Mapping radiation dose distribution on the Fractional Anisotropy Map: application in the assessment of treatment-induced white matter injury

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Discrepant FA reduction between the frontal and parietal lobes of post irradiation medulloblastoma survivors: preliminary findings of regional susceptibility?

In this study of 16 medulloblastoma survivors and corresponding age-matched control subjects, we tested the hypothesis that fractional anisotropy (FA) in the frontal lobe is more severely reduced than the parietal lobe after whole brain irradiation. Quantitative measurement of regional mean FA was performed using automatically generated masks. We found significant FA reduction in the frontal lobe, but not parietal lobe, in the medulloblastoma survivors compared to controls. Although more severe FA reduction in the frontal lobe was found, this difference did not achieve statistical significance. However, a trend of regional susceptibility of the frontal lobe to radiation was suggested.published_or_final_versio

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

High serum interleukin-6 level predicts future hepatocellular carcinoma development in patients with chronic hepatitis B

Increased interleukin-6 (IL-6) production is implicated in the pathogenesis of hepatocellular carcinoma (HCC) in animal models. Although previous studies showed that HCC patients had higher serum IL-6 level at the time of diagnosis, it is unclear if the cytokine contributes to the development of HCC or is just a reaction to cancer. To address this question, we performed a nested case-control study. Consecutive chronic hepatitis B patients were recruited from 1997 to 2000 and followed till 2008. Profiling of 27 cytokines, chemokines and growth factors was performed at baseline, date of peak alanine aminotransferase (ALT) level and the last visit. Thirty-seven patients developed HCC at a median follow-up of 62 months (interquartile range: 41-110). Serum IL-6 was higher in patients with HCC than controls both during peak ALT and at the last visit (both p = 0.02). Patients with IL-6 above 7 pg/ml during peak ALT had increased risk of HCC or death (adjusted hazard ratio 3.0; 95% confidence interval 1.2, 7.8; p = 0.02). The sensitivity, specificity, positive and negative predictive values of this cutoff to predict future HCC development were 70%, 73%, 72% and 71%, respectively. Combination of IL-6 and AFP improved the sensitivity in diagnosing HCC or predicting future HCC development. In conclusion, high serum IL-6 level predates the development of HCC in chronic hepatitis B patients, and has moderate accuracy in predicting future cancer. This may assist clinicians in selecting high-risk patients for HCC surveillance program. © 2009 UICC.link_to_subscribed_fulltex

High serum interleukin-6 level predicts future hepatocellular carcinoma development in patients with chronic hepatitis B

Increased interleukin-6 (IL-6) production is implicated in the pathogenesis of hepatocellular carcinoma (HCC) in animal models. Although previous studies showed that HCC patients had higher serum IL-6 level at the time of diagnosis, it is unclear if the cytokine contributes to the development of HCC or is just a reaction to cancer. To address this question, we performed a nested case-control study. Consecutive chronic hepatitis B patients were recruited from 1997 to 2000 and followed till 2008. Profiling of 27 cytokines, chemokines and growth factors was performed at baseline, date of peak alanine aminotransferase (ALT) level and the last visit. Thirty-seven patients developed HCC at a median follow-up of 62 months (interquartile range: 41-110). Serum IL-6 was higher in patients with HCC than controls both during peak ALT and at the last visit (both p = 0.02). Patients with IL-6 above 7 pg/ml during peak ALT had increased risk of HCC or death (adjusted hazard ratio 3.0; 95% confidence interval 1.2, 7.8; p = 0.02). The sensitivity, specificity, positive and negative predictive values of this cutoff to predict future HCC development were 70%, 73%, 72% and 71%, respectively. Combination of IL-6 and AFP improved the sensitivity in diagnosing HCC or predicting future HCC development. In conclusion, high serum IL-6 level predates the development of HCC in chronic hepatitis B patients, and has moderate accuracy in predicting future cancer. This may assist clinicians in selecting high-risk patients for HCC surveillance program. © 2009 UICC.link_to_subscribed_fulltex

Changes in Crohn's disease phenotype over time in the Chinese population: Validation of the Montreal classification system

