Role Of Rapid On-site Evaluation Research Articles

The Limited Role of Rapid On-Site Evaluation in Lymphoid Lesions

The Limited Role of Rapid On-Site Evaluation in Lymphoid Lesions

The Role of Rapid On-site Evaluation (ROSE) in EBUS/FNA and Concurrent Tissue Biopsies for Indeterminate Lung and Mediastinal Lesions

The Role of Rapid On-site Evaluation (ROSE) in EBUS/FNA and Concurrent Tissue Biopsies for Indeterminate Lung and Mediastinal Lesions

Comparison of the diagnostic yield of rapid versus non-rapid onsite evaluation in endoscopic ultrasound-guided fine-needle aspiration cytology of solid pancreatic lesions.

The role of rapid on-site evaluation (ROSE) for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions is debatable. In this study, we aimed to compare the diagnostic yield of ROSE vs. non-ROSE in solid pancreatic lesions. This retrospective single-center study included patients undergoing EUS-FNA of solid pancreatic lesions from 2019-2021. Patients with cystic lesions, those undergoing fine-needle core biopsy, those undergoing repeat procedures, and patients with non-diagnostic smears with less than 6-month follow up were excluded. The diagnostic yield, need for repeat procedures and number of passes required with and without ROSE were analyzed in these patients. Of the 111 patients included, 56 underwent ROSE. The majority of lesions were malignant in both groups (79.6% ROSE vs. 75% non-ROSE). The diagnostic yield was 96.4% in the ROSE group and 94.5% in the non-ROSE group. Repeat samples were needed in 1 ROSE and 2 non-ROSE patients. The median number of passes made was significantly fewer in the ROSE group (3.5, interquartile range - 3,4) compared with the non-ROSE group (4, interquartile range - 3,5) P=0.01. However, the frequency of procedure-related complications was similar in both groups. The utilization of ROSE during EUS-FNA of solid pancreatic lesions does not affect the diagnostic yield or the need for repeat samples, but reduces the number of passes needed for acquiring samples.

Recent Endoscopic Ultrasound-Related Publications With Potential to Influence Clinical Practice

AbstractThe field of endoscopic ultrasound (EUS) has evolved significantly over the last two decades from being a tool of only diagnostic purpose to tissue acquisition and now therapeutic potential. There have been several important publications in the field of EUS in the last few years, which had a major impact in the clinical management of various gastrointestinal disorders. In this review, we discuss four such articles that in our opinion will significantly impact the role of EUS in treating various conditions. The first article is a randomized controlled trial comparing EUS-guided gall bladder drainage with percutaneous gall bladder drainage for high-risk acute cholecystitis. The second article is a randomized controlled trial comparing EUS versus minimally invasive surgery for necrotizing pancreatitis. The third article is a novel human study of EUS-guided portal pressure measurement in patients with portal hypertension. The last article is also a randomized controlled trial evaluating the role of rapid on-site evaluation for EUS-guided fine needle biopsy in solid pancreatic lesions.

Linear Endobronchial Ultrasound in the Era of Personalized Lung Cancer Diagnostics-A Technical Review.

Major advances in molecular profiling for available targeted treatments and immunotherapy for lung cancer have significantly increased the complexity of tissue-based diagnostics. Endobronchial ultrasound-guided transbronchial needle aspirations (EBUS-TBNA) are commonly performed for diagnostic biopsies and lymph node staging. EBUS-TBNA has increasingly become one of the main sources of tumor cells for molecular analyses. As a result, there is a growing need for high quality EBUS-TBNA samples with adequate cellularity. This has increased the technical demands of the procedure and has created additional challenges, many of which are not addressed in the current EBUS guidelines. This review provides an overview of current evidence on the technical aspects of EBUS-TBNA in light of comprehensive sample processing for personalized lung cancer management. These include sonographic lymph node characterization, optimal needle choice, suction biopsy technique, and the role of rapid on-site evaluation. Attention to these technical details will be important to maximize the throughput of EBUS-TBNA biopsies for molecular testing.

Rapid on-site evaluation (ROSE) during endobronchial ultrasound bronchoscopy (EBUS) in the diagnosis of granulomatous diseases.

