Association of Trichomonas vaginalis and Cytological Abnormalities of the Cervix in Low Risk Women

Objective

Is Trichomonas vaginalis (TV) an inducing factor for the development of (pre-)cancerous lesions of the cervix?

Design

Cross sectional study.

Setting

Screening healthy Belgian women with low infection risk.

Sample

63,251 consecutive liquid based cervical samples.

Methods

Real time quantitative PCR for presence of TV, 18 HPV types and Pap smear analysis of cytologic abnormalities.

Main Outcome Measures

Association of TV and HPV with cervix dysplasia

Results

The overall prevalence of TV DNA was 0.37%, of low risk HPV 2%, of high risk HPV 13.2%, and 8.8 % had cytological abnormalities. Both LR-HPV and HR-HPV were significantly associated with all cytological abnormalities. Presence of TV was associated with LR- and HR-HPV, ASC-US and HSIL, but not with other abnormalities. All women with TV and HSIL also had HR-HPV, while the latter was present in only 59% of women with TV and ASC-US. Amongst HPV negative women, TV was found in 1.3% of women with ASC-US, but only in 0.03% of women with normal cytology (OR 4.2, CL95% 2.1-8.6). In HR-HPV positive women, presence of TV increased the likelihood of cytological abnormalities somewhat (P=0.05), mainly due to an increase in ASC-US and LSIL, but not HSIL.

Conclusions

We conclude that TV infection is associated with both LR and HR-HPV infection of the cervix, as well as with ASC-US and HSIL. TV is a concomitant STI, but is not thought to be a co-factor in the causation of HSIL and cervical cancer. However, TV may cause false positive diagnoses of ASC-US.     

Usefulness of High Suction Pressure for Sufficient Tissue Collection During Endobronchial Ultrasound Guided Transbronchial Needle Aspiration

Introduction

The optimal suction pressure during endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) remains to be determined. The aim of this study was to compare suction pressures for performance in collecting sufficient tissue specimens from mediastinal and hilar lymph nodes during EBUS-TBNA.

Methods

Retrospective analysis of consecutive patients with mediastinal and hilar lymphadenopathy who underwent EBUS-TBNA over a 3-year period. Results from patients who underwent EBUS-TBNA using a dedicated 20-mL VacLoc (Merit Medical Systems, Inc, South Jordan, UT) syringe (conventional method, group C) were compared with results from patients in whom a disposable 30-mL syringe (high pressure group, group H) was used. The yield for sufficient histologic specimen retrieval and amount of tissue obtained were compared between the 2 groups.

Results

Of 178 patients who underwent EBUS-TBNA, 131 had lung cancer confirmed by EBUS-TBNA: 35 in group C and 96 in group H. There were 7 patients in group C and 6 in group H who received final diagnoses by cytology alone. There were 28 in group C and 90 in group H who were diagnosed by both cytology and histology. There was a statistically significant difference between the groups in terms of the rate of sufficient sampling for histological specimens (p = 0.04). The H group revealed a tissue area approximately twice that of the C group (p = 0.003). There were no major procedure-related complications in either group.

Conclusion

Higher suction pressures with larger syringe volumes during EBUS-TBNA may be useful for safely collecting sufficient tissue specimens.     

GeneXpert MTB/RIF Assay for the Diagnosis of Tuberculous Lymphadenitis on Concentrated Fine Needle Aspirates in High Tuberculosis Burden Settings

Introduction

The diagnosis of tuberculous lymphadenitis (TBL) remains challenging. The routinely used methods (cytology and smear microscopy) have sub-optimal sensitivity. Recently, WHO recommends GeneXpert to be used as the initial diagnostic test in patients suspected of having extra-pulmonary tuberculosis (EPTB). However, this was a conditional recommendation due to very low-quality evidence available and more studies are needed. In this study we evaluated the performance of Xpert for the diagnosis of TBL on concentrated fine needle aspirates (FNA) in Southwest Ethiopia.

