Utility of bronchoscopically obtained frozen cytology pellets for next-generation sequencing.

BACKGROUND: Next-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay. METHODS: We retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine. We investigated the amount of extracted DNA and RNA and determined the NGS success rates. We also compared the amount of DNA and RNA by bronchoscopy methods. To create the frozen cytology pellets, we first effectively collected the cells and then quickly centrifuged and cryopreserved them. RESULTS: A total of 132 patients were enrolled in this study between May 2016 and December 2022; of them, 75 were subjected to frozen cytology pellet examinations and 57 were subjected to frozen tissue examinations. The amount of DNA and RNA obtained by frozen cytology pellets was nearly equivalent to frozen tissues. Frozen cytology pellets collected by endobronchial ultrasound-guided transbronchial needle aspiration yielded significantly more DNA than those collected by transbronchial biopsy methods. (P < 0.01) In RNA content, cytology pellets were not inferior to frozen tissue. The success rate of NGS analysis with frozen cytology pellet specimens was comparable to the success rate of NGS analysis with frozen tissue specimens. CONCLUSIONS: Our study showed that frozen cytology pellets may have equivalent diagnostic value to frozen tissue for NGS analyses. Bronchial cytology specimens are usually used only for cytology, but NGS analysis is possible if enough cells are collected to create pellet specimens. In particular, the frozen cytology pellets obtained by endobronchial ultrasound-guided transbronchial needle aspiration yielded sufficient amounts of DNA. TRIAL REGISTRATION: This was registered with the University Medical Hospital Information Network in Japan (UMINCTR registration no. UMIN000052050).

Impact of endoscopic ultrasound-guided tissue acquisition on prognosis and peritoneal lavage cytology in resectable or borderline resectable pancreatic ductal adenocarcinoma.

OBJECTIVES: This study aimed to evaluate the clinical impact of preoperative endoscopic ultrasound-guided tissue acquisition (EUS-TA) on the prognosis and incidence of positive peritoneal lavage cytology (PLC) during laparotomy or staging laparoscopy in patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively collected data from patients diagnosed with body and tail PDAC with/without EUS-TA at our hospital from January 2006 to December 2021. RESULTS: To examine the effect of EUS-TA on prognosis, 153 patients (122 in the EUS-TA group, 31 in the non-EUS-TA group) were analyzed. There was no significant difference in overall survival between the EUS-TA and non-EUS-TA groups after PDAC resection (P = 0.777). In univariate and multivariate analysis, preoperative EUS-TA was not identified as an independent factor related to overall survival after pancreatectomy [hazard ratio 0.96, 95 % confidence interval (CI) 0.54-1.70, P = 0.897]. Next, to examine the direct influence of EUS-TA on the results of PLC, 114 patients (83 in the EUS-TA group and 31 in the non-EUS-TA group) were analyzed. Preoperative EUS-TA was not statistically associated with positive PLC (odds ratio 0.73, 95 % CI 0.25-2.20, P = 0.583). After propensity score matching, overall survival and positive PLC were the same in both groups. CONCLUSIONS: EUS-TA had no negative impact on postoperative survival and PLC-positive rates in R/BR PDAC.

Comparing a 19-gauge fine-needle biopsy needle with a 22-gauge fine-needle biopsy needle for EUS-guided liver biopsy sampling: a prospective randomized study.

BACKGROUND AND AIMS: EUS-guided liver biopsy (EUS-LB) sampling is being increasingly used. We performed a prospective randomized trial to compare specimen adequacy of a 19-gauge fine-needle biopsy (FNB) needle with a 22-gauge FNB Franseen tip needle for EUS-LB sampling. METHODS: Forty-two consecutive patients referred for EUS-LB sampling were prospectively randomized to a 19-gauge or 22-gauge FNB needle. When the specimen with the 22-gauge needle was macroscopically inadequate, an additional pass with the 19-gauge needle was done. Bilobar EUS-LB sampling was performed with heparinized wet suction using 1 pass and 3 actuations per lobe. Descriptive statistics were computed for all variables. RESULTS: Biopsy sampling was performed for abnormal liver enzymes in 95.5% of patients (57% women; average age, 51 years). Five patients undergoing sampling with the 22-gauge FNB needle had macroscopically inadequate specimens and required additional biopsy sampling with the 19-gauge FNB needle. Mean preprocessing length of the longest tissue core was 21.5 ± 6.3 mm with a 19-gauge FNB needle compared with 9.4 ± 5.5 mm with the 22-gauge FNB needle (P < .001). Postprocessing specimens were significantly longer with 19-gauge than with 22-gauge FNB needles (17.4 mm vs 6.8, P < .001). There were no adverse events, and postprocedure pain and discomfort was similar in both groups (14% for 19-gauge vs 10% for 22-gauge, P = .99). CONCLUSIONS: Liver core biopsy sampling using the 19-gauge FNB needle is superior to the 22-gauge FNB needle in terms of length of longest core and aggregate specimen length. Considerably more fragmentation of the 22-gauge cores occurs during tissue processing. No increased postprocedure pain or AEs were found with the 19-gauge needle. A 19-gauge FNB needle is preferred to the 22-gauge FNB needle for EUS-LB. (Clinical trial registration number: NCT04806607.).

