Analysis of morphologic patterns of fine-needle aspiration of the breast to reduce false-negative results in breast cytology

BACKGROUND: The identification of specific morphologic diagnostic criteria is of paramount importance to optimize the accuracy of fine-needle aspiration cytology (FNAC) and to reduce the rate of false-negative results. In the current study, the authors reviewed a consecutive series of false-negative findings observed in the study center to define the presence and degree of cytologic abnormalities. False-negative cases were randomly mixed with true-negative cases and were reviewed by a panel of expert readers in a blinded fashion. The main objective of the current study was to identify a morphologic pattern that may permit the reduction of false-negative findings while maintaining the specificity of FNAC. METHODS: A blind review of a set of 41 consecutive false-negative and 49 true-negative breast aspiration samples was performed by a panel of 10 expert cytologists who were asked to give a final report and to classify the samples according to classic morphologic parameters. RESULTS: The majority final report sensitivity was 54% (range, 19-61%) and specificity was 73% (range, 65-92%). The average concordance with the majority report, adjusted for chance agreement (kappa statistic), was moderate at 0.54 (range, 0.40-0.65). Enlarged nuclear size, a hyperchromatic nucleus, the absence of naked nuclei, and the absence of apocrine metaplasia were reported more frequently in carcinoma cases, although not to a significant extent. The only variable found to be associated significantly (P = 0.041) with a diagnosis of carcinoma was the presence of microcalcifications, which nevertheless were found to occur in only a minority of carcinoma cases (7 of 41 cases) or controls (2 of 49 controls). Multivariate analysis demonstrated that the presence of microcalcifications (odds ration [OR] of 3.0; 95% confidence interval [95% CI], 1.2-7.4), the absence of naked nuclei (OR of 2.4; 95% CI, 1.3-4.4), and enlargement of the nucleus (OR of 1.9; 95% CI, 1.1-3.4) were all independently associated with false-negative findings. Diagnostic accuracy using a morphology-based score did not appear to improve the results substantially compared with the final report (sensitivity of 0.46 vs. 0.54 [P = 0.508] and a specificity of 0.80 vs. 0.73 [P = 0.218]). CONCLUSIONS: The results of the current study confirm that breast FNAC false-negative results are at least partially the result of underreporting of abnormalities that may be noted at review. Detailed analysis of a single morphologic characteristic was found to be of limited diagnostic value, suggesting that operators do perceive abnormalities but cannot translate these findings into distinct morphologic categories.     

Increased levels of circulating endothelial cells in chronic periaortitis as a marker of active disease

BACKGROUND: The pathogenesis of chronic periaortitis (CP) has not been clarified. The histologic features and the association with autoimmune diseases suggest an immune-mediated disorder with marked inflammatory vascular and perivascular lesions. To clarify the role of vascular damage we looked for the presence and the surface phenotype of circulating endothelial cells (CECs) in the peripheral blood of patients with chronic periaortitis. METHODS: Eleven patients with CP were evaluated for the presence of CECs; 9 patients had active and 2 inactive disease. Three patients with active disease were also evaluated 3 months after therapy. Ten atherosclerotic patients, 10 patients with renal insufficiency of variable degree and etiology, and 40 healthy subjects were evaluated as controls. Five-parameter, 3-color flow cytometry was performed with a FACScan. CECs were defined as CD45 negative, CD31, P1H12, and CD36 positive, and activated CECs as CD45 negative and P1H12, CD62 positive. RESULTS: The median number of CECs in patients with CP (10(6) cells/mL) was significantly higher than in healthy controls (16 cells/mL, P= 0.0004) and atherosclerotic patients (25 cells/mL, P= 0.0005) Two patients with inactive disease had a CEC count comparable to that of normal subjects. In 2 of the 3 patients reevaluated, 3 months after therapy CEC numbers normalized. Almost all CECs were microvascular in origin and showed an activated phenotype. CONCLUSION: The presence of a high number of CECs in the active phase of chronic periaortitis and their normalization during inactive disease suggest that endothelial damage may play a role in the pathogenesis of the disease.     

Effects of surgical repair of congenital diaphragmatic hernia on cerebral hemodynamics evaluated by near-infrared spectroscopy

Background

Cardiorespiratory stabilization is recommended before surgical repair of congenital diaphragmatic hernia (CDH) because surgery may induce a transitory deterioration of chest compliance and gas exchange. It is not known if surgical intervention can affect cerebral circulation and oxygenation.