Methods

FNA was collected from presumptive TBL cases. Two smears were prepared from each aspirate and processed for cytology and conventional microscopy. The remaining aspirate was treated with N-acetyl-L-cysteine-NaOH and centrifuged for 15minutes at 3000g. The concentrated sediment was used for culture and Xpert test. Capilia TB-Neo test was used to differentiate M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM). Composite bacteriological methods (culture and/or smear microscopy) were considered as a reference standard.

Result

Out of 143 enrolled suspects, 64.3% (92/143) were confirmed TBL cases by the composite reference standard (CRS). Xpert detected M. tuberculosis complex (MTBC) in 60.1% (86/143) of the presumptive TBL cases. The sensitivity of Xpert compared to CRS was 87.8% [95% CI: 81.0–94.5] and specificity 91.1% [95% CI: 82.8–99.4]. The sensitivity was 27.8% for smear microscopy and 80% for cytology compared to CRS. Cytology showed the lowest specificity (57.8%). Xpert was positive in 4 out of 45 culture- and smear-negative cases. Among 47 cytomorphologically non-TBL cases, 15 were positive on Xpert. More than half of Xpert-positive cases were in the range of very low cut-off threshold values (28<Ct<38). Resistance to rifampicin was identified in 4.7% (4/86) of Xpert-positive cases.

Conclusion

Xpert test showed a high sensitivity and specificity for the diagnosis of TBL on concentrated FNA samples. In addition, Xpert offered rapid detection of rifampicin-resistant M. tuberculosis strains from lymph node aspirates.     

Diagnostic Efficacy of Cell Block Immunohistochemistry,Smear Cytology,and Liquid-Based Cytology in Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Lesions: A Single-Institution Experience

Background

The diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology varies widely depending on the treatment method of the specimens. The present study aimed to evaluate the diagnostic efficacy of cell block (CB) immunohistochemistry, smear cytology (SC), and liquid-based cytology (LBC) in patients with pancreatic lesions without consulting an on-site cytopathologist.

Methods

This study prospectively enrolled 72 patients with pancreatic lesions. The EUS-FNA specimens were examined by SC, LBC, and CB immunohistochemistry. The diagnostic efficacy of the 3 methods was then compared. Patients’ final diagnosis was confirmed by surgical resection specimens, diagnostic imaging, and clinical follow-up.

Results

Our results included 60 malignant and 12 benign pancreatic lesions. The diagnostic sensitivity (90%), negative predictive value (66.7%), and accuracy (91.7%) of CB immunohistochemistry were significantly higher than those of SC (70.0%, 30.0%, and 75.0%, respectively) and LBC (73.3%, 31.6%, and 77.8%, respectively) (all P<0.05). The combination of CB and SC, or CB and LBC, did not significantly increase the efficacy compared to CB immunohistochemistry alone.

Conclusion

Our findings suggest that in the absence of an on-site cytopathologist, CB immunohistochemistry on EUS-FNA specimens offers a higher diagnostic efficacy in patients with pancreatic lesions than does SC and LBC.     

A Study of Cytological Changes in the Bone Marrow of Patients with Severe Fever with Thrombocytopenia Syndrome

Background

Peripheral blood leucopenia and thrombocytopenia are the main manifestations in severe fever with thrombocytopenia syndrome (SFTS) patients. However, the underlying causes are poorly understood. Therefore, we aimed to investigate cytology of bone marrow samples collected from SFTS patients.

Methods

10 SFTS patients were identified by typical clinical manifestations, detection of peripheral blood leucopenia and thrombocytopenia, and nucleic acid-based detection of the newly identified bunyavirus. SFTS patients, along with 10 participants with acute aplastic anemia and 10 healthy volunteers were enrolled in this study after written informed consent to undergo bone marrow cytological examination.

