Wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS) markedly improves detection of esophageal dysplasia and Barrett's esophagus: analysis from a prospective multicenter community-based study.

The 4-quadrant forceps biopsy (FB) protocol for identifying Barrett's esophagus (BE) and esophageal dysplasia (ED) suffers from poor sensitivity due to significant sampling error. We investigated the benefit of wide-area transepithelial sampling with 3-dimensional computer-assisted analysis (WATS) used adjunctively to the combination of random and targeted FB in the detection of ED, and as a secondary outcome, BE. In this multicenter prospective trial, community endoscopists at 21 sites utilized WATS as an adjunct to both targeted and random FB in patients undergoing BE screening and surveillance. Investigators alternated taking FB and WATS samples first. WATS specimens were analyzed at CDx Diagnostics (Suffern, NY) while FB samples were analyzed by each site's regular pathologists. Data were de-identified and then aggregated for analysis. Of 12,899 patients enrolled, FB identified 88 cases of ED, and WATS detected an additional 213 cases missed by FB. These 213 cases represented an absolute increase of 1.65%, raising the yield from 0.68% to 2.33%. Adding WATS to FB increased the overall detection of ED by 242% (95% CI: 191%-315%). Fewer than 61 patients needed to be tested with WATS to identify an additional case of ED. The combination of random and targeted FB identified 1,684 cases of BE, and WATS detected an additional 2,570 BE cases. The absolute incremental yield of adding WATS to FB is 19.9%, increasing the rate of detection from 13.1% to 33%. Adding WATS to FB increased the overall detection of BE by 153% (95% CI: 144-162%). The number needed to test with WATS in order to detect an additional case of BE was 5. Whether FB or WATS was done first did not impact the results. In this study, comprised of the largest series of patients evaluated with WATS, adjunctive use of the technique with targeted and random FB markedly improved the detection of both ED and BE. These results underscore the shortcomings of FB in detecting BE-associated neoplasia, which can potentially impact the management and clinical outcomes of these patients.

A comparison of high definition-image enhanced colonoscopy and standard white-light colonoscopy for colorectal polyp detection.

BACKGROUND AND STUDY AIMS: Colonoscopy is widely used to detect and remove precancerous polyps, but fails to detect some polyps. Recent studies evaluating different image-enhanced methods have revealed conflicting results. The efficacy of colonoscopy imaging with simultaneous use of commercially available improvements, including high definition narrow band imaging (HD-NBI), and monochromatic charge-coupled device (CCD) video, was compared with a widely used standard definition white light (SDWL) colonoscopy system for detecting colorectal polyps. The primary aim was to determine whether the combination of image-enhanced colonoscopy systems resulted in fewer missed polyps compared with conventional colonoscopy. PATIENTS AND METHODS: In a randomized controlled trial (Clinicaltrials.gov. study number NCT00825292) patients having routine screening and surveillance underwent tandem colonoscopies with SDWL and image-enhanced (HD-NBI) colonoscopy. The main outcome measurement was the per-polyp false-negative ("miss") rate. Secondary outcomes were adenoma miss rate, and per-patient polyp and adenoma miss rates. RESULTS: 100 patients were randomized and 96 were included in the analysis. In total, 177 polyps were detected; of these, 72 (41 %) were adenomatous. Polyp and adenoma miss rates for SDWL colonoscopy were 57 % (60/105) and 49 % (19/39); those for image-enhanced colonoscopy were 31 % (22/72) and 27 % (9/33) (P = 0.005 and P = 0.036 for polyps and adenomas, respectively). Image-enhanced and SDWL approaches had similar per-patient miss rates for polyps (6/35 vs. 9/32, P = 0.27) and adenomas (4/22 vs. 8/20, P = 0.11). CONCLUSIONS: Utilization of multiple recent improvements in image-enhanced colonoscopy was associated with a reduced miss rate for all polyps and for adenomatous polyps. It is not known which individual feature or combination of image-enhancement features led to the improvement.

The safety of fine-needle aspiration guided by endoscopic ultrasound: a prospective study.

BACKGROUND AND STUDY AIMS: Fine-needle aspiration (FNA) is commonly performed in conjunction with endoscopic ultrasound (EUS) procedures. The complication rate associated with FNA is considered to be low but requires further evaluation with prospective studies. PATIENTS AND METHODS: A total of 483 consecutive patients who underwent EUS-guided FNA over a 12-month period were prospectively enrolled in the study. The patients were screened for postprocedural complications, including abdominal pain, nausea, vomiting, and gastrointestinal bleeding. Complications were assessed immediately after EUS-FNA and 30 days later with a telephone call, when inquiries were made about emergency room and physician's office visits or hospitalizations during this 30-day period. RESULTS: Complete information was obtained from 414 patients (86 %). Complications occurred in seven patients during the first day. Five of these patients had unplanned admissions to hospital: two patients were observed because they had abdominal pain after FNA of pancreatic cysts; one patient was observed because they developed chest pain after mediastinal lymph node FNA; and two patients were monitored after celiac node FNA, one with a transient fever and one with self-limited melena. All five of these patients were discharged within 24 hours of admission, none required blood transfusion, and none showed any evidence of pancreatitis or infection. Two other patients visited the emergency department but were discharged on oral analgesics after appropriate evaluation. By day 30 six patients had died as a result of their primary disease process. There was no unexpected morbidity or mortality attributable to the EUS-FNA. CONCLUSIONS: FNA is a safe intervention in patients undergoing EUS in a high-volume academic center, with a low postprocedural complication rate.