Aim

The aim of the study was to assess noninvasively, by near-infrared spectroscopy, the possible changes in cerebral hemodynamics and oxygenation associated with surgical repair of CDH.

Subjects

Twenty-five newborns with severe CDH (birth weight, 3057 ± 354 g; gestational age, 37.8 ± 1.8 weeks; male/female newborns, 15/10; left/right CDH, 19/6) were sedated, paralyzed, and mechanically ventilated by conventional gentle ventilation and surgically corrected at a median age of 2.7 days (min-max, 2-14 days) after cardiorespiratory stabilization.

Methods

Heart rate (HR [beats per minute]), preductal transcutaneous oxygen saturation (tcSao₂ [%]), carbon dioxide tension (tcPco₂ [Torr]), and mean arterial blood pressure (mm Hg) were continuously monitored. Inspired fractional oxygen concentration (Fio₂) was adjusted to maintain and preductal tcSao₂ of greater than 80%, whereas the ventilator's settings were kept unchanged throughout the surgical procedure. Cerebral hemodynamics was assessed by near-infrared spectroscopy (NIRO 300, Hamamatsu Photonics, Japan), recording continuously and noninvasively the relative changes in concentration of oxygenated (ΔO₂Hb [μmol/L]), deoxygenated (ΔHHb [μmol/L]), and total (ΔtHb [μmol/L]) hemoglobin; the tissue oxygenation index (TOI [%]) was also calculated (TOI = O₂Hb/O₂Hb + HHb). Total hemoglobin concentration is considered to be representative of cerebral blood volume. Arterial blood gases were also measured at the beginning (T₁) and at the end of surgery (T₂). For all measurements, results at T₁ and at T₂, as well as the differences between T₁ and T₂, have been expressed as means or medians and SDs or 95% confidence intervals or ranges. The differences between T₁ and T₂ were considered statistically significant for a P value of less than .05 by the Student t test for paired values.

Results

At T₁, mean tcSao₂% was 94.1 % (SD, 4.6) with a Fio₂ of 0.25 (SD, 0.1); at T₂, to obtain similar values of tcSao₂ (93.4%; SD, 4.4), it was necessary to increase the Fio₂ to 0.37 (SD, 0.14; P < .001). Mean HR at T₁ was 149.5 beats per minute (SD, 9.1) and increased significantly (P < .05) at T₂ (165.2 beats per minute; SD, 14.2). Mean arterial blood pressure was 54.7 mm Hg (SD, 7.7) at T₁ and did not change appreciably at T₂ (55.6 mm Hg; SD, 8.1). Moreover, tcPco₂ did not change significantly during the procedure (mean tcPco₂ = 49.9 Torr [SD, 12.8] at T₁ and 57.3 mm Hg [SD, 17.9] at T₂). O₂Hb and tHb decreased (P < .001 and <.005) and HHb increased (P < .05) significantly during the surgical procedure (mean Δ [SD]: ΔO₂Hb= −10.9 μmol/L [9.7], ΔtHb = −7.5 μmol/L [11.7], and ΔHHb = −3.5 μmol/L [6.8]). Mean TOI was 70% at T₁ (normal values >60%) and decreased significantly at T₂ (mean ΔTOI = −6.1% [SD, 10.6]). In all infants, the greatest changes occurred when the viscera were positioned into the abdomen.

Conclusions

Notwithstanding the initial cardiorespiratory stabilization, surgical repair of CDH was associated with a rise in HR and oxygen requirement and a drop in cerebral tHb and O₂Hb, suggesting a reduction in cerebral blood volume and oxygenation. These events were probably due to the combined effects of an increase in right to left shunting (as indicated by the increased oxygen requirement) and a decrease in venous return (possibly due to compression of the inferior vena cava by the viscera positioned into the abdomen). These preliminary results reinforce the importance of achieving a good cardiorespiratory stability before undertaking surgical correction of CDH to minimize the possible interference of the procedure with cerebral circulation and oxygenation.     

