Apoptosis in breast cancer

OBJECTIVE: To evaluate apoptotic rates on fine needle aspiration (FNA) samples of infiltrating duct carcinoma of the breast and to determine whether cytologic grading improved with consideration of the apoptotic rate in comparison with histologic grading. STUDY DESIGN: We studied 35 women who underwent mastectomy following an FNA diagnosis of infiltrating ductal carcinoma. Concordance between cytologic and histologic grades was calculated. Next, cytologic grades were considered with the apoptotic rates and compared with the histologic grades. RESULTS: An overall concordance of 82.9% was noted between the cytologic and histologic grading systems, with maximum concordance in grade 1 and minimum in grade 3 breast cancers. A highly significant difference in the apoptotic rates, as calculated on cytology, existed between the three histologic grades, indicating a significant increase in apoptosis with rising histologic grade. Applying multiple regression analysis, a significant improvement of cytologic grade with consideration of the apoptotic rate was observed. CONCLUSION: Employing histologic grade as the yardstick, cytology was less sensitive for the purpose of grading breast ductal carcinoma. However, by considering the apoptotic rates, the sensitivity of cytologic grading significantly rose in relation to histologic grade. Larger studies are required to determine whether apoptosis can be incorporated into the existing cytologic grading systems to increase their sensitivity.     

Preoperative brush and impression cytology in ocular surface squamous neoplasms

OBJECTIVE: Preoperative cytologic diagnoses of ocular surface squamous neoplasms were evaluated and compared with histologic diagnoses. STUDY DESIGN: Impression cytology (Millipore filter paper) and brush cytology were applied to 32 patients who had conjunctival neoplasms. Papanicolaou-stained cytologic preparations and hematoxylin and eosin-stained histologic sections were examined by light microscopy. RESULTS: The brush technique was used on 27 patients; impression cytology was applied in 5 cases. Cytologic and histologic diagnoses were concordant in 26 cases. Squamous cell carcinoma or carcinoma in situ was diagnosed in 18 and dysplasia in 4 cases. Squamous metaplasia and normal-appearing conjunctival epithelial cells were diagnosed cytologically in four cases; of those histologic diagnoses, one was pterygium and three, conjunctival nevus. Four cases revealed discrepancies between the cytologic and histologic preparations. There was one false positive result, and one case was subconjunctival invasion of basal cell carcinoma of the eyelid. CONCLUSION: Impression and brush cytology are fast, cost-effective, reliable and noninvasive diagnostic tools for ocular surface squamous neoplasms. However, the brush technique has several advantages over impression cytology.     

Aspiration cytology of the conjunctival surface

OBJECTIVE: To evaluate a method of obtaining conjunctival cells that utilizes aspiration of the conjunctival surface. STUDY DESIGN: Eighteen eyes from 16 patients with epibulbar lesions underwent aspiration of the conjunctival surface using a tuberculin syringe without a needle. The aspirated cells were prepared by the cytocentrifuge or Millipore filter technique. The lesions were subsequently biopsied, and the cytologic and histologic diagnoses were compared. RESULTS: Diagnoses of the conjunctival lesions, in decreasing order of frequency, were conjunctival intraepithelial neoplasia (dysplasia, carcinoma in situ), squamous cell carcinoma, squamous metaplasia, nevus, lymphoma and inflammation. In this feasibility study, the cytologic diagnosis accurately correlated with the histologic diagnosis in most cases. There were two cases in which the cytologic diagnosis led to the correct histologic diagnosis. CONCLUSION: Aspiration cytology of the conjunctival surface is useful in obtaining diagnostic material and may be used as a guide to where a biopsy should be performed. Limitations include inadequate samples and lack of observer experience.     

