Cytological Class Research Articles

Nonlinear relationship between viral load and TCT in single/multiple HPV52 infection

PurposeTo determine the correlation between HPV (human papillomavirus) 52 viral load, multiple infections and ThinPrep cytology test (TCT), to inform clinical management of HPV52-positive women after cervical cancer screening.MethodsA total of 1,882 female patients who had positive quantitative HPV tests at Yuebei People's Hospital from January 2020 to December 2022, of whom 533 tested positive for HPV52. We excluded patients who combined HPV16 and/or HPV 18 positivity and whom HPV52 viral load could not be calculated. The final enrollment was 488 patients, including 400 NILM, 48 ASC-US, 28 LSIL and 12 HSIL. The HPV test is a quantitative multiplexed fluorescent PCR assay that provides both HPV genotyping and viral load.ResultsIn our study, there were differences in the median distribution of viral loads among various cytological class categories. The risk of TCT results (LSIL or worse) was increased with the increase of HPV52 viral load, for every LOG unit increase in HPV52 viral load, the risk increased by 26.6%. More importantly, we found a nonlinear relationship between HPV52 viral load and TCT results (LSIL or worse) in both single and multiple infections. When the viral load reaches a threshold, the risk of abnormal cytological results increases significantly.ConclusionHPV52 viral load is an independent risk factor for TCT results (LSIL or worse). The relationship between HPV52 viral load and TCT results (LSIL or worse) is not linear. Viral load may be used as a triage indicator for HPV52-positive patients, thus improving the post-screening clinical management of HPV52-positive women.

Patient characteristics correlate with diagnostic performance of photodynamic diagnostic assisted transurethral resection of bladder tumors: A retrospective, single-center study

BackgroundIdentification of patient subclasses that correlate with the diagnostic performance of photodynamic diagnostic (PDD)-assisted transurethral resection of bladder tumors (TURBT) may improve outcomes. MethodsData were extracted from patients that underwent PDD-assisted TURBT at the University of Tsukuba Hospital between 2018 and 2023. Sensitivity and specificity were evaluated based on PDD findings (excluding WL findings) and pathology results. Cluster analysis using uniform manifold approximation and projection and k-means methods was performed, focusing on patients with malignant lesions. ResultsA total of 267 patients and 2082 specimens were extracted. Sensitivity was lowest with regard to BCG treatment (53.7 %), followed by flat lesions (57.2 %), urine cytology class ≥ III (62.9 %), and recurrent tumors (64.5 %). In the cluster analysis of 231 patients with malignant lesions, two showed lower sensitivity: Cluster 3 (62.4 %), consisting of patients with recurrent tumors and post-BCG treatment, and Cluster 4 (55.7 %), consisting of patients with primary tumors and urine cytology class ≥ III. Clusters 1 and 2, consisting of patients without BCG treatment and patients with lower urine cytology classes, exhibited higher sensitivities (94.4 % and 87.7 %). Among all clusters, Cluster 4 had the highest proportion of specimens which were negative for both PDD and white light (WL) findings but actually had malignant lesions (20.8 %). ConclusionsPDD-assisted TURBT sensitivity was lower in subclasses after BCG treatment or with cytology class III or higher. Random biopsy for PDD/WL double-negative lesions may improve diagnostic accuracy in these subclasses.

Exploring the dynamics of Programmed Death-Ligand 1 in canine lymphoma: unraveling mRNA amount, surface membrane expression and plasmatic levels.

Programmed Death-Ligand 1 is a well-known immune checkpoint molecule. Recent studies evaluated its expression in different canine cancer types through different laboratory techniques. The present study aims to evaluate the surface membrane protein expression (mPD-L1) by means of flow cytometry (FC) in different canine lymphoma immunophenotypes. Furthermore, in a subset of cases, mRNA and plasmatic soluble protein (sPD-L1) have been assessed in the same patient, and correlations among results from the three analyses investigated. Samples obtained for diagnostic purpose from untreated dogs with a confirmed lymphoma immunophenotype were included: surface protein was assessed via FC and quantified with median fluorescence index ratio (MFI ratio), gene expression was evaluated by real time quantitative polymerase chain reaction (RT-qPCR) and plasmatic concentration of soluble protein (sPD-L1) measured with ELISA. Statistical analyses were performed to investigate any difference among FC immunophenotypes, updated Kiel cytological classes, and in the presence of blood infiltration. Considering FC, most B-cell lymphomas (BCL) were positive, with higher MFI ratios than other subtypes (81%, median MFI ratio among positive samples = 1.50, IQR 1.21-2.03, range 1.01-3.47). Aggressive T-cell lymphomas had a lower percentage of positive samples (56%) and showed low expression (median MFI ratio in positive samples = 1.14, IQR 1.07-1.32, range 1.02-2.19), while T-zone lymphomas (TZL) were frequently positive (80%) but with low expression (median MFI ratio in positive samples = 1.19, IQR 1.03-1.46, range 1.02-6.03). Cellular transcript and sPD-L1 were detected in all samples, without differences among immunophenotypes. No correlation between results from different techniques was detected, but sPD-L1 resulted significantly increased in FC-negative lymphomas (p = 0.023). PD-L1 molecule is involved in canine lymphoma pathogenesis, with differences among immunophenotypes detected by FC. Specifically, BCL have the highest expression and aggressive T-cell lymphomas the lowest, whereas TZL need further investigations.