Hydroquinone modulates the GM-CSF signaling pathway in TF-1 cells.

Human leukemogens, including alkylating chemotherapeutic agents and benzene, enhance granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent proliferation of human CD34+ bone marrow (BM) cells. The extracellular signal-regulated kinase (ERK) pathway plays an important role in GM-CSF-dependent proliferation and also has been implicated in the pathogenesis of acute myelogenous leukemia. Therefore, we investigated the effects of the benzene metabolite, hydroquinone (HQ), on alterations in the GM-CSF signaling pathway in TF-1 erythroleukemia cells and human CD34+ BM cells. HQ treatment in TF-1 cells results in a strong proliferative response that is dependent on ERK activation and GM-CSF production. HQ also induces ERK-dependent AP-1 activation with concomitant increased transcriptional activity of AP-1 reporter gene. However, the kinetics of ERK activation are different between rhGM-CSF and HQ in TF-1 cells: rhGM-CSF results in immediate activation of ERK, whereas HQ activation of ERK is delayed. Further, HQ and rhGM-CSF together produce an immediate increase in ERK phosphorylation, which is sustained for over 48 h. HQ also stimulates colony formation, AP-1 DNA binding and GM-CSF production in human CD34+ BM cells. These results suggest that HQ stimulates proliferation via activation of ERK/AP-1 and is at least partially mediated via the production of GM-CSF.

Mural thrombi in myocardial infarctions. Prospective evaluation by two-dimensional echocardiography.

Fifty-four consecutive patients with acute anterior myocardial infarctions were studied to determine the incidence and natural history of mural thrombus formation. Two-dimensional echocardiography was performed in the immediate postinfarction period. Multiple views were utilized. Standard criteria for defining mural thrombus formation and minimizing false-positive readings were adhered to. Correlation with clinical data was obtained in all patients to define a subgroup at high risk for the development of a mural thrombus. Follow-up was obtained for all patients to assess the natural history of mural thrombus formation, treated and untreated, with regard to peripheral embolization. Seventeen patients (32 percent) had mural thrombus formation. Statistically significant (p less than 0.001) correlation for mural thrombus formation was found with markedly elevated creatine kinase and lactate dehydrogenase levels and with apical dyskinesis. Ten patients with mural thrombi received anticoagulation therapy. None has had clinically evident emboli at a mean of 10.8 months follow-up. Resolution of the mural thrombus was demonstrated with serial two-dimensional echocardiography in eight patients (80 percent). Six of seven patients who did not receive anticoagulation therapy (86 percent) had embolic events within three months (p less than 0.001). None of the 36 patients without a mural thrombus has had a spontaneous clinical embolus. Thus, the presence of a mural thrombus can be accurately identified in patients with acute myocardial infarction and predicted in a subgroup of those patients. Such patients should be considered for anticoagulation to prevent systemic embolization and should be followed with serial two-dimensional echocardiography.

Amiodarone-associated changes in human neutrophils.

Amiodarone and its major metabolite, desethylamiodarone, were measured in the plasma, white blood cells (WBCs) and red blood cells (RBCs) of 14 patients receiving chronic amiodarone therapy. The mean plasma concentrations (+/- standard error of the mean) of amiodarone and desethylamiodarone were 2.4 +/- 0.6 and 1.6 +/- 0.4 microgram/ml, respectively. The drug level in the WBCs was 62 +/- 12 micrograms/g protein during the early loading phase and 106 +/- 33 micrograms/g protein during maintenance phase of amiodarone therapy. Desethylamiodarone concentration in the WBCs was 42 +/- 18 and 190 +/- 33 micrograms/g protein during the loading and maintenance phases, respectively. Although a trend in WBC to plasma concentration was seen, there was no linear correlation between these levels. In 1 patient with severe neuropathy, biopsy of the nerve and muscle showed high concentrations of both amiodarone and desethylamiodarone. Although there was a decrease in tissue drug levels, proportionately high tissue:plasma drug levels were detected at the time of necropsy approximately 6.5 months after amiodarone was discontinued in this patient. Neutrophils from all patients receiving chronic amiodarone therapy showed multiple myelin-like polymorphic inclusion bodies (onionoid bodies) upon electron microscopic examination. Our observations suggest that WBC drug concentrations and electron microscopic changes may provide a means of correlating tissue concentrations and of following patients receiving chronic amiodarone therapy.

