The utility of EUS and EUS-guided fine needle aspiration in detecting celiac lymph node metastasis in patients with esophageal cancer: a single-center experience.

BACKGROUND: The aims of this study were to determine the utility of EUS and EUS-guided fine needle aspiration (EUS-FNA) in the detection and confirmation of celiac lymph node metastasis in patients with esophageal cancer and to define EUS features predictive of celiac lymph node metastasis in these patients. METHODS: The records of 211 patients with esophageal cancer who underwent EUS staging were reviewed. The operating characteristics of EUS were determined in patients where either surgery, EUS-FNA of a celiac lymph node, or both were performed (n = 102). The association between selected variables and the presence of celiac lymph node metastasis was evaluated by univariate and multivariable analyses. RESULTS: EUS in 48 patients provided a true-positive diagnosis of celiac lymph node involvement, a false-positive and false-negative result, respectively, in 6 and 14 patients, and a true-negative diagnosis in 34 patients. The sensitivity of EUS in detecting celiac lymph node was 77% (95% CI [67, 88]), specificity 85% (95% CI [74, 96]), negative predictive value 71% (95% CI [58, 84]), and the positive predictive value 89% (95% CI [81, 97]). EUS-FNA was performed in 94% (51/54) of patients with celiac lymph nodes. The accuracy of EUS-FNA in detecting malignant celiac lymph nodes was 98% (95% CI [90, 100]). Advanced T-stage, the need for dilation, detection of peritumoral lymph nodes, and black race were associated with celiac lymph node involvement. In multivariable analysis, advanced T-stage was the strongest predictor of celiac lymph node involvement. CONCLUSION: EUS and EUS-FNA are highly accurate in detecting and confirming celiac lymph nodes metastasis. Depth of tumor invasion as assessed by EUS is a strong predictor of celiac lymph node metastasis in patients with esophageal cancer.     

Use of plain radiography to screen for cervical spine injuries.

STUDY OBJECTIVE: Standard radiographic screening may fail to reveal any evidence of injury in some patients with spinal injury. The purposes of this investigation were to document the efficacy of standard radiographic views and to categorize the frequencies and types of injuries missed on plain radiographic screening of the cervical spine. METHODS: All patients with blunt trauma selected for radiographic cervical spine imaging at 21 participating institutions underwent a standard 3-view series (cross-table lateral, anteroposterior, and odontoid views), as well as any other imaging deemed necessary by their physicians. Injuries detected with screening radiography were then compared with final injury status for each patient, as determined by review of all radiographic studies. RESULTS: The study enrolled 34,069 patients with blunt trauma, including 818 patients (2.40% of all patients; 95% confidence interval [CI] 2.40% to 2.40%) having a total of 1,496 distinct cervical spine injuries. Plain radiographs revealed 932 injuries in 498 patients (1.46% of all patients; 95% CI 1.46% to 1.46%) but missed 564 injuries in 320 patients (0.94% of all patients; 95% CI 0.94% to 0.94%). The majority of missed injuries (436 injuries in 237 patients [representing 0.80% of all patients]; 95% CI 0.80% to 0.80%) occurred in cases in which plain radiographs were interpreted as abnormal (but not diagnostic of injury) or inadequate. However, 23 patients (0.07% of all patients; 95% CI 0.05% to 0.09%) had 35 injuries (including 3 potentially unstable injuries) that were not visualized on adequate plain film imaging. These patients represent 2.81% (95% CI 1.89% to 3.63%) of all injured patients with blunt trauma undergoing radiographic evaluation. CONCLUSION: Standard 3-view imaging provides reliable screening for most patients with blunt trauma. However, on rare occasions, such imaging may fail to detect significant unstable injuries. In addition, it is difficult to obtain adequate plain radiographic imaging in a substantial minority of patients.     

