Estimate of Increase in Colorectal Cancer Diagnoses with Expansion of Fecal Immunochemical Testing in an Urban Safety-Net Population.

BACKGROUND: Fecal immunochemical test (FIT) is less effective in detecting advanced adenomas (AA) than colonoscopy. Increase in FIT for colorectal cancer (CRC) screening may lead to an increased number of undetected AAs which may develop into future CRCs. AIM: We determined the potential impact of FIT expansion on missed AAs and future CRC diagnoses in an urban, tertiary-care, safety-net hospital. METHODS: CRC and AA diagnoses were identified in patients undergoing colonoscopy for average-risk CRC screening or positive FIT between 2017 and 2019 at Boston Medical Center. Poisson regression modeling was used to estimate the frequency of AAs per year by age group using data from 2017 to 2019, assuming average outpatient volume and proportion of screening colonoscopies. Total number of patients who received FIT was extrapolated from those who underwent colonoscopy for positive FIT. We estimated AAs per year if 'one-time' FIT was used for screening in 75% and 100% of the population and subtracted this from the estimated AAs per year under the Poisson model to determine missed AAs. We used previously described, age and gender specific estimates of the annual progression of AA to CRC. RESULTS: The estimated number of CRCs detected per year is 4.6/1785 males and 4.6/2086 females screened. With 75% FIT expansion, we estimate an additional 3.5 (95% CI 1.3, 9.5) and 2.2 (95% CI 0.64, 7.6) CRCs; with 100% FIT expansion, we estimate an additional 7.4 (95% CI 3.7, 14.9) and 4.2 (95% CI 1.7, 10.5) CRCs, in 5 years, in males and females, respectively. CONCLUSION: Expansion of FIT may substantially increase CRC incidence.

The impact of social risk factors on the presentation, treatment and survival of patients with hepatocellular carcinoma at an urban, academic safety-net hospital.

BACKGROUND: Vulnerable populations have worse hepatocellular carcinoma (HCC) outcomes. We sought to understand if this could be mitigated at a safety-net hospital. METHODS: A retrospective chart review of HCC patients was conducted (2007-2018). Stage at presentation, intervention and systemic therapy were analyzed (Chi-square for categorical variables and Wilcoxon tests for continuous variables) and median survival calculated by Kaplan-Meier method. RESULTS: 388 HCC patients were identified. Sociodemographic factors were similar for stage at presentation, except insurance status (diagnosis at earlier stages for commercial insurance and later stages for safety-net/no insurance). Higher education level and origin of mainland US increased intervention rates for all stages. Early-stage disease patients had no differences in receipt of intervention or therapy. Late-stage disease patients with higher education level had increased intervention rates. Median survival was not impacted by any sociodemographic factor. CONCLUSION: Urban safety-net hospitals with a focus on vulnerable patient populations provide equitable outcomes and can serve as a model to address inequities in HCC management.

Procedural-Related Bleeding in Hospitalized Patients With Liver Disease (PROC-BLeeD): An International, Prospective, Multicenter Observational Study.

BACKGROUND & AIMS: Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors. METHODS: Hospitalized patients were prospectively enrolled and monitored until surgery, transplantation, death, or 28 days from admission. The study enrolled 1187 patients undergoing 3006 nonsurgical procedures from 20 centers. RESULTS: A total of 93 procedural-related bleeding events were identified. Bleeding was reported in 6.9% of patient admissions and in 3.0% of the procedures. Major bleeding was reported in 2.3% of patient admissions and in 0.9% of the procedures. Patients with bleeding were more likely to have nonalcoholic steatohepatitis (43.9% vs 30%) and higher body mass index (BMI; 31.2 vs 29.5). Patients with bleeding had a higher Model for End-Stage Liver Disease score at admission (24.5 vs 18.5). A multivariable analysis controlling for center variation found that high-risk procedures (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.44-8.84), Model for End-Stage Liver Disease score (OR, 2.37; 95% CI, 1.46-3.86), and higher BMI (OR, 1.40; 95% CI, 1.10-1.80) independently predicted bleeding. Preprocedure international normalized ratio, platelet level, and antithrombotic use were not predictive of bleeding. Bleeding prophylaxis was used more routinely in patients with bleeding (19.4% vs 7.4%). Patients with bleeding had a significantly higher 28-day risk of death (hazard ratio, 6.91; 95% CI, 4.22-11.31). CONCLUSIONS: Procedural-related bleeding occurs rarely in hospitalized patients with cirrhosis. Patients with elevated BMI and decompensated liver disease who undergo high-risk procedures may be at risk to bleed. Bleeding is not associated with conventional hemostasis tests, preprocedure prophylaxis, or recent antithrombotic therapy.

Impact of Direct Acting Antiviral Agent Therapy upon Extrahepatic Manifestations of Hepatitis C Virus Infection.

PURPOSE OF REVIEW: Direct acting antiviral agents (DAAs) have emerged as simple, short, safe, and effective treatments for chronic hepatitis C (CHC) infection. CHC is a systemic disease with frequent and multiple extrahepatic manifestations. The beneficial effects of DAA treatment regimens extend beyond improvement in liver-related outcomes to amelioration of extra hepatic manifestations and are likely to have economic implications. The purpose of this review is to evaluate the effect of DAAs on extra hepatic manifestations of CHC virus infection. RECENT FINDINGS: Recent studies indicate that DAAs are associated with reduction in all-cause mortality, even in patients without significant hepatic fibrosis. They are also associated with reduction in incident cardiovascular disease and diabetes. DAAs are the mainstay of treatment in HCV-associated cryoglobulinemia and lymphoma. Successful HCV therapy with DAAs also improves patient-related outcomes such as health-related quality of life. DAAs improve extrahepatic manifestations of CHC virus infection. Future studies are needed to evaluate the long-term durability of treatment response and for accounting amelioration of extrahepatic manifestations into the cost effectiveness of DAA regimens.

