Economic implications of ACOSOG Z0011 trial application into clinical practice at the European Institute of Oncology.

BACKGROUND AND OBJECTIVES: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that in clinically node-negative women undergoing breast-conserving therapy (BCT) and found to have metastases to 1 or 2 sentinel nodes, sentinel lymph node biopsy (SLNB) alone resulted in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection (ALND), but with significantly lower morbidity. Application of the Z0011 guidelines resulted in fewer ALNDs without affecting locoregional recurrence or survival. Changes in practice inevitably affect health care costs. The current study investigated the actual impact of applying the Z0011 guidelines to eligible patients and determined the costs of care at a single institution. PATIENTS AND METHODS: We compared axillary nodal management and cost data in breast cancer patients who met the Z0011 criteria and were treated with BCT and SLNB. Patients were allocated into two mutually exclusive cohorts based on the date of surgery: pre-Z0011 (June 2013 to December 2015) and post-Z0011 (June 2016 to December 2018). RESULTS: Of 3912 patients, 433 (23%) and 357 (17.6%) patients in the pre- and post-Z0011 era had positive lymph nodes. ALND decreased from 15.3% to 1.57% in the post-Z0011 era. The mean overall cost of SLNB in the pre-Z0011 cohort was €1312 per patient, while that for SLNB with completion ALND was €2613. Intraoperative frozen section (FS) use decreased from 100% to 12%. Omitting the FS decreased mean costs from €247 to €176. The mean total cost in the pre-Z0011 cohort was €1807 per patient, while in the post-Z0011 cohort it was €1498. The application of Z0011 resulted in an overall mean cost savings of €309 for each patient. CONCLUSIONS: Application of the Z0011 criteria to patients undergoing BCT at our institution results in more than half a million Euro cost savings.

Is there a clinical role for frozen section analysis during partial nephrectomy? A multicenter experience over 10 years.

BACKGROUND: Frozen section analysis (FSA) is frequently performed during partial nephrectomy (PN). We investigate the utility of intraoperative FSA by evaluating its impact on final surgical margin (SM) status. METHODS: Between January 1995 and December 2005, a series of patients who were treated with open PN for renal cell carcinoma was prospectively analyzed. During PN, each patient underwent a FSA on renal parenchyma distal margin. If FSA was positive for infiltration a deeper excision was performed till obtaining a negative FSA. SM outcome of the FSA was compared with the final pathology report. Recurrence-free survival (RFS) and cost analysis on the FSA performed were analyzed. RESULTS: A total number of 373 patients were enrolled. FSA was performed in all the patients considered for PN. Fifteen patients had a conversion to radical nephrectomy. Positive SMs at the definitive pathological outcome were found in 36 patients (9.6%). FSA was positive in eight patients (2.1%). In that eight cases after a deeper excision the definitive pathological outcome on SM was still positive in two cases. FSA revealed just 14.3% of the positive SM. Patients with positive SM had a worse follow up considering RFS (P<0.05). Kaplan-Meier analysis revealed that FSA did not considerably contribute to prevent recurrence (P=0.35). 1438 euros was the mean cost of performing a FSA during PN. CONCLUSIONS: FSA during PN does not reduce the risk of positive SMs. The use of FSA has also a higher cost related to the procedure.

Frozen section is not cost beneficial for the assessment of margins in oral cancer.

BACKGROUND: Routine use of frozen section (FS) is a costly procedure and sparsely available in resource poor countries. A proper cost benefit analysis may help to reduce its routine use and would empower surgeons to perform oral cancer surgeries without having FS facility. FS is performed to identify microscopic spread beyond gross disease that cannot be assessed clinically. OBJECTIVE: Our primary aim was to determine the cost benefit analysis of FS in the assessment of margins in oral cavity squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Retrospective study of prospectively collected data of 1311 consecutive patients who were operated between January 2012 and October 2013. The gross and microscopic margin status of each patient was extracted from the patient's chart. The cost estimates were performed to calculate the financial burden of FS as well as expenses incurred on adjuvant treatment resulting from inadequate margins. RESULT: Microscopic spread changed the gross margin status in 5.2% (65/1237) patients. Of this entire cohort of 1237 patients, FS helped 29 (2.3%) patients to achieve tumor free margin, and it changed the adjuvant treatment plan in 9 (0.7%) patients. The cost of FS for each patient was INR 11052. The cost-benefit ratio of FS was 12:1. Gross examination alone could have identified majority of the inadequate margins. CONCLUSION: Frozen section for assessment of margin status bears poor cost-benefit ratio. Meticulous gross examination of the entire surgical specimen is sufficient to identify majority of inadequate margins.