Prognostic fine needle aspiration biopsy of uveal melanoma: Molecular and genetic factors of metastasis risk

Introduction. Molecular genetic testing is actively used for prognostication in patients with uveal melanoma (UM). Tissue for genetic analysis may be obtained either by surgical excision or through fine-needle aspiration biopsy (FNAB). Performing genetic testing and FNAB in each institution can differ in surgical techniques and laboratory methodologies.Aim. To present our own experience of performing FNAB-based molecular genetic testing for prognostication in patients with uveal melanoma.Materials and methods. Prognostic FNAB (n = 151) were combined with brachytherapy or stereotactic surgery. Genetic testing was performed by methods based on polymerase chain reaction (GNAQ, GNA11, EIF1AX and SF3B1 mutations) and fluorescence in situ hybridization (copy numbers of PPARG and MYC genes); cytology of FNAB material was also assessed.Results. Fine-needle aspiration biopsy material was informative in 91 % of cases. At the median follow-up of 36 months, 12 cases of distant metastases were detected. Occurrence of the assessed mutations and copy numbers were related to other representative studies. PPARG deletion was shown to be a significant prognostic factor for metastasis-free survival (p <0,01), which was demonstrated for the first time; EIF1AX and SF3B1 mutations, MYC amplification and cytological class were not shown to be significantly associated with survival in our study.Conclusion. FNAB-based molecular genetic testing for prognostication in patients with uveal melanoma was shown to be a reliable and highly informative approach. Some of the prognostic factors need to be evaluated further with longer follow-up.

Abstract 5104: Extracellular vesicles expressing CEACAM proteins in the urine of bladder cancer patients

Abstract Purpose: Early detection and long-term monitoring are important for urothelial carcinoma of the bladder (UCB). Urine cytology and existing markers have insufficient diagnostic performance. Here, we used medium-sized extracellular vesicles (EVs) in urine to find specific markers for UCB and evaluate their usefulness as diagnostic material. Experimental Design: To search for specific markers in urinary EVs derived from UCB, we performed a comparative analysis using shotgun proteomics with urine from four UCB patients and four healthy subjects. Next, we used male 24 healthy specimens, 18 non-cancer specimens, and 29 UCB specimens for analysis of urinary EVs using a flow cytometer to evaluate the diagnostic performance of UCB-specific EVs. Results. NTA analysis showed that the size of EVs extracted from urine by centrifugation was mostly less than 400 nm. By shotgun analysis of EVs, we detected several proteins characteristic of UCB and found that CEACAM proteins was increased in patients. Flow cytometric analysis revealed that the degree of expression of CEACAM1, 5, and 6 antigens on the surface of EVs varied among patients. EVs expressing CEACAM antigens also expressed MUC1, suggesting that they were derived from tumorigenic uroepithelial cells. The number of EVs expressing CEACAM1, 5, and 6 proteins (CEACAMs+EVs) was significantly increased in UCB (Mean9.5%±SD14%), non-bladder cancer (0.69±0.46), and healthy (0.37±0.31) by flow cytometry. The results of ROC analysis showed a good score of AUC=0.929. A provisional CEACAMs+EVs cutoff % was established with a sensitivity of 83% and specificity of 98%. Here, seven out of nine cases of negative urine cytology (class 2) were determined to be positive. Conclusions: The presence of CEA antigen in the urine of patients with bladder cancer is known, but it has not yet been practically used for diagnosis. We have discovered EVs that specifically express these antigens and have obtained useful diagnostic performance. EVs expressing CEACAM proteins in urine are expecting target as a new liquid biopsy for UCB patients. Citation Format: Ko Igami, Takeshi Uchiumi, Masaki Shiota, Saori Ueda, Masatoshi Eto, Dongchon Kang. Extracellular vesicles expressing CEACAM proteins in the urine of bladder cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5104.

Access to colposcopy in the State of São Paulo, Brazil: probabilistic linkage study of administrative data.

