Immunohistochemical and ultrastructural correlates of muscle-actin expression in pleomorphic adenomas and myoepitheliomas based on comparison of formalin and methanol fixation

Summary The degree and range of differentiation of the cells referred to as myoepithelial-like in pleomorphic adenomas and the tumour cells of myoepitheliomas are not definitely established. This type of information is critical for establishing reliable diagnostic criteria, such as expression of muscle-specific actin and ultrastructural identification of myofilaments, in these and other salivary gland tumours. Pleomorphic adenomas (18) and myoepitheliomas (5), of which 10 cases were fixed only in formalin and 13 cases where tissues were fixed in both formalin and methanol/acetic acid, were studied. Each tumour and normal accompanying parotid was immunostained with two monoclonal antibodies for smooth muscle actin, HHF35 and MSA. Staining of myoepithelial cells was absent in certain samples of normal gland with both HHF35 (15%) and MSA (69%) when formalin-fixed tissue was used. Using formalin-fixed tissue from 15 pleomorphic adenomas/myoepitheliomas, 2 (14%) had focal positivity with HHF35, while 8 cases (57%) were positive with MSA. However, a certain degree of false positivity was suspected since in samples of normal parotid, both acinar and duct cells were frequently stained, particularly with MSA. With methanol/ acetic acid-fixed tissue only 4 of 13 cases (31%) were positive with either MSA or HHF35 and 2 of these only had a minor proportion of the tumour cells expressing muscle-specific actin. Using alcohol-fixed tissue, myoepithelial cells were strongly stained in all examples of normal parotid gland with both anti-actin antibodies. In 5 cases examined by electron microscopy, there was no apparent correlation between immunohistochemical results and the presence or absence of cytoplasmic filament accumulation. The results indicate considerable tumour cell heterogeneity in muscle-specific actin expression and suggest that non-luminal cells in pleomorphic adenomas and the tumour cells in myoepitheliomas may differentiate as classical myoepithelial cells, as partially differentiated (i.e. modified myoepithelial cells) or as the counterpart of basal cells present in the intra- and interlobular ducts of normal salivary gland.     

Comparison of donor scores in bilateral lung transplantation—A large single-center analysis

Objectifying donor lung quality is difficult and currently there is no consensus. Several donor scoring systems have been proposed in recent years. They all lack large-scale external validation and widespread acceptance. A retrospective evaluation of 2201 donor lungs offered to the lung transplant program at the Medical University of Vienna between January 2010 and June 2018 was performed. Five different lung donor scores were calculated for each offer (Oto, ET, MALT, UMN-DLQI, and ODSS). Prediction of organ utilization, 1-year graft survival, and long-term outcome were analyzed for each score. 1049 organs were rejected at the initial offer (group I), 209 lungs declined after procurement (group II), and 841 lungs accepted and transplanted (group III). The Oto score was superior in predicting acceptance of the initial offer (AUC: 0.795; CI: 0.776–0.815) and actual donor utilization (AUC: 0.660; CI: 0.618–0.701). Prediction of 1-year graft survival was best using the MALT score, Oto score, and UMN-DLQI. Stratification of early outcome by MALT was significant for length of mechanical ventilation (LMV), PGD3 rates, ICU stay and hospital stay, and in-hospital-mortality, respectively. To the best of our knowledge, this study is the largest validation analysis comparing currently available donor scores. The Oto score was superior in predicting organ utilization, and MALT score and UMN-DLQI for predicting outcome after lung transplantation.     

Multipoint dilution hemofiltration: A new technology for maximum convective clearance

Convection-based renal replacement therapies (RRTs) have the potential to improve patient outcomes when compared to diffusion-based RRT such as hemodialysis (HD), but have limited clearance rates. We propose and characterize multipoint dilution hemofiltration (MPD-HF), a purely convective blood purification technology which removes the fundamental filtration limit associated with convective RRT resulting in clearance rates on par with HD. In MPD-HF, filtration of liquid and solutes occurs along the length of the hollow fibers that convey the blood, and substitution fluid is pushed into the fibers at multiple points along their length. Since multiple filtration and dilution steps are contained within one pass of the blood through the hollow fiber, the fraction of fluid that can be filtered may be increased to allow a high clearance rate that removes a wide range of toxins. In vitro tests yielded an average steady-state filtrate fraction of 68%, exceeding commercial HDF cartridge filtrate fractions by a factor of approximately 3. The molecular weights of molecules cleared spans up to the cutoff of 66 kDa for albumin.     