True diagnostic ability of EUS-guided fine-needle aspiration/biopsy sampling for small pancreatic lesions ≤10 mm and salvage diagnosis by pancreatic juice cytology: a multicenter study.

BACKGROUND AND AIMS: The diagnostic performance of EUS-guided fine-needle aspiration/biopsy sampling (EUS-FNAB) for pancreatic ductal adenocarcinoma (PDAC) ≤10 mm in diameter is relatively low. Pancreatic juice cytology (PJC) has gained attention because of its high sensitivity for small PDACs. We aimed to clarify the diagnostic ability of EUS-FNAB and the salvage ability of PJC for PDAC ≤10 mm. METHODS: Data obtained from attempted EUS-FNAB for patients with EUS-confirmed pancreatic tumors ≤10 mm (excluding pancreatic metastases/malignant lymphomas) were retrospectively analyzed. Patients who experienced technical failure or had a negative EUS-FNAB result and had a strong likelihood of PDAC based on imaging characteristics underwent PJC. PDAC was diagnosed using resected histologic specimens, EUS-FNAB-positive tumor growth on the imaging examination, or additional EUS-FNAB-positive results after increase in tumor size. The primary endpoint was the diagnostic ability of EUS-FNAB for PDAC ≤10 mm. The salvage ability of PJC was also assessed. RESULTS: Overall, 86 of 271 patients with pancreatic tumors ≤10 mm who underwent attempted EUS-FNAB were diagnosed with PDAC. The technical success rate, sensitivity, specificity, and accuracy of EUS-FNAB for PDAC ≤10 mm were 80.8%, 82.3%, 94.9%, and 91.3%, respectively. Among the 35 PDAC patients who experienced technical failure or false-negative results of EUS-FNAB, 26 (74.3%) were correctly diagnosed using salvage PJC. CONCLUSIONS: The true success rate and sensitivity of EUS-FNAB for PDAC ≤10 mm were relatively low. When EUS-FNAB for a pancreatic lesion ≤10 mm strongly suspected to be PDAC is unsuccessful or yields a negative result, PJC is recommended. (Clinical trial registration number: UMIN000049965.).

Establishment of a patient-specific avatar organoid model derived from EUS-guided fine-needle biopsy for timely clinical application in pancreatic ductal adenocarcinoma (with video).

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate among tumors. At the time of diagnosis, more than 80% of PDACs are considered to be surgically unresectable, and there is an unmet need for treatment options in these inoperable PDACs. This study aimed to establish a patient-derived organoid (PDO) platform from EUS-guided fine-needle biopsy (EUS-FNB) collected at diagnosis and to determine its clinical applicability for the timely treatment of unresectable PDAC. METHODS: Patients with suspected PDAC were prospectively enrolled at the Samsung Medical Center from 2015 to 2019. PDAC tissues were acquired by means of EUS-FNB to establish PDAC PDOs, which were comprehensively analyzed for histology, genomic sequencing, and high-throughput screening (HTS) drug sensitivity test. RESULTS: PDAC PDOs were established with a success rate of 83.2% (94/113). It took approximately 3 weeks from acquiring minimal EUS-FNB specimens to generating sufficient PDAC PDOs for the simultaneous HTS drug sensitivity test and genomic sequencing. The high concordance between PDAC tissues and matched PDOs was confirmed, and whole-exome sequencing revealed the increased detection of genetic alterations in PDOs compared with EUS-FNB tissues. The HTS drug sensitivity test showed clinical correlation between the ex vivo PDO response and the actual chemotherapeutic response of the study patients in the real world (13 out of 15 cases). In addition, whole-transcriptome sequencing identified candidate genes associated with nab-paclitaxel resistance, such as ITGB7, ANPEP, and ST3GAL1. CONCLUSIONS: This PDAC PDO platform allows several therapeutic drugs to be tested within a short time window and opens the possibility for timely personalized medicine as a "patient avatar model" in clinical practice.

Diagnostic yield of endoscopic and EUS-guided biopsy techniques in subepithelial lesions of the upper GI tract: a systematic review.

