A decision analysis comparing three strategies for peritoneal lavage cytology testing in staging of gastric cancer in China.

BACKGROUND: Positive peritoneal cytology (PCY) indicates metastasis (M1) in gastric cancer (GC) patients; both the American and Chinese guidelines recommend laparoscopic peritoneal lavage (LPL) for cytology. However, relatively high costs impair the widespread use of LPL in some resource-limited regions in China, and the cost-effectiveness of PCY testing remains unclear. Therefore, we performed a decision analysis to evaluate the cost-effectiveness of PCY testing by comparing the guideline-recommended intraoperative LPL, a newly proposed preoperative percutaneous peritoneal lavage (PPL), and a third strategy of exploratory laparotomy with no cytology testing (ELNC) among GC patients. METHODS: We developed a decision-analytic Markov model of the aforementioned three strategies for a hypothetical cohort of GC patients with curative intent after initial imaging, from the perspective of Chinese society. We estimated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) as primary outcomes; we also conducted one-way and probabilistic sensitivity analyses to investigate the model's robustness. RESULTS: We found that ELNC was dominated (i.e., more expensive and less effective) by PPL and LPL. LPL was the most cost-effective method with an ICER of US$17,200/QALY compared to PPL, which was below the Chinese willingness-to-pay (WTP) threshold of US$29,313 per QALY gained. In sensitivity analyses, PPL was more likely to be cost-effective with a lower WTP threshold. CONCLUSIONS: Cytology testing through either LPL or PPL was less expensive and more effective than ELNC among GC patients. Moreover, LPL was the most cost-effective modality at the current WTP threshold, while PPL could potentially be cost-effective in lower-income areas.

Use of cytology centrifuged supernatants improves cost and turnaround time for targeted next generation sequencing.

BACKGROUND: Molecular testing is an essential step in providing patients with advanced non-small-cell lung cancer (NSCLC), the most appropriate front-line targeted therapies. We recently implemented targeted NGS on previously discarded cytology centrifuged supernatant (CCS). METHODS: In this study, we reviewed our implementation process to evaluate its performance. Performance and turnaround time (TAT) of molecular testing on all cytology NSCLC cases submitted for targeted NGS from June 2018 to September 2019 were evaluated, which included 46 and 62 cytology cases before and after implementation of CCS, respectively. Associated cost savings using CCS was also analyzed. RESULTS: The mean TAT defined as the time of collection to time of reporting was 8.5 ± 1.8 days in CCS cohort (range 5-13) as compared with 12.2 ± 5.3 days in the (FFPE) cell block (CB) cohort (range: 6-27). The success rate of sequencing was similar for both cohorts (100% in CCS and 96% in FFPE CB). CONCLUSION: Our results demonstrate that NGS using CCS improves TAT, preserves FFPE CB for other testing, and results in cost savings of $50 per case.

ThyroSeq v2 Testing: Impact on Cytologic Diagnosis, Management, and Cost of Care in Patients with Thyroid Nodule.