Development of Functional Requirements for Ex Vivo Pathology Applications of In Vivo Microscopy Systems: A Proposal From the In Vivo Microscopy Committee of the College of American Pathologists.

CONTEXT.­: In vivo microscopy (IVM) allows direct, real-time visualization of tissue histology in living patients without the need for tissue removal, processing, or staining. The IVM technologies in clinical use include confocal microscopy and optical coherence tomography. These technologies also show promise for use with pathology specimens (ex vivo microscopy [EVM]). However, few systems designed for EVM are commercially available, at least in part because of the lack of defined minimal functional requirements (FRs). OBJECTIVE.­: To develop minimal FRs for likely high-volume pathology applications of EVM. DESIGN.­: The IVM Committee of the College of American Pathologists identified potential EVM pathology applications based on the published literature. A subcommittee of IVM and EVM early adopters and experts then defined FRs for the most likely EVM applications. RESULTS.­: Potential EVM applications include assessment of margins, adequacy of needle biopsies and aspirates for diagnosis, and transplant tissues; selection of tissue for molecular studies or biorepository; and guidance in block selection from gross specimens. The first 3 applications were selected for development of FRs. The FRs were identified based on existing laboratory practices and guidelines and input from experts in the field and included device footprint and portability, specimen preparation, imaging time, field of view or resolution, morphologic diagnostic capability, yield, accuracy, ease of use, safety, and cost. CONCLUSIONS.­: Consensus was achieved on FRs that would accommodate the selected EVM applications. Publication and dissemination of those FRs will provide guidance to engineers, researchers, and vendors on how to optimally adapt IVM technologies for EVM for widespread adoption by pathologists.

Utility of Intraoperative Frozen Section in Large Thyroid Nodules.

OBJECTIVE: To determine if the routine use of intraoperative frozen section (iFS) results in cost savings among patients with nodules >4 cm with nonmalignant cytology undergoing a thyroid lobectomy. STUDY DESIGN: Case series with chart review; cost minimization analysis. SETTING: Single academic center. SUBJECTS AND METHODS: Records were reviewed on a consecutive sample of 48 patients with thyroid nodules >4 cm and nonmalignant cytology who were undergoing thyroid lobectomy in which iFS was performed between 2010 and 2015. A decision tree model of thyroid lobectomy with iFS was created. Comparative parameters were obtained from the literature. A cost minimization analysis was performed comparing lobectomy with and without iFS and the need for completion thyroidectomy with costs estimated according to 2014 data from Medicare, the Bureau of Labor Statistics, and the Nationwide Inpatient Sample. RESULTS: The overall malignancy rate was 25%, and 33% of these malignancies were identified intraoperatively. When the malignancy rates obtained from our cohort were applied, performing routine iFS was the less costly scenario, resulting in a savings of $486 per case. When the rate of malignancy identified on iFS was adjusted, obtaining iFS remained the less costly scenario as long as the rate of malignancies identified on iFS exceeded 12%. If patients with follicular lesions on cytology were excluded, 50% of malignancies were identified intraoperatively, resulting in a savings of $768 per case. CONCLUSIONS: For patients with nodules >4 cm who are undergoing a diagnostic lobectomy, the routine use of iFS may result in decreased health care utilization. Additional cost savings could be obtained if iFS is avoided among patients with follicular lesions.

Costs and effects of intra-operative fluorescence molecular imaging - A model-based, early assessment.