Medicare part D and antiretroviral therapy: issues for HIV clinicians

As of January 1, 2006, Medicare Plan D will add a drug benefit to Medicare, potentially affecting antiretroviral therapy for some 60,000 to 80,000 beneficiaries with HIV infection or AIDS. Health care providers should know the basic details of Plan D and how it may affect coverage for Medicare beneficiaries with or without a previous drug benefit under Medicaid. Steps may need to be taken to ensure that there are no lapses in antiretroviral therapy during the transition from one pharmacy plan to another. This article summarizes a presentation on Medicare Plan D and antiretroviral therapy for patients with HIV or AIDS, given by Laura W. Cheever, MD, at the 8th Annual Clinical Conference for Ryan White CARE Act clinicians in New Orleans in June 2005, and developed by Dr Cheever and Mary R. Vienna, RN.     

Biological prognostic factors for early stage completely resected non-small cell lung cancer

BACKGROUND AND OBJECTIVES: The different and unpredictable outcomes in early-stage non-small cell lung cancer patients requires urgent research concerning the biological pathway of this neoplasm. Our study investigated the frequency of expression and the clinicopathologic and prognostic significance of a series of biological markers in stage I and II resected non-small cell lung cancer. METHODS: A total of 99 cases of pathologic stage I and II were analyzed. The mean follow-up of surviving patients was 41 months. The expressions of the following biological markers were tested: bcl-2, p53, Ki-67, angiogenesis, and tumor vessel invasion. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical variables and biological markers using Cox's model for multivariate analysis. RESULTS: Tumoral vessel invasion was present in 22 (22%) pathologic samples, the angiogenesis mean value was 37 +/- 13, and median was 35; 13 (13%) patients showed positive immunostaining for bcl-2 oncoprotein. P53 oncoprotein expression was present in 48 patients (48.5%). All samples presented Ki-67 expression (mean value = 25.3 +/- 19.3, median = 20). The pathologic staging of the tumor was the most important independent prognostic factor for survival (P = 0.037) and for recurrence of disease (P = 0.040). Tumoral vessel invasion was the only marker with an independent predictive factor for survival and recurrence of disease in the group of patients without lymph node involvement (P = 0.02). CONCLUSION: Our data do not support a relevant prognostic role for p53, bcl-2, or Ki-67 immunohistochemical markers in non-small cell cancer. Tumor vessel invasion was an independent predictive factor of poor outcome in the group of patients without lymph node involvement. Pathological stage was confirmed as the most important independent prognostic factor.     

Survival in patients undergoing transjugular intrahepatic portosystemic shunt: ePTFE-covered stentgrafts versus bare stents

In patients with liver cirrhosis, implantation of a transjugular intrahepatic shunt (TIPS) leads to reduction of portal pressure, but not of mortality compared with other therapies. The high stenosis rates of conventional bare stents causes high reintervention rates and costs and may be correlated with poor survival. ePTFE-covered stentgrafts provide much improved patency rates, but their impact on survival is unclear. All suitable patients receiving either bare TIPS (419/466) or undergoing implantation of ePTFE endoprostheses (89/100) in several centers in Austria up to 2002 were included in this retrospective analysis. Both patient groups were compared regarding survival with Kaplan-Meier and Cox regression analysis. Unmatched and 1:1-matched survival analyses were performed. Patients undergoing ePTFE stentgraft implantation had significantly higher survival rates in all analyses. The 3-month, 1-year, and 2-year survival rates were 93%, 88%, and 76% for the ePTFE-group and 83%, 73%, and 62% for conventional TIPS patients, respectively. The matched survival analyses validated these findings. The model of the stent, patient age, and Child-Pugh Class (CPC) were independent predictors of survival. In conclusion, patients undergoing ePTFE-endoprosthesis implantation had higher survival rates within 2 years after TIPS-implantation. This may be the result of improved patency rates after correct placement (up to the inferior caval vein [ICV]) of the ePTFE stentgraft. These data should be validated in a prospective series.