Thomas Riley

Utilization of Surveillance Colonoscopy in Community Practice

BACKGROUND & AIMS The recommended timing of surveillance colonoscopy for individuals with adenomatous polyps is based on adenoma histology, size, and number. The burden and cost of surveillance colonoscopy are significant. The aim of this study was to examine the use of surveillance colonoscopy on a community-wide basis. METHODS We retrospectively queried participants in the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial in 9 US communities about use of surveillance colonoscopy. Subjects whose initial colonoscopy showed advanced adenoma (AA), nonadvanced adenoma (NAA), or no adenoma (NA) findings were included. Colonoscopy examinations were confirmed by reviewing colonoscopy reports. RESULTS Of 3876 subjects selected for inquiry, 3627 (93.6%) responded. The cumulative probability of a surveillance colonoscopy within 5 years was 58.4% (n = 1342) in the AA group, 57.5% in those with >or=3 NAAs (n = 117), 46.7% in those with 1-2 NAAs (n = 905), and 26.5% (n = 1263) in subjects with NAs. Within 7 years, 33.2% of subjects with AAs received >or=2 surveillance examinations versus 26.9% for those with >or=3 NAAs, 18.2% for those with 1 or 2 NAAs, and 10.4% for those with NAs. Incomplete colonoscopy, family history of colorectal cancer, or interval adenomatous findings could explain only a minority of surveillance colonoscopy in low-risk subjects. CONCLUSIONS In community practice, there is substantial overuse of surveillance colonoscopy among low-risk subjects and underuse among subjects with AAs. Interventions to better align use of surveillance colonoscopy with risk for advanced lesions are needed.

Race and Colorectal Cancer Disparities: Health-Care Utilization vs Different Cancer Susceptibilities

BACKGROUND It is unclear whether the disproportionately higher incidence and mortality from colorectal cancer among blacks compared with whites reflect differences in health-care utilization or colorectal cancer susceptibility. METHODS A total of 60, 572 non-Hispanic white and black participants in the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial underwent trial-sponsored screening flexible sigmoidoscopy (FSG) without biopsy at baseline in 10 geographically dispersed centers from November 1993 to July 2001. Subjects with polyps or mass lesions detected by FSG were referred to their physicians for diagnostic workup, the cost of which was not covered by PLCO. The records of follow-up evaluations were collected and reviewed. We used log binomial modeling with adjustment for age, education, sex, body mass index, smoking, family history of colorectal cancer, colon examination within previous 3 years, personal history of polyps, and screening center to examine whether utilization of diagnostic colonoscopy and yield of neoplasia differed by race. RESULTS Among 57 561 whites and 3011 blacks who underwent FSG, 13,743 (23.9%) and 767 (25.5%) had abnormal examinations, respectively. A total of 9944 (72.4%) whites and 480 (62.6%) blacks had diagnostic colonoscopy within 1 year following the abnormal FSG screening. When compared with whites, blacks were less likely to undergo diagnostic evaluation (adjusted risk ratio = 0.88, 95% confidence interval = 0.83 to 0.93). Overall, among subjects with diagnostic colonoscopy (n = 10 424), there was no statistically significant difference by race in the prevalence of adenoma, advanced adenoma, advanced pathology in small adenomas (high-grade dysplasia or villous histology in adenomas <10 mm), or colorectal cancer. CONCLUSIONS We observed a lower follow-up for screen-detected abnormalities among blacks when compared with whites but little difference in the yield of colorectal neoplasia. Health-care utilization may be playing more of a role in colorectal cancer racial disparity than biology.

Ibuprofen-induced hepatotoxicity in patients with chronic hepatitis C: a case series.

Hepatitis C is a common chronic infection. Nonsteroidal anti-inflammatory drugs are commonly ingested both over-the-counter and by prescription. This case report describes three cases where ibuprofen use leads to a marked rise in hepatic transaminases with one case repeating on rechallenge. These cases support the recommendation of acetaminophen over nonsteroidal anti-inflammatory drug use in patients with chronic hepatitis C.