INTRODUCTION: Successful breast conserving cancer surgeries come along with tumor free resection margins and account for cosmetic outcome. Positive margins increase the likelihood of tumor recurrence. Intra-operative fluorescence molecular imaging (IFMI) aims to focus surgery on malignant tissue thus substantially lowering the presence of positive margins as compared with standard techniques of breast conservation (ST). A goal of this paper is to assess the incremental number of surgeries and costs of IFMI vs. ST. METHODS: We developed a decision analytical model and applied it for an early evaluation approach. Given uncertainty we considered that IFMI might reduce the proportion of positive margins found by ST from all to none and this proportion is assumed to be reduced to 10% for the base case. Inputs included data from the literature and a range of effect estimates. For the costs of IFMI, respective cost components were added to those of ST. RESULTS: The base case reduction lowered number of surgeries (mean [95% confidence interval]) by 0.22 [0.15; 0.30] and changed costs (mean [95% confidence interval]) by €-663 [€-1,584; €50]. A tornado diagram identified the Diagnosis Related Group (DRG) costs, the proportion of positive margins of ST, the staff time saving factor and the duration of frozen section analysis (FSA) as important determinants of this cost. CONCLUSIONS: These early results indicate that IFMI may be more effective than ST and through the reduction of positive margins it is possible to save follow-up surgeries-indicating further health risk-and to save costs through this margin reduction and the avoidance of FSA.

Economic Impact of Frozen Section for Thyroid Nodules with "Suspicious for Malignancy" Cytology.

Objective To perform a cost analysis of the routine use of intraoperative frozen section (iFS) among patients undergoing a thyroid lobectomy with "suspicious for malignancy" (SUSP) cytology in the context of the 2015 American Thyroid Association guidelines. Study Design Case series with chart review; cost minimization analysis. Setting Academic. Subjects and Methods Records were reviewed for patients with SUSP cytology who underwent thyroid surgery between 2010 and 2015 in which iFS was utilized. The diagnostic test performance of iFS and the frequency of indicated completion/total thyroidectomies based on the 2015 guidelines were calculated. A cost minimization analysis was performed comparing lobectomy, with and without iFS, and the need for completion thyroidectomy according to costs estimated from 2014 data from Medicare, the Bureau of Labor Statistics, and the Nationwide Inpatient Sample. Results Sixty-five patients met inclusion criteria. The malignancy rate was 61.5%, 45% of which was identified intraoperatively. The specificity and positive predictive value were 100%. The negative predictive value and sensitivity were 83% and 95%, respectively. Completion/total thyroidectomy was indicated for 9% of patients; 83% of these individuals had findings on iFS that would have changed management intraoperatively. Application of the new guidelines would have resulted in a significant reduction in the frequency of conversion to a total thyroidectomy when compared with the actual management (26.1% vs 7.7%, P = .005). Performing routine iFS was the less costly scenario, resulting in a savings of $474 per case. Conclusion For patients with SUSP cytology undergoing lobectomy, routine use of iFS would result in decreased health care utilization.

Minimal Clinical Impact of Intraoperative Examination of Sentinel Lymph Nodes in Patients With Ductal Carcinoma In Situ: An Opportunity for Improved Resource Utilization.

OBJECTIVES: There is little information regarding sentinel lymph node (SLN) frozen-section examination in patients with a history of ductal carcinoma in situ (DCIS). We evaluated the usage, clinical impact, and pathology resources used for SLN cryosectioning in mastectomy cases with a DCIS history. METHODS: Mastectomies with SLNs submitted from 2012 to 2013 at a tertiary care center were analyzed. Medicare reimbursement was used to estimate pathology health care expenditures of intraoperative frozen sections. RESULTS: There was no difference in the rate of SLN frozen-section examination or parts submitted, total blocks frozen, total blocks submitted, or total SLNs identified per case between the DCIS (n = 139) and invasive (n = 369) groups. Nine patients with DCIS had SLN metastases (three macrometastases, two micrometastases, and four isolated tumor cells), all of which were examined by frozen section. Only the macrometastases were identified by cryosectioning, which led to two synchronous axillary lymph node dissections that did not yield any additional positive nodes. A total of $19,313 was spent for pathology per DCIS patient with surgical management affected, whereas only $1,019 was spent per invasive carcinoma patient affected. CONCLUSIONS: Decreasing SLN frozen-section use in patients with a history of DCIS represents an opportunity for pathology cost containment.