Background: Novel molecular tests (MTs), such as ThyroSeq, may improve the management of thyroid nodules with indeterminate cytologic diagnoses; however, the impact of these tests on cost and outcome of management is unknown. Here, we evaluated the impact of ThyroSeq testing on the cytopathologic diagnosis, management, and cost of care in patients with thyroid nodules. Methods: In a retrospective study, using actual patient cohorts, the outcome and cost of management of patients with thyroid nodules seen before the introduction of ThyroSeq v2 at our institution (standard of care [StC] cohort) were compared with those seen after the introduction of this test (MT cohort). Results: A total of 773 consecutive patients entered the study (393 StC, 380 MT). The incidence of cytologically benign nodules decreased from 71.0% (StC) to 53.2% (MT) and those of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) increased from 8.9% (StC) to 21.3% (MT) and from 3.1% (StC) to 6.3% (MT), respectively. The overall rate of surgery did not change significantly (23.4% in StC vs. 23.2% in MT). Among patients who underwent surgery, the rate of overtreatment (surgeries performed on histologic benign nodules without clinical indication: compressive symptoms, hyperthyroidism resistant to medication, and nodule size >4 cm) slightly decreased from 18.8% (StC) to 16.7% (MT). The rate of malignancy decreased from 45.5% (StC) to 37.9% (MT) in AUS/FLUS and increased from 40.0% to 53.8% in FN/SFN. However, the overall rate of malignancy remained equal (47.8% in StC vs. 47.7% in MT). The average cost of care per patient in the AUS/FLUS and FN/SFN categories increased from $6,566 (StC) to $8,444 (MT) and from $9,313 (StC) to $10,253 (MT), respectively. Similarly, the overall average cost of care of a patient who underwent thyroid fine-needle aspiration increased from $3,088 (StC) to $4,282 (MT). Finally, the average cost per thyroid cancer detected increased from $26,312 (StC) to $38,746 (MT). Conclusions: Introduction of ThyroSeq v2 resulted in a shift toward indeterminate cytology results. The institutional rate of surgery, overtreatment, and malignancy did not change significantly. Lack of decrease in the rate of surgery along with the additional cost of ThyroSeq v2 increased the overall cost of care of patients including those with indeterminate cytology results.

Cervical cancer screening program based on primary DNA-HPV testing in a Brazilian city: a cost-effectiveness study protocol.

BACKGROUND: The causal relationship between high-risk (hr) HPV infection and precancerous lesions or cervical cancer has led to the development of strategies to increase screening performance and prevent this cancer. The increased sensitivity of DNA-HPV testing compared to cervical cytology favors DNA-HPV testing as a primary screening test. Cervical cancer screening in Brazil is opportunistic, and this cancer remains a considerable health problem with a high proportion of diagnoses in advanced stages. This paper aims to describe the design and implementation of the Cervical Cancer Screening Program with primary DNA-HPV testing (CCSP-HPV) planned for Indaiatuba City (SP), Brazil; the strategies to achieve higher population coverage; and a study protocol for cost-effectiveness analyses. METHODS: The CCSP-HPV was designed based on successful guidelines that replaced cervical cytology-based screening by the DNA-HPV test performed at 5-year intervals. The screening will be performed for the female population aged 25-64 years cared for by the public health system and aim to reach 80% coverage after completing the first round. The chosen DNA-HPV test detects 14 hr-HPV types and genotypes HPV-16 and 18. All women with a negative test will be reassessed after five years. Women showing a positive test for HPV-16 and/or 18 will be referred for colposcopy. Those showing the other 12 hr-HPV types will be tested by cytology, and if any abnormality is detected, they will also be referred for colposcopy. The histopathologic evaluation will be reviewed by a pathologist panel and aided by p16 immunohistochemistry. A cost-effectiveness analysis will be performed by a Markov model comparing the cost of the new program and the screening performed by conventional cytology five years prior (2011-2016). DISCUSSION: The new screening program is considered a breakthrough for public health regarding cervical cancer, which is the third leading cause of cancer death among Brazilian women. Achieving at least 80% coverage will have the possibility to change this scenario. The proposed program will provide a modern cervical cancer screening method for women, and information about cost-effectiveness will help other similar places support the decision of implementing cervical cancer screening using the DNA-HPV test.

Cost-effectiveness of fine-needle aspiration cytology (FNAC) and watchful observation for incidental thyroid nodules.