Correction: Biophotonic detection of high order chromatin alterations in field carcinogenesis predicts risk of future hepatocellular carcinoma: A pilot study.

[This corrects the article DOI: 10.1371/journal.pone.0197427.].

Biophotonic detection of high order chromatin alterations in field carcinogenesis predicts risk of future hepatocellular carcinoma: A pilot study.

PURPOSE: Hepatocellular carcinoma (HCC) results from chronic inflammation/cirrhosis. Unfortunately, despite use of radiological/serological screening techniques, HCC ranks as a leading cause of cancer deaths. Our group has used alterations in high order chromatin as a marker for field carcinogenesis and hence risk for a variety of cancers (including colon, lung, prostate, ovarian, esophageal). In this study we wanted to address whether these chromatin alterations occur in HCC and if it could be used for risk stratification. EXPERIMENTAL DESIGN: A case control study was performed in patients with cirrhosis who went on to develop HCC and patients with cirrhosis who did not develop cancer. We performed partial wave spectroscopic microscopy (PWS) which measures nanoscale alterations on formalin fixed deparaffinized liver biopsy specimens, 17 progressors and 26 non-progressors. Follow up was 2089 and 2892 days, respectively. RESULTS: PWS parameter disorder strength Ld were notably higher for the progressors (Ld = 1.47 ± 0.76) than the non-progressors (Ld = 1.00 ± 0.27) (p = 0.024). Overall, the Cohen's d effect size was 0.907 (90.7%). AUROC analysis yielded an area of 0.70. There was no evidence of confounding by gender, age, BMI, smoking status and race. CONCLUSIONS: High order chromatin alterations, as detected by PWS, is altered in pre-malignant hepatocytes with cirrhosis and may predict future risk of HCC.

Systemic Mastocytosis Complicated by Non-Cirrhotic Portal Hypertension and Variceal Bleeding.

Systemic mastocytosis is a myeloproliferative disorder characterized by extracutaneous involvement of at least one organ. Although rare, infiltration of inflammatory mast cells within the portal vein may lead to obstruction of the sinusoids resulting in non-cirrhotic portal hypertension. We present a patient with known history of systemic mastocytosis with bone marrow involvement presenting with new-onset esophageal variceal bleeding. Although systemic mastocytosis is uncommon, the subsequent development of hepatic involvement and non-cirrhotic portal hypertension are discussed. Further highlighted is a lack of organization guidelines and the potential for gastrointestinal and hepatic screening of mastocytosis patients with known extracutaneous involvement.

MRI steatosis grading: development and initial validation of a color mapping system.

OBJECTIVE: The purpose of this article is to develop and validate a chemical-shift imaging-derived color mapping system for evaluation of liver steatosis. MATERIALS AND METHODS: Opposed phase MRI was evaluated for 85 subjects (51 with presumed nonalcoholic fatty liver disease and 34 healthy volunteers). Liver signal intensity loss was compared with histologic analysis for 52 subjects, assuming grade 0 steatosis for healthy volunteers, to determine signal-intensity-loss threshold points differentiating steatosis grades and subsequent Spearman correlation. Color scale grading was then applied for 78 subjects. Interpretation of color maps for steatosis severity and heterogeneity was performed by three readers. Analyses of agreement among readers and of color map steatosis grade with biopsy were performed using weighted kappa values. RESULTS: The numbers of subjects with steatosis grades 0, 1, 2, and 3 were 41, 12, 13, and 19, respectively. A correlation of 0.90 was obtained using selected threshold values of 5.9% or less, 6-26.1%, 26.2-36.8%, and greater than 36.8% for steatosis grades 0, 1, 2, and 3, respectively. Interobserver agreement for color map grading of steatosis was excellent (κ = 0.93-0.94). Color map interpretation for all readers also showed excellent agreement with histologic findings for whole liver (κ = 0.82-0.86) and estimated biopsy site location (κ = 0.81-0.86; anterior region of right lobe). Heterogeneous steatosis on color maps was identified in 56-60% of subjects with nonalcoholic fatty liver disease and in 7% of healthy volunteers and was associated with greater disagreement between color map and histology grading (61-74%) compared with the whole group (37-40%). CONCLUSION: MRI-derived color map estimation of liver steatosis grade appears to be reproducible and accurate.

New perspectives on bone marrow contrast agents and molecular imaging.

Magnetic resonance (MR) imaging of bone marrow provides a noninvasive diagnosis of the vascularity, cell quantity, and composition of the normal and pathological bone marrow. This article reviews new and evolving techniques for bone marrow MR imaging with a special focus on translational and clinical applications. Evaluations of bone marrow perfusion with standard small molecular contrast agents and, more recently, with macromolecular contrast agents are currently being applied for therapy monitoring. Cell-specific contrast agents are expected to improve the sensitivity and specificity of bone marrow MR imaging. Novel cellular and molecular imaging techniques for the depiction of cell metabolism and specific biochemical pathways are discussed. Cell tracking techniques may allow specific diagnoses of inflammatory processes as well as monitoring of novel therapies based on stem cells. Future developments of fusion imaging techniques and bifunctional contrast agents are directed to combine comprehensive information about bone marrow structure and function with targeted and image-guided therapies.