Results

We observed similar bone marrow properties in SFTS patients and healthy volunteers, significantly different from the characteristics observed in acute aplastic anemia patients.

Conclusion

Similarities between bone marrow samples collected from SFTS patients and healthy volunteers suggest that peripheral blood leucopenia and thrombocytopenia do not result from bone marrow cell plasticity.     

Aetiology of Pulmonary Symptoms in HIV-Infected Smear Negative Recurrent PTB Suspects in Kampala,Uganda: A Cross-Sectional Study

Introduction

Previously treated TB patients with pulmonary symptoms are often considered recurrent TB suspects in the resource-limited settings, where investigations are limited to microscopy and chest x-ray. Category II anti-TB drugs may be inappropriate and may expose patients to pill burden, drug toxicities and drug-drug interactions.

Objective

To determine the causes of pulmonary symptoms in HIV-infected smear negative recurrent pulmonary tuberculosis suspects at Mulago Hospital, Kampala.

Methods

Between March 2008 and December 2011, induced sputum samples of 178 consented HIV-infected smear negative recurrent TB suspects in Kampala were subjected to MGIT and LJ cultures for mycobacteria at TB Reference Laboratory, Kampala. Processed sputum samples were also tested by PCR to detect 18S rRNA gene of P.jirovecii and cultured for other bacteria.

Results

Bacteria, M. tuberculosis and Pneumocystis jirovecii were detected in 27%, 18% and 6.7% of patients respectively and 53.4% of the specimens had no microorganisms. S. pneumoniae, M. catarrhalis and H. influenzae were 100% susceptible to chloramphenicol and erythromycin but co-trimoxazole resistant.

Conclusion

At least 81.5% of participants had no microbiologically-confirmed TB. However our findings call for thorough investigation of HIV-infected smear negative recurrent TB suspects to guide cost effective treatment.     

Human Papillomavirus Type-Specific Prevalence in the Cervical Cancer Screening Population of Czech Women

Background

Infection with high-risk human papillomavirus (HPV)types has been recognized as a causal factor for the development of cervical cancer and a number of other malignancies. Today, vaccines against HPV, highly effective in the prevention of persistent infection and precancerous lesions, are available for the routine clinical practice.

Objectives

The data on the prevalence and type-specific HPV distribution in the population of each country are crucial for the surveillance of HPV type-specific prevalence at the onset of vaccination against HPV.

Methods

Women attending a preventive gynecological examination who had no history of abnormal cytological finding and/or surgery for cervical lesions were enrolled. All samples were tested for the presence of HPV by High-Risk Hybrid Capture 2 (HR HC2) and by a modified PCR-reverse line blot assay with broad spectrum primers (BS-RLB).

Results

Cervical smears of 1393 women were analyzed. In 6.5% of women, atypical cytological findings were detected. Altogether, 28.3% (394/1393) of women were positive for any HPV type by BS-RLB, 18.2% (254/1393) by HR HC2, and 22.3% (310/1393) by BS-RLB for HR HPV types. In women with atypical findings the prevalence for HR and any HPV types were significantly higher than in women with normal cytological findings. Overall, 36 different HPV types were detected, with HPV 16 being the most prevalent (4.8%). HPV positivity decreased with age; the highest prevalence was 31.5% in the age group 21-25 years.

Conclusions

Our study subjects represent the real screening population. HPV prevalence in this population in the Czech Republic is higher than in other countries of Eastern Europe. Also the spectrum of the most prevalent HPV types differs from those reported by others but HPV 16 is, concordantly, the most prevalent type. Country-specific HPV type-specific prevalences provide baseline information which will enable to measure the impact of HPV vaccination in the future.     

Diagnosis of post-surgical fine-needle aspiration biopsies of thyroid lesions with indeterminate cytology using HRMAS NMR-based metabolomics

Introduction

Ultrasound examination coupled with fine-needle aspiration (FNA) cytology is the gold standard for the diagnosis of thyroid cancer. However, about 10–40% of these analyses cannot be conclusive on the malignancy of the lesions and lead to surgery. The cytological indeterminate FNA biopsies are mainly constituted of follicular—patterned lesions, which are benign in 80% of the cases.