We aimed to evaluate the role of Rapid On-Site Evaluation (ROSE) in improving the diagnostic contribution of EBUS-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of granulomatous lymphadenitis. We retrospectively included all patients in the study who underwent EBUS-TBNA (n=405) from September 2013 to September 2017. All cases who underwent EBUS-TBNA and were found to have "granuloma" in the final pathological diagnosis (n=143) were included in the research. One hundred forty-three cases who underwent EBUS and whose final pathological diagnosis was granuloma were included in the study. A total of 231 lymph nodes were sampled. The final diagnosis was found to be compatible with the examination during the procedure for 55 (85.9%) out of 64 patients for whom ROSE was performed. In addition, while 79.7% of the 64 patients who underwent ROSE were tested positive for granuloma, 9.4% were suspected to have granuloma, and no diagnostic result was obtained for 10.9%. The number of lymph node needle aspirations was statistically significantly lower in patients for whom ROSE was performed (P<.001). The final diagnosis was found to be compatible with the examination during the procedure for 55 (85.9%) out of 64 patients for whom ROSE was performed. According to the evaluation made on the duration, the procedure was completed in the first 15minutes in 95.4% of the patients for whom ROSE was performed, while the procedure took longer than 15minutes in 93.6% of the patients for whom ROSE was not performed. We found a high incidence of congruence between ROSE and the final cytological diagnosis if granulomas were identified in the final cytology. Performing ROSE shortens the duration of the procedure and reduced sampling thus preventing complications that may occur due to prolongation of the procedure.

Fine needle aspiration and core needle biopsy of the spleen: A case series illustrating current practices and challenges.

Splenic fine needle aspiration (FNA) and core needle biopsies (CNB) are rare specimen types, potentially avoided due to clinical concern for hemorrhagic complications. The safety and utility of splenic FNA, the role of rapid onsite evaluation (ROSE), as well as the diagnostic utility of CNB versus FNA have not been recently reviewed. A 10-year retrospective review was performed of percutaneous image-guided FNA and CNB of the spleen. Clinical indications, outcomes, ROSE findings, and final diagnoses were reviewed and correlated. Forty-four specimens from 39 patients were identified. The commonest indication for biopsy was a radiographic mass found during assessment for patient complaint (45%, 20/44), evaluation for malignancy (primary or metastatic) (39%, 17/44), and incidentally (16%, 7/44). Malignant diagnoses were rendered in 10 cases, 80% hematolymphoid and 20% nonhematolymphoid. Thirty-one cases were nonneoplastic and identified as infectious/inflammatory processes 39%, cysts 10%, vascular lesions 13%, benign splenic elements 22%, accessory or atrophic spleen 10%, and extramedullary hematopoiesis 6%. The nondiagnostic rate was 7%. Cases with subsequent splenectomy showed 100% specificity and 86% sensitivity. The concordance of ROSE and final interpretation was 90% within the neoplastic category. Finally, the significant complication rate was 6.8% with no bias to occurrence following FNA or CNB. This series affirms the safety and efficacy of splenic FNA and CNB by complication rates comparable to prior studies and high rate of concordance. The diagnostic accuracy may be further improved by ROSE, and CNB in cases reliant on staining and tissue architecture.

Processing of Fine-Needle Aspiration Specimens from Pancreatic Lesions.

It is important to adequately process and triage the specimen obtained from fine-needle aspirations (FNAs) of pancreatic lesions. Many echo endoscopists rely on rapid on-site evaluation (ROSE) for adequacy of FNA from solid pancreatic lesions. The role of ROSE in FNA of pancreatic lesions is discussed, as is the triage of material for making smears and cell block preparation. Different techniques of cell block preparation are briefly mentioned. Pancreatic cystic fluid obtained from pancreatic cysts is triaged differently as compared to specimens obtained from solid pancreatic lesions. An algorithmic approach to the processing of pancreatic cystic fluid for molecular and biochemical assays and cytology is discussed. Proper specimen handling is crucial to the accurate interpretation of pancreatic FNA specimens. The methods used to process a sample depend on whether the aspirated sample is solid or cystic and the type of device used for sampling. ROSE has been shown to reduce the number of inadequate specimens and to improve specimen preparation. The details of the various cytological preparation methods available are described in numerous texts. Here we focus on providing a broad overview of specimen collection and processing as it relates to pancreatic FNA, with guidance to the reader based on published and personal experiences.