Sustainable Development of Pathology in Sub-Saharan Africa: An Example From Ghana.

CONTEXT: - Pathology services are poorly developed in Sub-Saharan Africa. Komfo Anokye Teaching Hospital in Kumasi, Ghana, asked for help from the pathology department of the University Hospital of North Norway, Tromsø. OBJECTIVE: - To reestablish surgical pathology and cytology in an African pathology department in which these functions had ceased completely, and to develop the department into a self-supporting unit of good international standard and with the capacity to train new pathologists. DESIGN: - Medical technologists from Kumasi were trained in histotechnology in Norway, they were returned to Kumasi, and they produced histologic slides that were temporarily sent to Norway for diagnosis. Two Ghanaian doctors received pathology training for 4 years in Norway. Mutual visits by pathologists and technologists from the 2 hospitals were arranged for the introduction of immunohistochemistry and cytology. Pathologists from Norway visited Kumasi for 1 month each year during 2007-2010. Microscopes and immunohistochemistry equipment were provided from Norway. Other laboratory equipment and a new building were provided by the Ghanaian hospital. RESULTS: - The Ghanaian hospital had a surgical pathology service from the first project year. At 11 years after the start of the project, the services included autopsy, surgical pathology, cytopathology, frozen sections, and limited use of immunohistochemistry, and the department had 10 residents at different levels of training. CONCLUSIONS: - A Ghanaian pathology department that performed autopsies only was developed into a self-supported department with surgical pathology, cytology, immunohistochemistry, and frozen section service, with an active residency program and the capacity for further development that is independent from assistance abroad.

Economic Implications of Widespread Expansion of Frozen Section Margin Analysis to Guide Surgical Resection in Women With Breast Cancer Undergoing Breast-Conserving Surgery.

PURPOSE: In the current health care environment, cost effectiveness is critically important in policy setting and care of patients. This study performed a health economic analysis to assess the implications to providers and payers of expanding the use of frozen section margin analysis to minimize reoperations for patients undergoing breast cancer lumpectomy. METHODS: A health care economic impact model was built to assess annual costs associated with breast lumpectomy procedures with and without frozen section margin analysis to avoid reoperation. RESULTS: If frozen section margin analysis is used in 20% of breast lumpectomies and under a baseline assumption that 35% of initial lumpectomies without frozen section analysis result in reoperations, the potential annual cost savings are $18.2 million to payers and $0.4 million to providers. Under the same baseline assumption, if 100% of all health care facilities adopted the use of frozen section margin analysis for breast lumpectomy procedures, the potential annual cost savings are $90.9 million to payers and $1.8 million to providers. On the basis of 10,000 simulations, use of intraoperative frozen section margin analysis yields cost saving for payers and is cost neutral to slightly cost saving for providers. CONCLUSION: This economic analysis indicates that widespread use of frozen section margin evaluation intraoperatively to guide surgical resection in breast lumpectomy cases and minimize reoperations would be beneficial to cost savings not only for the patient but also for payers and, in most cases, for providers.

Analysis of an institutional protocol for thyroid lobectomy: Utility of routine intraoperative frozen section and expedited (overnight) pathology.

BACKGROUND: Intraoperative frozen section (FS) often is performed in patients who undergo thyroid lobectomy to determine the need for completion thyroidectomy. At our institution, if FS pathology is benign, final pathology is expedited overnight. The aim of this study was to determine the utility of FS and to identify a cost-effective management algorithm for thyroid lobectomy. METHODS: A retrospective review was performed of patients who underwent thyroid lobectomy between January 2009 and May 2013. Preoperative cytology ranged from "benign" to "suspicious for malignancy." Clinically significant cancers were defined as >1 cm in size, or multifocal microcarcinomas. RESULTS: Of the 192 patients who underwent thyroid lobectomy with FS, FS was suspicious for malignancy in 5 (3%) patients; 1 (0.5%) underwent immediate completion thyroidectomy. On final pathology, 9 (5%) patients had clinically significant cancers and underwent completion thyroidectomy. FS had a sensitivity and positive predictive value of 22% and 40%, respectively, in identifying clinically significant thyroid cancer. Cost of thyroid lobectomy at varying rates of same-day discharge favored thyroid lobectomy without FS but with expedited pathology for all scenarios. CONCLUSION: At our institution, there appears to be limited utility of FS at the time of thyroid lobectomy given the low predictive value for diagnosing a clinically significant thyroid cancer. In patients who are admitted overnight, expedited pathology is slightly less costly and may improve patient quality-of-life and decrease costs by avoiding delayed completion thyroidectomy. Overnight pathology for patients who undergo thyroid lobectomy may achieve modest cost-savings depending on institutional FS results and rates of malignancy.