Background: Phenotypic evolution of Crohn's disease occurs in whites but has never been described in other populations. The Montreal classification may describe phenotypes more precisely. The aim of this study was to validate the Montreal classification through a longitudinal sensitivity analysis in detecting phenotypic variation compared to the Vienna classification. Methods: This was a retrospective longitudinal study of consecutive Chinese Crohn's disease patients. All cases were classified by the Montreal classification and the Vienna classification for behavior and location. The evolution of these characteristics and the need for surgery were evaluated. Results: A total of 109 patients were recruited (median follow-up: 4 years, range: 6 months-18 years). Crohn's disease behavior changed 3 years after diagnosis (P = 0.025), with an increase in stricturing and penetrating phenotypes, as determined by the Montreal classification, but was only detected by the Vienna classification after 5 years (P = 0.015). Disease location remained stable on follow-up in both classifications. Thirty-four patients (31%) underwent major surgery during the follow-up period with the stricturing [P = 0.002; hazard ratio (HR): 3.3; 95% CI: 1.5-7.0] and penetrating (P = 0.03; HR: 5.8; 95% CI: 1.2-28.2) phenotypes according to the Montreal classification associated with the need for major surgery. In contrast, colonic disease was protective against a major operation (P = 0.02; HR: 0.3; 95% CI: 0.08-0.8). Conclusions: This is the first study demonstrating phenotypic evolution of Crohn's disease in a nonwhite population. The Montreal classification is more sensitive to behavior phenotypic changes than is the Vienna classification after excluding perianal disease from the penetrating disease category and was useful in predicting course and the need for surgery. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.link_to_subscribed_fulltex

Serum Hepatitis B Surface Antigen Levels To Guide The Cessation Of Entecavir In Hepatitis B E Antigen-Negative Chronic Hepatitis B: An Interim Analysis

Poster Session - 07C. Viral Hepatitis B & D: Clinical (Therapy, New Compounds, Resistance)Background: Cessation of nucleoside analogue therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) is controversial. It is uncertain whether serum hepatitis B surface antigen (HBsAg) levels can predict virologic kinetics after treatment cessation. Methods: Entecavir was stopped in HBeAg-negative patients treated for at least 2 years with no co-existing or decompensated liver disease. All patients had undetectable HBV DNA levels on at least 3 separate occasions 6 months apart before treatment cessation. Serum HBsAg (Elecsys II, lower limit of detection 0.05 IU/mL), HBV DNA (Cobas Taqman, lower limit of detection 20 IU/mL) and liver biochemistry were monitored at every 6–12 weeks for 1 year. Entecavir was restarted if virologic relapse, defined as HBV DNA >2,000 IU/mL occurred. The primary endpoint was sustained virologic remission, defined as HBV DNA persistently ≤200 IU/mL. Results: 184 patients (median age 54 years, 67.9% male) were recruited. The median baseline HBsAg level was 892 (range 2.3–24,100) IU/mL. Median duration of entecavir therapy before cessation was 3.05 (range 2.02–5.95) years. At the time of writing, 158 (85.9%) and 104 (56.2%) patients have been followed up for 12 and 24 weeks respectively. The cumulative rates of virologic relapse, calculated using the Kaplan–Meier method, were 11.2% at week 12 and 78.1% at week 24 respectively. Among patients with 24 weeks of follow-up (n = 104), patients achieving sustained virologic remission (n = 9), when compared to patients without virologic remission (n = 93) had a significantly longer median duration of entecavir treatment before therapy cessation (4.05 and 3.03 years respectively, p = 0.007), a higher probability of undetectable viremia at week 12 (88.9% and 17.9% respectively, p<0.001) and a trend towards a lower median baseline HBsAg level (701 and 936 IU/mL respectively, p = 0.088). Conclusion: Base on this interim analysis, a longer duration of prior nucleoside analogue therapy and off-treatment HBV DNA undetectability at week 12 were associated with a higher chance of sustained virologic remission after treatment cessation. Subsequent analysis would determine if baseline and off-treatment HBsAg levels could predict virologic remission after treatment cessation. Acknowledgement: This study was supported by an unrestricted grant from Roche Diagnostic

Viral Hepatitis (+Antiviral Therapy) HBsAg and HBV DNA levels guiding entecavir cessation in HBeAg-negative chronic hepatitis B

Poster PresentationObjective: The role of hepatitis B surface antigen (HBsAg) and HBV DNA levels in predicting virologic kinetics after nucleoside analogue cessation has not been well-investigated. Methods: Following APASL guidelines, entecavir was stopped in HBeAg-negative patients treated for ≥2 years and undetectable HBV DNA levels on ≥3 separate occasions 6 months apart before treatment cessation. HBsAg and HBV DNA levels were monitored at every 6–12 weeks for 1 year. Entecavir was restarted if virologic relapse (defined HBV DNA >2,000 IU/mL) occurred. Results: 184 patients (mean age 53.9 years, 67.9% male) were recruited. The mean baseline HBsAg level was 2.86 (SD ± 0.56) log IU/mL. Mean duration of entecavir therapy before cessation was 3.06 (SD ± 0.63) years. At the time of writing, 168 (91.3%) and 119 (72.6%) patients have been followed up for 24 and 36 weeks respectively. Cumulative rates of virologic relapse, calculated using the Kaplan-Meier method, were 75.9% and 86.9% at weeks 24 and 36 respectively. Among patients with at least 24 weeks of follow-up, patients without virologic relapse (n = 25), when compared to patients with virologic relapse (n = 143), had a higher probability of undetectable viremia at week 12 off-treatment (64.0% and 18.2% respectively, p < 0.001). Mean HBsAg levels at entecavir commencement, entecavir cessation and the mean rate of HBsAg reduction during entecavir therapy had no association with virologic relapse (p = 0.738, 0.829 and 0.605 respectively). Off-treatment week-12 HBV DNA levels achieved an AUROC of 0.766 (p < 0.001, 95%CI 0.662–0.869) in predicting virologic relapse. Among patients with HBsAg <1,000 and <500 IU/mL at entecavir cessation, week-12 HBV DNA achieved an AUROC of 0.811 (p = 0.004, 95%CI 0.690–0.931) and 0.868 (p = 0.004, 95%CI 0.736–0.993) respectively. Conclusion: The combination of HBsAg levels at treatment cessation and off-treatment HBV DNA levels could predict virologic remission after entecavir cessation

