Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma.

Aims: Recent studies have suggested that oesophageal submucosal gland (ESMG) ducts harbour progenitor cells that may contribute to oesophageal metaplasia. Our objective was to determine whether histological differences exist between the ESMGs of individuals with and without oesophageal adenocarcinoma (EAC).

Methods And Results: We performed histological assessment of 343 unique ESMGs from 30 control patients, 24 patients with treatment-naïve high-grade columnar dysplasia (HGD) or EAC, and 23 non-EAC oesophagectomy cases.

Sample Size Requirements and Study Duration for Testing Main Effects and Interactions in Completely Randomized Factorial Designs When Time to Event is the Outcome.

In this paper we develop the methodology for designing clinical trials with any factorial arrangement when the primary outcome is time to event. We provide a matrix formulation for calculating the sample size and study duration necessary to test any effect with a pre-specified type I error rate and power. Assuming that a time to event follows an exponential distribution, we describe the relationships between the effect size, the power, and the sample size.

Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype.

The addition of arsenic trioxide (ATO) to frontline therapy of acute promyelocytic leukemia (APL) has been shown to result in significant improvements in disease-free survival (DFS). FLT3 mutations are frequently observed in APL, but its prognostic significance remains unclear. We analyzed 245 newly diagnosed adult patients with APL treated on intergroup trial C9710 and evaluated previously defined biological and prognostic factors and their relationship to FLT3 mutations and to additional karyotypic abnormalities.

Learning experience of linear endobronchial ultrasound among pulmonary trainees.

Background: Linear endobronchial ultrasound (EBUS) allows real-time guidance of transbronchial needle aspiration of thoracic structures and has become an increasingly important diagnostic tool for chest physicians. Little has been published about the learning experience of operators with this technology. The purpose of this study was to define the learning experience of EBUS-guided transbronchial needle aspiration (EBUS-TBNA) among pulmonary trainees.

Hemorrhagic complications of thoracentesis and small-bore chest tube placement in patients taking clopidogrel.

Rationale: Clopidogrel is a commonly used antiplatelet medication. The risk of local hemorrhage associated with use of this drug during routine thoracentesis or small-bore chest tube placement is not well established.

Objectives: We conducted a prospective cohort study to assess the risk of hemothorax in patients taking clopidogrel while undergoing either pleural procedure.

Bortezomib added to daunorubicin and cytarabine during induction therapy and to intermediate-dose cytarabine for consolidation in patients with previously untreated acute myeloid leukemia age 60 to 75 years: CALGB (Alliance) study 10502.

Purpose: The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with consolidation chemotherapy consisting of intermediate-dose cytarabine (Int-DAC).

Patients And Methods: Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m(2) intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m(2) on days 1 through 3 and cytarabine 100 mg/m(2) by continuous IV infusion on days 1 through 7.

Post-transplantation B cell function in different molecular types of SCID.

Purpose: Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T, B and sometimes NK cell function. Non-ablative HLA-identical or rigorously T cell-depleted haploidentical parental bone marrow transplantation (BMT) results in thymus-dependent genetically donor T cell development in the recipients, leading to a high rate of long-term survival. However, the development of B cell function has been more problematic.

Treatment-influenced associations of PML-RARα mutations, FLT3 mutations, and additional chromosome abnormalities in relapsed acute promyelocytic leukemia.

Mutations in the all-trans retinoic acid (ATRA)-targeted ligand binding domain of PML-RARα (PRα/LBD+) have been implicated in the passive selection of ATRA-resistant acute promyelocytic leukemia clones leading to disease relapse. Among 45 relapse patients from the ATRA/chemotherapy arm of intergroup protocol C9710, 18 patients harbored PRα/LBD+ (40%), 7 of whom (39%) relapsed Off-ATRA selection pressure, suggesting a possible active role of PRα/LBD+. Of 41 relapse patients coanalyzed, 15 (37%) had FMS-related tyrosine kinase 3 internal tandem duplication mutations (FLT3-ITD+), which were differentially associated with PRα/LBD+ depending on ATRA treatment status at relapse: positively, On-ATRA; negatively, Off-ATRA.

FLT3 mutation status is a predictor of early death in pediatric acute promyelocytic leukemia: a report from the Children's Oncology Group.

Background: FLT3 mutations (FLT3/Mut) are prevalent in de novo AML and are associated with early relapse. The prevalence and prognostic significance of FLT3/Mut have not been well defined in childhood acute promyelocytic leukemia (APL).

Procedure: Diagnostic specimens from 104 pediatric APL patients were screened for FLT3/Mut (FLT3/ITD or FLT3/ALM).

Estimation and testing of the relative risk of disease in case-control studies with a set of k matched controls per case with known prevalence of disease.

The analysis of case-control studies with matched controls per case is well documented in the medical literature. Of primary interest is the estimation of the relative risk of disease. Matched case-control studies fall into two scenarios: the probability of exposure is constant within each of the case and control groups, or the probability of exposure varies within each group.

Partner-assisted emotional disclosure for patients with GI cancer: 8-week follow-up and processes associated with change.

Purpose: We recently reported that a partner-assisted emotional disclosure intervention for gastrointestinal cancer led to improvements in relationship quality and intimacy for couples in which the patient initially reported higher levels of holding back from discussing cancer-related concerns. The purposes of the present study were to examine outcomes at 8-week follow-up and process variables that may influence treatment effects.

Methods: One hundred thirty couples were randomly assigned to either partner-assisted emotional disclosure or an education/support control condition.

Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease in developed countries, may progress to nonalcoholic steatohepatitis (NASH) in a minority of people. Those with NASH are at increased risk for cirrhosis and hepatocellular carcinoma. The potential risk and economic burden of utilizing liver biopsy to stage NAFLD in an overwhelmingly large at-risk population are enormous; thus, the discovery of sensitive, inexpensive, and reliable noninvasive diagnostic modalities is essential for population-based screening.

Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710.

Arsenic trioxide (As(2)O(3)) is a highly effective treatment for patients with relapsed acute promyelocytic leukemia (APL); its role as consolidation treatment for patients in first remission has not been defined. We randomized 481 patients (age ≥ 15 years) with untreated APL to either a standard induction regimen of tretinoin, cytarabine, and daunorubicin, followed by 2 courses of consolidation therapy with tretinoin plus daunorubicin, or to the same induction and consolidation regimen plus two 25-day courses of As(2)O(3) consolidation immediately after induction. After consolidation, patients were randomly assigned to one year of maintenance therapy with either tretinoin alone or in combination with methotrexate and mercaptopurine.

High dose cytarabine plus gemtuzumab ozogamicin for patients with relapsed or refractory acute myeloid leukemia: Cancer and Leukemia Group B study 19902.

Gemtuzumab ozogamicin (GO), an anti-CD33 immunoconjugate, was combined with high dose cytarabine (HiDAC; cytarabine 3g/m(2) over 3h daily for 5 days) for adults with relapsed or refractory AML. HiDAC plus GO 9mg/m(2) on day 7 and 4.5mg/m(2) on day 14 was not tolerated, but HiDAC followed by GO 9mg/m(2) on day 7 was safe: 12/37 (32%) patients with relapsed AML achieved complete remission.

Partner-assisted emotional disclosure for patients with gastrointestinal cancer: results from a randomized controlled trial.

Background: For patients with cancer who are married or in an intimate relationship, their relationships with their partners play a critical role in their adaptation to illness. However, cancer patients and their partners often have difficulty in talking with each other about their cancer-related concerns. Difficulties in communication ultimately may compromise both the patient-partner relationship and the patient's psychological adjustment.

Thymic output, T-cell diversity, and T-cell function in long-term human SCID chimeras.

Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T, B, and sometimes NK-cell function. Nonablative human leukocyte antigen-identical or rigorously T cell-depleted haploidentical parental bone marrow transplantation (BMT) results in thymus-dependent genetically donor T-cell development in the recipients, leading to long-term survival. We reported previously that normal T-cell numbers, function, and repertoire developed by 3 to 4 months after transplantation in SCID patients, and the repertoire remained highly diverse for the first 10 years after BMT.

Reformulating the hazard ratio to enhance communication with clinical investigators.

Background: Clinical trials with time to event outcomes are often designed utilizing the Cox [1] proportional hazard model with a hazard ratio parameter Delta.

Purpose: The purpose of this article is to demonstrate that a Cox proportional hazard model with a hazard ratio parameter is equivalent to a Cox proportional hazard model with a parameter equal to the probability that a patient given one treatment will have an event earlier than if the same patient were given a different treatment. This probability will subsequently be referred to as theta.

Calving sex ratio as related to the predicted Y-chromosome-bearing spermatozoa ratio in bull ejaculates.

The first objective was to correlate calving sex-ratio data from semen lots with the semen sex ratio obtained by two duplex polymerase chain reaction (PCR)/gel electrophoresis techniques. The two techniques involved different starting DNA amounts, PCR conditions, agarose gel concentrations, sample placement on the gels, lane size, number of lanes per gel, and duration of electrophoresis. The second objective was to sequence the duplex PCR products to verify their match to genes and chromosomes for which they were designed.

A general formulation for a one-sided group sequential design.

Background: A major contribution to the statistical literature on group sequential designs was provided by Pampallona and Tsiatis who developed closed form functions that can be used to iteratively calculate the boundary points of a family of popular group sequential designs. A related area of interest is the use of conditional probability calculations to make interim decisions in stochastic curtailment procedures.

Purpose: The purpose of the paper is to develop group sequential designs based on conditional probabilities, to compare our results to the general closed form family of designs developed by Pampallona and Tsiatis, and to relate these to commonly used stochastic curtailment procedures.

Impact of the Cancer Risk Intake System on patient-clinician discussions of tamoxifen, genetic counseling, and colonoscopy.

The Cancer Risk Intake System (CRIS), a computerized program that "matches" objective cancer risks to appropriate risk management recommendations, was designed to facilitate patient-clinician discussion. We evaluated CRIS in primary care settings via a single-group, self-report, pretest-posttest design. Participants completed baseline telephone surveys, used CRIS during clinic visits, and completed follow-up surveys 1 to 2 months postvisit.

Patients' interest in discussing cancer risk and risk management with primary care physicians.

Little is known about patients' preferences for discussing cancer risks and risk management with primary care physicians. We sought to determine whether patients want to discuss such topics and what factors are associated with this interest. Participants (375 patients ages 40-85, of diverse race and education level) completed a telephone survey prior to scheduled physician visits.

Improving the accuracy of syndromic diagnosis of genital ulcer disease in Malawi.

Objectives/goal: Most resource-poor settings rely on syndromic criteria to diagnose genital ulcer disease (GUD). However, the etiologic pathogens of GUD vary temporally and geographically, and current criteria may not reflect changes in the prevalence of specific pathogens.

Study: In 1999, we estimated the prevalence of Treponema pallidum (Tp), herpes simplex virus (HSV), and Haemophilus ducreyi (Hd) in Malawi.