Longitudinal analysis of taurine induced effects on the tear proteome of contact lens wearers and dry eye patients using a RP-RP-Capillary-HPLC-MALDI TOF/TOF MS approach

Tear proteomic studies revealed distinct similarities between contact lens wearers and dry eye patients. AMO Complete® multipurpose contact lens cleaning solutions containing taurine seem to have a beneficial effect regarding contact lens induced dry eye. To illuminate the effect of taurine on the tear proteome of contact lens wearers and sicca patients we developed a gel-based RP-RP capillary HPLC–MALDI TOF/TOF MS strategy. Two contact lens wearer groups, one using eye drops containing 0.05% taurine; the other for control physiological NaCl solution were monitored. Also, a third group of sicca patients using taurine solution was studied (N = 4 individuals/group). Tear pools of each group at six time points over 5 weeks were analyzed. In summary 267 tear proteins were identified. We found a protein subset showing a linear taurine response with R² values ≥ 0.5. Taurine effects were detected predominantly in the contact lens group demonstrated by distinct level decreases. Most protein candidates were related to inflammation. Since levels of these proteins differentiate from those of a healthy non-contact lens wearer reference they are supposed to be involved in contact lens induced dry eye and should be focused on in further studies.     

Impression cytology changes and corneoconjunctival calcification in patients with chronic renal failure

OBJECTIVE: To evaluate the relationship between corneoconjunctival calcification and conjunctival squamous metaplasia in patients with chronic renal failure (CRP). STUDY DESIGN: We studied impression cytology in 45 CRF patients on regular hemodialysis and 30 age- and sex-matched controls. Specimens were obtainedfrom the temporal bulbar conjunctiva using cellulose acetate filter paper. The samples were fixed in a mixture of 70% ethyl alcohol, 37% formaldehyde and glacial acetic acid and then stained with a combination of periodic acid- Schiff and Gill's modified Papanicolaou stain and graded by a masked observer. Corneoconjunctival calcification was graded by the Porter-Crombie classification. RESULTS: Of 45 study patients, 4 (9%) disclosed grade 0, 23 (51%) grade 1, 14 (31%) grade 2 and 4 grade 3 (9%) impression cytology changes. There was a statistically significant difference between the patient and control groups (p < 0.001). Calcium deposits were more frequent and extensive in CRF patients than in controls (p = 0.01). There was no correlation between impression cytology and calcium deposit grades (p = 0.128). However the presence of conjunctival inflammation correlated with the existence of extensive squamous metaplasia (p < 0.001). CONCLUSION: The severity of conjunctival changes in CRF patients on regular hemodialysis are not related to calcium deposition but to acute conjunctival inflammation.     

Conjunctival dysplasia in soldiers exposed to mustard gas during the Iraq-Iran war: scrape cytology.

OBJECTIVE: To describe the conjunctival scrape cytology findings in Iraq-Iran war veterans exposed to mustard gas and to detect malignant transformation at an early stage. STUDY DESIGN: Twenty-two male war veterans (29-54 years old) who were exposed to chemical bombing about 14 years earlier, formed the base of this study. All of them had chronic eye problems, such as dryness, conjunctival scarring and decreased visual acuity. Conjunctival scrape cytology was performed for cytologic study. RESULTS: Among 22 cases of conjunctival scarring, 9 were diagnosed as dysplasia. Mild inflammation and squamous metaplasia were also noted. Squamous cell carcinoma was not identified. CONCLUSION: Conjunctival scraping cytology is useful for the diagnosis of dysplasia in soldiers exposed to mustard gas during of the Iraq-Iran war. This method is also effective for follow-up study.     

Diagnostic impression cytology: a simple technique for the diagnosis of external eye disease

Diagnostic impression cytology: a simple technique for the diagnosis of external eye disease
The technique of impression cytology was used for cytologic examination of conjunctival samples from 128 patients with a variety of external eye diseases. The method of sample collection and the staining procedure are described. Microscopic examination showed 62 cases with allergic conjunctivitis, 23 with bacterial or viral infection, 26 cases with changes typical of dry eye and 17 cases with non-specific chronic inflammation. The cytologic features and numerous applications of impression cytology are discussed.     