Efficacy of cap-assisted colonoscopy in comparison with regular colonoscopy: A randomized controlled trial

OBJECTIVES: Colonoscopy cannot be completed in up to 10 of cases. We postulate that cap-assisted colonoscopy (CAC), by fitting a mucosectomy cap to the tip of a colonoscope, could improve the outcome. METHODS: We conducted a prospective randomized controlled trial in two regional endoscopy centers. All colonoscopies were performed by experienced colonoscopists. Patients 18 years or older undergoing their first colonoscopy were recruited. Patients were randomized to the CAC group or to the regular colonoscopy (RC) group. The first successful cecal intubation rate, rescue cecal intubation rate, cecal intubation and total colonoscopy times, and polyp detection rate were compared. RESULTS: One thousand patients were enrolled (mean age 52.6 years, 46 men). There was no statistically significant difference in the first successful cecal intubation rate between CAC and RC groups (96.2 vs. 94.6, P0.23). The cecal intubation and total colonoscopy times were shorter in the CAC group than in the RC group (6.0±4.0min vs. 7.2±4.8min, P<0.001; 14.7±8.6min vs. 16.7±10.3min, P0.001). The adenoma detection rate was significantly lower in the CAC group than in the RC group (30.5 vs. 37.5, P0.018), but there was no significant difference in the detection of advanced lesions. In case of failing cecal intubation, use of CAC as a rescue method could achieve a higher success rate than RC (66.7 vs. 21.1, P0.003). CONCLUSIONS: Among experienced colonoscopists, CAC did not improve the initial cecal intubation rate and had a lower adenoma detection rate. However, it shortened the cecal intubation time and performed better as a rescue method. Its utilization should be reserved for selected cases, especially when initial cecal intubation fails. © 2009 by the American College of Gastroenterology.link_to_subscribed_fulltex

Polymorphisms Near IL28B and Serologic Response to Peginterferon in HBeAg-Positive Patients With Chronic Hepatitis B

BACKGROUND & AIMS: A limited number of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B respond to treatment with peginterferon alfa (PEG-IFN). We investigated whether IL28B genotypes are associated with response. METHODS: We studied 205 HBeAg-positive patients who were treated with PEG-IFN (some were also treated with lamivudine) at 11 European and Asian hospitals; genotype analysis was performed for IL28B rs12980275 and rs12979860. Response was defined as HBeAg loss with the appearance of antibodies to hepatitis B e antigen (anti-HBe) at the end of PEG-IFN therapy (HBeAg seroconversion), along with HBeAg seroconversion and hepatitis B surface antigen clearance during long-term follow-up. RESULTS: The patients were infected with hepatitis B virus (HBV) genotypes A (13%), B (20%), C (47%), and D (13%). The proportions of IL28B genotypes were 77%, 19%, and 5% for AA/AG/GG at rs12980275 and also for CC/CT/TT at rs12979860, respectively. IL28B genotype was significantly associated with HBeAg seroconversion at the end of treatment (P < .001); the adjusted odds ratio for seroconversion was 3.16 (95% confidence interval [CI], 1.26 - 8.52; P = .013) for AA versus AG/GG at rs12980275 after adjustment for HBV genotype, age, levels of HBV DNA and alanine aminotransferase, and combination therapy. IL28B genotype was independently associated with an increased probability of HBeAg seroconversion during long-term follow-up (adjusted hazard ratio [HR], 2.14; 95% CI, 1.14 - 4.31; P = .018 for AA vs AG/GG by Cox regression analysis). Similar results were obtained for rs12979860. IL28B genotype was also associated with hepatitis B surface antigen clearance (HR, 3.47 for AA vs AG/GG; 95% CI, 1.04 - 13.48; P = .042). CONCLUSIONS: Polymorphisms near IL28B are independently associated with serologic response to PEG-IFN in patients with HBeAg-positive chronic hepatitis B