Objectives

The development of a FNAB classification approach based on the metabolic phenotype of the lesions, complementary to cytology and other molecular tests in order to limit the number of patients undergoing unnecessary thyroidectomy.

Methods

We explored the potential of a NMR-based metabolomics approach to improve the quality of the diagnosis from FNABs, using thyroid tissues collected post-surgically.

Results

The NMR-detected metabolites were used to produce a robust OPLSDA model to discriminate between benign and malignant tumours. Malignancy was correlated with amino acids such as tyrosine, serine, alanine, leucine and phenylalanine and anti-correlated with myo-inositol, scyllo-inositol and citrate. Diagnosis accuracy was of 84.8% when only indeterminate lesions were considered.

Conclusion

These results on model FNAB indicate that there is a clear interest in exploring the possibility to export NMR metabolomics to pre-surgical diagnostics.

     

Effectiveness and Complications of Ultrasound Guided Fine Needle Aspiration for Primary Liver Cancer in a Chinese Population with Serum α-Fetoprotein Levels ≤200 ng/ml - A Study Based on 4,312 Patients

Background

Hepatocellular carcinoma (HCC) can be diagnosed by noninvasive approaches with serum α-fetoprotein (AFP) levels >200 ng/ml and/or a radiological imaging study of tumor mass >2 cm in patients with chronic liver disease. Percutaneous fine needle aspiration (FNA) under ultrasound (US) guidance has a diagnostic specificity of 95% and is superior to radiological imaging studies.

Aim

The aim of this study is to elucidate the effectiveness and complications of fine needle aspiration in a Chinese population with primary liver cancer and AFP levels ≤200 ng/ml.

Materials and Methods

A retrospective study was conducted over a period of 28 years. This selection period included patients with a suspected diagnosis of primary liver cancer whose AFP levels were ≤200 ng/ml and who underwent US-FNA. This data was then analyzed with cytomorphological features correlating with medical history, radiological imaging, AFP, and follow-up information.

Results

Of the 1,929 cases with AFP ≤200 mg/ml, 1,756 underwent FNA. Of these, 1,590 cases were determined malignant and the remaining 166 were determined benign. Further, 1,478 malignant cases were diagnosed by FNA alone, and of these, 1,138 were diagnosed as PLC. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the diagnoses were 92.96%, 100%, 100%, 59.71%, and 93.62% respectively. There was no significant difference in the sensitivity, specificity, PPV and NPV between the subgroups with tumor size<2 cm and ≥2 cm. Major complications included implantation metastasis and hemorrhage.

Conclusion

Patients with PLC, especially those who present with an AFP ≤200 ng/ml, should undergo FNA. If negative results are obtained by FNA, it still could be HCC and repeated FNA procedure may be needed if highly suspicious of HCC on imaging study. The superiority of FNA in overall accuracy may outweigh its potential complications, such like hemorrhage and implantation metastasis.     

Usefulness of core needle biopsy for the diagnosis of thyroid Burkitt’s lymphoma: a case report and review of the literature

Background

Thyroid lymphomas are an exceptional finding in patients with thyroid nodules. Burkitt’s lymphoma is one of the rarest and most aggressive forms of thyroid lymphomas, and its prognosis depends on the earliness of medical treatment. Given the rarity of this disease, making a prompt diagnosis can be challenging. For instance, fine-needle aspiration (FNA) cytology, which is the first-line diagnostic test that is performed in patients with thyroid nodules, is often not diagnostic in cases of thyroid lymphomas, with subsequent delay of the start of therapy.