Cervical cancer screening is a multistage process, therefore access to both the primary test and subsequent diagnostic procedures is essential. Considering women undergoing screening on the public health system in the State of São Paulo, Brazil, we aimed to estimate the proportion of women accessing colposcopy within six months of an abnormal smear result. We retrieved records from two administrative databases, the Information System on Uterine Cervical Cancer (SISCOLO) that contains smear results and the Outpatient Information System of the Brazilian Unified National Health System (SIA/SUS) that records colposcopies. A reference cohort consisted of women, aged 25 years or older, with an abnormal smear result between May 1, 2014, and June 30, 2014. We excluded prevalent cases. We linked the reference cohort and records in the SIA/SUS extending to December 31, 2014. After excluding prevalent cases, 1,761 women with abnormal cytology results were left. A total of 700 (39.8%) women were linked to a colposcopy record within the follow-up period; this dropped to 671 (38.1%) women when follow-up was censored at six months. We could notice a slightly higher attendance in women living in the metropolitan region of São Paulo compared with residents of the rest of the state. We found no association between colposcopy attendance and age or cytology class. These results emphasize that access to colposcopy in the public health system in São Paulo is limited. This compromises the quality of screening, and the issue needs to be prioritized in service planning.

Use of Diagnostic Criteria from ACR and EU-TIRADS Systems to Improve the Performance of Cytology in Thyroid Nodule Triage.

Simple SummaryFrom a prospective series of 480 thyroid nodules, we compared the performances of the American College of Radiology (ACR) and the European Thyroid Association (EU) scoring systems in triaging thyroid nodules for fine-needle aspiration (FNA). FNA was recommended on 46.5% and 51.9% of the nodules using the ACR and EU-TIRADS scores, respectively. The ACR system demonstrated a higher specificity as compared to the EU-TIRADS (59.0% vs. 52.4%, p = 0.0012) in predicting ≥TIR3A/III (SIAPEC/Bethesda) nodules. Moreover, specific radiological features (i.e., echogenic foci and margins), combined with the cytological classes improved the specificity (97.5% vs. 91%, p < 0.0001) and positive predictive value (77.5% vs. 50.7%, p < 0.0001) of the cytology alone, maintaining an excellent sensitivity and negative predictive value.Objective: The American College of Radiology (ACR) and the European Thyroid Association (EU) have proposed two scoring systems for thyroid nodule classification. Here, we compared the ability of the two systems in triaging thyroid nodules for fine-needle aspiration (FNA) and tested the putative role of an approach that combines ultrasound features and cytology for the detection of malignant nodules. Design and Methods: The scores obtained with the ACR and EU Thyroid Imaging Reporting and Data Systems (TIRADS) from a prospective series of 480 thyroid nodules acquired from 435 subjects were compared to assess their performances in FNA triaging on the final cytological diagnosis. The US features that showed the highest contribution in discriminating benign nodules from malignancies were combined with cytology to improve its diagnostic performance. Results: FNA was recommended on 46.5% and 51.9% of the nodules using the ACR and EU-TIRADS scores, respectively. The ACR system demonstrated a higher specificity as compared to the EU-TIRADS (59.0% vs. 52.4%, p = 0.0012) in predicting ≥ TIR3A/III (SIAPEC/Bethesda) nodules. Moreover, specific radiological features (i.e., echogenic foci and margins), combined with the cytological classes improved the specificity (97.5% vs. 91%, p < 0.0001) and positive predictive values (77.5% vs. 50.7%, p < 0.0001) compared to cytology alone, especially in the setting of indeterminate nodules (TIR3A/III and TIR3B/IV), maintaining an excellent sensitivity and negative predictive value. Conclusions: The ACR-TIRADS system showed a higher specificity compared to the EU-TIRADS in triaging thyroid nodules. The use of specific radiological features improved the diagnostic ability of cytology.

Implementation of molecular genetic tests in the diagnostics of thyroid cancer: own research