The anatomical distribution of colorectal polyps at colonoscopy

BACKGROUND: Colorectal carcinoma is one of the most common causes of cancer-related deaths in Australia. The distribution of polyps in the colon may effect the efficacy of a screening modality. The aim of this study was to determine the age-matched anatomic location and histologic type of colorectal polyps observed at colonoscopy over a 10-year period at our endoscopy unit. STUDY: Endoscopy reports on 2,578 patients were reviewed; polyp/lesion histology and location (left, right, or both) were determined in 2,553. RESULTS: Of all polyps observed, 1,310 (51%) cases were left-sided, 510 (20%) were right-sided, and 733 (29%) were synchronous. Adenomas were present in 1,659 cases (65%); of these, 734 (44%) were left-sided only and 405 (24.5%) were right-sided only. Carcinoma was observed in 189 (7%) cases, of which 71 (37.5%) were left-sided only. There was an increased right-sided prevalence of adenoma or carcinoma with age (p = 0.0029). CONCLUSION: This was not a screening study, but it has shown that a significant number of adenomas and carcinomas lie proximal to the splenic flexure. Thus, in the absence of left-sided lesions, it is expected that examination of the colon limited to the splenic flexure would miss 23% of such lesions. The increasing right-sided prevalence of these lesions with age suggests that evaluation of the proximal bowel is particularly important in older people.     

Spatial-temporal imaging of bacterial infection and antibiotic response in intact animals

We describe imaging the luminance of green fluorescent protein (GFP)-expressing bacteria from outside intact infected animals. This simple, nonintrusive technique can show in great detail the spatial-temporal behavior of the infectious process. The bacteria, expressing the GFP, are sufficiently bright as to be clearly visible from outside the infected animal and recorded with simple equipment. Introduced bacteria were observed in several mouse organs including the peritoneal cavity, stomach, small intestine, and colon. Instantaneous real-time images of the infectious process were acquired by using a color charge-coupled device video camera by simply illuminating mice at 490 nm. Most techniques for imaging the interior of intact animals may require the administration of exogenous substrates, anesthesia, or contrasting substances and require very long data collection times. In contrast, the whole-body fluorescence imaging described here is fast and requires no extraneous agents. The progress of Escherichia coli-GFP through the mouse gastrointestinal tract after gavage was followed in real-time by whole-body imaging. Bacteria, seen first in the stomach, migrated into the small intestine and subsequently into the colon, an observation confirmed by intravital direct imaging. An i.p. infection was established by i.p. injection of E. coli-GFP. The development of infection over 6 h and its regression after kanamycin treatment were visualized by whole-body imaging. This imaging technology affords a powerful approach to visualizing the infection process, determining the tissue specificity of infection, and the spatial migration of the infectious agents.     

Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in northeastern Irian Jaya, Indonesia.

Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium falciparum malaria. We conducted a hospital-based 28-day in vivo test comparing chloroquine/doxycycline to chloroquine or doxycycline alone for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya, Indonesia. Eighty-nine patients with uncomplicated falciparum malaria were randomized to standard dose chloroquine (n = 30), doxycycline (100 mg every 12 hours [7 days], n = 20), or chloroquine with doxycycline (n = 39); corresponding numbers for vivax malaria (n = 63) were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI/RII/RIII). Of the 105 evaluable patients, chloroquine/doxycycline cured (S) 20/22 (90.9% [95% CI 78.9-100%]) patients with P. falciparum malaria; 2/22 (9.1% [0-21%]) were RIII resistant. Doxycycline cured 11/17 (64.7% [42.0-87.4%]) patients, and chloroquine 4/20 (20% [2.5-37.5%]). Against P. vivax, chloroquine/doxycycline cured (S) 12/17 (70.6% [48.9-92.2%]) patients, doxycycline 4/12 (33.3% [6.6-59.9%]), and chloroquine 5/17 (29.4% [7.7-51.1%]). Chloroquine/doxycycline was effective against P. falciparum but only modestly effective against P. vivax. These findings support the use of chloroquine/doxycycline as an inexpensive alternative to mefloquine for treating chloroquine-resistant P. falciparum but not chloroquine-resistant P. vivax in this setting.     

Rapid, real-time detection of acute HIV infection in patients in Africa

BACKGROUND: We conducted a prospective study to evaluate methods of detecting clients with sexually transmitted diseases (STDs) who were acutely coinfected with human immunodeficiency virus (HIV) in Lilongwe, Malawi. METHODS: After informed consent was obtained, all clients with acute STDs were offered voluntary HIV counseling and testing by 2 rapid antibody tests. Samples from rapid test-negative or -discordant subjects were pooled (50 : 5 : 1) and tested for HIV RNA. Western blots were performed on all rapid test-discordant specimens with detectable HIV RNA. A subset of specimens received p24 antigen testing with standard and/or ultrasensitive methods. Patients with possible acute HIV infection were followed to confirm seroconversion. RESULTS: A total of 1450 clients (34% female and 66% male) agreed to testing, of whom 588 (40.55%) had established HIV infection and 21 (1.45%) had acute infection. Discordant rapid antibody tests identified 7 of 21 (33.3% sensitivity), standard p24 antigen identified 12 of 16 (75% sensitivity), and ultrasensitive p24 antigen identified 15 of 17 (88% sensitivity) acute cases. By definition, the sensitivity of the RNA assay was 100%. CONCLUSIONS: Real-time pooled RNA testing for the detection of acute HIV infection is feasible in resource-limited settings. However, parallel rapid testing and p24 antigen testing are technologically simpler and together may detect approximately 90% of acute cases.     