Acanthamoeba spp.: Efficacy of Bioclen FR One Step®, a povidone-iodine based system for the disinfection of contact lenses

Pathogenic strains of Acanthamoeba are causative agents of a serious sight-threatening infection of the eye known as Acanthamoeba keratitis. The prevalence of this infection has risen in the past 20 years, mainly due to the increase in number of contact lens wearers. Bioclen FR One Step® (Ophtecs Corporation) is the only available povidone-iodine based system for the disinfection of silicone hydrogel lenses and soft contact lenses on the market. Bioclen FR has been proven to be highly effective against bacteria and fungi that can cause problems for contact lens users. In this study, Bioclen FR One Step® was tested against three clinical Acanthamoeba isolates from contact lens cases. The results demonstrated that the tested Acanthamoeba clinical strains were sensitive to Bioclen FR One Step®.     

Robinson cytologic grading of invasive ductal breast carcinoma: correlation with histologic grading and regional lymph node metastasis

OBJECTIVE: To evaluate the importance of cytologic grading of breast carcinoma and its association with histologic grading and the existence of axillary lymph node metastasis. STUDY DESIGN: Aspirates and surgical samples from 100 patients with invasive ductal breast carcinoma not otherwise specified were studied. In 50 patients, > or = 1 metastatic nodes were identified. The cytologic grade was evaluated using the Robinson method and the histologic grade using the Elston modification of the Bloom-Richardson method. A study was undertaken to establish the association between histologic and cytologic grades and to compare the various parameters used to evaluate cytologic grade with the presence of axillary node metastasis. RESULTS: A statistically significant association was observed between cytologic and histologic grades (p < 0.0005) and between cytologic grade and presence of axillary metastasis (p < 0.0005). Similarly, cell dissociation (p < 0.0005), cell uniformity (p = 0.0010) and the appearance of nuclear margins (p < 0.0005) all displayed a positive correlation with regional metastasis. CONCLUSION: Cytologic grade may provide relevant information on the aggressiveness of invasive ductal breast carcinoma and could be a useful parameter to take into consideration when selecting neoadjuvant therapy.     

Cytologic grading and DNA image cytometry of breast carcinoma on fine needle aspiration cytology smears

OBJECTIVE: To correlate the cytologic grade of breast carcinoma with DNA image cytometry (ICM) and nuclear area on fine needle aspiration cytology (FNAC) smears. STUDY DESIGN: In this prospective study, FNAC material from 28 breast carcinomas were studied for cytologic grade and DNA ICM. Breast carcinomas were classified as grade 1-3 (low to high). DNA histograms were classified by the modified Auer method. Degree of hyperploidy (DH), ploidy balance (PB) and nuclear area (NA) were measured on Feulgen-stained smears by a CAS 200 image cytometer. Cytologic grade was correlated with DNA ICM findings and NA. RESULTS: There were 3 cytologic grade 1, 13 grade 2 and 12 grade 3 breast carcinomas. Seven of eight cases of hypertetraploid aneuploidy were grade 3 tumors. All cytologic grade 1 tumors were diploid. There were significant differences in DH, PB and NA in different grades of breast carcinoma (one-way ANOVA). CONCLUSION: DNA image cytometry in combination with cytologic grading might offer additional information for the characterization of breast carcinomas diagnosed by FNAC. These observations are of particular interest with the introduction of preoperative chemotherapy.     

Effect of Three Interventions on Contact Lens Comfort in Symptomatic Wearers: A Randomized Clinical Trial

Purpose

To investigate whether carrying out various interventions part way through the day influences comfort in symptomatic daily disposable (DD) contact lens wearers.

Methods

A subject-masked, randomized, controlled clinical trial was conducted in thirty symptomatic soft lens wearers who wore their habitual DD contact lenses bilaterally for 12 h on two separate days. Five hours after lens application, one of the following three interventions or a control was performed on each eye: replacing the existing lens with a new lens; removing and reapplying the same lens; performing a ‘scleral swish’; and no action (control). Comfort scores were recorded using SMS text messages every hour following lens application using a 0 (causes pain) to 100 (excellent comfort) scale. Comfort scores before lens application, at 6 mins post-application, and at 6 mins post-intervention were also recorded.