Aim — to investigate the significance of BRAFV600E, NRAS, KRAS, HRAS, RET/PTC (RET/PTC1 and RER/PTC3), PAX8/PPARg mutations for the development and course of thyroid cancer with the determination of a significant predictor mutation. Materials and methods. The analysis included 63 selected case histories of patients who, at the preoperative stage, underwent molecular genetic testing (MHT) of the thyroid gland (TG) masses and subsequently underwent surgical treatment in the surgical department of the Ukrainian Scientific and Practical Center for Endocrine Surgery, Transplantation of Endocrine Organs and Tissues. The average age of the patients was 41.0 ± 1.8 years; from them 7men and56women. All patients underwent fine-needle aspiration puncture biopsy(FNAB) of thyroid nodules according to the standard method followed by a cytological conclusion in accordance with the Bethesda system.The Bethesda III category was revealed in 3 patients (4.8 %), Bethesda IV — 13 patients (20.6 %), Bethesda V — 12 patients (19.0 %), Bethesda VI in 35 (55.6 %) patients. The pathogenic mutations were detected in 47 (74.6 %) patients (group 1), among them two mutations were simultaneously found in two subjects. In 16 cases (25.4 %), no pathogenic mutation was found at all (group 2). Results. The genes that occurred most often were BRAFV600E — in 35 patients (55.6 %), NRAS — in 11 patients (17.5 %), KRAS — in 3 patients (4.8 %). In case of thyroid cancerdiagnosis, pathogenic mutations were found in 38 (79.1 %) subjects. The BRAFV600E gene mutation was observed when establishing a cytological conclusion classified as Bethesda III—V in 28.9 %, and in Bethesda V and in 77.1 %. Accordingly, the sensitivity of the test was low — 0.646, specificity — 0.733. The high prognostic significance of a positive result(PPV) value (from 0.784 to 0.943) indicated the likelihood of detecting thyroid cancer. This assumption confirms the calculation of the c-square criterion with the Yates correction, which is 5.207 (p = 0.023). The use of this test for the presence of the NRAS gene to detect thyroid cancer was ineffective, the value of the c -square criterion with Yates correction = 0.009 (p = 0.927). The incidence of thyroid cancer in group 1 in the cytological class Bethesda III—V was higher than in group 2, but it did not differ significantly between the groups. The aggressiveness of thyroid cancer in patients of group 1 with a positive MHT result did not have significant differences compared with the results obtained in group 2 (39.5 % and 33.3 %, respectively). Conclusions. The use of the kit for the determination of MHTmade it possible to identify pathogenic mutations in the genes BRAFV600E, NRAS, KRAS in 79.1 % of cases. The presence of these genes in combination with the analysis of cytomorphological findings classified according to the Bethesda III—V system did not increase the detection of thyroid cancer in the studied patients. The BRAFV600E gene, which was observed in 64.6 % of cases (PPV from 0.784 to 0.943), was a significant predictor among the studied candidate genes for establishing the diagnosis of thyroid cancer. Detection of a pathogenic mutation in patients with thyroid cancer did not indicate in favour of its aggressive course.&#x0D;

Thyroid nodules with indeterminate cytology: association between nodule size, histopathological characteristics and clinical outcome in differentiated thyroid carcinomas\xa0\u2014\xa0a multicenter retrospective cohort study on 761 patients

A great number of surgical diagnostic procedures are performed every year for thyroid nodules that are included in undetermined cytological classes that reveal to be malignant thyroid carcinomas in one-third of cases. In the most recent guidelines, lobectomy is the most recommended surgical approach for this classes of nodules, but total thyroidectomy is the recommended treatment for undetermined nodules larger than 4 cm. The main study aim is to support or question the dimensional criteria as an independent clinical decision element for undetermined thyroid nodules management. We examined data regarding 761 patients undergoing thyroid surgery for undetermined thyroid nodules at two high-volume endocrine surgery units in Italy. Patients were divided into three groups based on the preoperative size of the nodules (N < 1, 1 < N < 4, N > 4 cm). Among the patients belonging to the different groups, we analyzed: differences in malignancy rate, histological characteristics of invasiveness and neoplastic aggressiveness, rates of recurrence and response to therapy. Nodule size (evaluated as a categorical variable and as a continuous variable) did not show any statistically significant correlation with the rate of malignancy, histopathological characteristics of tumor aggressiveness and the patient’s clinical outcome. Most of the tumors found were included in the low risk class (79.2%) and only one was classified as high risk. Follow up of cancer cases showed excellent results in terms of survival, response to therapy and disease recurrence. Malignant thyroid tumors of any size resulting from a nodule identified as cytologically indeterminate are usually characterized by a low risk follicular pattern, well-differentiated and with an excellent outcome. As a result, preferring an extended surgical attitude for undetermined nodules based on tumor size, in absence of other risk factors, can lead to overtreatment in a significant percentage of cases.

Utilizando os conhecimentos prévios sobre célula de estudantes de um curso de enfermagem como ponto de partida do planejamento de ensino

The prior knowledge of the student is extremely important for learning new content, and the diagnosis of such knowledge can assist teacher’s education planning. In this article the free association of words method was carried out to survey the students' previous knowledge in order to formulate a Cytology lesson plan. Thus, 60 freshman nursing students were asked to provide 15 words about the topic “Cell” during their first Cytology class. The initial analysis found that students had adequate prior knowledge with 210 terms (123 central terms and 87 derived terms) and 752 citation obtained. All terms were categorized into eleven categories and were used as references to construct a teacher education planning guide aiming a systematized knowledge by the common sense between the terms and frequencies of these categories. The teaching strategy sought the activation of student’s prior knowledge, content leveling and contextualized learning by focusing on concrete applications in students’ everyday life. The strategy allowed for greater assimilation of the content, motivation and participation in class by the students. In addition, an initial diagnostic evaluation form to collect associated free terms was formulated to facilitate the organization and analysis of prior knowledge data by the teacher.

