An Unsuccessful Randomized Trial of Percutaneous vs Endoscopic Drainage of Suspected Malignant Hilar Obstruction.

Percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiopancreatography (ERCP) are widely accepted but competing approaches for the management of malignant obstruction at the hilum of the liver. ERCP is favored in the United States on the basis of high success rates for non-hilar indications, the perceived safety and superior tissue sampling capability of ERCP relative to PTBD, and the avoidance of external drains that are undesirable to patients. A recent randomized controlled trial (RCT) comparing the 2 modalities in patients with resectable hilar cholangiocarcinoma was terminated prematurely because of higher mortality in the PTBD group.1 In contrast, most observational data suggest that PTBD is superior for achieving complete drainage.2-6 Because the preferred procedure remains uncertain, we aimed to compare PTBD and ERCP as the primary intervention in patients with cholestasis due to malignant hilar obstruction (MHO).

Role of Hepatitis E Virus Infection in North American Patients With Severe Acute Liver Injury.

INTRODUCTION: The aim of this study was to determine the role of hepatitis E virus (HEV) infection in a large cohort of prospectively enrolled patients with severe acute liver injury (ALI). METHODS: Serum samples from 594 consecutive adults enrolled between 2008 and 2018 in the US Acute Liver Failure Study Group ALI registry were tested for anti-HEV IgM and anti-HEV IgG levels. Those with detectable anti-HEV IgM underwent further testing for HEV RNA using real-time polymerase chain reaction. RESULTS: The median age of patients was 38 years; 41% were men and 72% Caucasian. Etiologies of ALI included acetaminophen hepatotoxicity (50%), autoimmune hepatitis (8.9%), hepatitis B virus (8.9%), and idiosyncratic drug-induced liver injury (7.9%). Overall, 62 patients (10.4%) were negative for anti-HEV IgM but positive for IgG, whereas only 3 men (0.5%) were positive for both anti-HEV IgM and IgG. These 3 cases were initially diagnosed as having indeterminate, HEV, and hepatitis B virus-related ALI. One of these patients had detectable HEV RNA genotype 3, and another anti-HEV IgM+ patient had detectable HEV antigens by immunohistochemistry on liver biopsy. On multivariate modeling, older (odds ratio: 1.99) and non-Caucasian subjects (odds ratio: 2.92) were significantly more likely to have detectable anti-HEV IgG (P < 0.0001). DISCUSSION: Acute HEV infection is an infrequent cause of ALI in hospitalized North American adults. The anti-HEV IgG+ patients were significantly older and more likely to be non-Caucasian. These data are consistent with other population-based studies that indicate exposure to HEV in the general US population is declining over time and might reflect a cohort effect.

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial.

BACKGROUND: The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). METHODS: The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. DISCUSSION: The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.

Variation of agreement in polyp size measurement between computed tomographic colonography and pathology assessment: clinical implications.

BACKGROUND & AIMS: Clinical management of polyps discovered by computed tomographic (CT) colonography depends on polyp size. However, size measured by CT colonography is an estimate, and its agreement with other measures is not well characterized. We hypothesized that size measurement by CT colonography varies substantially compared with measurement by other methods. METHODS: We performed a secondary data analysis of a multicenter study of CT colonography in comparison with colonoscopy. Polyp size was determined by CT colonography, at colonoscopy, and measurement prefixation with a ruler. Agreement was assessed using descriptive statistics and Bland-Altman methodology. RESULTS: Six hundred trial participants completed both tests. Ninety-five percent limits of agreement indicated that estimates of size by CT colonography were between 52% lower to 64% higher than prefixation polyp size estimates. Ninety-five percent limits of agreement stratified by categories of clinical importance indicated that estimates of size by CT colonography were between 44% lower to 84% higher for polyps 0.6 cm or smaller, 44% lower to 44% higher for polyps 0.6 to 0.9 cm, and 48% lower to 22% higher for polyps smaller than 0.6 cm, 44% lower to 44% higher for polyps 0.6 cm to 0.9 cm, and 48% lower to 22% higher for polyps larger than 0.9 cm compared with prefixation estimates. Analysis of participants with 1 identified polyp in the same colon segment showed that categorization based on CT colonography measurement (ie, <0.6 cm, 0.6-0.9 cm, or >0.9 cm) differed from prefixation measurement for 43% of participants. CONCLUSIONS: Polyp size estimation by CT colonography varies from prefixation and colonoscopic measures of size. Future studies should clarify whether size estimation by CT colonography is sufficiently reliable as a primary factor to guide clinical management.