Results

There was a significant reduction in comfort from pre-lens application to 6 mins post-application for all groups (all p<0.05). Comfort gradually decreased from 6 mins to 5 h after lens application for each group (p<0.0001) with no significant difference between groups over the 5-h period (p = 0.09). There was no significant difference in comfort 6 mins post-intervention for any group (all p>0.05). After the intervention, comfort continued to decline (p<0.0001) with slightly lower mean scores for the control group compared to the new lens group (p = 0.003). Change in comfort relative to pre-intervention (5 h) was similar for all groups (p = 0.81). There was no difference in comfort at 12 h between groups (p = 0.83).

Conclusion

This work has confirmed that comfort shows a continual and significant decline over a 12-h wearing period in symptomatic DD contact lens wearers. None of the interventions investigated had any significant impact on end-of-day comfort. These data suggest discomfort in lens wearers is more heavily influenced by changes to the ocular environment rather than to the lens itself.

Trial Registration

Controlled-Trials.com ISRCTN10419752 http://www.controlled-trials.com/ISRCTN10419752     

Cytologic evaluation of prognostic markers in breast carcinoma

To type breast carcinomaon on fine needle aspiration cytology (FNAC) material and correlate the results with histologic typing, to grade breast carcinoma on FNAC material and correlate the findings with Bloom-Richardson histologic grading, and to determine the estrogen receptor (ER) status in cases of breast carcinoma by immunocytochemical (ICC) staining of FNA cytologic material and correlate the findings with ER status, as determined by immunohistochemical (IHC) staining of tissue sections. STUDY DESIGN: Seventy-seven cases of breast carcinoma diagnosed on FNAC formed the basis of this study. Typing was done in all cases on the basis of cytologic features and grading in 62. (Fifteen cases were special types of breast carcinoma). In all cases, ER status was determined by immunostaining of cytologic smears. Results of tumor typing, grading and ER status on cytologic material were compared with the results of histologic typing, grading and immunostaining of histologic material obtained from mastectomy or wide excision specimens. RESULTS: Tumor typing was accurate in 73 of 77 cases (94.8%). Fifteen of 18 cases that were cytologically grade 3 were confirmed on histology, while 3 proved to be grade 2. Of 40 cytologic grade 2 cases, 26 were confirmed on histology, while 14 cases were grade 3. Three of 4 cytologically grade 1 cases were confirmed on histology while 1 was grade 2. The overall accuracy for cytologic grading was 71% (44 of 62 cases). Thirty-seven of 40 ER-positive cases (92.5%) were labeled ER positive on ICC. One case was ER negative on cytology, while in 2 cases the cellularity of the cytologic smear was insufficient to assess ER expression. Thirty-seven cases were negativefor ER on IHC. Nine of these showed ER positivity on ICC, 26 were negative, and 2 had cellularity that was inadequate for assessment of ER. Sensitivity and specificity rates for ER detection on ICC were 97.4% and 74.3%, respectively. CONCLUSION: Tumor typing, grading and evaluation of ER status on FNA C material in breast carcinomas are simple, quick and moderately reliable techniques that compare and correlate favorably with histologic typing, grading and ER status on IHC.     

Use of cytomorphometry and cytology in the diagnosis of transitional-cell carcinoma of the upper urinary tract

Because of the rise in incidence of upper urinary tract tumors, there is a need for a simple and reliable method for diagnosing these tumors, especially in people in a "high-risk" group. This retrospective study showed the usefulness of cytology and cytomorphometry in making the diagnosis of transitional-cell carcinoma of the upper urinary tract. The study also emphasized that the methods of collection and processing are of the utmost importance: the cytologic evaluation of ureteral catheterized urine specimens gave 100% accuracy as compared with a 40% false-negative rate in the cytologic diagnosis of voided urine specimens. A higher accuracy of urinary cytology for the diagnosis of upper urinary tract lesions clearly requires selective catheterization of the ureter. Objective cytomorphologic grading of the urinary cytology specimens was shown to compare favorably with histologic grading. Cytomorphologic grading not only can offer important information in determining the prognosis and in planning treatment but can also assist in quality control of other diagnostic methods and can help to resolve apparent diagnostic discrepancies.     

