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Item Ensuring a Successful Transition From Cytology to Human Papillomavirus-Based Primary Cervical Cancer Screening in Canada by Investigating the Psychosocial Correlates of Women's Intentions: Protocol for an Observational Study(JMIR, 2022-06-16) Griffin-Mathieu, Gabrielle; Haward, Ben; Tatar, Ovidiu; Zhu, Patricia; Perez, Samara; Shapiro, Gilla K.; McBride, Emily; Thompson, Erika L.; Smith, Laurie W.; Lofters, Aisha K.; Daley, Ellen M.; Guichon, Juliet R.; Waller, Jo; Steben, Marc; Decker, Kathleen M.; Mayrand, Marie-Helene; Brotherton, Julia M. L.; Ogilvie, Gina S.; Zimet, Gregory D.; Norris, Teresa; Rosberger, Zeev; Pediatrics, School of MedicineBackground: The human papillomavirus (HPV) test has emerged as a significant improvement over cytology for primary cervical cancer screening. In Canada, provinces and territories are moving toward implementing HPV testing in cervical cancer screening programs. Although an abundance of research exists on the benefits of HPV-based screening, there is a dearth of research examining women's understanding of HPV testing. In other countries, failure to adequately address women's concerns about changes has disrupted the implementation of HPV-based screening. Objective: The aims of the multipart study described in this paper are to develop psychometrically valid measures of cervical cancer screening-related knowledge, attitudes, and beliefs; to examine the feasibility of a questionnaire examining psychosocial factors related to HPV-based screening; and to investigate psychosocial correlates of women's intentions to participate in HPV-based screening. Methods: We conducted a web-based survey (study 1) of Canadian women to assess the acceptability and feasibility of a questionnaire, including the validation of scales examining cervical cancer knowledge, HPV testing knowledge, HPV testing attitudes and beliefs, and HPV test self-sampling attitudes and beliefs. Preferences for cervical cancer screening were assessed using the best-worst scaling methodology. A second web-based survey (study 2) will be administered to a national sample of Canadian women between June 2022 and July 2022 using the validated scales. Differences in the knowledge, attitudes, beliefs, and preferences of women who are currently either underscreened or adequately screened for cervical cancer will be examined through bivariate analyses. Multinomial logistic regression will be used to estimate the associations between psychosocial and sociodemographic factors and intentions to undergo HPV-based screening. Results: Between October 2021 and November 2021, a total of 1230 participants completed the questionnaire in study 1, and 1027 (83.49%) responses were retained after data cleaning methods were applied. Feasibility was comparable with similar population-based surveys in terms of survey length, participant attrition, and the number of participants excluded after data cleaning. As of May 2022, analysis of study 1 is ongoing, and results are expected to be published in the summer of 2022. Data collection is expected to begin for study 2 in the summer of 2022. Results are expected to be published between late 2022 and early 2023. Conclusions: Findings will provide direction for Canadian public health authorities to align guidelines to address women's concerns and optimize the acceptability and uptake of HPV-based primary screening. Validated scales can be used by other researchers to improve and standardize the measurement of psychosocial factors affecting HPV test acceptability. Study results will be disseminated through peer-reviewed journal articles; conference presentations; and direct communication with researchers, clinicians, policy makers, media, and specialty organizations.Item Etiologic factors related to unsatisfactory ThinPrep cervical cytology: Evaluation and potential solutions to improve(Wolters Kluwer, 2015-09-22) Kalinicheva, Tatyana; Frisch, Nora; Giorgadze, Tamar; Madan, Shashi; Shidham, Anushree; Bhalla, Amarpreet; Mejias-Badillo, Linette; Tranchida, Paul; Bandyopadhyay, Sudeshna; Dhillon, Inderpreet; Shidham, Vinod B.; Department of Pathology & Laboratory Medicine, IU School of MedicineBACKGROUND: In cervical cytology, the unsatisfactory rates for ThinPrep (TP) are slightly higher compared to SurePath. We examined various causes and explored potential for resolution of this discrepancy. MATERIALS AND METHODS: Totally, 19,422 cases were reviewed and 1000 unsatisfactory specimens were selected and analyzed. 