Combined molecular and mathematical analysis of long noncoding RNAs expression in fine needle aspiration biopsies as novel tool for early diagnosis of thyroid cancer

PurposeIn presence of indeterminate lesions by fine needle aspiration (FNA), thyroid cancer cannot always be easily diagnosed by conventional cytology. As a consequence, unnecessary removal of thyroid gland is performed in patients without cancer based on the lack of optimized diagnostic criteria. Aim of this study is identifying a molecular profile based on long noncoding RNAs (lncRNAs) expression capable to discriminate between benign and malignant nodules.MethodsPatients were subjected to surgery (n = 19) for cytologic suspicious thyroid nodules or to FNA biopsy (n = 135) for thyroid nodules suspicious at ultrasound. Three thyroid-specific genes (TG, TPO, and NIS), six cancer-associated lncRNAs (MALAT1, NEAT1, HOTAIR, H19, PVT1, MEG3), and two housekeeping genes (GAPDH and P0) were analyzed using Droplet Digital PCR (ddPCR).ResultsBased on higher co-expression in malignant (n = 11) but not in benign (n = 8) nodules after surgery, MALAT1, PVT1 and HOTAIR were selected as putative cancer biomarkers to analyze 135 FNA samples. Cytological and histopathological data from a subset of FNA patients (n = 34) were used to define a predictive algorithm based on a Naïve Bayes classifier using co-expression of MALAT1, PVT1, HOTAIR, and cytological class. This classifier exhibited a significant separation capability between malignant and benign nodules (P < 0.0001) as well as both rule in and rule out test potential with an accuracy of 94.12% and a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 91.67%.ConclusionsddPCR analysis of selected lncRNAs in FNA biopsies appears a suitable molecular tool with the potential of improving diagnostic accuracy.

Abstract 1309: Distinct molecular subtypes and a high diagnostic urinary biomarker of upper urinary tract urothelial carcinoma

Abstract [Backgrounds] Upper urinary tract urothelial carcinomas (UTUCs) are rare malignancies with a histological similarity to urothelial bladder carcinomas (UBCs). Unlike UBCs, little is known about the genetic basis of UTUCs, for which no useful biomarkers are currently available. [Material &amp; Methods] Surgical specimens and matched normal samples were obtained from 209 UTUC patients with various stages and were subjected to integrated molecular analysis including whole exome/transcriptome sequencing. We also investigated a possibility of UTUC diagnosis using urinary sediment-derived DNA. [Result] Hypermutation (≥20/Mb) was observed in 15 samples (6.7%), of which 12 harbored biallelic mismatch repair genes alterations suggestive of Lynch syndrome. The most frequently affected driver genes included TERT (promoter) (50%), followed by KMT2D (46%), FGFR3 (44%), CDKN2A (44%), and TP53 (36%). Mutually exclusive patterns were observed among alterations in FGFR3, RAS (H-/K-/NRAS), TP53, and MDM2, which covered 93.8% of the entire cohort. Approximately 40% of the samples showed highly complexed karyotype (CK) with frequent aneuploidy and chromothripsis. Based on these findings, UTUC cases were classified into 5 genetic subgroups: hypermutated, FGFR3-mutated, RAS-mutated, TP53-mutated with CK, and other cases with none of these features, which were significantly associated distinct clinical outcomes. While hypermutated and FGFR3 subtypes showed favorable prognosis, the TP53/CK subtype exhibited an aggressive clinical course and a shorter survival. Expression-based molecular classification identified unique gene expression subtypes: clusters 1-5, which showed a strong correlation with the mutation-based classification. Of interest, cluster 3 was highly enriched for TP53/CK and showed high expression of PDL1 and PDL2, suggesting a possible role of checkpoint inhibitions. The sequencing analysis of urinary sediment-derived DNA successfully captured those mutations and copy number alterations (CNAs) that had been detected in the corresponding preoperative samples in 84.4% of the cases (38/45), which was significantly higher than the positive diagnosis in urine cytology (class 4 and 5, 31.1%). Failure of detecting mutations were found in 5 tumors that were associated with severe hydronephrosis, which might prevented tumor-containing urinary flow. None of the post operative (0/34) and control (0/19) samples showed mutations/CNAs, including two with positive cytology (class4), both of which were diagnosed as benign pelvis tumors after surgery. [Conclusion] UTUC are classified into 5 distinct genetic subtypes characterized by unique profiles of gene mutations, expression and clinical outcomes, which help an optimal choice of therapeutics, including novel molecular-targeted drugs and checkpoint-inhibitors. Sequencing urinary sediments is a useful, non-invasive biomarker for precise diagnosis and proper treatment. Citation Format: Yoichi Fujii, Yusuke Sato, Hiromichi Suzuki, Tetsuichi Yoshizato, Kenichi Yoshida, Yuichi Shiraishi, Taketo Kawai, Tohru Nakagawa, Hiroaki Nishimatsu, Toshikazu Nishimatsu, Masashi Sanada, Hideki Makishima, Satoru Miyano, Haruki Kume, Seishi Ogawa. Distinct molecular subtypes and a high diagnostic urinary biomarker of upper urinary tract urothelial carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1309.