Mechanical failure (leaflet disruption) of a porcine aortic heterograft: rare cause of acute aortic insufficiency.

Use of the Hancock, glutaraldehyde-preserved, stented heterograft for aortic valve replacement has gained wide acceptance in the past 7 years. Nevertheless, very little is known about the long-term mechanical and pathological characteristics following implantation. A rare case is presented in which mechanical valve failure occurred secondary to leaflet disruption in the absence of infection 23 months after implantation. The literature is reviewed and the implications of this unusual complication are discussed.

Aberrant innervational pattern in Duane's syndrome type II without globe retraction.

Using extraocular muscle electromyography we studied a patient with an adduction defect and face turn. The patient was found to have an anomalous firing pattern in the medial and lateral rectus muscles consistent with Duane's syndrome type II but globe retraction was absent. On the basis of this finding we concluded that mechanical factors appear to play a significant role in the globe retraction seen in Duane's syndrome.

Magnetic resonance imaging of optic tract involvement in multiple sclerosis.

We studied two cases of optic tract involvement in multiple sclerosis with documentation by magnetic resonance imaging. In one, incongruous homonymous hemianopsia was accompanied by a decrease in visual acuity in one eye from chiasmal involvement. In the other, the involvement was restricted to the optic tract and the homonymous hemianoptic visual field defect was nearly congruous.

The prostate in pregnant and non-pregnant Praomys (Mastomys) Natalensis at the subcellular level.

The prostate of the pregnant Praomys appears more active than that of the non-pregnant Praomys. At the light microscopic level, the most obvious features are heightening of secretory cells and increased secretory product in acinar lumina. Apparent at the electron microscopic level are an increase and dilation of the rough endoplasmic reticulum, numerous scattered secretion granules, and a dilated Golgi apparatus. Therefore, stimulation of the gland is evident upon cytological evaluation and this increased activity may be due to the direct or indirect effects of androgenic stimulation.

Subcellular changes of rat myocardium after treatment with amiodarone or desethylamiodarone, studied with electron microscopy.

Amiodarone, an antiarrhythmic agent, has proven to be unique in its capability to control arrhythmias unresponsive to conventional drugs. However, its association with many undesirable side effects after chronic usage has become just as clear. Chronic clinical toxicity with amiodarone is associated with intracellular lamellar or myelinoid inclusion bodies (onionoid bodies or corpora cepiformia) in various organs (i.e. skin, cornea, lung, liver, and lymph nodes). Previous study has demonstrated formation of these inclusion bodies in canine myocardium following multiple doses of amiodarone. The present study was designed to develop a more convenient animal model, and to measure the concentration of amiodarone, as well as desethylamiodarone (its major metabolite) in this rodent model. The direct role of desethylamiodarone in formation of lamellar inclusion bodies in rat myocardium was also investigated. Amiodarone (50 mg/kg) or desethylamiodarone (25 mg/kg) was injected intraperitoneally daily for a period of 14 days. Myocardial sections revealed the presence of lamellar inclusion bodies, round or oval in appearance, in the form of laminated or concentrically arranged membranes after either amiodarone or desethylamiodarone treatment. This is the first reference to the induction of these myelinoid inclusion bodies with desethylamiodarone. Myocardial tissue concentrations of amiodarone and desethylamiodarone exceeding plasma concentrations were found in the present study and indicate the capability of these compounds to easily distribute and accumulate in the myocardium.

An evidence-based analysis of epidemiologic associations between lymphatic and hematopoietic cancers and occupational exposure to gasoline.

The presence of benzene in motor gasoline has been a health concern for potential increased risk of acute myelogenous leukemia and perhaps other lymphatic/hematopoietic cancers for approximately 40 years. Because of the widespread and increasing use of gasoline by consumers and the high exposure potential of occupational cohorts, a thorough understanding of this issue is important. The current study utilizes an evidence-based approach to examine whether or not the available epidemiologic studies demonstrate a strong and consistent association between occupational exposure to gasoline and lymphatic/hematopoietic cancers. Among 67 epidemiologic studies initially identified, 54 were ranked according to specific criteria relating to the relevance and robustness of each study for answering the research question. The 30 highest-ranked studies were sorted into three tiers of evidence and were analyzed for strength, specificity, consistency, temporality, dose-response trends and coherence. Meta statistics were also calculated for each general and specific lymphatic/hematopoietic cancer category with adequate data. The evidence-based analysis did not confirm any strong and consistent association between occupational exposure to gasoline and lymphatic/hematopoietic cancers based on the epidemiologic studies available to date. These epidemiologic findings, combined with the evidence showing relatively low occupational benzene vapor exposures associated with gasoline formulations during the last three decades, suggest that current motor gasoline formulations are not associated with increased lymphatic/hematopoietic cancer risks related to benzene.