Hepatic fine-needle aspiration cytology: The role of rapid on-site evaluation in the assessment of hepatic lesions.

Radiologically guided fine-needle aspiration cytology (FNAC) of internal organs is not cost-effective. Rapid on-site evaluation (ROSE) of smears by a cytopathologist can improve the diagnostic yield of FNACs and save time and money by reducing the need for repeat procedure/biopsy. To determine the role of ROSE in the diagnostic outcome of hepatic lesions by comparative analysis of FNAC with and without ROSE by a cytopathologist. Hepatic FNACs were retrospectively analyzed over two separate time periods from January 2011 to June 2013 and from January 2015 to July 2016. Smears from 2015-2016 were subjected to ROSE by a cytopathologist after staining with toluidine blue for 1 min to assess adequacy of the material. Final report was given after hematoxylin and eosin, May Grünwald Giemsa, and Papanicolaou staining were performed. Chi-square test (non-parametric) was used to determine if there was a statistically significant increase in the diagnostic yield with ROSE. During 2011-2013, of the 160 radiologically guided FNACs for hepatic lesions, 22 were non-diagnostic, whereas during 2015-2016, of 142 radiologically guided hepatic FNACs, only six were non-diagnostic. With the application of ROSE, there was a statistically significant increase in the diagnostic yield of hepatic FNACs from 86.25% to 95.8% (p=0.015). ROSE performed by a cytopathologist using toluidine blue can increase the diagnostic yield of hepatic FNACs and reduce the cost of healthcare by eliminating the need for a repeat procedure.

Evolution of a rapid onsite evaluation (ROSE) service for endobronchial ultrasound guided (EBUS) fine needle aspiration (FNA) cytology in a UK Hospital: A 7 year audit

Endobronchial ultrasound fine needle aspiration (EBUS FNA) is a well-established procedure for the diagnosis and staging of lung cancer. We review our provision of this service at the Royal Devon and Exeter NHS Foundation Trust and the role of rapid onsite evaluation (ROSE) with the increasing demand for molecular markers in this era of personalized medicine. A review of the changes in the Endoscopy clinic over the 7years from the introduction of EBUS at the end of 2010 until 2017 was carried out. This included the availability of material obtained for diagnosis, accurate subtyping, and molecular testing. We also assessed the success of molecular genetics DNA techniques from EBUS material versus formalin fixed paraffin embedded tissue (FFPE). A total of 1218 EBUS cases with ROSE were reported between 2011 and 2017 Percentage diagnostic rates were calculated as 83, 82, 84, 92, 93, 94, and 92 for 2011, 2012, 2013, 2014, 2015, 2016, and 2017, respectively. Availability of material for immunocytochemistry ranged from 86 to 100% over the 7years. Molecular testing was successfully performed for EGFR in 89-100% of requested cases and ALK testing in 87-100% of requested cases. EBUS sourced material gave on average twice the amount of DNA and fewer amplicon repeats per patient compared to FFPE material. ROSE at EBUS FNA provides access to suitable material for molecular testing with increased yields in the form of needle washings for EGFR with FFPE materials for ALK and PDL1 testing.

Role of Rapid On-site Evaluation in CT-guided Fine Needle Aspiration Cytology of Lung Nodules.

