Olaparib-Induced Immune-Mediated Liver Injury.

Immune-mediated drug-induced liver injury can be triggered by multiple classes of medications including immunotherapies. Olaparib is a first-in-class oral inhibitor of poly (adenosine diphosphate-ribose) polymerase (an enzyme involved in DNA replication and repair) that is approved as maintenance treatment in platinum-sensitive, epithelial ovarian, tubal, or primary peritoneal cancers with breast cancer 1/2 mutation. We report the first case in the United States of an acute and severe liver injury with associated jaundice and liver synthetic dysfunction secondary to olaparib. The liver injury was resolved with drug cessation and treatment with prednisone taper.

Comparative outcomes of radiofrequency ablation and cryoballoon ablation in dysplastic Barrett's esophagus: a propensity score-matched cohort study.

BACKGROUND AND AIMS: Strong evidence supports the use of radiofrequency ablation (RFA) in the management of dysplastic/neoplastic Barrett's esophagus (BE). Recently, the efficacy of the cryoballoon ablation (CBA) system was demonstrated in multicenter cohort studies. We aimed to assess the comparative effectiveness and safety of these 2 ablation modalities for endoscopic eradication therapy (EET) in a cohort study. METHODS: Data were abstracted on patients with dysplastic BE or intramucosal carcinoma undergoing EET using RFA or CBA as the primary ablation modality at 2 referral centers. The primary outcome was the rate of complete remission intestinal metaplasia (CRIM). Secondary outcomes were rates of complete remission of dysplasia (CRD) and adverse events. Cox proportional hazards models and propensity scored-matched analyses were conducted to compare outcomes. RESULTS: Three hundred eleven patients (CBA, 85 patients; RFA, 226 patients) with a median follow-up of 1.5 years (interquartile range, .8, 2.5) in the RFA group and 2.0 years (interquartile range, 1.3, 2.5) in the CBA group were studied. On multivariable analyses, the chances of reaching CRD and CRIM were not influenced by ablation modality. Propensity score-matched analysis revealed a comparable chance of achieving CRIM (CBA vs RFA: hazard ratio, 1.24; 95% confidence interval, .79-1.96; P = .35) and CRD (CBA vs RFA: hazard ratio, 1.19; 95% confidence interval, .82-1.73; P = .36). The CBA group had a higher stricture rate compared with the RFA group (10.4% vs 4.4%, P = .04). CONCLUSIONS: Histologic outcomes of EET using CBA and RFA for dysplastic BE appear to be comparable. A randomized trial is needed to definitively compare outcomes between these 2 modalities.

Preclinical cardiac disease in nonalcoholic fatty liver disease with and without metabolic syndrome.

BACKGROUND: Metabolic syndrome is associated with preclinical cardiac disease and nonalcoholic fatty liver disease (NAFLD). It is uncertain whether preclinical cardiac disease is present in patients with NAFLD without metabolic syndrome (MetS). OBJECTIVE: To explore preclinical cardiac disease in patients with NAFLD. METHODS: A total of 64 patients with NAFLD, based on computed tomography scans liver attenuation, were identified. A control group, matched to age and gender, comprising of 94 patients was also drafted. Finally, two additional groups of patients with metabolic syndrome, with (n = 40) and without (n = 74) NAFLD, were also identified. Patients with hypertension, diabetes mellitus, and other concomitant liver diseases were excluded from the NAFLD group. Echocardiograms of all groups were reviewed. RESULTS: Severe NAFLD compared to control was associated with a higher left ventricular mass after normalization for height2.7 (LVMHt2.7) (95% CI = 0.39, 12.92) and lower ratio of peak "E" (early) and "A" (late) diastolic ventricular filling velocities (E/A) - 0.39 (95% CI = -0.58, -0.19). Patients with metabolic syndrome (95% CI = 0.02, 0.09), metabolic syndrome with NAFLD (95% CI = 0.02, 0.08), or severe NAFLD (95% CI = 0.02, 0.09) compared to control was associated with a higher relative wall thickness (RWT). CONCLUSION: Healthy adults with NAFLD without metabolic syndrome, after adjusting for body mass index, demonstrated significant echocardiographic changes. Our results show that NAFLD is associated with preclinical cardiac disease, and this association is independent of traditional risk factors like systemic hypertension and diabetes mellitus.

Mutational load may predict risk of progression in patients with Barrett's oesophagus and indefinite for dysplasia: a pilot study.