531 specimens were available for wash protocol. Out of 114 unsatisfactory specimens associated with atrophic cellular changes (ACC), 48 were resubmitted by provider and reevaluated. RESULTS: Lubricant and lubricant-like debris/contamination (LUBE) was the most common cause of unsatisfactory specimens (68%; 681/1000) followed by blood (7.5%); ACC only (without other interfering factors) (2.4%); inflammation (3.0%); and combinations thereof (1.9%). 11.5% showed scant cellularity without an identifiable cause. 3.3% were virtually acellular. Wash protocol improved cellularity in 48% (256/531) of cases. However, only 29% (73/256) of those were satisfactory (with more than 5000 cells). Quantitative reduction in LUBE after wash protocol varied with different morphological subtypes. Interpretation patterns on satisfactory specimens after wash protocol were comparable to the results on selected cohort of specimens during the same study period. Out of 114 ACC, wash protocol was performed on 68 ACC specimens leading to satisfactory TP in 24% (16/68). Totally, 48 cases reported as unsatisfactory with ACC, were resubmitted by the providers between 2 weeks and 2 years. 44 (92%) showed increased cellularity, out of which 52% (23/44) did not show ACC. CONCLUSION: LUBE was the most common cause of unsatisfactory TP in addition to interference by blood and association with atrophic changes. Knowing the morphological spectrum of LUBE would help to identify it as the cause of unsatisfactory TP. Communicating the cause of unsatisfactory TP such as LUBE, ACC, and blood would hint the provider to take appropriate precaution during submission of the repeat specimen, leading to improved patient care.Item EUS-guided Fine Needle Aspiration-based Clues to Mistaken or Uncertain Identity: Serous Pancreatic Cysts(Elsevier, 2023) Yip-Schneider, Michele T.; Muraru, Rodica; Kim, Rachel C.; Wu, Howard H.; Sherman, Stuart; Gutta, Aditya; Al-Haddad, Mohammad A.; Dewitt, John M.; Schmidt, C. Max; Surgery, School of MedicineBackground/objectives: Pancreatic serous cystic neoplasms (SCN) present a diagnostic challenge given their increasing frequency of detection and benign nature yet relatively high rate of misdiagnosis. Here, imaging and analyses associated with EUS-guided fine-needle aspiration (EUS-FNA) are evaluated for their ability to provide a correct preoperative diagnosis of SCN. Methods: A surgical cohort with confirmed pathological diagnosis of SCN (n = 62) and a surveillance cohort with likely SCN (n = 31) were assessed for imaging (CT/MRI/EUS) and EUS-FNA-based analyses (cytology/DNA analysis for Von Hippel-Lindau [VHL] gene alterations/biomarkers). Results: In the surgical cohort, CT/MRI and EUS respectively predicted SCN in 4 of 58(7%) and 19 of 62(31%). Cyst fluid cytology and VHL alterations predicted SCN in 1 of 51(2%) and 5 of 21(24%), respectively. High specificity cyst fluid biomarkers (vascular endothelial growth factor [VEGF]/glucose/carcinoembryonic antigen [CEA]/amylase) correctly identified SCN in 25 of 27(93%). In the surveillance cohort, cyst fluid biomarkers predicted SCN in 12 of 12(100%) while VHL alterations identified SCN 3 of 10(30%). Conclusion: High specificity cyst fluid biomarkers provided the most sensitive means of diagnosing SCN preoperatively. To obtain a preoperative diagnosis of SCN at the highest level of certainty, a multidisciplinary approach should be taken to inform appropriate SCN management.Item Invasive fungal infections in liver diseases(Wolters Kluwer, 2023-08-28) Barros, Nicolas; Rosenblatt, Russell E.; Phipps, Meaghan M.; Fomin, Vladislav; Mansour, Michael K.; Medicine, School of MedicinePatients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring invasive fungal infections (IFIs). These infections carry high morbidity and mortality. Multiple factors, including host immune dysfunction, barrier failures, malnutrition, and microbiome alterations, increase the risk of developing IFI. Candida remains the most common fungal pathogen causing IFI. However, other pathogens, including Aspergillus, Cryptococcus, Pneumocystis, and endemic mycoses, are being increasingly recognized. The diagnosis of IFIs can be ascertained by the direct observation or isolation of the pathogen (culture, histopathology, and cytopathology) or by detecting antigens, antibodies, or nucleic acid. Here, we provide an update on the epidemiology, pathogenesis, diagnosis, and management of IFI in patients with liver disease and liver transplantation.Item The 5th Edition of the World Health Organization Classification of Tumours of the Eye and Orbit(Karger, 2023) Milman, Tatyana; Grossniklaus, Hans E.; Goldman-Levy, Gabrielle; Kivelä, Tero T.; Coupland, Sarah E.; White, Valerie A.; Mudhar, Hardeep Singh; Eberhart, Charles G.; Verdijk, Robert M.; Heegaard, Steffen; Gill, Anthony J.; Jager, Martine J.; Rodríguez-Reyes, Abelardo