High-Risk HPV Testing in Primary Screening for Cervical Cancer in the Public Health System, São Paulo, Brazil

Every year there are approximately 16,000 new cases of cervical cancer in Brazil. Novel screening technologies may reduce this number by expanding the population coverage but also by improving the detection rate of precursor lesions. We aimed to evaluate human papillomaviruses (HPV)-DNA testing in the context of routine cervical cancer screening in the public health system of the city of São Paulo, Brazil. Women participating in the primary screening program were invited to enroll. Liquid-based cytology samples were collected and cytology and Hr-HPV DNA testing were performed in parallel. Cytologists were blind to HPV results. Women older than 24 years with a positive high-risk HPV test and/or cytology class ≥ ASC-US were referred to colposcopy. From December 2014 to December 2016, 16,102 women joined the study. High-risk human papillomavirus (HR HPV) DNA prevalence was 14.9%, whereas cytologic abnormalities were found in 7.2% of the women. Per protocol, 1,592 Hr-HPV+ women, in addition to 72 patients with cytologic classification > low-grade squamous intraepithelial lesion (LSIL) were referred. A total of 80 cervical intraepithelial neoplasia (CIN2+) cases were diagnosed, 79 were Hr-HPV DNA+ and 18 had normal cytology. Hr-HPV DNA detected a significant number of patients with premalignant lesions missed by cytology and all 16 CIN3+ cases were Hr-HPV DNA+ HPV genotyping may be useful in the management of Hr-HPV+ women, reducing the burden of colposcopic referral for those harboring genotypes with a weaker association to CIN3+ Use of HPV-DNA testing was shown to be feasible and advantageous over current cytologic screening in the public health system.

Gender-specific correlation of intranodular chronic lymphocytic thyroiditis with thyroid nodule size, echogenicity, and histologically-verified cytological class of malignancy risk

No data are available on the cytologically and histologically demonstrated presence of intranodular chronic lymphocytic thyroiditis (ICLT) and on the ICLT relationship with thyroid nodule characteristics such as size, echotexture and nature (benign or malignant). We wished to fill this gap by analyzing data in a gender-specific fashion. We studied 408 thyroid nodules from 408 consecutive persons (325 females and 83 males). Nodules were isoechoic (n = 268) or hypoechoic (n = 140), ICLT +ve (n = 113 [27.7%]) or ICLT −ve (n = 295), cytologically low-risk (n = 197) or high-risk (n = 211), histologically benign (n = 263) or malignant (n = 145). ICLT prevailed in females (97/113) and in hypoechoic nodules (58/140 [41.4%] vs 55/268 [20.5%], P < 0.0001). Compared to males, females had (i) smaller nodules (18.5 ± 9.4 vs 23.3 ± 13.4 mm, P = 0.0002), a difference due to the isoechoic nodules (21.1 ± 9.8 vs 26.6 ± 14.1 mm, P = 0.0006), (ii) lower rates of high-risk nodules (161/325 [49.5%] vs 50/83 [60.2%], P = 0.082) and malignant nodules (110/325 [33.8%] vs 35/83 [42.2%] P = 0.16). ICLT +ve nodules were smaller than the ICLT −ve ones (15.4 ± 6.9 vs 20.9 ± 11.2 mm, P < 0.0001), a difference due to the isoechoic nodules (17.5 ± 6.5 vs 23.6 ± 11.7 mm, P = 0.0003). The smallest nodules were hypoechoic, cancerous and ICLT +ve nodules in males (9.5 ± 4.0 mm); the largest were isoechoic, cytologically risky and ICLT −ve in males (29.1 ± 13.2 mm). Compared to ICLT −ve nodules, malignancy prevailed in ICLT +ve nodules (55/113 [48.7%] vs 90/295 [30.5%], P = 0.0006), both in hypoechoic (37/58 [63.8%] vs 41/82 [50.0%]) and isoechoic nodules (18/55 [32.7%] vs 49/213 [23.0%]). ICLT +ve hypoechoic nodules of females and ICLT −ve hypoechoic nodules of males had the greatest rate of malignancy (67% both), while ICLT −ve isoechoic nodules of females had the lowest (19%).In conclusion, presence/absence of ICLT is associated with some sexually dimorphic characteristics of thyroid nodules. Adding the specification of ICLT positivity/negativity in cytological reports may help improving the risk of malignancy at least in some groups of thyroid nodules.