Objective:To prospectively investigate the value of rapid on-site evaluation (ROSE) in transthoracic fine needle aspiration cytology (FNAC) of patients with pulmonary nodules. Computed tomography (CT)-guided FNA is commonly employed for the diagnosis of lung lesions and the most common reason for not being able to provide a diagnosis in FNA is inadequacy of samples.Materials and Methods:This was a prospective study conducted in the departments of pathology and radiology of our cancer centre. This study had approval from the institutional review board and ethical committee of our institute. Fifty consecutive cases undergoing CT-guided transthoracic FNAC in our centre were included in the study. The smear submitted for ROSE was stained using toluidine blue stain. The specimen adequacy and diagnosis in ROSE was compared with that of the final cytology report, and the concordance regarding adequacy and diagnosis were noted.Results:Smears were adequate in 34 cases (68%) and inadequate in 16 cases (32%) Out of the 16 inadequate cases, 5 (31%) were converted to adequate due to the application of ROSE, thus increasing the adequate number of cases to 39 (78%). A diagnosis of malignancy was made in all 39 adequate cases. Sensitivity of ROSE in determining adequacy was 92% and specificity was 100%. The most common malignancy was adenocarcinoma in 26 cases. Pnemothorax occurred in 2 cases. No significant complications occurred in other cases.Conclusion:CT-guided FNA with ROSE is a safe and useful tool in the diagnostic work-up of lung cancer patients. A multidisciplinary approach along with onsite evaluation of adequacy will increase the diagnostic utility of cytology in lung lesions.

Efficacy of endoscopic ultrasound-guided fine-needle aspiration and core needle biopsy in the diagnosis of upper gastrointestinal submucosal lesions

Endoscopic ultrasonographically guided fine-needle aspiration (EUS-FNA) has been increasingly utilized to evaluate submucosal lesions of the upper gastrointestinal (UGI) tract. Our study aims to determine the efficacy of UGI EUS-FNA/core needle biopsy (CNB), including the frequency and cytomorphologic features of encountered submucosal lesions, and to investigate contributing factors including the role of rapid on-site evaluation (ROSE). We analyzed all UGI submucosal lesions diagnosed at our institution by EUS-FNA/CNB from September 2008 through August2015. During this 8-year study period, 94 patients underwent 110 UGI EUS-FNA/CNB, including 89 (81%) gastric, 11 (10%) duodenal, and 10 (9%) esophageal lesions. Twenty-seven (25%) were gastrointestinal stromal tumors (GISTs), followed by 13 (12%) leiomyomas, 5 (5%) schwannomas, 4 (4%) gastric adenocarcinomas, 3 (3%) neuroendocrine tumors (NETs), and 3 (3%) pancreatic heterotopias. All GISTs, leiomyomas, and NETs were ultimately diagnosed by EUS biopsies, as well as 75% of adenocarcinomas, 60% of schwannomas, and 33% of pancreatic heterotopias. The specificity of EUS-FNA/CNB for these 6 most commonly encountered lesions was 100%, with sensitivity of 82%. Sensitivity was 100% for esophageal and duodenal biopsies, and 80% and 75% for gastric and gastroesophageal procedures, respectively. Factors that contributed to poor yield included the lack of ROSE, small lesional size, lesion location and histology, and needle type. Neither number of needle passes nor operator experience appeared to influence specimen adequacy. EUS-FNA/CNB is an effective modality for diagnosing UGI submucosal lesions. Awareness of potential errors due to sampling of the bowel wall, lesional cystic degeneration, as well as pancreatic heterotopia and Brunner gland hamartoma is essential in order to avoid false diagnoses.

Endoscopic ultrasound core needle for diagnosing of solid pancreatic lesions: is rapid on-site evaluation really necessary?

Endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) has a crucial role in the diagnosis of solid pancreatic lesions and rapid on-site evaluation (ROSE) can increase its diagnostic yield. Rapid on-site evaluation is not always available and after EUS-FNA provides a cytology specimen with scant cellularity. Fine needle biopsy (FNB) specimens containing core tissue may theoretically overcome the limitations of EUS-FNA sampling. It could be hypothesized that EUS-FNB without ROSE could achieve the same adequacy and accuracy of EUS-FNB with ROSE. The aim of this review is to evaluate the evidence on the role of ROSE in the setting of EUS-guided tissue acquisition with core needles in patients with solid pancreatic lesions. All relevant articles were extracted up to February 2017 based on the results of searches in PubMed, Scopus and Google Scholar. A total of 21 pertinent articles were finally included. Among the included studies, 11 were performed without ROSE, 8 with ROSE, and 2 were performed both with and without ROSE. In the ROSE group we found a sensitivity, specificity, overall diagnostic adequacy and overall diagnostic accuracy of 96%, 100%, 86.5%, 85.5%, respectively, while in the no-ROSE group 86.6%, 100%, 89.5%, 86.1% were found, respectively. Mild pancreatitis (mean rates, 3.43%) and abdominal pain (mean rates, 3.6%) were reported as most frequent adverse events. Endoscopic ultrasound guided-FNB without ROSE offers similar results in terms of adequacy and accuracy as in the presence of an on-site cytopathologist.