How often does ultrasound marking change the liver biopsy site

Abstract OBJECTIVES: The aim of this study was to answer the question: How often does ultrasound change the liver biopsy position, when a percussion technique is applied, because of intervening structures? A secondary objective is to compare the performance of the hepatologist to a radiology technician to demonstrate safety of a self-training technique. METHODS: One hundred sixty-five consecutive outpatient liver biopsies were studied. Using a standard percussion technique, a biopsy site was chosen and marked. Ultrasound was applied to the marked site. An adequate site was determined to be one without intervening structure within 6 cm of liver depth. If an intervening structure was found, an alternative site was chosen by ultrasound. Data recorded included reason for change of position, distance of moved site from original site, and complications. The first third of liver biopsies were done with assistance of a certified radiology technician performing ultrasound, the last two-thirds were done by the hepatologist after observing the first 64 biopsies. RESULTS: Ultrasound changed the position in 21 of 165 patients. The ultrasound caused an abortion of the procedure in 4 of 165 patients. Ultrasound changed management in 15.1% of patients. Reasons for change were lung (10 patients), gallbladder (6), large central vessel (4), >4-cm rim of ascites (2), colonic loop (1), slim liver edge (1), and focal liver lesions (1 patient). There was a 1.8% multiple pass rate. No serious complications occurred. CONCLUSIONS: Ultrasound changed management 15.1% of patients. A hepatologist could perform ultrasound marking after a period of observation, without compromising results. A low multiple pass rate was observed when applying ultrasound and percussion. Avoided structures could explain decrease in pain when ultrasound is applied.

Bedside ultrasound in the diagnosis of nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States. While the American Association for the Study of Liver Diseases guidelines define NAFLD as hepatic steatosis detected either on histology or imaging without a secondary cause of abnormal hepatic fat accumulation, no imaging modality is recommended as standard of care for screening or diagnosis. Bedside ultrasound has been evaluated as a non-invasive method of diagnosing NAFLD with the presence of characteristic sonographic findings. Prior studies suggest characteristic sonographic findings for NAFLD include bright hepatic echoes, increased hepatorenal echogenicity, vascular blurring of portal or hepatic vein and subcutaneous tissue thickness. These sonographic characteristics have not been shown to aid bedside clinicians easily identify potential cases of NAFLD. While sonographic findings such as attenuation of image, diffuse echogenicity, uniform heterogeneous liver, thick subcutaneous depth, and enlarged liver filling of the entire field could be identified by clinicians from bedside ultrasound. The accessibility, ease of use, and low-side effect profile of ultrasound make bedside ultrasound an appealing imaging modality in the detection of hepatic steatosis. When used with appropriate clinical risk factors and steatosis involves greater than 33% of the liver, ultrasound can reliably diagnose NAFLD. Despite the ability of ultrasound in detecting moderate hepatic steatosis, it cannot replace liver biopsy in staging the degree of fibrosis. The purpose of this review is to examine the diagnostic accuracy, utility, and limitations of ultrasound in the diagnosis of NAFLD and its potential use by clinicians in routine practices.

Impact of geographic disparity on liver allocation for hepatocellular cancer in the United States

BACKGROUND & AIMS Liver allocation for hepatocellular cancer (HCC) is undergoing constant re-evaluation in the United States, but the impact of geographic differences in organ access has not been examined. METHODS From February 28th, 2002 until November 20th, 2009, 9730 adult patients with T2 HCC and 326 Beyond Milan HCC patients were studied using the UNOS database. Kaplan-Meier survival curves were generated and log-rank tests were used to test for differences in survival curves. RESULTS Length of waiting time and presence/absence of loco-regional therapy in T2 HCC patients did not significantly impact transplant recipient (p=0.65) and graft survival (p=0.74) (Fig. 1B). Regions with median waiting times >6 months performed more loco-regional therapy (Fig. 1D) and had significantly higher waiting list dropout rates (Regions 1: p=0.01; 5: p<0.001, and 9: p<0.001). T2 HCC post-transplant outcomes were not significantly different between UNOS regions (Fig. 2) or between T2 and Beyond Milan HCC patients (transplant recipient p=0.37, and graft p=0.72 survival) (Fig. 1C). The Beyond Milan cohort had significantly greater dropout/death (p=0.007) and a worse overall survival trend (p=0.11) (Fig. 1C). CONCLUSIONS Analysis of the UNOS database shows inhomogeneous access to liver transplantation in the United States. Regions with longer waiting times had significantly higher T2 HCC dropout rates (Table 2), and used more loco-regional therapy (Fig. 1D). Conversely, T2 HCC patients had uniform liver transplant outcomes despite geographic differences (Fig. 2). Beyond Milan HCC patients showed significantly greater dropout/death (p=0.007) and a worse overall survival trend in an intent-to-treat analysis (p=0.11) (Fig. 1C).

Amantadine therapy for chronic hepatitis C: a dose escalation study.

