Archive for August, 2010
Posted by James
Autofluorescence Imaging Versus Zoom-Narrow-Band Imaging for Endoscopic Imaging in BE
Video-autofluorescence imaging (AFI) and magnification narrow-band imaging (zoom-NBI) provide multimodal-ity imaging with a single endoscope, allowing for greater detection of high-grade intraepithelial neoplasia (HGIN) in patients with BE. Whereas zoom-NBI is interpreted based upon the presence of regular versus irregular patterns, AFI is interpreted based upon color changes and, thus, may be easier to interpret. To further evaluate differences between the 2 modalities, Kim and colleagues undertook a study comparing interobserver agreement in images obtained via AFI and zoom-NBI in patients with BE. Images with corresponding biopsies were obtained from a prospective trial of tandem AFI and zoom-NBI that used a prototype multimodality endoscope capable of switching between the 2 modalities. The current study compared findings determined by 6 endoscopists, including 3 experts and 3 trainees. The participants first underwent an hour-long structured teaching session using 8 AFI/NBI images and then evaluated a set of 36 AFI images (17 with high-grade dysplasia or cancer) and 44 zoom-NBI images (21 with high-grade dysplasia or cancer) obtained from 25 patients. The endoscopists all reported a median image quality score of 3 (good) on a scale of 1—5. Overall, interobserver agreement was good for both AFI (mean kappa value, 0.48) and zoom-NBI (mean kappa value, 0.50). Mean kappa values for prediction of histology were 0.48 and 0.50 for AFI and zoom-NBI, respectively. No differences in interpretation were noted between experts and nonexperts for images obtained with AFI (mean kappa values, 0.48 and 0.44, respectively). However, for images obtained with zoom-NBI, kappa values were lower in experts versus nonexperts (0.39 and 0.63, respectively). Based upon these findings, the researchers suggested that AFI is easier to interpret and has a shorter learning curve. The sensitivity, specificity, and accuracy for detecting HGIN was 79%, 80%, and 80%, respectively, for AFI, and 89%, 68%, and 77%, respectively, for zoom-NBI. The investigators suggested that further improvements are needed to increase the accuracy of detection with both modalities.
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Posted by James
Radiofrequency Ablation in Barrett Esophagus Associated With Durable Epithelial Reversion
For many patients with dysplastic Barrett esophagus (BE), treatment with radiofrequency ablation (RFA) is associated with complete eradication of dysplasia and intestinal metaplasia, though the durability of eradication has not been well defined. Moreover, the efficacy of RFA in patients without complete eradication at 1 year is not known. The randomized, sham-controlled AIM Dysplasia Trial evaluated RFA plus surveillance versus surveillance alone in patients with dysplastic BE. Following stratification by degree of dysplasia and length of BE (<4 vs 4-8 cm), patients were randomly assigned 2:1 to RFA or sham treatment. Patients in the active treatment arm received step-wise circumferential and focal RFA. All enrolled patients underwent surveillance with biopsy every 3 months for high-grade disease or every 6 months for low-grade disease. Patients in the active arm received continued surveillance, whereas those in the control arm were offered RFA. After 1 year, 65 of 78 patients in the RFA arm (83%) had attained a complete response for intestinal metaplasia (CR-IM). These patients were a median of 66 years old; 85% were male; the mean BE length was 4.7 cm; and 34 patients had high-grade disease. Of the 13 patients with persistent BE at 1 year, the median age was 67; 92% were male; the mean BE length was 6.0 cm; 7 patients (54%) had high-grade disease; and 12 patients (92%) had multifocal dysplasia. The investigators conducted additional follow-up to evaluate the durability of CR-IM and the feasibility of response in patients not attaining CR-IM after 1 year. After a follow-up of 2 years in 62 RFA-treated patients attaining CR-IM at 1 year, CR-IM was maintained in 59 patients (95.2% in a per-protocol analysis/90.8% in an intent-to-treat analysis). In the remaining 3 patients, who had 5-6-cm, multifocal, high-grade disease at baseline, the dysplasia grade had improved at Year 2. In the 13 patients with persistent BE at 1 year, 11 patients (84.6%) achieved CR-IM at 2 years, with an average of 1.2 focal RFA sessions during the second year. Finally, a 3-year follow-up of patients with CR-IM at Year 1 showed durable responses, with maintenance of CR-IM in 13 of 13 evaluable patients.