Utility of rapid on-site cytologic evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions.

The utility of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions is unclear. The aim of this study was to evaluate the role of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions. Consecutive patients who underwent endobronchial ultrasound with a guide sheath for the diagnosis of peripheral pulmonary lesions at our hospital between September 2012 and July 2014 were included in this retrospective study. Cytology slides were air-dried, and modified Giemsa (Diff-Quik) staining was used for rapid on-site evaluation. Additional smears were prepared for Papanicolaou staining and tissue samples were placed in formalin for histologic evaluation. The results of rapid on-site evaluation were compared with the final diagnoses of endobronchial ultrasound with a guide sheath. A total of 718 cases were included in the study population. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions was 88.6%, 65.9%, 81.2%, 77.7% and 80.1%, respectively. There were no procedure-related deaths. Rapid on-site evaluation during endobronchial ultrasound with a guide sheath had high sensitivity for peripheral pulmonary lesions. When carrying out rapid on-site evaluation of transbronchial biopsy samples from peripheral pulmonary lesions, careful interpretation and clinical correlation are necessary.

Role of Rapid Onsite Evaluation (ROSE) of EUS-FNAC in Diagnostic Yield of Solid Mass Lesions

Introduction: Endoscopic ultrasound guided fine needle aspiration cytology (EUS-FNA) is a preferred minimally invasive modality with low complication rates for cytological diagnosis of various gastrointestinal and mediastinal lesions.The present study was conducted to determine whether rapid on-site evaluation (ROSE) of cytology smears by cytopathologist improves the diagnostic yield of solid mass lesions on EUS–FNA. Material and Methods: Total 112 patients from June 2014 through October 2015 referred for EUS-FNA of solid mass lesions were prospectively enrolled in this single center study out of which 56 were in group-I (without onsite cytopathologist) and 56 in group-II ( with onsite

Improving the diagnostic yield of single-operator cholangioscopy-guided biopsy of indeterminate biliary strictures: ROSE to the rescue? (with video)

Tissue diagnosis, regardless of technique or endoscope used, can be challenging in patients with indeterminate biliary strictures (IDBSs). This exploratory study evaluated the utility and role of rapid onsite evaluation of touch imprint cytology (ROSE-TIC) when single-operator cholangioscopy (SOC)-guided biopsies of IDBSs are performed. Patients with IDBSs were evaluated by intraprocedural ROSE-TIC during SOC-guided biopsy procedures. Final diagnosis was established by long-term patient follow-up in conjunction with off-site findings or surgical histology. The main outcome measure was to evaluate the utility of ROSE-TIC by determination of its operating characteristics and comparison with off-site histologic assessment. Of 31 patients with IDBSs, tissue diagnosis was indeterminate at prior ERCP-guided brush and/or biopsyin 14, prior EUS-guided FNA (EUS-FNA) in 6, and a mass could not be identified at EUS in 11. Themean number of biopsies performed was 3.3 (range 1-8), and diagnostic interpretation by ROSE-TIC was diagnostic and/or suspicious for carcinoma in 15, benign in 13, atypical-reactive in 2, and bile duct intraductal papillary mucinous neoplasm in 1. Final diagnosis by surgical histology (n= 4), death by disease (n= 10), and patient follow-up (n= 17) showed that the overall sensitivity of ROSE-TIC for diagnosing malignancy was100%, specificity 88.9%, positive predictive value 86.7%, negative predictive value 100%, and diagnostic accuracy 93.5%. Preliminary data suggest that the diagnostic outcomes of SOC-guided biopsies in IDBSs can be significantly improved by using ROSE-TIC. This technique also may benefit centers that rely mainly on fluoroscopy-guided intraductal biopsies.

