Blast phase in chronic myelogenous leukemia is skewed toward unusual blast types in patients treated with tyrosine kinase inhibitors: a comparative study of 67 cases.

OBJECTIVES: To compare the features of the blast phase of chronic myelogenous leukemia (CML) in patients treated with tyrosine kinase inhibitors (TKIs) with those in the pre-TKI era. METHODS: Sixty-seven patients with blast phase CML were identified in the Duke Pathology database from 1991 to 2011. The morphology and immunophenotype of blasts were evaluated, along with cytogenetic studies and associated findings in the peripheral blood and bone marrow. RESULTS: In the TKI era, the blasts were more frequently of a type other than the usual myeloid or lymphoid types when compared with the pre-TKI era. Blast phase in TKI-treated patients was associated with a higher peripheral WBC count and a lower blast percentage in the bone marrow. Of the 23 patients with cytogenetic studies during blast phase, additional cytogenetic changes more frequently occurred in patients with an unusual blast type, and some patients showed these changes months before the onset of blast phase. CONCLUSIONS: Blast phase CML in TKI- and non-TKI-treated patients differs in the morphology and immunophenotype of blasts, cytogenetic findings, and associated findings in the peripheral blood and bone marrow.

Developing patient-friendly genetic and genomic test reports: formats to promote patient engagement and understanding.

With the emergence of electronic medical records and patient portals, patients are increasingly able to access their health records, including laboratory reports. However, laboratory reports are usually written for clinicians rather than patients, who may not understand much of the information in the report. While several professional guidelines define the content of test reports, there are no guidelines to inform the development of a patient-friendly laboratory report. In this Opinion, we consider patient barriers to comprehension of lab results and suggest several options to reformat the lab report to promote understanding of test results and their significance to patient care, and to reduce patient anxiety and confusion. In particular, patients' health literacy, genetic literacy, e-health literacy and risk perception may influence their overall understanding of lab results and affect patient care. We propose four options to reformat lab reports: 1) inclusion of an interpretive summary section, 2) a summary letter to accompany the lab report, 3) development of a patient user guide to be provided with the report, and 4) a completely revised patient-friendly report. The complexity of genetic and genomic test reports poses a major challenge to patient understanding that warrants the development of a report more appropriate for patients.

Histopathologic and immunohistochemical sequelae of bariatric embolization in a porcine model.

PURPOSE: To evaluate the histopathologic sequelae of bariatric embolization on the gastric mucosa and to correlate with immunohistochemical evaluation of the gastric fundus, antrum, and duodenum. MATERIALS AND METHODS: This study was performed on 12 swine stomach and duodenum specimens after necropsy. Of the 12 swine, 6 had previously undergone bariatric embolization of the gastric fundus, and the 6 control swine had undergone a sham procedure with saline. Gross pathologic, histopathologic, and immunohistochemical examinations of the stomach and duodenum were performed. Specifically, mucosal integrity, fibrosis, ghrelin-expressing cells, and gastrin-expressing cells were assessed. RESULTS: Gross and histopathologic evaluation of treatment animals showed healing or healed mucosal ulcers in 50% of animals, with gastritis in 100% of treatment animals and in five of six control animals. The ghrelin-immunoreactive mean cell density was significantly lower in the gastric fundus in the treated animals compared with control animals (15.3 vs 22.0, P < .01) but similar in the gastric antrum (9.3 vs 14.3, P = .08) and duodenum (8.5 vs 8.6, P = .89). The gastrin-expressing cell density was significantly lower in the antrum of treated animals compared with control animals (82.2 vs 126.4, P = .03). A trend toward increased fibrosis was suggested in the gastric fundus of treated animals compared with controls (P = .07). CONCLUSIONS: Bariatric embolization resulted in a significant reduction in ghrelin-expressing cells in the gastric fundus without evidence of upregulation of ghrelin-expressing cells in the duodenum. Healing ulcerations in half of treated animals underscores the need for additional refinement of this procedure.

Bariatric embolization for suppression of the hunger hormone ghrelin in a porcine model.

PURPOSE: To prospectively test in a porcine model the hypothesis that bariatric embolization with commercially available calibrated microspheres can result in substantial suppression of systemic ghrelin levels and affect weight gain over an 8-week period. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. Twelve healthy growing swine (mean weight, 38.4 kg; weight range, 30.3-47.0 kg) were evaluated. Bariatric embolization was performed by infusion of 40-µm calibrated microspheres selectively into the gastric arteries that supply the fundus. Six swine underwent bariatric embolization, while six control animals underwent a sham procedure with saline. Weight and fasting plasma ghrelin and glucose levels were obtained in animals at baseline and at weeks 1-8. Statistical testing for differences in serum ghrelin levels and weight at each time point was performed with the Wilcoxon signed rank test for intragroup differences and the Wilcoxon rank sum test for intergroup differences. RESULTS: The pattern of change in ghrelin levels over time was significantly different between control and experimental animals. Weekly ghrelin levels were measured in control and experimental animals as a change from baseline ghrelin values. Average postprocedure ghrelin values increased by 328.9 pg/dL ± 129.0 (standard deviation) in control animals and decreased by 537.9 pg/dL ± 209.6 in experimental animals (P = .004). The pattern of change in weight over time was significantly different between control and experimental animals. The average postprocedure weight gain in experimental animals was significantly lower than that in control animals (3.6 kg ± 3.8 vs 9.4 kg ± 2.8, respectively; P = .025). CONCLUSION: Bariatric embolization can significantly suppress ghrelin and significantly affect weight gain. Further study is warranted before this technique can be used routinely in humans.

Reproducibility of left atrial ablation with high-intensity focused ultrasound energy in a calf model.

OBJECTIVE: Achieving transmural tissue ablation might be necessary for successful treatment of atrial fibrillation. The purpose of this study was to evaluate the reproducibility of transmural left atrial ablation using a high-intensity focused ultrasound energy system in a calf model. METHODS: Nine heparinized bovines underwent a beating-heart left atrial ablation with a single application of the high-intensity focused ultrasound device. All animals were acutely killed, and the left atrium was fixed in formalin. Protocolized histological sections (5 µm) were obtained throughout each lesion and prepared with Masson trichrome and hematoxylin and eosin staining. Measurements were performed on a total of 359 slides from the 9 lesions. In addition, fresh left atrial tissues from 18 unused human donor hearts that did not meet the criteria for cardiac transplantation were measured at the site where the high-intensity focused ultrasound device is normally applied. RESULTS: Calf left atrial thickness ranged between 2.5 and 20.1 mm, with a mean of 9.10 mm. High-intensity focused ultrasound ablation consistently produced a 100% transmural lesion in left atrial thickness up to 6 mm. In addition, a transmural lesion was observed in 91% of tissues that were up to 10 mm thick and in 85% that were up to 15 mm thick. Human left atrial thickness ranged between 1.2 to 6 mm, with a mean of 3.7 mm. CONCLUSIONS: Calf left atrial thickness in this study was greater than human left atrial thickness. Human left atrial thickness is generally less than 6 mm, and in this range high-intensity focused ultrasound ablation achieved 100% transmurality. These histological results might correlate with a high success rate of atrial fibrillation ablation by using the high-intensity focused ultrasound system.