout rate from tumor progression despite long wait list times and a sustained low tumor recurrence rate upon post-LT follow-up of up to 10 years. (Hepatology 2017;65:1979-1990).

Preliminary Outcome of Microwave Ablation of Hepatocellular Carcinoma: Breaking the 3-cm Barrier?

PURPOSE: To evaluate preliminary outcomes after microwave ablation (MWA) of hepatocellular carcinoma (HCC) up to 5 cm and to determine the influence of tumor size. MATERIALS AND METHODS: Electronic records were searched for HCC and MWA. Between January 2011 and September 2014, 173 HCCs up to 5 cm were treated by MWA in 129 consecutive patients (89 men, 40 women; mean age, 66.9 y ± 9.5). Tumor characteristics related to local tumor progression and primary and secondary treatment efficacy were evaluated by univariate analysis. Outcomes were compared between tumors ≤ 3 cm and tumors > 3 cm. RESULTS: Technical success, primary efficacy, and secondary efficacy were 96.5%, 99.4%, and 94.2% at a mean follow-up period of 11.8 months ± 9.8 (range, 0.8-40.6 mo). Analysis of tumor characteristics showed no significant risk factor for local tumor progression, including subcapsular location (P = .176), tumor size (P = .402), and perivascular tumor location (P = .323). The 1-year and 2-year secondary or overall treatment efficacy rates for tumors measuring ≤ 3 cm were 91.2% and 82.1% and for tumors 3.1-5 cm were 92.3% and 83.9% (P = .773). The number of sessions to achieve secondary efficacy was higher in the larger tumor group (1.13 vs 1.06, P = .005). There were three major complications in 134 procedures (2.2%). CONCLUSIONS: With use of current-generation MWA devices, percutaneous ablation of HCCs up to 5 cm can be achieved with high efficacy.

Variable refocusing flip angle single-shot fast spin echo imaging of liver lesions: increased speed and lesion contrast.

PURPOSE: To evaluate acquisition time and clinical image quality of a variable refocusing flip angle (vrf) single-shot fast spin echo (SSFSE) sequence in comparison with a conventional SSFSE sequence for imaging of liver lesions in patients undergoing whole-body PET/MRI for oncologic staging. METHODS: A vrfSSFSE sequence was acquired in 43 patients with known pancreatic neuroendocrine tumors undergoing 68Ga-DOTA-TOC PET on a simultaneous time-of-flight 3.0T PET/MRI. Liver lesions ≥1.5 cm with radionucleotide uptake were analyzed. Contrast-to-noise ratios (CNRs) were measured, and four blinded radiologists assessed overall image quality. Differences in repetition time and CNR were assessed using a paired Student's t test with p < 0.05 considered statistically significant. Inter-reader variability was assessed with Fleiss' kappa statistic. RESULTS: 53 eligible lesions in 27 patients were included for analysis. vrfSSFSE demonstrated higher mean lesion CNR compared to SSFSE (9.9 ± 4.1 vs. 6.7 ± 4.1, p < 0.001). Mean repetition time (TR) was 679 ± 97 ms for the vrfSSFSE sequence compared to 1139 ± 106 ms for SSFSE (p < 0.0001), corresponding to a 1.7-fold decrease in acquisition time. Overall quality of liver lesion and common bile duct images with the vrfSSFSE sequence was graded as superior than or equivalent to the SSFSE sequence for 59% and 67% of patients, respectively. CONCLUSIONS: Compared to conventional SSFSE, vrfSSFSE resulted in improved lesion contrast on simultaneous PET/MRI in patients with liver metastases. Due to decreased SAR demands, vrfSSFSE significantly decreased TR, allowing coverage of the entire liver in a single twenty-second breath hold. This may have important clinical implications in the setting of PET/MRI, where scan time is limited by the necessity of whole-body image acquisition in addition to bed specific imaging.

Comparison of diffusion-weighted imaging and T2-weighted single shot fast spin-echo: Implications for LI-RADS characterization of hepatocellular carcinoma.

PURPOSE: To evaluate the performance of diffusion-weighted imaging (DWI) and T2-weighted single shot fast spin-echo (SSFSE) imaging of the liver in the detection of hepatocellular carcinoma (HCC) in reference to the LI-RADS classification system. METHODS: MR images of 40 patients with 68 LI-RADS grade 3-5 lesions were analyzed. Two readers independently reviewed sequences and characterized lesion signal intensity, followed by consensus evaluation. CE-MRI served as reference standard. Sensitivities were compared across sequences. Lesion-to-liver contrast-to-noise ratios (CNRs) and apparent diffusion coefficients (ADCs) were measured and compared using the Wilcoxon signed-rank test across sequences and the Mann-Whitney U or Kruskal-Wallis test between LI-RADS categories. Inter-reader variability was assessed using Cohen's kappa statistic. RESULTS: Consensus sensitivities of LI-RADS 3-5 lesions using SSFSE images versus DWI were similar (0.53-0.63, p=0.089), however, the sensitivity with DWI b=700 was higher (0.63) than DWI b=0 (0.53, p=0.039). Lesion-to-liver CNRs were larger for all DWI sequences compared to SSFSE images (p<0.001 for all). ADCs of large (>2cm) LIRADS 3-5 lesions were lower than those of small lesions (1.09±0.33 vs. 1.31±0.26, p=0.02), however lesion ADCs were not different from those of adjacent hepatic parenchyma for any LI-RADS lesion. CONCLUSIONS: DWI has a similar sensitivity compared to SSFSE, but intensity on DWI likely represents intrinsic T2 signal hyper-intensity rather than restricted diffusion as the ADC values were not lower than adjacent parenchyma. Therefore it may not be appropriate to consider hyper-intensity on high b-value as a separate ancillary criteria to T2 hyper-intensity in LI-RADS.