OBJECTIVES: A trial-based comparison of the use of resources, costs and health utility outcomes of fine-needle aspiration cytology (FNAC), and watchful observation for incidental small (< 2 cm) thyroid nodules was performed using data from the randomized controlled trial (RCT). METHODS: Using data from 314 patients, healthcare-related use of resources, costs, health utility, and quality-adjusted life years (QALYs) were estimated at 12 months after first presentation of incidental thyroid nodule(s) on an intention-to-treat basis with adjustment for covariates. Uncertainty about the incremental cost-effectiveness ratio for FNAC versus watchful management at 12 months of follow-up was incorporated using bootstrapping. Multiple imputation methods were used to deal with missing data. RESULTS: FNAC management was associated with greater use of healthcare resources and mean direct healthcare costs per patient (US$542.47 vs US$411.55). Lower mean 12-month QALYs per patient in FNAC was observed in comparison to watchful observation (0.752 versus 0.758). The probability that FNAC management was cost-effective compared with watchful management at a willingness-to-pay threshold of US50,000 per QALY gained was 26.5%. CONCLUSION: Based on 12-month data from RCT, watchful observation appeared cost-saving compared to FNAC in patients with incidental thyroid nodules that have a low-suspicion sonographic pattern and measure between 1.0 and 2.0 cm from healthcare provider perspective. CLINICALTRIALS. GOV IDENTIFIER: NCT02398721.

Clinical evaluation and budget impact analysis of cervical cancer screening using cobas 4800 HPV screening technology in the public sector of South Africa.

Cytology remains the mainstay of cervical cancer screening in South Africa (SA), however false negative rates are 25-50%. In contrast, human papillomavirus (HPV) screening techniques have higher sensitivity for cervical cancer precursors. The cobas® 4800 HPV test detects pooled high-risk HPV types and individual genotypes HPV 16 and 18. Using a mathematical budget impact model, the study objective was to evaluate the clinical and budget impact of replacing primary liquid-based cytology (LBC) with primary HPV-based screening strategies. In SA, current LBC screening practice recommends one test every ten years, followed by large loop excision of the transformation zone (LLETZ) if indicated. HPV testing can be performed from an LBC sample, where no additional consultations nor samples are required. In the budget impact model, LBC screening for 2 cycles (one test every ten years) was compared to cobas® 4800 HPV test for 2 cycles (one test every 5 years). The model inputs were gathered from literature and primary data sources. Indicative prices for LBC and cobas® 4800 HPV test were R189 and R457, respectively. Model results indicate that best outcomes for detection of disease were seen using cobas® 4800 HPV test. Forty-eight percent of cervical cancer cases were detected compared to 28% using LBC, and 50% of cervical intraepithelial neoplasia (CIN) 2 and CIN3 cases, compared to 25% with LBC. The budget impact analysis predicted that the cost per detected case of CIN2 or higher would be R 56,835 and R46,980 for the cobas® 4800 HPV and LBC scenarios, respectively. This equates to an incremental cost per detected case of CIN2 or higher of R9 855. From this model we conclude that a primary HPV screening strategy will have a significant clinical impact on disease burden in South Africa.

Touch Imprint Cytology: A Rapid and Accurate Method for Diagnosis of Oral Cancer.

OBJECTIVES: Touch imprint cytology (TIC) is a rapid and cheap method and can be used as an adjunct to biopsy for the evaluation of suspected malignancy. We evaluated the advantages and limitations of TIC for the preoperative diagnosis of oral squamous cell carcinoma. STUDY DESIGN: We used 280 incisional biopsies of clinically suspected oral squamous cell carcinoma and compared TIC diagnosis to histopathological sections. The sensitivity, specificity, and diagnostic accuracy of TIC were evaluated. RESULTS: A total of 201 (82.5%) cases were diagnosed as malignant, 22 (7.9%) cases were diagnosed as suspicious of malignancy, and 54 (19.3%) cases as benign/negative on TIC. The overall sensitivity of TIC was 98.2%, specificity was 89.3%, the positive-predictive value 97.3%, and the negative-predictive value was 92.6%. The accuracy of the test was 96.4%. CONCLUSIONS: TIC is an accurate, simple, rapid, and cost-effective method that aids the diagnosis of oral squamous cell carcinoma but does not replace incisional biopsy. The cytologic examination of imprints of biopsies also helps determine the adequacy of the specimen for histologic examination.

Budget impact analysis of cervical cancer screening in Portugal: comparison of cytology and primary HPV screening strategies.