Case presentation

Here we report the case of a 52-year-old woman presenting with a rapidly enlarging thyroid mass. Thyroid ultrasonography demonstrated a solid hypoechoic nodule. FNA cytology was only suggestive of a lymphoproliferative disorder and did not provide a definitive diagnosis. It is core needle biopsy (CNB) that helped us to overcome the limitations of routine FNA cytology, showing the presence of thyroid Burkitt’s lymphoma. Subsequent staging demonstrated bone marrow involvement. The early start of an intensive multi-agent chemotherapy resulted in complete disease remission. At 60 months after the diagnosis, the patient is alive and has not had any recurrence.

Conclusions

Clinicians should be aware that thyroid Burkitt’s lymphoma is an aggressive disease that needs to be treated with multi-agent chemotherapy as soon as possible. To diagnose it promptly, they should consider to order/perform a CNB in any patient with a rapidly enlarging thyroid mass that is suspicious for lymphoma.

     

A Multi-Site Evaluation of Innovative Approaches to Increase Tuberculosis Case Notification: Summary Results

Background

Globally, TB notifications have stagnated since 2007, and sputum smear positive notifications have been declining despite policies to improve case detection. We evaluate results of 28 interventions focused on improving TB case detection.

Methods

We measured additional sputum smear positive cases treated, defined as the intervention area''s increase in case notification during the project compared to the previous year. Projects were encouraged to select control areas and collect historical notification data. We used time series negative binomial regression for over-dispersed cross-sectional data accounting for fixed and random effects to test the individual projects'' effects on TB notification while controlling for trend and control populations.

Results

Twenty-eight projects, 19 with control populations, completed at least four quarters of case finding activities, covering a population of 89.2 million. Among all projects sputum smear positive (SS+) TB notifications increased 24.9% and annualized notification rates increased from 69.1 to 86.2/100,000 (p = 0.0209) during interventions. Among the 19 projects with control populations, SS+TB case notifications increased 36.9% increase while in the control populations a 3.6% decrease was observed. Fourteen (74%) of the 19 projects'' SS+TB notification rates in intervention areas increased from the baseline to intervention period when controlling for historical trends and notifications in control areas.

Conclusions

Interventions were associated with large increases in TB notifications across many settings, using an array of interventions. Many people with TB are not reached using current approaches. Different methods and interventions tailored to local realities are urgently needed.     

Contrast-Enhanced Harmonic Endoscopic Ultrasound-Guided Fine-Needle Aspiration in the Diagnosis of Solid Pancreatic Lesions: A Retrospective Study

Background

The negative predictive value of endoscopic ultrasonography-guided fine needle aspiration for the diagnosis of solid pancreatic lesions remains low, and the biopsy specimens are sometimes inadequate for appropriate pathological diagnosis.

Aims

To evaluate the usefulness of a novel method of contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration for the differential diagnosis and adequate sampling of solid pancreatic lesions.

Methods

Patients with a diagnosis of solid pancreatic lesions who underwent fine-needle aspiration guided by contrast-enhanced harmonic endoscopic ultrasonography or by endoscopic ultrasonography from October 2010 to July 2013 were retrospectively identified and classified into the CH-EUS or EUS group, respectively. Surgical pathology and/or follow-up results were defined as the final diagnosis. Operating characteristics and adequacy of biopsy specimens by fine-needle aspiration were compared between the two groups.

Results

Operating characteristics for contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration in solid pancreatic lesions were as follows: area under the curve = 0.908, sensitivity = 81.6%, specificity = 100%, positive predictive value = 100%, negative predictive value = 74.1%, and accuracy = 87.9%. The percentage of adequate biopsy specimens in the CH-EUS group (96.6%) was greater than that in the EUS group (86.7%).

Conclusion

Simultaneous contrast-enhanced harmonic endoscopic ultrasonography during fine-needle aspiration is useful for improving the diagnostic yield and adequate sampling of solid pancreatic lesions.     

