Why oral histopathology suffers inter-observer variability on grading oral epithelial dysplasia: an attempt to understand the sources of variation

The present study attempted to assess the reasons behind the inter-observer variation in grading oral epithelial dysplasia (OED). Three oral pathologists and one general pathologist examined 68 histological slides of OED lesions of variable grade for scoring the presence of each individual characteristic of the architecture and cytology changes that were established by the 2005 WHO classification. The assigned features in each case were correlated with clinical outcomes to understand which features are more commonly associated with malignant transformation. Interestingly, for all individual characteristics, the pairwise inter-examiner and group kappa values ranged from poor to moderate. It appeared that for each characteristic separately there was much dissension. Despite these observations, comparing these data with that from our previous paper on the same slides showed that the inter-observer agreement on the degree of dysplasia either by using the new binary system of "low-risk" or "high-risk" or by using the 2005 WHO classification turned out to be better than the agreement on the individual characteristics of architecture and cytology changes. Certain features show significant association with the clinical outcomes. In the discussion, some explanations to help understanding the sources of variation in grading OED are put forward. In conclusion, grading dysplasia is not an exact science and pathologists are doing their best to reach optimal results. Improvement in the standard of the histopathology reporting of OED lesions could be achieved by consideration of several issues. Of these, there is need for a universal definition of the architectural and cytological features that are the basis of any OED grading process. A minimum dataset for reporting OED lesions should be set up. Also, the use of a consensus scoring process between two or more observers should be encouraged as this would improve inter-observer agreement.     

Dosimetric predictors of laryngeal edema

PURPOSE: To investigate dosimetric predictors of laryngeal edema after radiotherapy (RT). METHODS AND MATERIALS: A total of 66 patients were selected who had squamous cell carcinoma of the head and neck with grossly uninvolved larynx at the time of RT, no prior major surgical operation except for neck dissection and tonsillectomy, treatment planning data available for analysis, and at least one fiberoptic examination of the larynx within 2 years from RT performed by a single observer. Both the biologically equivalent mean dose at 2 Gy per fraction and the cumulative biologic dose-volume histogram of the larynx were extracted for each patient. Laryngeal edema was prospectively scored after treatment. Time to endpoint, moderate or worse laryngeal edema (Radiation Therapy Oncology Group Grade 2+), was calculated with log rank test from the date of treatment end. RESULTS: At a median follow-up of 17.1 months (range, 0.4- 50.0 months), the risk of Grade 2+ edema was 58.9% +/- 7%. Mean dose to the larynx, V30, V40, V50, V60, and V70 were significantly correlated with Grade 2+ edema at univariate analysis. At multivariate analysis, mean laryngeal dose (continuum, hazard ratio, 1.11; 95% confidence interval, 1.06-1.15; p < 0.001), and positive neck stage at RT (N0-x vs. N +, hazard ratio, 3.66; 95% confidence interval, 1.40-9.58; p = 0.008) were the only independent predictors. Further stratification showed that, to minimize the risk of Grade 2+ edema, the mean dose to the larynx has to be kept < or =43.5 Gy at 2 Gy per fraction. CONCLUSION: Laryngeal edema is strictly correlated with various dosimetric parameters; mean dose to the larynx should be kept < or =43.5 Gy.     

Contemporary revision penile prosthesis surgery is not associated with a high risk of implant colonization or infection: a single-surgeon series

IntroductionRevision penile prosthesis surgery has traditionally been associated with a greater risk of postoperative infection than primary implant placement. This has been attributed to the high prevalence of asymptomatic bacteria found surrounding the implant at the time of revision surgery.AimTo validate whether contemporary revision surgery remains associated with a high risk of asymptomatic colonization and postoperative infection.MethodsA comprehensive, prospective database consisting of consecutive patients undergoing primary and revision penile prosthesis surgery at our center was analyzed.Main Outcome MeasuresThe infection risk in primary and revision implant surgery was compared. The prevalence of asymptomatic implant colonization during revision surgery, and whether this was associated with clinical infection was evaluated. The spectrum of bacterial species causing infection in this contemporary single-surgeon series was described.ResultsOne hundred seventeen primary and 72 revision implant recipients were studied. Infection developed in four (3.4%) patients undergoing primary implants, two (4.3%) patients undergoing removal and replacement for mechanical malfunction, and three (12%) patients undergoing rerouting for extrusion (P = 0.26). Intraoperative cultures were positive in 5 (9.8%) of 51 revision patients, none of whom developed infections. Organisms causing infection included Staphylococcus aureus and Enterobacter aerogenes. Unexpectedly, an adjuvant, alcohol-based skin prep in our last 83 patients reduced the infection risk to 1.2%.ConclusionsIn our series, the infection risk associated with revision of malfunctioning devices was no greater than primary implant placement. Rerouting was associated with a higher infection risk, likely due to technical factors, and not implant colonization. Less than 10% of our revision implants were colonized, and this had no bearing on the development of a postoperative infection. S. epidermidis was not the most common organism implicated in device infections. Finally, our experience with an adjuvant, alcohol-based skin prep warrants further randomized prospective evaluation. Kava BR, Kanagarajah P, and Ayyathurai R. Contemporary revision penile prosthesis surgery is not associated with a high risk of implant colonization or infection: A single-surgeon series.     