BACKGROUND: Primary Human Papilloma Virus (HPV) testing is the currently recommended cervical cancer (CxCa) screening strategy by the Portuguese Society of Gynecology (SPG) clinical consensus. However, primary HPV testing has not yet been adopted by the Portuguese organized screening programs. This modelling study compares clinical benefits and costs of replacing the current practice, namely cytology with ASCUS HPV triage, with 2 comparative strategies: 1) HPV (pooled) test with cytology triage, or 2) HPV test with 16/18 genotyping and cytology triage, in organized CxCa screenings in Portugal. METHODS: A budget impact model compares screening performance, clinical outcomes and budget impact of the 3 screening strategies. A hypothetical cohort of 2,078,039 Portuguese women aged 25-64 years old women is followed for two screening cycles. Screening intervals are 3 years for cytology and 5 years for the HPV strategies. Model inputs include epidemiological, test performance and medical cost data. Clinical impacts are assessed with the numbers of CIN2-3 and CxCa detected. Annual costs, budget impact and cost of detecting one CIN2+ were calculated from a public healthcare payer's perspective. RESULTS: HPV testing with HPV16/18 genotyping and cytology triage (comparator 2) shows the best clinical outcomes at the same cost as comparator 1 and is the most cost-effective CxCa screening strategy in the Portuguese context. Compared to screening with cytology, it would reduce annual CxCa incidence from 9.3 to 5.3 per 100,000, and CxCa mortality from 2.7 to 1.1 per 100,000. Further, it generates substantial cost savings by reducing the annual costs by €9.16 million (- 24%). The cost of detecting CIN2+ decreases from the current €15,845 to €12,795. On the other hand, HPV (pooled) test with cytology triage (comparator 1) reduces annual incidence of CxCa to 6.9 per 100,000 and CxCa mortality to 1.6 per 100,000, with a cost of €13,227 per CIN2+ detected with annual savings of €9.36 million (- 24%). The savings are mainly caused by increasing the length of routine screening intervals from three to five years. CONCLUSION: The results support current clinical recommendations to replace cytology with HPV with 16/18 genotyping with cytology triage as screening algorithm.

Cost-effectiveness of rapid on-site evaluation of the adequacy of FNA cytology samples performed by nonpathologists.

BACKGROUND: Rapid on-site evaluation (ROSE) can increase adequacy and reduce needle passes in fine-needle aspiration cytology (FNAC) procedures. However, ROSE increases the cost of FNAC. Costs may be reduced if ROSE is performed by an alternate evaluator (AE), such as a cytotechnologist (CT), endoscopist, or pulmonologist, rather than a cytopathologist (CP). Studies have shown that AEs can perform ROSE with high accuracy but are generally not as accurate as CPs. The objective of this study was to evaluate the impact of AEs on the cost-effectiveness of ROSE. METHODS: A cost model, based on a mathematical sampling model, was developed. The cost model was used to compare the impact of the evaluator type on overall costs. RESULTS: CTs were likely to be cost-effective for simple procedures and were unlikely to be cost-effective for only the most complex procedures. The model demonstrated the tradeoff in cost savings from using AEs and the potential costs associated with repeated procedures due to the lower accuracy of AEs. CONCLUSIONS: The cost-effectiveness of AEs is context-dependent. AEs can be cost-effective even if they are less accurate than CPs. AEs are likely to be cost-effective in most contexts.

Use of a low-cost telecytopathology method for remote assessment of thyroid FNAs.