A.; Esmaeli, Bita; Hodge, Jennelle C.; Cree, Ian A.; WHO Classification of Tumours Editorial Board; Medical and Molecular Genetics, School of MedicineItem The Role of Fluorescence In Situ Hybridization in Pancreatobiliary Brushing Cytology: A Large Retrospective Review with Histologic Correlation(MDPI, 2022-10-14) Khan, Jaffar; De la Sancha, Carlo; Saad, Mohammed; Alkashash, Ahmad; Ullah, Asad; Alruwaii, Fatimah; Velasquez Zarate, Luis; Cramer, Harvey M.; Wu, Howard H.; Pathology and Laboratory Medicine, School of Medicine(1) Background: Although the specificity of brush cytology for the detection of malignant pancreaticobiliary strictures is high, its sensitivity is low. Fluorescence in situ hybridization (FISH) can be used to detect chromosomal aneuploidy in biliary brushing specimens, and when used as an adjunct to routine cytology, it significantly improves diagnostic sensitivity. (2) Methods: We searched our laboratory information system to identify all bile duct brush cytology cases with follow-up surgical pathology between January 2001 and September 2019. Cytologic diagnoses were classified as negative, atypical, suspicious, or malignant. Correlated surgical pathological diagnoses were classified as benign or malignant. FISH test results were obtained for a subset of cytology cases with concurrent FISH testing, and the sensitivity, specificity, positive predictive value, and negative predictive value in identifying malignancy for cytology alone, FISH alone, and combined cytology and FISH were calculated. (3) Results: A total of 1017 brushing cytology cases with histologic correlation were identified. A total of 193 FISH tests were performed concurrently with cytological specimens. Malignant diagnoses were identified in 623 of 1017 patients, while 394 patients had benign strictures. The sensitivity, specificity, positive predictive, and negative predictive rate were 65%, 78%, 83%, and 49% for cytology alone; 72%, 67%, 63%, and 68% for FISH alone; and 85%, 42%, 60%, and 74% for combined cytology and FISH, respectively. Among FISH-positive cases, the risk of malignancy for polysomy was 82% and 32% for trisomy. (4) Conclusions: FISH improves the sensitivity and negative predictive rate of bile duct brush cytology. The combination of cytology and FISH has increased the sensitivity from 65% to 85% and the negative predictive rate from 49% to 74% when compared to cytology alone. A patient with a polysomy FISH result had a significantly higher risk of malignancy than a patient with a trisomy 7 result (82% vs. 32%, p < 0.00001).Item Urine Cytology in Patients with Gender Confirmation Surgery and Hormone Therapy: Evaluation of Urine Cytology Performance in an Underserved Patient Population(Elsevier, 2023-07-01) Khorsandi, Nikka; Ding, Chien-Kuang Cornelia; VandenBussche , Christopher J.; Verduzco, Carlo De la Sancha; Greenland, Nancy; Vohra, Poonam; Pathology and Laboratory Medicine, School of MedicineIntroduction: There is a practice gap and educational need regarding urine cytology (UC) performance in patients with history of gender confirmation surgery (GCS) and/or hormone therapy (HT). This potentially impacts diagnostic accuracy in this medically underserved population. We report a methodology that identifies relevant cases and evaluates the performance of UC in this cohort. Materials and methods: Two institutional pathology archives from 2000 to 2021 were searched using relevant keywords to identify UC specimens from patients with GCS and/or HT for this retrospective study. For each specimen, patient demographics, relevant clinical history, and history of HT and/or GCS were noted. Each case was blindly reviewed by a cytopathologist according to The Paris System. Results: A total of 32 UC specimens from 15 patients with history of GCS and/or HT were identified. There were 13 male to female and 2 female to male transgender patients. The original diagnosis was negative for high-grade urothelial carcinoma (NHGUC) in 24 of 32 (75%) and atypical urothelial cells (AUC) in 8 of 32 (25%) cases. The most common atypical features were irregular nuclear membranes and prominent small nucleoli in 7 of 8 (87.5%). Degenerative changes were present in 5 of 8 (62.5%). On re-review, with relevant clinical history, 100% of cases were re-classified as NHGUC. Conclusions: The original diagnosis of AUC in these cases likely reflects reactive changes post GCS and/or HT. This cohort may be at risk of AUC overdiagnosis, particularly if the pathologist is unaware of this clinical history. Pathologists need to recognize reactive cytomorphologic changes in these patients. Further multi-institutional studies are warranted to expand knowledge about UC performance in these patients.