FNA of breast fibroadenoma: observer variability and review of cytomorphology with cytohistological correlation

OBJECTIVE: To determine the observer variability in reporting fibroadenoma of the breast by fine needle aspiration (FNA) and to review the cytomorphological features of the lesion with cytohistological correlation. METHODS: Retrospective analysis of FNA smears from 110 cases diagnosed as fibroadenoma of which surgical pathology follow-up was available in 33. Two pathologists were asked to categorize smears from 67 cases of breast lesions while blinded to the clinical finding as fibroadenoma, epithelial hyperplasia (usual and atypical) and malignant. All fibroadenoma (33) and cancer (15) cases were biopsy-proven. The same set of slides was re-circulated to one of the pathologists, and his first and second round results were compared. RESULTS: Pre-review cytohistological correlation was attained in 32 of 33 cases of fibroadenoma (97%). The overall agreement between the two observers was 87% [Kappa = 0.74, 95% confidence interval (CI) 0.72-0.76]. Cytohistological correlation was achieved in 26 of 33 (79%) cases. Intra-observer agreement was 91% (Kappa = 0.82, 95% CI 0.89-0.93) with cytohistological correlation in 29 of 33 (87%) cases. Causes of diagnostic errors included marked dissociation, pleomorphism, poorly cellular smears from hyalinized fibrodenoma, lacational changes and apocrine metaplasia with cystic changes. Multinucleated giant cells were frequently encountered in FNA smears from fibroadenoma (31.8%), but in none of the lumpectomy specimens. Their histiocytic nature was suggested by immunohistochemistry. CONCLUSION: FNA was a highly sensitive method for the diagnosis of fibroadenoma. Current cytological criteria were reliable and gave high inter- and intra-observer reproducibility.     

Concentration of Lymph Node Aspirate Improves the Sensitivity of Acid Fast Smear Microscopy for the Diagnosis of Tuberculous Lymphadenitis in Jimma,Southwest Ethiopia

Background

Tuberculous lymphadenitis (TBLN) is the most common form of extrapulmonary tuberculosis. The cytomorphological features of lymph node smears have reduced specificity for the diagnosis of tuberculosis. The diagnosis of TBLN with direct smear microscopy lacks sensitivity due to the limited number of bacilli in lymph node aspirate. Therefore, we aimed to assess whether the concentration of lymph node aspirate improves the sensitivity of acid fast smear microscopy for the diagnosis of tuberculous lymphadenitis.

Methods

A cross-sectional comparative study was conducted on 200 patients clinically suspected for tuberculous lymphadenitis in Jimma, Ethiopia. Lymph node aspirate was collected. The first two drops were used for cytomorphological study and direct acid fast staining. The remaining aspirate was treated with N-acetyl-L-cysteine (NALC) and concentrated by centrifugation at 3000 g for 15 minutes. The sediment was used for acid fast staining and culture. Differentiation of M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM) was done by para-nitrobenzoic acid susceptibility test.

Result

Complete data were available for 187 study subjects. 68% (127/187) were positive for M. tuberculosis on culture. Four isolates, 2.1% (4/187), were identified as NTM. The detection rate of direct smear microscopy was 25.1% and that of the concentration method 49.7%. Cytomorphologically, 79.7% of cases were classified as TBLN. The sensitivity of direct smear microscopy was 34.6%, for concentrated smear microscopy 66.1%, and for cytomorphology 89.8%. Two AFB positive cases on concentration method were non-tuberculosis mycobacteria (NTM). The concentration method yielded a positive result from seven cases diagnosed as suppurative abscess by cytology. Both for the direct and concentration methods the highest rate of AFB positivity was observed in smears showing caseous necrosis alone. Smear positivity rate decreased with the appearance of epithelioid cell aggregates.

Conclusion

The concentration of lymph node aspirates for acid fast smear microscopy had significantly higher sensitivity than direct microscopy.     