BACKGROUND: Rapid on-site evaluation is a great tool for optimizing the adequacy and quality of cytologic samples. The objective of the current study was to analyze a low-cost telecytopathology method for the remote assessment of thyroid fine-needle aspiration biopsies (FNABs), with comparison of the primarily rendered adequacy and diagnosis with the final conventional analysis. METHODS: Material collected from thyroid FNABs was immediately smeared onto glass slides and stained with Diff-Quik. A conventional microscope attached to a smart device was operated on-site by either a medical student or a pathology resident for Wi-Fi transmission of the images by Skype. The cytopathologist would remotely guide the screening of the slides, zooming in and out of areas of interest. Remote assessment included an analysis of material adequacy and a preliminary diagnosis. The quality of the transmission and the number of slides also were recorded. After a washout period of 3 weeks, final diagnosis and adequacy were assigned by conventional microscopy. RESULTS: The final agreement rate for adequacy between remote and conventional analysis was 90.5%. For diagnosis, the final agreement rate was 83.3%. The diagnosis agreement rate varied, depending on the quality of transmission: there was 88% agreement when the quality was excellent, 77.8% agreement when it was good, and 62.5% agreement when it was poor. CONCLUSIONS: Low-cost telecytopathology is an efficient method for the remote assessment of thyroid FNAB adequacy and diagnosis. The wide use of such technology in low-resource or remote centers may have a positive impact on the number of adequate or satisfactory samples, optimizing the management of patients who have thyroid nodules.

Validation of a New Low-Cost, Methanol-Based Fixative for Cervical Cytology and Human Papillomavirus Detection.

OBJECTIVE: To test the performance of a new fixative for pap smear collection for liquid-based cervical cytology, CellPreserv® and compare it with the commercially available, PreservCyt® used in the diagnosis and detection of human papillomavirus (HPV). METHODS: Seven hundred twenty five women participated in this study after signing an informed consent. The specimens were collected using a traditional device, agitated in PBS, and equally divided in both fixatives. The slides were prepared routinely, stained by Papanicolaou, examined blindly by 2 cytologists, and reviewed by one cytopathologist. To search for HPV, 1,000 µL from each fixative was taken and processed by polymerase chain reaction. RESULTS: Considering the adequacy of samples, both fixatives had similar results - 0.33 and 0.32% of the cases unsatisfactory for PreservCyt® and CellPreserv®, respectively. Considering the 701 satisfactory cases and comparing the new fixative to the traditional fixative, there was 99.3% concordance between both. The results regarding the HPV detection was 100% concordant between the 2 fixatives. CONCLUSION: The new methanol-based fixative, CellPreserv®, is cheaper and equally efficient for treating cervical cancer screening and for HPV detection, and can be safely used by the health system prevailing in low-income countries.

Comparative analysis of diagnostic performance, feasibility and cost of different test-methods for thyroid nodules with indeterminate cytology.

Since it is impossible to recognize malignancy at fine needle aspiration (FNA) cytology in indeterminate thyroid nodules, surgery is recommended for all of them. However, cancer rate at final histology is <30%. Many different test-methods have been proposed to increase diagnostic accuracy in such lesions, including Galectin-3-ICC (GAL-3-ICC), BRAF mutation analysis (BRAF), Gene Expression Classifier (GEC) alone and GEC+BRAF, mutation/fusion (M/F) panel, alone, M/F panel+miRNA GEC, and M/F panel by next generation sequencing (NGS), FDG-PET/CT, MIBI-Scan and TSHR mRNA blood assay.We performed systematic reviews and meta-analyses to compare their features, feasibility, diagnostic performance and cost. GEC, GEC+BRAF, M/F panel+miRNA GEC and M/F panel by NGS were the best in ruling-out malignancy (sensitivity = 90%, 89%, 89% and 90% respectively). BRAF and M/F panel alone and by NGS were the best in ruling-in malignancy (specificity = 100%, 93% and 93%). The M/F by NGS showed the highest accuracy (92%) and BRAF the highest diagnostic odds ratio (DOR) (247). GAL-3-ICC performed well as rule-out (sensitivity = 83%) and rule-in test (specificity = 85%), with good accuracy (84%) and high DOR (27) and is one of the cheapest (113 USD) and easiest one to be performed in different clinical settings.In conclusion, the more accurate molecular-based test-methods are still expensive and restricted to few, highly specialized and centralized laboratories. GAL-3-ICC, although limited by some false negatives, represents the most suitable screening test-method to be applied on a large-scale basis in the diagnostic algorithm of indeterminate thyroid lesions.