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Posted by James
Recurrent HCV is a major cause of allograft loss and mortality in liver transplant recipients with chronic HCV infection. The development of strategies designed to optimize patient and graft survival in this population is critical, as HCV is currently the most common indication for liver transplantation. A greater understanding of the risk factors for progressive disease and vigilant post- transplant monitoring through histologic assessment may guide management aimed toward reducing the potential for graft failure as well as helping identify candidates for antiviral therapy. Read the rest of this entry »
Posted by James
Ultimately, repeat liver transplantation may be considered in select patients with HCV recurrence and allograft failure. Although prior data have identified HCV infection as an independent predictor of mortality following retrans- plantation, more recent reports have described similar rates of survival in HCV and non-HCV recipients. A key factor associated with the observed improvement in outcomes related to retransplantation for recurrent HCV is patient selection. It is well recognized that the development of fibrosing cholestatic HCV is a major risk factor for severe recurrent disease following repeat transplantation with a negative impact on post-transplant survival. In a recent multicenter retrospective study that reported similar survival in HCV-infected and non-HCV patients listed for retransplantation, the most common reasons for not relisting potential candidates included rapid recurrence of HCV within 6 months and fibrosing cholestatic HCV. A recent review of the United Network for Organ Sharing database noted improved 1-year patient and graft survival in HCV-infected individuals undergoing repeat transplantation over subsequent study periods from 1994 to 2005. In this study, factors independently associated with an increased risk of mortality following retransplantation in patients with HCV included increased recipient age, MELD score greater than 25, retransplantation within 1 year of the first transplant, donor age 60 years or greater, and prolonged warm ischemia time. These findings emphasize the importance of not only patient selection, but also donor selection when considering repeat liver transplantation in patients with recurrent HCV.
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Posted by James
Immunosuppressive regimens initiated at the time of liver transplantation, as well as methods of treating acute cellular rejection during the post-transplant course, appear to have a significant role in the development of liver disease associated with HCV recurrence. Consequently, several strategies have emerged with the goal of minimizing the negative impact of high-dose or pulse corticosteroids. Some data have suggested that a treatment approach characterized by slow tapering of corticosteroids following transplantation may be associated with a reduced severity of recurrent HCV and fibrosis progression, in contrast to more rapid or abrupt decreases in corticosteroid doses. It is not clear that avoiding corticosteroids entirely may result in improved long-term outcomes; however, a recent meta-analysis noted a potential decrease in the risk of recurrent HCV based upon histologic parameters in addition to a decrease in the risk of CMV infection.
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Posted by James
Achievement of SVR in the setting of recurrent HCV following liver transplantation may have a major impact on long-term outcomes, including improved graft and patient survival. Identifying patients with a greater likelihood of achieving SVR is an important consideration in the selection of potential treatment candidates and is a key factor in developing strategies for optimizing response to therapy. HCV genotype remains an important predictor of SVR in the post-transplant setting, as sustained clearance may be significantly higher in non- genotype 1 patients, with reported SVR rates greater than 60%, particularly in patients with HCV genotype 2 or 3 infection. The most important predictor of successful response during a course of antiviral therapy before transplant is the serum HCV RNA level, with achievement of rapid virologic response (RVR) at week 4 and early virologic response (EVR) at week 12 providing the highest positive and negative predictive values of SVR, respectively. In the post-transplant setting, rapid HCV clearance during therapy is also a key predictor of sustained response, as demonstrated in several prospective studies, including the PROTECT study, in which the greatest response was observed in those who cleared HCV within 4 weeks (RVR), followed by those who achieved viral clearance within 12 weeks (complete EVR).
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Posted by James
Treatment Before Transplantation
Although PegIFN in combination with RBV remains the gold standard for the treatment of chronic HCV infection in the pretransplant setting, long-term viral suppression can be achieved in only approximately one half of patients. Antiviral therapy in patients with HCV cirrhosis awaiting liver transplantation should be considered in select individuals; however, poor tolerability may limit virologic response. Although successful response to PegIFN therapy has been described in compensated cirrhotics, sustained virologic response (SVR) can be significantly reduced in those with decompensated disease. Up to 50% of decompensated cirrhotics may experience significant hematologic side effects associated with PegIFN and RBV, leading to dose reductions and treatment discontinuation. Consequently, low SVR rates have been reported in 7-13% of genotype 1 patients and up to 50% of nongenotype 1 patients. In light of the potential benefit of viral eradication and avoidance of allograft re-infection, antiviral therapy prior to liver transplantation is recommended in patients who are candidates, primarily those with Child-Turcotte-Pugh scores of no more than 7 and model for end-stage liver disease (MELD) scores of no more than 18.
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