Endoscopic sedation in the United States: results from a nationwide survey.

OBJECTIVES: The introduction of new sedative agents as well as a desire for improved patient satisfaction and greater efficiency has changed the practice of endoscopic sedation. This survey was designed to provide national and regional data on endoscopic sedation and monitoring practices within the United States. METHODS: A 22-item survey regarding current practices of endoscopy and sedation was mailed to 5,000 American College of Gastroenterology physician members nationwide. RESULTS: A total of 1,353 questionnaires (27.1%) were returned. Respondents performed an average of 12.3 esophagogastroduodenoscopies (EGDs) and 22.3 colonoscopies per wk. Endoscopic procedures were performed within a hospital setting (55.2) more often than at an ambulatory center (35.8%) or private office (8.8%). The vast majority of EGDs and colonoscopies (>98%) were performed with endoscopic sedation. Almost three quarters (74.3%) of the respondents used a narcotic and benzodiazepine for sedation, while propofol was preferred by 25.7%. Sedation practices varied considerably within different geographic regions of the United States. Respondents routinely monitored vital signs and pulse oximetry (99.2% and 98.6%, respectively), and supplemental oxygen was administered to all patients during EGD by 72.7% of endoscopists. Endoscopist satisfaction with sedation was greater among those using propofol than conventional sedation (10 vs 8, p < 0.0001). CONCLUSIONS: During the past 15 yr, the volume of procedures performed by endoscopists in the United States has increased two- to fourfold. Propofol is currently being used for sedation in approximately one quarter of all endoscopies in the United States. The findings from this survey may help in the formulation of updated policies and practice guidelines pertaining to endoscopic sedation.

Analysis of trichotomous pharmaceutical endpoints.

Many important clinical trial endpoints are measured on an ordered categorical scale. These include objective tumor response in oncology trials, the Thombolysis in Myocardial Infarction (TIMI) flow in cardiovascular trials, and the American College of Radiology (A CR) criterion in rheumatology trials. A common tendency among researchers is to simplify the ordered outcomes and collapse the data into a 2 x 2 contingency table in order to perform simpler statistical tests, such as the chi-square test or Fisher's exact test. Recently, more appropriate approaches, such as adaptive tests, have been developed for the analysis of ordered categorical endpoints. Each test in the adaptive class of tests is exact and balances good global power with nearly optimal power to detect a specific alternative of most interest. Prior knowledge of the direction of the treatment effect and the level of confidence in this prior information can be used to select a specific test from this class. However, little guidance has been offered regarding the selection of adaptive parameters when prior information is available. The purpose of this paper is to fill this gap by offering an objective approach for parameter selection, and to provide real data examples to illustrate the use of this objective approach.

Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia.

CONTEXT: Conventional colonoscopy is the best available method for detection of colorectal cancer; however, it is invasive and not without risk. Computed tomographic colonography (CTC), also known as virtual colonoscopy, has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers. OBJECTIVE: To assess the accuracy of CTC in a large number of participants across multiple centers. DESIGN, SETTING, AND PARTICIPANTS: A nonrandomized, evaluator-blinded, noninferiority study design of 615 participants aged 50 years or older who were referred for routine, clinically indicated colonoscopy in 9 major hospital centers between April 17, 2000, and October 3, 2001. The CTC was performed by using multislice scanners immediately before standard colonoscopy; findings at colonoscopy were reported before and after segmental unblinding to the CTC results. MAIN OUTCOME MEASURES: The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm. Secondary outcomes included detection of all lesions, detection of advanced lesions, possible technical confounders, participant preferences, and evidence for increasing accuracy with experience. RESULTS: A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures; 104 participants had lesions sized at least 6 mm. The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants were without any lesion sized at least 6 mm. The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively. Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC varied considerably between centers and did not improve as the study progressed. Participants expressed no clear preference for either technique. CONCLUSIONS: Computed tomographic colonography by these methods is not yet ready for widespread clinical application. Techniques and training need to be improved.