Analysis of human papillomavirus 16 E6, E7 genes and Long Control Region in cervical samples from Uruguayan women

ObjectiveThis study aims to investigate the HPV16 variant distribution by sequence analyses of E6, E7 oncogenes and the Long Control Region (LCR), from cervical cells collected from Uruguayan women, and to reconstruct the phylogenetic relationships among variants. MethodsForty-seven HPV16 variants, obtained from women with HSIL, LSIL, ASCUS and NILM cytological classes were analyzed for LCR and 12 were further studied for E6 and E7. Detailed sequence comparison, genetic heterogeneity analyses and phylogenetic reconstruction were performed. ResultsA high variability was observed among LCR sequences, which were distributed in 18 different variants. E6 and E7 sequences exhibited novel non-synonymous substitutions. Uruguayan sequences mainly belonged to the European lineage, and only 5 sequences clustered in non-European branches; 3 of them in the Asian-American and North-American linage and 2 in an African branch. Additionally, 6 new variants from European and African clusters were identified. ConclusionsHPV16 isolates mainly belonged to the European lineage, though strains from African and Asian-American lineages were also identified. Herein is reported for the first time the distribution and molecular characterization of HPV16 variants from Uruguay, providing novel insights on the molecular epidemiology of this infectious disease in the South America. SynopsisA high variability among HPV 16 isolates mainly belonged to European lineage, provides an extensive sequence dataset from a country with high burden of cervical cancer.

The Prevalence of Genus Alpha Human Papillomavirus in Women with Uterine Cervical Infection and/or Inflammation in Western Iran

Introduction:Human papillomavirus (HPV) infection is strongly associated with risk of cervical cancer and genital warts.Aim:The study aimed to report the prevalence of genus alpha human papillomavirus (HPV) types in women with cervical infection and/or inflammatory in Western Iran.Materials and Methods:In a cross-sectional study, 435 women were clinically diagnosed with cervical infections. The method of HPVs detection was polymerase chain reaction (PCR). The majority of patients (304 patients) did Pap smear based on liquid-based specimens.Results:Out of 435 patients, 150 patients (34.5%) had HPV positivity that the prevalence of high-risk HPVs was 52.7%. Out of 76 patients with Pap smear positivity, 68.4% had atypical squamous cells of undetermined significance cytology class and 31.6% had low-grade squamous intraepithelial lesion cytology class. The most prevalence rate of HPV was in age ≤30 years. HPV 16 and HPV 56 were the most prevalence rate among high-risk HPVs. Overall HPV alpha-10 (59%) and HPV alpha-9 (32.2%) had the most prevalence rate.Conclusions:Among high-risk HPVs, HPV 16 was the most common HPV detected in our population with a very low prevalence of HPV 18. In addition, HPV 6 and then HPV 11 had the most prevalence rate in the women with uterine cervix (cervical) infection among low-risk HPVs.

Laparoscopic Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Gastric Cancer: Its Beneficial Effects on Reduction and Exact Evaluation of the Peritoneal Cancer Index

We assessed whether the laparoscopic hyperthermic intraperitoneal chemotherapy (L-HIPEC) + neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) could reduce the peritoneal cancer index (PCI; which is defined by Sugerbaker) and improve the possibility to obtain a complete cytoreductive surgery (CRS with peritonectomy; basically according to the Sugerbaker's procedure). After L-HIPEC + NIPS, the PCI score was decreased in 89.5 per cent of patients, and the average score was significantly reduced. The average PCI reduction of improved PCI cases was 10.2 ± 8.4. The hypothetical cut-off was at a PCI score of six with significant higher possibility of CRS completeness. Twelve patients had high-PCI (PCI > 6), and six of them (50.0%) were converted to low-PCI (PCI ≦ 6) and got a complete CRS. There was a significant relationship between post-PCI (PCI after L-HIPEC + NIPS) and CRS completeness; however, pre-PCI (PCI before L-HIPEC + NIPS) value was not a relevant factor. The high-PCI and increased PCI even after L-HIPEC + NIPS (deteriorated-PCI) were suggested as important risk factors for surgical completeness. Neither pre- nor postcytological results had a significant relationship between CRS completeness. However, the deteriorated cytological class was considered as a risk factor for CRS completeness. The second-look laparoscopy would be recommended for the better selection of the patients who can receive benefits by this extensive surgery.

The impact of the non-invasive follicular thyroid neoplasm with papillary-like nuclear feature terminology in the routine diagnosis of thyroid tumours.