A versatile cost-effective method for the analysis of fresh frozen tissue sections via matrix-assisted laser desorption/ionisation imaging mass spectrometry.

RATIONALE: There are currently multiple methods available for the preparation of fresh frozen tissue samples for analysis via matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) imaging mass spectrometry (IMS). Although these methods report excellent results, many are expensive automated approaches. With no published attempt to standardise less expensive manual processes, our work aims to provide a robust and repeatable method of sample preparation for MALDI-TOF-IMS that is applicable to a variety of tissue types, well explained, simple and cost effective. METHODS: Fresh frozen tissue was sectioned at 12 µm and mounted onto liquid nitrocellulose coated slides, washed in a graded alcohol series and then mounted into a modified sublimation apparatus. Matrix is deposited onto the slide to achieve a desired coating of 0.2 mg/cm(2). Once coated, the slide is mounted into a custom-built vapor chamber and recrystallised with 50% acetonitrile (ACN), 0.1% trifluoroacetic acid (TFA) for 1 h at 37°C. The slide is then analysed using MALDI-IMS. RESULTS: We have successfully implemented this method for a host of tissue samples, including brain, liver, kidney and heart, with no variation in relative spectra or processing method required. When the protocol is followed correctly, sublimations and recrystallisations are highly predictable with limited variation between samples and a very low failure rate. Additional apparatuses can be easily constructed by following the included instructions, that perform as per specifications with no variation. CONCLUSIONS: We believe that we have described a complete protocol for MALDI-IMS that is easy to use and highly reproducible. The lack of expensive commercially available equipment makes this process very cheap with a relatively low initial outlay and our hope is that more laboratories will begin IMS-based avenues of research based on the work we have performed.

Los orígenes caribeños del Sistema Nacional de Salud Pública en los EEUU: una aproximación global a la historia de la medicina y de la salud pública en Latinoamérica / The Caribbean origins of the National Public Health System in the USA: a global approach to the history of medicine and public health in Latin America

Este artículo define la historia global en relación con historia de la medicina y la salud pública. Defiende que una aproximación global a la historia abre un espacio para reverberaciones transmitidas desde la periferia geográfica hacia regiones occidentales, las cuales, tradicionalmente, han dominado la historiografía moderna. Analiza dos intervenciones médicas, en el Caribe, a finales del siglo XIX y principios del XX, y señala que estos sucesos tuvieron profundas consecuencias en los EEUU. Los logros alcanzados en el Caribe, en lo relativo al control de la fiebre amarilla y del anquilostoma, además de servir de modelo para campañas sanitarias en el sur de los EEUU, impulsaron la centralización de la salud pública norteamericana bajo el control centralizador del gobierno federal.

This article defines global history in relation to the history of medicine and public health. It argues that a global approach to history opens up a space for examining the reverberations transmitted from the geographic periphery towards western regions, which have traditionally dominated modern historiography. It analyzes two medical interventions in the Caribbean in the late nineteenth and early twentieth century, showing how these events had profound consequences in the USA. The successes achieved in the Caribbean in terms of yellow fever and ancylostoma control, as well as providing a model for health campaigns in the southern USA, inspired the centralization of public health in North America under the centralizing control of the federal government.

Virtual slide telepathology with scanner systems for intraoperative frozen-section consultation.