Conjunctival brush cytology

In order to collect conjunctival cells efficiently, we developed a special brush that is a modification of the Cytobrush used in cervical cytology. The conjunctival brush is small and made of nylon bristles. Cells collected by these brushes were rinsed into a buffered solution, from which filter preparations were made. This technique produced adequately cellular samples from temporal bulbar conjunctiva; these preparations stained well with the Papanicolaou stain. Under normal conditions, three cell types were observed in the brushing samples; one was the polygonal epithelial cell, the second type was a small rounded cell, and the third type was a mucus-secreting goblet cell. Samples from dry-eyed patients contained keratinized cells with or without a decrease in goblet cells. Elongated cells were seen in samples from postirradiation and postoperative patients. Irritation caused by the brushing was of the same intensity as irritation caused by collecting cytologic specimens by impression or by the use of cotton swabs. These findings suggest that brushing cytology of the conjunctiva is a relatively noninvasive technique and can provide valuable information for evaluation of conjunctival conditions.     

Comparative accuracy of anal and cervical cytology in screening for moderate to severe dysplasia by magnification guided punch biopsy: a meta-analysis

Background

The accuracy of screening for anal cancer precursors relative to screening for cervical cancer precursors has not been systematically examined. The aim of the current meta-analysis was to compare the relative accuracy of anal cytology to cervical cytology in discriminating between histopathologic high grade and lesser grades of dysplasia when the reference standard biopsy is obtained using colposcope magnification.

Methods and Findings

The outcome metric of discrimination was the receiver operating characteristic (ROC) curve area. Random effects meta-analysis of eligible studies was performed with examination of sources of heterogeneity that included QUADAS criteria and selected covariates, in meta-regression models. Thirty three cervical and eleven anal screening studies were found to be eligible. The primary meta-analytic comparison suggested that anal cytologic screening is somewhat less discriminating than cervical cytologic screening (ROC area [95% confidence interval (C.I.)]: 0.834 [0.809–0.859] vs. 0.700 [0.664–0.735] for cervical and anal screening, respectively). This finding was robust when examined in meta-regression models of covariates differentially distributed by screening setting (anal, cervical).

Conclusions

Anal cytologic screening is somewhat less discriminating than cervical cytologic screening. Heterogeneity of estimates within each screening setting suggests that other factors influence estimates of screening accuracy. Among these are sampling and interpretation errors involving both cytology and biopsy as well as operator skill and experience.     

Fine needle aspiration cytology of soft tissue chondroma. A case report

BACKGROUND: Soft tissue chondroma, though rare, is well known to histopathologists and radiologists. Cytologic features of soft tissue chondroma mimic those of its malignant counterpart to a considerable extent. To our knowledge, this is the first case in which the aspiration cytology of soft tissue chondroma is described as an aid to definitive diagnosis. CASE: A 54-year-old male presented with a 6 x 5-cm swelling on his right forearm that had existed for 20 years. Its extraskeletal location was confirmed. Aspiration cytology showed myxofibrillary material and pleomorphic cells. CONCLUSION: The clinical, radiologic and cytologic triad is important for the correct cytologic diagnosis of soft tissue chondroma despite worrisome cell atypia.     