OBJECTIVES:Amantadine reduces liver transaminase levels in some patients with chronic hepatitis C at doses of 200 mg daily and may improve the sustained virological response (SVR) when given with interferon and ribavirin. The primary purpose of the present investigation was to study the safety and toxicity of higher doses of amantadine in subjects who previously failed or were intolerant to interferon. The secondary aim was to test the efficacy of higher dose of amantadine against hepatitis C.METHODS:An open-labeled prospective study was conducted starting with amantadine 200 mg daily and increasing to 500 mg daily while monitoring for safety, toxicity, and efficacy. An amantadine blood level exceeding 1,600 ng/ml was considered toxic requiring dose reduction. The patients symptoms, laboratory tests, and quality of life were monitored.RESULTS:One hundred patients enrolled in the study. Normalization of alanine aminotransferase (ALT) for each dose was as follows: 200 mg (35%), 300 mg (49%), 400 mg (53%), and 500 mg (56%). The incidence of toxic amantadine plasma levels increased with dose, i.e., 200 mg (0%), 300 mg (6%), 400 mg (27%), and 500 mg (49%). The frequency and severity of arthralgias and fatigue improved at all dosages administered. No changes in the occurrence or severity of headache, insomnia, or depression were reported. Serious adverse events included myocardial infarction and suicide attempt. Other side effects included impotence, confusion, alopecia, and hoarseness.CONCLUSIONS:Amantadine given at a dose of 300 mg daily is safe, and significantly lowers ALT blood levels more than 200 mg daily. The enzyme response rate does not significantly improve above 300 mg, but toxicity increases.

Colorectal cancers not detected by screening flexible sigmoidoscopy in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

BACKGROUND AND OBJECTIVE Diagnosis of colorectal cancer after negative findings on endoscopic evaluation raises concern about the effectiveness of endoscopic screening. We contrast screening-detected cancers with cancers not detected by screening among participants assigned to flexible sigmoidoscopy (FSG) in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to determine the reasons for the lack of detection of prevalent lesions. DESIGN Cancers detected within 1 year of a screening FSG with abnormal findings were classified as screening detected. All other cancers were categorized, based on cancer stage and years until detection, as either not detectable or prevalent but not detected at the time of screening. SETTING/PATIENTS A total of 77,447 subjects in the multicenter PLCO trial. MAIN OUTCOME MEASUREMENTS A total of 977 colorectal cancers were diagnosed with a mean follow-up of 11.5 years. RESULTS A total of 243 (24.9%) cancers were screening detected, 470 (48.1%) were not detectable at screening, and 264 (27.0%) were considered prevalent but not detected. Among prevalent nondetected lesions, 35.6% (n = 94) were attributed to problems in patient compliance (58 never screened, 34 delayed colonoscopy follow-up, and 2 inadequate bowel preparation), 43.9% (n = 116) were attributable to a limitation in the FSG procedure (97 beyond the reach of the sigmoidoscope and 19 inadequate depth of insertion on FSG), and 20.5% (n = 54) were caused by endoscopist limitation (33 missed on FSG, 21 missed at initial colonoscopy) (P < .0001). Had colonoscopy instead of FSG been used for screening, an additional 15.6% and as many as 19.0% of cancers may have been screening-detected. LIMITATIONS These estimates are reasonable approximations, but biological variability precludes precise determinations. CONCLUSIONS Prevalent nondetected cancers were more often attributable to problems with patient compliance or limitations in the FSG procedure than to missed lesions. Colonoscopy instead of FSG could have moderately increased the detection of cancer via screening.

Immune functional assay for immunosuppressive management in post‐transplant malignancy

Uemura T, Riley TR, Khan A, Hollenbeak C, Schreibman I, Ghahramani N, Reeves B, Domen RE, Zander DS, Kadry Z. Immune functional assay for immunosuppressive management in post‐transplant malignancy.
Clin Transplant 2011: 25: E32–E37.

Amantadine Therapy for Chronic Hepatitis C

OBJECTIVE: Although treatment of hepatitis C has improved, up to 50% do not respond to standard therapy with interferon regimes or cannot tolerate the treatment due to side effects. The purpose of the present investigation was to evaluate the safety and effectiveness of the antiviral drug amantadine for the treatment of hepatitis C in those who had either previously failed interferon therapy or were not candidates for interferon.DESIGN: A prospective double-blind randomized placebocontrolled trial.SETTING: Outpatient research clinic of a teaching hospital.PATIENTS/PARTICIPANTS: One hundred fifty-two patients with confirmed hepatitis C with abnormal liver enzymes, detectable hepatitis C RNA in the blood, and abnormal liver histology by biopsy were randomized to receive treatment or placebo.MEASUREMENTS AND MAIN RESULTS: Patients received either amantadine 100 mg twice daily by mouth or placebo for 6 months. After 6 months, placebo-treated patients were crossed over and treated with amantadine for 6 months and amantadine-treated subjects received 6 additional months of therapy. Amantadine therapy resulted in a significant decline in serum alanine aminotransferase compared to placebo (P=.03). Nine percent cleared the virus at the end of therapy and 6.8% had a sustained virologic response 6 months after discontinuation of amantadine, but this was not statistically significant. Side effects were minimal, and the social quality of life survey improved with 12 months of amantadine (P=.02).CONCLUSIONS: Oral amantadine may provide a safe alternative treatment for those patients who are intolerant or unresponsive to interferon.