Challenges of Improving the Evidence Base in Smaller Surgical Specialties,as Highlighted by a Systematic Review of Gastroschisis Management

Objective

To identify methods of improving the evidence base in smaller surgical specialties, using a systematic review of gastroschisis management as an example.

Background

Operative primary fascial closure (OPFC), and silo placement with staged reduction and delayed closure (SR) are the most commonly used methods of gastroschisis closure. Relative merits of each are unclear.

Methods

A systematic review and meta-analysis was performed comparing outcomes following OPFC and SR in infants with simple gastroschisis. Primary outcomes of interest were mortality, length of hospitalization and time to full enteral feeding.

Results

751 unique articles were identified. Eight met the inclusion criteria. None were randomized controlled trials. 488 infants underwent OPFC and 316 underwent SR. Multiple studies were excluded because they included heterogeneous populations and mixed intervention groups. Length of stay was significantly longer in the SR group (mean difference 8.97 days, 95% CI 2.14–15.80 days), as was number of post-operative days to complete enteral feeding (mean difference 7.19 days, 95%CI 2.01–12.36 days). Mortality was not statistically significantly different, although the odds of death were raised in the SR group (OR 1.96, 95%CI 0.71–5.35).

Conclusions

Despite showing some benefit of OPFC over SR, our results are tempered by the low quality of the available studies, which were small and variably reported. Coordinating research through a National Paediatric Surgical Trials Unit could alleviate many of these problems. A similar national approach could be used in other smaller surgical specialties.     

Attendance at Cervical Cancer Screening and Use of Diagnostic and Therapeutic Procedures on the Uterine Cervix Assessed from Individual Health Insurance Data (Belgium, 2002-2006)

Objective

To assess the coverage for cervical cancer screening as well as the use of cervical cytology, colposcopy and other diagnostic and therapeutic interventions on the uterine cervix in Belgium, using individual health insurance data.

Methods

The Intermutualistic Agency compiled a database containing 14 million records from reimbursement claims for Pap smears, colposcopies, cervical biopsies and surgery, performed between 2002 and 2006. Cervical cancer screening coverage was defined as the proportion of women aged 25–64 that had a Pap smear within the last 3 years.

Results

Cervical cancer screening coverage was 61% at national level, for the target population of women between 25 and 64 years old, in the period 2004–2006. Differences between the 3 regions were small, but varied more substantially between provinces. Coverage was 70% for 25–34 year old women, 67% for those aged 35–39 years, and decreased to 44% in the age group of 60–64 years. The median screening interval was 13 months. The screening coverage varied substantially by social category: 40% and 64%, in women categorised as beneficiary or not-beneficiary of increased reimbursement from social insurance, respectively. In the 3-year period 2004–2006, 3.2 million screen tests were done in the target group consisting of 2.8 million women. However, only 1.7 million women got one or more smears and 1.1 million women had no smears, corresponding to an average of 1.88 smears per woman in three years of time. Colposcopy was excessively used (number of Pap smears over colposcopies = 3.2). The proportion of women with a history of conisation or hysterectomy, before the age of 65, was 7% and 19%, respectively.

Conclusion

The screening coverage increased slightly from 59% in 2000 to 61% in 2006. The screening intensity remained at a high level, and the number of cytological examinations was theoretically sufficient to cover more than the whole target population.     

C-Erbb-2 Expression and Dna Ploidy Status In Breast Cancer Cells Obtained By Fine Needle Aspiration (Fna)

The aim of this study was to determine the relative rate of c-erbB-2 oncoprotein immuno-detection on matched fine needle aspiration (FNA) smears and surgical specimens of breast cancer, and to correlate the c-erbB-2 expression with the assessment of the DNA ploidy status. the expression of c-erbB-2 oncoprotein was evaluated using an immunoalkaline phosphatase technique in 49 breast aspirates (four benign and 45 malignant lesions) and 21 matched surgical specimens. the DNA ploidy status was assessed by densitometric techniques on Feulgen-stained smears. Fifty-eight per cent of the smears obtained from 45 malignant lesions and 43% of the 21 corresponding paraffin sections contained cells that were stained by the antibody. the higher incidence of c-erbB-2 expression on smears seems to be due mainly to the better antigen preservation in the fresh cytological preparations. the correlation between c-erbB-2 oncogene expression and DNA ploidy assessment showed an increased incidence of oncogene expression in aneuploid tumours (71% vs 29%; P > 0.05).     