Telepathology provides pathology services over a distance using digital imaging and telecommunication for primary diagnostic practice, including intraoperative frozen sections. Virtual slide technology provides digitizing of histological slides by scanner systems and improved remote assessment substantially. In this retrospective study, diagnostic accuracy of intraoperative frozen sections assessed as virtual slide was determined. Tissue assessment was mainly requested for urological, gynecological and dermatological resections. Issues of time consumption, cost and cost effectiveness of this diagnostic method are discussed. 1204 intraoperative frozen sections were conducted in the course of this study at our department over a period of 2.5 years. 98.59% of all intraoperative frozen sections were accurately diagnosed in the initial telepathological assessment. Tumor affection was present in 15.6% of frozen sections, in 174 instances already assessed in the initial slides (sensitivity 92.6%). Discrepant diagnoses compared to the final diagnosis occurred in 1.41%. Our determined averaged time for virtual slide technology of 10.58±8.19min can be ranged in well. Our study did not allow a full economic assessment, but some preliminary insights are pointed out. The quality of services is highly acceptable and the investment costs and the labor cost of virtual slide technology are lower than those of robotic microscopy.

Cost analysis of thyroid lobectomy and intraoperative frozen section versus total thyroidectomy in patients with a cytologic diagnosis of "suspicious for papillary thyroid cancer".

BACKGROUND: The optimal operation for a patient with a thyroid nodule "suspicious for papillary thyroid cancer (PTC)" on fine-needle aspiration (FNA) is unclear. This study examines the incremental cost-utility of thyroid lobectomy with intraoperative frozen section (thyroid lobectomy) versus total thyroidectomy. METHODS: Cost-utility analysis was performed for patients with a cytologic diagnosis of "suspicious for PTC" on FNA. Patients underwent either initial total thyroidectomy or thyroid lobectomy and, if needed, completion thyroidectomy. The incremental cost-utility ratio (ICUR; US$/quality-adjusted-life-year [QALY]), was determined from a societal perspective. RESULTS: The base-case ICUR of thyroid lobectomy is $90,776/QALY, strongly favoring total thyroidectomy as a more cost-effective modality. On sensitivity analyses, the model is sensitive to the accuracy of frozen section and to the rate of injury to the recurrent laryngeal nerve (RLN). Thyroid lobectomy is more cost-effective only if both frozen section and final pathology are benign in ≥92% of patients (ICUR $47,959/QALY at 92%). With increasing rates of unilateral (>5%) or bilateral (>2%) RLN injury associated with total thyroidectomy, there is a trend toward thyroid lobectomy being more cost effective ($53,127 and $51,325/QALY, respectively). CONCLUSION: In our model, initial total thyroidectomy is cost-effective for patients with a single thyroid nodule suspicious for PTC on FNA. Our results strongly support total thyroidectomy for initial treatment; thyroid lobectomy is preferred only when complications reach unacceptable levels.

Cost effectiveness of intraoperative pathology examination during diagnostic hemithyroidectomy for unilateral follicular thyroid neoplasms.

BACKGROUND: The use of intraoperative pathology examination (IPE) during diagnostic hemithyroidectomy for a follicular neoplasm is controversial. Although this service rarely alters intraoperative decision making, it does provide patients with the possibility of avoiding reoperation for completion thyroidectomy if malignancy is detected. We hypothesized diagnostic hemithyroidectomy with IPE for a unilateral follicular thyroid neoplasm diagnosed on fine-needle aspiration is not cost effective compared with diagnostic hemithyroidectomy alone. STUDY DESIGN: Cost-effectiveness analysis with a Markov decision model was performed comparing diagnostic hemithyroidectomy without IPE, diagnostic hemithyroidectomy with IPE, and total thyroidectomy. Treatment outcomes and their probabilities were identified based on literature review. Costs were estimated using data from Medicare, the US Bureau of Labor Statistics, and the Nationwide Inpatient Sample. Sensitivity analysis and a 1,000-iteration Monte Carlo simulation were used to examine the uncertainty of cost, probability, and utility estimates in the model. RESULTS: Diagnostic hemithyroidectomy without IPE had an expected cost of US$7,665 and an effectiveness of 23.95 quality-adjusted life years and dominated both the IPE and total thyroidectomy strategies. Intraoperative pathology examination became cost effective during one-way sensitivity analysis if the sensitivity of IPE increased from 14.3% to 34.4%, the specificity increased from 98.6% to 99.8%, or the pretest probability of malignancy increased from 25% to 43%. Monte Carlo simulation demonstrated that the intraoperative pathology strategy was not cost effective in 92.7% of iterations. CONCLUSIONS: Intraoperative pathology examination is not cost effective in the diagnosis of follicular thyroid neoplasms during diagnostic hemithyroidectomy. Improvements in both the sensitivity and specificity of this service would be needed to justify its use.