Is intraoperative touch imprint cytology indicated in the surgical treatment of early breast cancers?

INTRODUCTION: Intraoperative touch imprint cytology (TIC) of the sentinel lymph node(s) (SLN(s)) in the treatment of breast cancer has significantly reduced the number of axillary block dissections (ABD) required during second surgeries. Based on recent studies, ABD was not considered necessary if the presence of tumor cells/micrometastasis was confirmed in the SLN(s) or in the case of macrometastases in a patient group meeting the inclusion criteria for the ACOSOG Z0011 study. Our aim was to determine the sensitivity and usefulness of TIC with regard to these results. METHODS: TICs of the SLN(s) were examined in 1168 patients operated on for breast cancer. The method was also analyzed retrospectively based on the guidelines for the Z0011 study. During TIC, new samples were cut every 250 µm; impression smears were evaluated after being stained with hematoxylin eosin. RESULTS: TIC confirmed metastasis in 202 cases (202/1168, 17.29%). Metastasis was confirmed in SLN(s) in 149 additional cases during a final histological examination. The sensitivity of TIC was found to be 57.18%, and its specificity was 99.63%. An analysis was then performed except for cases that met the inclusion criteria for the Z0011 study and with metastasis smaller than 2 mm (micrometastasis/isolated tumor cells) considered to be positive during intraoperative cytology. The sensitivity of the method decreased to 34.23%, while its specificity was still high at 99.76%. CONCLUSIONS: Based on the new guidelines for ABD, imprint cytology cannot be considered a beneficial and cost-effective intervention in the surgical treatment of early breast cancer.

Improvements in cell block processing: The Cell-Gel method.

BACKGROUND: The ability to produce adequate cell blocks profoundly impacts the diagnostic usefulness of cytology specimens. Cell blocks are routinely processed from fine-needle aspiration specimens or concentrated fluid samples. Obtaining directed passes for the sole purpose of producing a cell block is common practice, particularly when the cytopathologist anticipates the need for ancillary immunocytochemical stains and/or molecular studies. METHODS: The authors developed an effective and inexpensive process for producing cell blocks that consistently yields abundant cellular material, which they have termed the Cell-Gel method. This method can be simplified into 3 main steps: 1) preparing the sample; 2) constructing the cell block; and 3) processing the cell block. Highlights of the protocol include using a hemolytic fixative for sample preparation and disposable base molds for cell block construction. RESULTS: The cell block failure rate in the current study decreased from 18% with the HistoGel Tube method (January 2014-December 2014) to 6% with the Cell-Gel method (January 2015-December 2016). The authors evaluated 110 cell blocks processed with the HistoGel Tube method and 110 cell blocks processed with the Cell-Gel method, for a total evaluation of 220 cell blocks. CONCLUSIONS: The authors have developed an effective and inexpensive protocol for producing cell blocks that consistently yields abundant cellular material. The Cell-Gel method uses a hemolytic fixative and disposable base molds to produce adequate cell blocks. When the method was implemented, the cell block failure rate of the study laboratory decreased by approximately 67%. Cancer Cytopathol 2017;125:267-276. © 2016 American Cancer Society.

The impact on women's health and the cervical cancer screening budget of primary HPV screening with dual-stain cytology triage in Belgium.

Dual stain cytology, or "diagnostic cytology", offers a significant increase in sensitivity compared to cytology, with a slight decrease in specificity. This can reduce additional investigations like colposcopies, biopsies, and follow-up visits. Cervical cancer screening for women between 25 and 65 years of age with diagnostic cytology is estimated to reduce the incidence of cervical cancer by 36% and reduce annual cervical cancer mortalities by 40%. The reduced number of screening visits and the decrease in incidence and mortality will improve quality of life. In this article, a model was created to evaluate the cost-effectiveness of diagnostic cytology for Belgium. In this approach, precancerous cells are more likely to be immediately identified during the first screening visit. This reduces both the number and frequency of follow-up visits required. After two cycles (6 years), the prevalence of CIN and cervical cancer is decreased significantly in the screened population. At a population level, these shifts can reduce the screening budget by 21%, resulting in savings of 5.3 million euro a year in Belgium. Diagnostic cytology benefits all stakeholders involved in cervical cancer screening.