Repeat Diagnoses of Bethesda Category III Thyroid Nodules: What To Do Next?

Objectives

To assess the malignancy rates of thyroid nodules repeatedly classified as Bethesda category III on fine needle aspiration (FNA), and to suggest management guidelines for these lesions.

Methods

This is a retrospective study that included 395 thyroid nodules categorized as Bethesda III undergone either surgery or ultrasound (US) follow-up. There were 67 nodules classified a second time as Bethesda category III on repeat FNA. We compared malignancy rates, clinicopathologic and ultrasonographic characteristics between direct surgery and repeat FNA groups and between the initial and repeat Bethesda category III groups, each. And in the repeat Bethesda III group, clinicopathologic and US variables were compared between benign and malignant nodules.

Results

Incidence of concurrent cancer, underlying thyroiditis and positive BRAF mutation were significantly higher in 142 nodules with direct surgery than 243 nodules with repeat FNA (p < 0.05). Of the 395 nodules with Bethesda category III cytology on initial FNA, the malignancy rate was 59.5%. In 67 nodules with repeat Bethesda III classification, however, the malignancy rate was 73.1% (p < 0.05). However, none of the variables were significantly different between the initial Bethesda category III group and the repeat Bethesda category III group (p > 0.05). In the repeat Bethesda category III group, solid consistency, irregular/microlobulated margins, nonparallel shape, and number of suspicious findings or “suspicious malignant” US assessments were associated with a high malignancy rate (p < 0.05). On multivariate logistic regression analysis, the factor associated with malignancy in the repeat Bethesda category III group was irregular/microlobulated margin (odds ratio = 15.576; 95% CI, 2.097–115.6804, p = 0.007) with a sensitivity, specificity, positive and negative predictive values, and accuracy of 81.6%, 83.3%, 93.0%, 62.5% and 82.1%, respectively.

Conclusion

Thyroid nodules with repeated Bethesda category III classification and irregular/microlobulated margins on US are at increased risk of malignancy, and operative management should be considered as opposed to repeat FNA.     

Molecular testing of BRAF,RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy

Objective

Liquid‐based (LB)‐FNA is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. However, up to 30% of LB‐FNA remain indeterminate according to the Bethesda system. Use of molecular biomarkers has been recommended to improve its pathological accuracy but implementation of these tests in clinical practice may be difficult. Here, we evaluated feasibility and performance of molecular profiling in routine practice by testing LB‐FNA for BRAF, N/HRAS and TERT mutations.

Methods

We studied a large prospective cohort of 326 cases, including 61 atypia of undetermined significance, 124 follicular neoplasms, 72 suspicious for malignancy and 69 malignant cases. Diagnosis of malignancy was confirmed by histology on paired surgical specimen.

Results

Mutated LB‐FNAs were significantly associated with malignancy regardless of the cytological classification. Overall sensitivity was 60% and specificity 89%. Importantly, in atypia of undetermined significance and follicular neoplasm patients undergoing surgery according to the Bethesda guidelines, negative predictive values were 85.4% and 90% respectively. TERT promoter mutation was rare but very specific for malignancy (5.5%) suggesting that it could be of interest in patients with indeterminate cytology.

Conclusions

Mutation profiling can be successfully performed on thyroid LB‐FNA without any dedicated sample in a pathology laboratory. It is an easy way to improve diagnostic accuracy of routine LB‐FNA and may help to better select patients for surgery and to avoid unnecessary thyroidectomies.