A simple, cost-effective and flexible method for processing of snap-frozen tissue to prepare large amounts of intact RNA using laser microdissection.

Understanding the molecular basis of disease requires gene expression profiling of normal and pathological tissue. Although the advent of laser microdissection (LMD) has greatly facilitated the procurement of specific cell populations, often only small amounts of low quality RNA is recovered. This precludes the use of global approaches of gene expression profiling which require sizable amounts of high quality RNA. Here we report a method for processing of snap-frozen tissue to prepare large amounts of intact RNA using LMD. Portions of small intestine from piglets (n = 6) were snap-frozen in Optimum Cutting Temperature compound (experimental) and in RNAlater (control). A randomly selected sample was laser microdissected using the developed protocol in multiple sessions totalling 4 h each day on four consecutive days. RNAs were extracted from these samples and its control and their quality (RIN) determined. RINs of the experimental samples were independent of time (p = 0.12) and day (p = 0.56) of the microdissection thereby suggesting that their RNA quality remained unaltered. These samples exhibited high quality (RIN ≥ 8) with good recovery (81.2%) and excellent yield (1539 ng/1.2 × 10(7) µm(2)). Their overall RIN, 8.029 ± 0.116, was not significantly different from 8.2 (p = 0.123), the value obtained from the control, non-laser microdissected, sample. This indicated that the RNA quality from the laser microdissected and non-microdissected samples was comparable. The method allowed LMD for up to 4 h each day for a total of four days. The microdissected samples can be pooled thereby increasing amount of RNA at least by ten-fold. The procedure did not require any expensive limited-shelf life RNase inhibitors, RNA protectors, staining kits or toxic chemicals. Furthermore, it was flexible and enabled the processing without affecting routine laboratory workflow. The method developed was simple, inexpensive and provided substantial amounts of high quality RNA suitable for gene expression profiling and other cellular and molecular analyses for biology and molecular medicine.

Cost analysis of intraoperative frozen section examinations in thyroid surgery in a Canadian tertiary center.

OBJECTIVE: To perform a cost analysis of the routine intraoperative frozen section (FS) examinations in the management of patients undergoing thyroid surgery for unilateral thyroid nodules with benign or indeterminate cytology on preoperative fine-needle aspiration biopsies (FNABs). METHOD: A retrospective chart review of 190 consecutive patients with unilateral thyroid nodules undergoing thyroid surgery was undertaken between March 2006 and March 2008. The results of FNAB, FS, and final histology were obtained from the pathology report. A cost analysis was performed to compare the cost of routine FS examinations to determine malignancy with the cost of performing a second surgical procedure. RESULTS: Of the 169 patients evaluated, there were 53 cases of malignant nodules. Malignancy was diagnosed by FS in 16 of these 53 cases, resulting in a total thyroidectomy and thereby avoiding the need for a completion thyroidectomy. The sensitivity and specificity of FS examination were 30.2% and 100.0%, respectively. The routine use of intraoperative FS examination in cases of benign or indeterminate nodules afforded a total cost savings of $3719.27, or a cost savings of $22.01 per patient. CONCLUSION: FS examination was useful in guiding our intraoperative management for patients with unilateral thyroid nodules with benign or indeterminate preoperative FNAB. The routine use of FS was cost-effective in our Canadian health care system, even without considering the intangible costs, such as patients' anxiety, emotional stress, and the loss of productivity owing to a second surgical procedure.