Role of gadd45 in myeloid cells in response to hematopoietic stress

The gadd45 family of genes is rapidly induced by different stressors, including differentiation-inducing cytokines, and there is a large body of evidence that their cognate proteins are key players in cellular stress responses. Induction of gadd45 genes at the onset of myeloid differentiation suggested that Gadd45 protein(s) play a role in hematopoiesis, yet no apparent abnormalities were observed in either the bone marrow or peripheral blood compartments of mice deficient for either gadd45a or gadd45b. However, under conditions of hematological stress, including acute stimulation with cytokines, myelo-ablation and inflammation, both gadd45a-deficient and gadd45b-deficient mice exhibited deficiencies. This topic is discussed within the context of what is known about Gadd45 proteins in stress signaling, hematopoietic development and the innate immune response.     

A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors

An array of cell-surface antigens expressed by human cancers have been identified as targets for antibody-based therapies. The great majority of these antibodies do not have specificity for cancer but recognize antigens expressed on a range of normal cell types (differentiation antigens). Over the past two decades, our group has analyzed thousands of mouse monoclonal antibodies for cancer specificity and identified a battery of antibodies with limited representation on normal human cells. The most tumor-specific of these antibodies is 806, an antibody that detects a unique epitope on the epidermal growth factor receptor (EGFR) that is exposed only on overexpressed, mutant, or ligand-activated forms of the receptor in cancer. In vitro immunohistochemical specificity analysis shows little or no detectable 806 reactivity with normal tissues, even those with high levels of wild-type (wt)EGFR expression. Preclinical studies have demonstrated that 806 specifically targets a subset of EGFR expressed on tumor cells, and has significant anti-tumor effects on human tumor xenografts, primarily through abrogation of signaling pathways. The present clinical study was designed to examine the in vivo specificity of a chimeric form of mAb 806 (ch806) in a tumor targeting/biodistribution/pharmacokinetic analysis in patients with diverse tumor types. ch806 showed excellent targeting of tumor sites in all patients, no evidence of normal tissue uptake, and no significant toxicity. These in vitro and in vivo characteristics of ch806 distinguish it from all other antibodies targeting EGFR.     

Focal organizing pneumonia on surgical lung biopsy: causes, clinicoradiologic features, and outcomes

BACKGROUND: Organizing pneumonia (OP) is a histologic pattern that is morphologically distinctive but nonspecific and can be seen in diverse clinical settings. Focal OP has been described as a discrete form of OP, but relatively little is known regarding this clinicopathologic entity. METHODS: We sought to clarify the clinicoradiologic presentation, underlying causes, and outcomes associated with focal OP by retrospectively reviewing 26 consecutive cases diagnosed by surgical lung biopsy over an 8-year period from January 1, 1997, to December 31, 2004. RESULTS: All patients presented with an unifocal opacity detected on chest radiography (20 patients) or CT scans (6 patients). At the time of presentation, 10 patients (38%) had symptoms, including cough, shortness of breath, or chest pain; 16 patients were asymptomatic. Contrast-enhancement CT scanning or positron emission tomography (PET) scan was performed in 11 patients, and the results were positive in all. Surgical procedures included wedge resection in 21 patients (81%), segmentectomy in 3 patients (11%), and lobectomy in 2 patients (8%). Three case of focal OP (12%) were related to infections, but the remaining cases were cryptogenic. Follow-up over a median interval of 11 months (range, 1 to 71 months) yielded no recurrence of OP. CONCLUSIONS: The radiologic features of focal OP are often indistinguishable from those of lung cancer, and include positivity on contrast-enhancement CT scan and PET scan. Most cases of focal OP are cryptogenic, and infection is identified in a minority of cases. Surgical resection alone appears to suffice in the management of cryptogenic focal OP.