A Survey of Oral Cancer Screening Insurance Coverage in New York City.

Clinical studies show that fewer than 25% of people who visit a dentist regularly are screened for oral cancer, and that the majority of oral cancers present at an advanced stage, when cure rates are already abysmal. This study explores the current status of oral cancer screening coverage among a variety of insurance providers in New York City. The study focuses on determining the coverage and frequency of the cluster of salient CDT (dental) codes surrounding oral cancer screenings.

Rapid onsite evaluation: A comparison of cytopathologist and pulmonologist performance.

BACKGROUND: Rapid onsite evaluation (ROSE) has several potential benefits but also can prolong procedures if one must wait for a cytopathologist, and it can involve a considerable time commitment on the part of the cytopathologist. At the University of Arkansas for Medical Sciences, interventional pulmonologists have routinely reviewed cytology specimens. This study was performed to determine prospectively how accurately pulmonologists could perform ROSE and whether they could contribute to the efficiency of the process. METHODS: For sequential cases, the procedural pulmonologist documented a ROSE reading before the reading by the cytopathologist. Readings were compared between the two for agreement and for accuracy. The time commitment for the cytopathologist was also recorded. RESULTS: One hundred sixty-four sites were biopsied in 102 patients. With respect to onsite adequacy, there was a high level of concordance between pulmonology and cytopathology as evidenced by the κ score ( ± standard error) of 0.72 ± 0.15 and by disagreement in only 3 cases (2%). For the diagnostic category, there was once again a high level of concordance; there was agreement in 141 of the 164 cases (86%), and the weighted κ score was 0.89 ± 0.02. The cytopathologist's time in the endoscopy suite averaged 4.02 ± 6.9 minutes per procedure. CONCLUSIONS: Procedural pulmonologists can effectively learn enough cytology to be able to make ROSE a collaborative process and to greatly increase the efficiency of the cytopathologist.

A multistep cytological approach for patients with jaundice and biliary strictures of indeterminate origin.

AIMS: Fluorescence in situ hybridisation (FISH) increases the sensitivity for detecting pancreatobiliary tract cancer over routine cytology. In this study, diagnostic accuracy and costs of cytology and FISH in detecting cancer in patients with jaundice with biliary strictures were assessed. METHODS: Brushing specimens from 109 patients with jaundice were obtained during endoscopic retrograde cholangiopancreatography and examined by cytology and FISH. The specimens were considered FISH-positive for malignancy if at least five polysomic cells or 10 cells with homozygous or heterozygous 9p21/p16 deletion were detected. Definitive diagnosis of the stricture as benign or malignant relied on surgical pathology (45 cases) or clinical-radiological follow-up >18 months (64 cases). We calculated costs of cytology and FISH based on the reimbursement from the Piedmont region, Italy (respectively, €33 and €750). RESULTS: Ninety of 109 patients had evidence of malignancy (44 pancreatic carcinomas, 36 cholangiocarcinomas, 5 gallbladder carcinomas, 5 other cancers), while 19 had benign strictures. Routine cytology showed 42% sensitivity, but 100% specificity for the diagnosis of malignancy, while FISH-polysomy showed 70% sensitivity with 100% specificity and FISH-polysomy plus homozygous or heterozygous 9p21/p16 deletion showed 76% sensitivity with 100% specificity. The cost per additional correct diagnosis of cancer obtained by FISH, in comparison with cytology, was €1775 using a sequential cytological approach (ie, performing FISH only in patients with negative or indeterminate cytology). CONCLUSIONS: FISH should be recommended as the second step in detecting cancer in patients with jaundice with pancreatobiliary tract strictures and cytology negative or indeterminate for malignancy.