Predictors of cardiovascular death in ESRD

End stage renal disease (ESRD) is a situation with a cardiovascular risk profile of almost unique severity. While traditional risk factors dominate the scene in the general population, non traditional risk factors like inflammation (high C Reactive Protein, CRP), high brain natriuretic peptide, as an expression of left ventricular hypertrophy and left ventricular dysfunction, and accumulation of the endogenous inhibitor of the NO synthase, asymmetric dimethyl arginine are all markers of high CV risk of ESRD patients. To obtain a quantitative insight on the predictive power of traditional and emerging risk factors in ESRD, we performed a detailed multivariate survival analysis in the cardiovascular risk extended evaluation (CREED) cohort database. As expected, traditional risk factors (ie, age, sex, smoking, diabetes, and risk factors peculiar to the uremic state such as low serum albumin level) and treatment modality contributed to explain the all-cause mortality (37%) and cardiovascular variation mortality (24%) variation as well. When cardiovascular comorbidities were considered in this analysis, the explained variation in mortality increased to 45.4% and 36.4%, respectively. Furthermore, a combined score based on 2 biomarkers (brain natriuretic peptide and C-reactive protein levels) increased the explanatory power of these models by about 10%. In conclusion, traditional risk factors explain about half of all-cause and cardiovascular mortality variation in the ESRD population. The combined use of 2 biomarkers reflecting inflammation and left ventricular mass and function increases by about one fifth the explained mortality variation in this population. Biomarkers give information beyond that provided by traditional risk factors and therefore represent an useful adjunct for the definition of the risk profile of ESRD patients.     

Monitoring of chemical elements and oxidative damage in patients affected by Alzheimer's disease

The haematic concentration of 26 metals and the oxidative damage in 60 patients (20 males and 40 females) affected by Alzheimer's disease and 44 healthy individuals (33 males and 11 females) were compared. In patients, the following significant (p < or = 0.05) discrepancies were found: i) increment of Ca, Cd, Hg, Mg, Si and Sn, and decrement of Al, Co, Fe and Zn in serum; ii) higher concentrations of Cu, Li, Mn, Sn and Zr and lower of Fe, Hg, Mo in blood; iii) overproduction of oxidant species (SOS) and decrease of the anti-oxidant capacity (SAC) (p < or = 0.001, for both). Variables that, joined, better discriminated between patients and controls resulted to be Si, SOS, SAC, Co, Ca, Al in serum (94% of cases correctly classified) and Cu, Zr, Mo and Fe in blood (90% of cases properly categorized).     

Quantitative assay of total dsDNA with PicoGreen reagent and real-time fluorescent detection

We describe a quantitative assay of dsDNA based on real-time PCR measurement of fluorescence due to the interaction of PicoGreen dye with dsDNA. An aliquot of 1 to 5 ml of the sample is mixed with 45 ml of diluted PicoGreen reagent within an optical PCR tube. This is placed into the real-time apparatus set to read SYBR Green I dye at the end of three cycles of 94 degrees C for 30 s and 65 degrees C for 30 s. The averaged fluorescence value is converted into DNA amount using a calibration curve prepared with lambda-DNA standard. The calibration curve has a dynamic linear range from 0.20 to 50 ng and a standard deviation variability below 5.0%. In conclusion, this method allows reliable determinations on minimal amounts of DNA from biological samples and PCR products in clinical applications of molecular biology.     

Cluster cases of malignant pleural mesothelioma in an oil factory

BACKGROUND: The traditional occupational hazards of the productive cycle of oils are attributable to chemicals (use of solvents, pesticides and other agents), dusts, labour accidents (trauma, ignition, explosion), noise, manual lifting, work organization and hot-wet microclimate. The latest risk is due to the use of high temperatures (from 50 up to 250 degrees C) during the processes of extraction with solvent and refining. No cases are reported in literature of asbestos related disease in subjects who worked in oil factories. Nevertheless the structure and organization of the workplace, which is similar to that of sugar refineries, where cases of malignant mesothelioma have been described (moreover in workers employed in running and maintenance of the plants), led to the assumption that even in oil factories asbestos for the insulation of pipes and boilers could be present. OBJECTIVES: To describe 3 cases of Malignant Mesothelioma that occurred in workers of the same oil factory. METHODS: Since this occupational sector is not conventionally known for asbestos exposure the Local Health Unit and the Lombardy Mesothelioma Registry decided to investigate this industrial plant. RESULTS: Following examination of the archives of the Local Health Unit and inspection of the plant, an environmental asbestos contamination (pipes and boilers) was found. The 3 cases were defined as occupational disease and the required legal procedures were initiated. This underlines the importance of close cooperation with Local Health Units of occupational medicine and the Regional Mesothelioma Registry in the study and acknowledgment of cases which would otherwise not have been recognized, with consequent loss of precious information.     