Slime-producing Staphylococcus epidermidis and S. aureus in acute bacterial conjunctivitis in soft contact lens wearers

In recent years, an increase in ocular pathologies related to soft contact lens has been observed. The most common infectious agents were Staphylococcus spp. Some strains produce an extracellular polysaccharidic slime that can cause severe infections. Polysaccharide synthesis is under genetic control and involves a specific intercellular adhesion (ica) locus, in particular, icaA and icaD genes. Conjunctival swabs from 97 patients with presumably bacterial bilateral conjunctivitis, wearers of soft contact lenses were examined. We determined the ability of staphylococci to produce slime, relating it to the presence of icaA and icaD genes. We also investigated the antibiotic susceptibility and Pulsed Field Gel Electrophoresis (PFGE) patterns of the clinical isolates. We found that 74.1% of the S. epidermidis strains and 61.1% of the S. aureus strains isolated were slime producers and showed icaA and icaD genes. Both S. epidermidis and S. aureus slime-producing strains exhibited more surface hydrophobicity than non-producing slime strains. The PFGE patterns overlapped in S. epidermidis strains with high hydrophobicity. The similar PFGE patterns were not related to biofilm production. We found scarce matching among the Staphylococcus spp. studied, slime production, surface hydrophobicity and antibiotic susceptibility.     

Cytologic grading of invasive breast carcinoma. Correlation with clinicopathologic variables and predictive value of nodal metastasis

OBJECTIVE: To estimate cytologic grade and correlate it with the other known prognostic factors, such as tumor differentiation, growth fraction, estrogen receptor status and nodal status. STUDY DESIGN: Fine needle aspirates from 104 invasive ductal carcinomas were stained by the Papanicolaou method and examined for necrosis, cellular size, nuclear/cytoplasmic ratio, nuclear pleomorphism, nucleoli, chromatin granularity and density of chromatin. We established a semiquantitative scoring system based on the above features and correlated cytologic findings with clinicopathologic variables. RESULTS: Histologic grade correlated positively with cytologic grade and negatively with estrogen receptor positivity. Moreover, high cytologic grade was associated with nodal metastasis and proliferative index labeling by MIB-1. CONCLUSION: This study showed that our grading system for breast cancer on fine needle aspiration cytology is feasible on a routine diagnostic basis. Cytologic grading can provide more information than usual on tumor biologic behavior.     

Viability of Acanthamoeba cysts in ophthalmic solutions

Acanthamoeba keratitis is a chronic infection of the human cornea. Many people who have this infection wear soft contact lenses. Usually lens wearers clean and maintain their lenses with various ophthalmic solutions including homemade saline. Recently it has been shown that homemade saline solutions play a role in lens contamination and thus in Acanthamoeba keratitis. We therefore evaluated the viability of cysts of three species of Acanthamoeba by exposing them for various time periods to saline, cleaning, and disinfectant solutions generally used to care for these lenses. We found that the viability of the cysts in saline solutions ranged from a minimum of 14 days to 90 days of exposure. In cleaning solutions, the survival times ranged from a minimum of 1 day to 90 days of exposure. Disinfectants, as expected, were the most effective of all tested solutions in killing Acanthamoeba cysts. The survival times ranged from 6 h to 14 days. None of these products were effective in destroying Acanthamoeba cysts in less than 6 h of exposure, which exceeds the suggested time that any given solution should be used for lens care.     

Viability of Acanthamoeba cysts in ophthalmic solutions.

Acanthamoeba keratitis is a chronic infection of the human cornea. Many people who have this infection wear soft contact lenses. Usually lens wearers clean and maintain their lenses with various ophthalmic solutions including homemade saline. Recently it has been shown that homemade saline solutions play a role in lens contamination and thus in Acanthamoeba keratitis. We therefore evaluated the viability of cysts of three species of Acanthamoeba by exposing them for various time periods to saline, cleaning, and disinfectant solutions generally used to care for these lenses. We found that the viability of the cysts in saline solutions ranged from a minimum of 14 days to 90 days of exposure. In cleaning solutions, the survival times ranged from a minimum of 1 day to 90 days of exposure. Disinfectants, as expected, were the most effective of all tested solutions in killing Acanthamoeba cysts. The survival times ranged from 6 h to 14 days. None of these products were effective in destroying Acanthamoeba cysts in less than 6 h of exposure, which exceeds the suggested time that any given solution should be used for lens care.