Accuracy of EUS criteria and primary tumor site for identification of mediastinal lymph node metastasis from non-small-cell lung cancer.

BACKGROUND: EUS with FNA is useful for staging non-small-cell lung cancer. However, benign mediastinal adenopathy is common. The aims of this study were to identify clinical factors, especially primary tumor location, and EUS lymph nodal characteristics predictive of aortopulmonary window and subcarinal lymph node metastases of non-small-cell lung cancer. METHODS: Patients with known or suspected non-small-cell lung cancer underwent EUS staging at which EUS-FNA was performed for all identified mediastinal lymph nodes. Clinical characteristics, primary tumor data, EUS findings, and histopathology were reviewed. Exact tests were performed for both aortopulmonary window and subcarinal lymph nodes to identify factors predictive of malignant cytology. RESULTS: Ninety-two patients with non-small-cell lung cancer were included. Fifty-one had aortopulmonary window, and 73 had subcarinal lymph nodes on EUS. The EUS with FNA specimens were interpreted as suspicious or diagnostic for malignancy for 9 aortopulmonary window and 9 subcarinal lymph nodes. When comparing benign vs. malignant EUS with FNA findings for aortopulmonary window and subcarinal lymph nodes, only lymph node size of 1 cm or greater and sharp lymph nodal edges were associated with malignancy in lymph nodes at both sites, whereas primary tumor site, lymph node shape, and echogenicity were associated with malignant subcarinal nodes. When 4 classic lymph nodal features of malignancy were evaluated, the presence of 3 or more typical features had positive and negative predictive values of, respectively, 41% and 96%. CONCLUSIONS: Although tumor location and EUS lymph nodal characteristics are associated with malignant involvement of lymph nodes, the accuracy of these predictors does not obviate the need for cytologic evaluation. EUS with FNA should be performed for all lymph nodes when an abnormal finding will alter management.

Accuracy of EUS for detection of intraductal papillary mucinous tumor of the pancreas.

BACKGROUND: Patients with intraductal papillary mucinous tumors of the pancreas (IPMT) present with symptoms similar to those of chronic pancreatitis. This study assessed the accuracy of EUS for detection of IPMT and identified features that discriminate IPMT from chronic pancreatitis. METHODS: EUS accuracy for detecting IPMT was determined with characteristic findings by endoscopic retrograde pancreatography as the reference standard. To determine EUS features characteristic of IPMT, EUS images from patients with IPMT were compared with those from patients (similar age, gender) with chronic pancreatitis. RESULTS: Thirty-eight patients (23 men, 15 women; age range 40-90 years) with IPMT were identified between 1994 and 2001. For EUS, the sensitivity was 86%, specificity 99%, positive predictive value 78%, and negative predictive value 99% for detection of IPMT. When compared with patients with chronic pancreatitis, the EUS features of dilation of pancreatic duct (89% vs. 42%, p < 0.0001), cysts (45% vs. 11%, p = 0.002), and pancreatic atrophy (32% vs. 3%, p = 0.002) were more common, whereas parenchymal features of chronic pancreatitis were less common with IPMT (21% vs. 97%, p < 0.0001). By multivariate analysis, the presence of no more than one parenchymal feature of chronic pancreatitis suggested the diagnosis of IPMT (odds ratio 43.84; 95% CI [4.13, 465.74]). CONCLUSIONS: EUS may be useful in the initial evaluation of patients suspected to have IPMT. Paucity of parenchymal features of chronic pancreatitis is important in differentiating IPMT from other causes of chronic pancreatitis.

The virtual colonoscopy study: a large multicenter clinical trial designed to compare two diagnostic screening procedures.

This paper reviews the design of a large multicenter clinical trial currently being conducted to test the equivalence of two screening procedures for colorectal polyps. The primary outcome is the sensitivity and specificity of the new and standard procedures for detecting subjects with and without polyps of a size > or =6 mm, respectively. An important secondary outcome is the accuracy of these procedures in detecting individual polyps. A total of 619 participants underwent virtual colonoscopy, the new procedure, followed by conventional colonoscopy, the standard procedure. Strategies for the design and implementation of the study are shared as well as the challenges encountered.