Low triiodothyronine: a new facet of inflammation in end-stage renal disease

Because inflammation influences thyroid function, it was hypothesized that low plasma free triiodothyronine (fT3) in ESRD may be an unsuspected expression of the inflammatory state of these patients. This study investigated (1) the steady-state relationship between fT3 and inflammation markers (IL-6 and C-reactive protein) and markers of endothelial activation (intercellular adhesion molecule-1 [ICAM-1] and vascular cellular adhesion molecule-1 [VCAM-1]) in 200 hemodialysis (HD) patients and (2) the effect of intercurrent acute inflammatory/infectious processes on plasma fT3 in a group of 17 patients with chronic kidney disease (CKD). HD patients displayed lower (P < 0.001) plasma fT3 than healthy subjects (n = 31) and clinically euthyroid patients with chronic diseases and normal renal function (n = 262). When HD patients were subdivided into IL-6 tertiles, fT3 was progressively lower across tertile increments (P < 0.001). Accordingly, regression analysis showed strong and inverse associations (P < or = 0.002) between fT3 and IL-6, C-reactive protein, ICAM-1, and VCAM-1, and, with the exception of the ICAM-fT3 relationship, these associations remained highly significant (P < or = 0.004) in multiple regression analyses adjusting for demographic variables, risk factors, and other potential confounders. In patients who had CKD and were studied during intercurrent inflammatory/infectious processes, fT3 was significantly lower (P = 0.008) at the zenith of inflammation than after its resolution. Low circulating fT3 is frequently observed in inflammatory illnesses, and the same association exists in patients with CKD and in ESRD. This association may entail a causal link because fT3 is acutely and reversibly suppressed in patients with CKD during inflammatory processes triggered by intercurrent infections.     

Transient facial nerve paralysis after mandibular sagittal osteotomy

Facial nerve injuries are rare complications after orthognathic surgery. A literature review shows that such damages can develop with various mechanisms and are usually transient. Two cases of delayed facial paralysis after mandibular osteotomy with spontaneous recovery are reported.     

Procalcitonin is useful whereas C-reactive protein is not, to predict complications following coronary artery bypass surgery

BACKGROUND: The respective value of procalcitonin (PCT) and C-reactive protein (CRP) as markers of postoperative complications after coronary bypass surgery is unclear. Therefore, complications during one week after surgery were studied to evaluate the predictive role of PCT and CRP changes during the immediate postoperative period. METHODS: Thirty-two patients, in whom an uneventful immediate postoperative course was anticipated, were prospectively enrolled and followed-up to the 7th postoperative day. At the end of the follow-up, patients were divided into two groups. Group A were patients with an uncomplicated postoperative course and Group B were patients with a complicated postoperative course. RESULTS: Serum samples were drawn for PCT and CRP determination after induction of anesthesia (baseline), at the end of surgery and daily until postoperative day 2. Baseline serum PCT concentrations were 0.11 +/- 0.09 and 0.20 +/- 0.21 ng/mL in Groups A and B, respectively (NS). Serum PCT concentration increased compared with baseline in both groups during the first two days after surgery. The increase in serum PCT concentration was significantly greater in Group B than A patients (p < 0.0002). Considering a perioperative abnormal cut-off value of >0.5 ng/mL, there were none in Group A versus 57% in Group B (p < 0.0001). Baseline serum CRP concentrations were 1.44 +/- 1.30 and 1.58 +/- 1.35 ng/mL in Groups A and B, respectively (NS). After surgery, CRP increased significantly compared with baseline in both groups. When changes in time-varying variables were included in a logistic model, complications were predicted by changes (between baseline and end of surgery values) of PCT (coefficient = 9.410; t = 2.18) and heart rate (coefficient = 0.075; t = 1.57), whereas changes of CRP, white blood cells, mean blood and central venous pressures did not contribute statistically. The model constant was -4.827 (t = -2.43) and the ROC curve area was 0.8971. Thus, absolute PCT changes of 0.20, 0.40 and 0.60 ng/mL carry an approximate risk of 5, 26 and 69%, respectively, of postoperative complications in the time frame of this study. CONCLUSIONS: A postoperative serum PCT concentration of >0.5 ng/mL is highly suggestive of a postoperative complication. CRP changes do not contribute to predictive information.