Synthesis, characterization and their anticonvulsant, anti-inflammatory studies of some novel chromeno oxadiazoles

In this study, a series of new 1,2,4-oxadiazole derivatives containing 3,4-dihydro-2H-chromen-2-amine moiety were synthesized by efficient microwave reaction of 2-amino-N′-hydroxychroman-3-carboxamidine and suitable aldehyde. Structures of all the synthesized compounds were confirmed by spectral studies and C, H, N analyses. Newly synthesized compounds were screened for their anticonvulsant and anti-inflammatory properties. Few of the compounds exhibited excellent anticonvulsant activity as compared to the standard drug Diazepam. Also compounds have exhibited moderate anti-inflammatory activity as compared to the standard drug Diclofenac sodium.     

Urinary megalin deficiency implicates abnormal tubular endocytic function in Fanconi syndrome.

Normal reabsorption of glomerular filtrate proteins probably requires recycling of the endocytic receptors megalin (gp330) and cubilin. Both receptors are located on the luminal surface of the renal proximal tubule epithelium. Whether abnormal amounts of receptor are present in the urine of patients with Dent's disease, Lowe's syndrome, or autosomal dominant idiopathic Fanconi syndrome was explored. They are all forms of the renal Fanconi syndrome and are associated with tubular proteinuria. Urine samples of equal creatinine contents were dialyzed, lyophilized, and subjected to electrophoresis on nonreducing sodium dodecyl sulfate-5% polyacrylamide gels. Proteins were blotted and probed with anti-megalin IgG, anti-cubilin IgG, or receptor-associated protein. Megalin and cubilin levels detected by immunochemiluminescence were measured as integrated pixels and expressed as percentages of the normal mean values. A striking deficiency of urinary megalin, compared with normal individuals (n = 42), was observed for eight of nine families with Dent's disease (n = 10) and for the two families with Lowe's syndrome (n = 3). The family with autosomal dominant idiopathic Fanconi syndrome (n = 2) exhibited megalin levels within the normal range. The measured levels of cubilin were normal for all patients. These results are consistent with defective recycling of megalin to the apical cell surface of the proximal tubules and thus decreased loss into urine in Dent's disease and Lowe's syndrome. This defect would interfere with the normal endocytic function of megalin, result in losses of potential ligands into the urine, and produce tubular proteinuria.     

Non-penetrance and late appearance of polyps in families with familial adenomatous polyposis.

One case of non-penetrance of the familial adenomatous polyposis (FAP) gene at 59 years of age and late onset of polyps on endoscopy and biopsy in this and two other families is described. Screening protocols should include dental screening as well as indirect ophthalmoscopy and endoscopy to detect minimal manifestations of the gene. In the absence of a specific DNA predictive test, bowel screening should continue well beyond 30 years of age.     

Malignant transformation of a potentially low risk lichenoid reaction

Lichenoid reaction represents a family of oral lesions identical, both clinically and histologically to oral lichen planus. The triggering factor for this lesion varies from medicines to dental materials, usually demonstrating a cause-effect relationship unlike lichen planus. We present a typical case of lichenoid reaction on the buccal mucosa that appeared in response to betel quid which progressed to carcinoma during a follow-up period of 6 months. Lichenoid reactions occurring in response to known carcinogens and that occurring in risk group population has to be observed more cautiously.     

Structural and Mechanical Characterization of Zr58.5Ti8.2Cu14.2Ni11.4Al7.7 Bulk Metallic Glass

Thermal stability, structure and mechanical properties of the multi-component Zr_58.5Ti_8.2Cu_14.2Ni_11.4Al_7.7 bulk metallic glass have been studied in detail. The glassy material displays good thermal stability against crystallization and a fairly large supercooled liquid region of 52 K. During heating, the alloy transforms into a metastable icosahedral quasicrystalline phase in the first stage of crystallization. At high temperatures, the quasicrystalline phase undergoes a transformation to form tetragonal and cubic NiZr₂-type phases. Room-temperature compression tests of the as-cast sample show good mechanical properties, namely, high compressive strength of about 1,630 MPa and fracture strain of 3.3%. This is combined with a density of 6.32 g/cm³ and values of Poisson’s ratio and Young’s modulus of 0.377 and 77 GPa, respectively. The mechanical properties of the glass can be further improved by cold rolling. The compressive strength rises to 1,780 MPa and the fracture strain increases to 8.3% for the material cold-rolled to a diameter reduction of 10%.