BACKGROUND AND AIMS: Mutational load (ML) has been shown to help risk-stratify those that may progress from non-dysplastic Barrett's oesophagus (BE) to dysplastic disease. Management of patients with BE and indefinite for dysplasia (BE-IND) is challenging and risk stratification tools are lacking. The aim of this pilot study is to evaluate the utility of ML for risk stratification in patients with BE-IND. METHODS: This is a single-centre, retrospective pilot study evaluating ML quantification in patients with BE-IND. Histology at follow-up endoscopy at least 1 year after the baseline endoscopy was used to determine if a patient progressed to low or high dysplasia. The ML levels were then compared among patients who progressed to dysplasia versus those who did not. RESULTS: Thirty-five patients who met the inclusion criteria were identified, and seven met the exclusion criteria. Twenty-eight patients were analysed, of whom eight progressed to low-grade dysplasia (6) and high-grade dysplasia (2). Seven of these eight patients had some level of genomic instability detected in their IND biopsy (ML ≥0.5). Ten of the 20 (50%) who did not progress had no ML level. At an ML cut-off above 1.5, the risk of progression to high-grade dysplasia was 33% vs 0% (p=0.005), with a sensitivity of 100% and a specificity of 85%. CONCLUSION: These results indicate that ML may be able to risk-stratify progression to high-grade dysplasia in BE-IND. Larger studies are needed to confirm these findings.

Adherence to quality indicators in endoscopic surveillance of Barrett's esophagus and correlation to dysplasia detection rates.

BACKGROUND AND AIMS: The American Gastroenterological Association introduced quality guidelines for the endoscopic management of Barrett's esophagus (BE) in 2015. Our aim was to determine if these guidelines are being followed and to correlate adherence with outcomes in surveillance endoscopy. METHODS: This is a retrospective study from December 2015 to June 2017. Charts were abstracted to determine if the recommended quality measures were successfully accomplished during surveillance endoscopic exams in BE. Five of the recommendations pertain to surveillance endoscopy. FINDINGS: One hundred and seventy-four patients with Barrett's esophagus who underwent endoscopic surveillance were included. Adherence to recommendations one (78%), two (70%), six (99%), and seven (95%) were generally observed (P<0.001) but not to recommendation five (41%). When recommendations one (documenting important landmarks) and two (documenting the Prague classification) were followed, there was a statistically significant increase in dysplasia detection compared with those that did not adhere to the recommendations (36% vs. 13%, P=0.006 and 36% vs. 19%, P=0.003). The odds of detecting dysplasia when recommendations one and two were followed were 3.7 (95% CI 1.37-10.2) and 2.4 (95% CI 1.1-5.2) respectively. Conversely, there was no statistical difference in dysplasia yield for adherers compared with non-adherers to statement five (if systematic biopsies were performed; 35% vs. 27%, P=0.3). CONCLUSION: Adherence to statements one and two resulted in higher dysplasia detection. This has implications for the use of quality indicators in BE management in endoscopy units.

Incremental yield of dysplasia detection in Barrett's esophagus using volumetric laser endomicroscopy with and without laser marking compared with a standardized random biopsy protocol.

BACKGROUND AND AIMS: Volumetric laser endomicroscopy (VLE) is a new wide-field advanced imaging technology for Barrett's esophagus (BE). No data exist on incremental yield of dysplasia detection. Our aim is to report the incremental yield of dysplasia detection in BE using VLE. METHODS: This is a retrospective study from a prospectively maintained database from 2011 to 2017 comparing the dysplasia yield of 4 different surveillance strategies in an academic BE tertiary care referral center. The groups were (1) random biopsies (RB), (2) Seattle protocol random biopsies (SP), (3) VLE without laser marking (VLE), and (4) VLE with laser marking (VLEL). RESULTS: A total of 448 consecutive patients (79 RB, 95 SP, 168 VLE, and 106 VLEL) met the inclusion criteria. After adjusting for visible lesions, the total dysplasia yield was 5.7%, 19.6%, 24.8%, and 33.7%, respectively. When compared with just the SP group, the VLEL group had statistically higher rates of overall dysplasia yield (19.6% vs 33.7%, P = .03; odds ratio, 2.1, P = .03). Both the VLEL and VLE groups had statistically significant differences in neoplasia (high-grade dysplasia and intramucosal cancer) detection compared with the SP group (14% vs 1%, P = .001 and 11% vs 1%, P = .003). CONCLUSION: A surveillance strategy involving VLEL led to a statistically significant higher yield of dysplasia and neoplasia detection compared with a standard random biopsy protocol. These results support the use of VLEL for surveillance in BE in academic centers.

Complete remission of primary hepatic lymphoma in a patient with human immunodeficiency virus.

Diffuse large B cell primary hepatic lymphoma is a rare disease with limited available information regarding treatment strategy. Although the liver contains lymphoid tissue and is an important site for lymphocytes activation, primary hepatic lymphoma is rare. Host factors make the liver a poor environment for malignant lymphoma development. Its coexistence with human immunodeficiency virus (HIV) infection increases morbidity and mortality risks. Additionally, jaundice increases chances of developing adverse effects from chemotherapy. Here, we report a case of diffuse large B cell primary hepatic lymphoma in a 32-year-old HIV positive man. Due to elevated liver enzyme levels and jaundice, the patient was initially treated with an R-DHAP regimen, which was replaced with an R-CHOP regimen. Restaging images with a positron emission tomography scan after the latest chemotherapy cycle confirmed remission. This is the first report of complete remission of primary hepatic diffuse large B cell lymphoma in an HIV positive patient in the English literature.