Rapid on-site evaluation of endoscopic-ultrasound-guided fine-needle aspiration diagnosis of pancreatic masses

Endoscopic ultrasound (EUS) has become an essential tool for the study of pancreatic diseases. Specifically, EUS plays a pivotal role evaluating patients with a known or suspected pancreatic mass. In this setting, differential diagnosis remains a clinical challenge. EUS-guided fine-needle aspiration (FNA) and fine-needle biopsy (FNB) have been proven to be safe and useful tools in this setting. EUS-guided FNA and FNB, by obtaining cytological and/or histological samples, are able to diagnose pancreatic lesions with high sensitivity and specificity. In this context, several methodological features, trying to increase the diagnostic yield of EUS-guided FNA and FNB, have been evaluated. In this review, we focus on the role of rapid on-site evaluation (ROSE). From data reported in the literature, ROSE may increase diagnostic yield of EUS-FNA specimens by 10%-30%, and thus, diagnostic accuracy. However, we should point out that many recent studies have reported adequacy rates of > 90% without ROSE, indicating that, perhaps, at high-volume centers, ROSE may not be indispensable to achieve excellent results. The use of ROSE can be considered important during the learning curve of EUS-FNA, and also in hospital with diagnostic accuracy rates < 90%.

Role of rapid on-site evaluation with cyto-histopathological correlation in diagnosis of lung lesion.

Aim:This study was conducted to assess the role of cytology in the diagnosis of lung lesions and to compare it with histopathology. It was also intended to evaluate the role of rapid on site evaluation (ROSE) as an adjunct to cytological diagnosis of lung lesions.Materials and Methods:The study included all the cases of lung lesions, which were diagnosed on cytology followed by histopathology over a period of 2½ years along with ROSE, wherever possible.Results:Cytology was done in total 782 cases of various lung lesions and of this cyto-histopathological correlation was available in 215 cases. ROSE was done in 93.4% of total cases and smears were considered on the site adequate in the first pass in 68.1% cases and in second pass adequacy increased to 93.4%. The diagnostic accuracy of cytology was 75.3%, and that of histology was 86.9% in the diagnosis of lung lesions. The diagnostic accuracy of cytology for squamous cell carcinoma (94.4%) and adenocarcinoma (96.5%) was higher than that of histology.Conclusion:Cytology is comparable to histology in the diagnosis of lung lesions and may even outperform biopsy in lung tumor diagnosis. The advantages of cytology may be further added by better sampling and preanalytical assessment for adequate diagnostic material and ROSE has proved to be an important, easy and cost effective adjunct in this regard. A multidisciplinary approach involving pulmonologist, radiologist and cytopathologist with ROSE, followed by vigilant morphological examination may increase diagnostic utility of cytology for lung lesions.

On‐site cytopathology for endoscopic ultrasound‐guided fine‐needle aspiration of solid pancreatic masses

On‐site cytopathology for endoscopic ultrasound‐guided fine‐needle aspiration of solid pancreatic masses

Cytological specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration: Sample handling and role of rapid on-site evaluation

Recently developed, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive modality for mediastinal lymph node staging in lung cancer patients as well as for the diagnosis of mediastinal and hilar lymphadenopathy. It has been shown in systematic reviews and meta-analysis that a high diagnostic yield can be achieved with EBUS-TBNA for staging lung cancer. Though still not a standard of practice, this novel technology has attracted physicians and surgeons as an alternative modality to surgical biopsy for the assessment of the mediastinum. Standard cytology, thin layer preparations in liquid medium or cell blocks of cells obtained by EBUS-TBNA can be applicable not only for pathological diagnosis but also for further investigations such as immunohistochemistry and fluorescence in situ hybridization. In addition, samples obtained by EBUS-TBNA can also be used for molecular analysis. The key to a successful EBUS-TBNA is to understand the anatomy of the mediastinum as well as the basic steps of the procedure. Moreover, handling of the sample obtained by EBUS-TBNA is crucial for diagnosis since no amount of skill or interest of the interpreter can make up for a badly prepared sample. The goals of rapid on-site evaluation during EBUS-TBNA include determination of whether sampling of the target has been achieved and more importantly triage of samples to secondary investigations. This manuscript explains the detailed techniques of EBUS-TBNA to master this innovative procedure.