Due to the recent proposal of the non-invasive follicular thyroid neoplasm with papillary-like nuclear feature (NIFTP) category, the authors analyse the state of the art in the challenging diagnosis of follicular thyroid neoplasms in routine practice. A consecutive series of 200 histological diagnoses, with complete cytological correlation, was analysed following the introduction of the NIFTP definition. The study was conducted in a general hospital with a high prevalence of thyroid benign nodules that accounted for approximately 60% of surgically-treated nodules. The significant incidence of the new NIFTP category was 7%. Concurrently, a gradual decrease of the follicular variant of papillary thyroid carcinoma (fvPTC) was observed (3.5%). When evaluating the FNA biopsies within the NIFTP group, despite the systematic evaluation of nuclear crowding, enlargement, irregularities and clearing, the final cytological class was often indeterminate for malignancy (Thy3/III-IV, 71%). At histology, the application of the semiquantitative NIFTP score for the evaluation of the PTC-like nuclear features was able to discriminate benign lesions (score 0/1) from fvPTC (score 2/3). A certain degree of overlapping still persisted between NIFTP and fvPTC (score 2) or between NIFTP and benign lesions (score 1). In the routine evaluation of FNA biopsies, the presence of subtle and questionable PTC-like nuclear features still remains a controversial aspect of the diagnostic workflow. Given that the NIFTP category was introduced to stratify the low-risk group of thyroid tumours more precisely, pathologists should force themselves to apply the nuclear score rigorously and to classify cases assigned a score of 1 as benign proliferations.

MP71-07 SERUM CORE FUCOSYLATED N-GLYCAN CARRYING IMMUNOGLOBRIN IS A DIAGNOSTIC AND PRE-OPERATIVE PROGNOSTIC MARKER OF UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma I1 Apr 2017MP71-07 SERUM CORE FUCOSYLATED N-GLYCAN CARRYING IMMUNOGLOBRIN IS A DIAGNOSTIC AND PRE-OPERATIVE PROGNOSTIC MARKER OF UPPER TRACT UROTHELIAL CARCINOMA Toshikazu Tanaka, Yuki Tobisawa, Shingo Hatakeyama, Kazuyuki Mori, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama, and Tohru Yoneyama Toshikazu TanakaToshikazu Tanaka More articles by this author , Yuki TobisawaYuki Tobisawa More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Kazuyuki MoriKazuyuki Mori More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Takuya KoieTakuya Koie More articles by this author , Chikara OhyamaChikara Ohyama More articles by this author , and Tohru YoneyamaTohru Yoneyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2263AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although hematuria and urine cytology is a powerful indicator for diagnosis of upper tract urothelial carcinoma (UTUC), there is a need to identify more powerful predictive biomarkers of UTUC to improve diagnostic accuracy. Prognostic biomarkers were also required to decide on therapeutic strategy of UTUC. The use of N-glycans of immunoglobrins (Igs) as a biomarkers of UTUC has not yet been tested. In the present study, we performed serum N-glycomics between healthy volunteer (HLT) and UTUC patients and evaluated its potential as a diagnostic and prognostic serum-based biomarkers of UTUC. METHODS N-glycomics in Igs fraction were performed in randomly selected 78 HLT and 73 UTUC (preoperative serum, n=52 and post-operative serum, n=21, respectively) patients. The putative structure of N-glycans was analyzed by MALDI-TOF-MS analysis. To confirm the result of N-glycomics of Igs, We performed lectin-array analysis utilizing recombinant lectin-array chip and evanescent fluorescence scanner. RESULTS N-glycomics of Igs reveled that preoperative serum core fucosylated biantennary (m/z 1590, 2073, and 2524) and core fucosylated bisecting (m/z 1647, 1793, 2955 and 2727) N-glycans of Igs levels in UTUC patients was significantly higher in HLT group. Receiver-operating characteristic area under the curve (AUC) for prediction of UTUC in significant core fucoslyalted N-glycans was 0.7290-0.8728 in contrast to hematuria positive status (AUC 0.8627) and urine cytology class =IV (AUC 0.7745), respectively. In post-operative serum analysis, we found that the level of serum core fucosylated N-glycans in cancer death group was tend to higher than that of surviving group. Furthermore, lectin-array analysis revealed that fucoslyted IgG (Fuc-IgG) level of UTUC was tend to higher than HLT. In post-operative serum analysis, we also found serum fuc-IgG levels in cancer death group was significantly higher than that of surviving group. CONCLUSIONS The serum core fucosylated N-glycans levels and Fuc-IgG levels may be a promising diagnostic and post-operative prognostic markers of UTUC. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e947-e948 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Toshikazu Tanaka More articles by this author Yuki Tobisawa More articles by this author Shingo Hatakeyama More articles by this author Kazuyuki Mori More articles by this author Yasuhiro Hashimoto More articles by this author Takuya Koie More articles by this author Chikara Ohyama More articles by this author Tohru Yoneyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

口腔細胞診におけるベセスダシステム SIL の取扱いに関する検討

口腔細胞診におけるベセスダシステム SIL の取扱いに関する検討