BACKGROUND AND AIMS: Obtaining adequate tissue samples in subepithelial lesions (SELs) remains challenging. Several biopsy techniques are available, but a systematic review including all available techniques to obtain a histologic diagnosis of SEL is lacking. The aim of this study was to evaluate the diagnostic yield and adverse event rates of endoscopic biopsies, EUS-guided FNA (EUS-FNA), EUS-guided fine-needle biopsy (FNB) (EUS-FNB), and mucosal incision-assisted biopsy (MIAB) for SELs in the upper GI tract. METHODS: A search strategy in multiple databases was performed. The primary outcome was diagnostic yield, defined as the percentage of procedures in which histology was obtained and resulted in a definitive histopathologic diagnosis. Secondary outcome measures included reported procedure-related adverse events, which were graded according to the AGREE (Adverse Events in Gastrointestinal Endoscopy) classification. RESULTS: A total of 94 original articles were included. Studies were classified per endoscopic technique to obtain histopathology. This resulted in 8 included studies for endoscopic biopsy methods, 55 studies for EUS-FNA, 33 studies for EUS-FNB, and 26 studies for MIAB. Pooled rates for diagnostic yield were 40.6% (95% confidence interval [CI], 30.8-51.2) for endoscopic biopsy, 74.6% (95% CI, 69.9-78.7) for EUS-FNA, 84.2% (95% CI, 80.7-87.2) for EUS-FNB, and 88.2% (95% CI, 84.7-91.1) for MIAB. Reported procedure-related adverse events graded AGREE II or higher were 2.8% to 3.9% for endoscopic biopsies, 1.0% to 4.5% for EUS-FNA, .9% to 7.7% for EUS-FNB, and 1.9% to 7.9% for MIAB. CONCLUSIONS: Based on the available evidence, MIAB and EUS-FNB seem to be most effective in terms of achieving a high diagnostic yield, with similar rates of adverse events.

Comparative diagnostic yield of different endoscopic techniques for tissue sampling of upper gastrointestinal subepithelial lesions: a network meta-analysis.

BACKGROUND: There is limited evidence on the comparative diagnostic performance of endoscopic tissue sampling techniques for subepithelial lesions. We performed a systematic review with network meta-analysis to compare these techniques. METHODS: A systematic literature review was conducted for randomized controlled trials (RCTs) comparing the sample adequacy and diagnostic accuracy of bite-on-bite biopsy, mucosal incision-assisted biopsy (MIAB), endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and EUS-guided fine-needle biopsy (FNB). Results were expressed as relative risk (RR) and 95%CI. RESULTS: Eight RCTs were identified. EUS-FNB was significantly superior to EUS-FNA in terms of sample adequacy (RR 1.20 [95%CI 1.05-1.45]), whereas none of the other techniques significantly outperformed EUS-FNA. Additionally, bite-on-bite biopsy was significantly inferior to EUS-FNB (RR 0.55 [95%CI 0.33-0.98]). Overall, EUS-FNB appeared to be the best technique (surface under cumulative ranking [SUCRA] score 0.90) followed by MIAB (SUCRA 0.83), whereas bite-on-bite biopsy showed the poorest performance. When considering lesions <20 mm, MIAB, but not EUS-FNB, showed significantly higher accuracy rates compared with EUS-FNA (RR 1.68 [95%CI 1.02-2.88]). Overall, MIAB ranked as the best intervention for lesions <20 mm (SUCRA score 0.86 for adequacy and 0.91 for accuracy), with EUS-FNB only slightly superior to EUS-FNA. When rapid on-site cytological evaluation (ROSE) was available, no difference between EUS-FNB, EUS-FNA, and MIAB was observed. CONCLUSION: EUS-FNB and MIAB appeared to provide better performance, whereas bite-on-bite sampling was significantly inferior to the other techniques. MIAB seemed to be the best option for smaller lesions, whereas EUS-FNA remained competitive when ROSE was available.

Outcomes of Endoscopic Ultrasound-guided Fine Needle Biopsy Using a Novel Hydrostatic Stylet Tissue Acquisition Technique.

BACKGROUND: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is frequently used to obtain core samples of solid lesions. Here, we describe and evaluate a novel hydrostatic stylet (HS) technique designed to optimize core sample acquisition, reporting diagnostic yield, efficacy, and safety relative to the conventional stylet slow-pull (SP) technique. METHODS: A novel HS technique was developed and validated retrospectively. Consecutive patients who underwent EUS-FNB with core biopsy of solid lesions through either the HS or SP technique between January 2020 and April 2022 were included. Exclusion criteria included cystic lesions, nonlesional liver biopsies, and specimens sent for cytologic analysis only. Patient and lesion characteristics, number of passes, sample adequacy, and adverse events were compared between the two techniques. RESULTS: A total of 272 patients were included with 138 in the HS group and 134 in the SP group. Lesion size and anatomic distribution were similar in both groups. Compared with the SP approach, the HS technique demonstrated significantly higher sample adequacy (97.8% vs 83.6%, P < 0.001), higher sensitivity (97.1% vs 89.7%, P = 0.03), and lower mean number of passes (1.2 vs 3.3, P < 0.001). Rates and severity of adverse events in the HS group were comparable to the SP group and existing literature. Similar associations were observed in pancreatic and nonpancreatic lesion subanalyses. CONCLUSIONS: The novel HS technique demonstrated excellent biopsy sample adequacy and diagnostic yield while requiring fewer passes to obtain diagnostic specimens compared with a conventional EUS-FNB approach. Further prospective evaluation is needed to confirm these pilot findings and optimize EUS-FNB acquisition techniques.

Performance and safety of diagnostic EUS FNA/FNB and therapeutic ERCP in patients with borderline resectable and locally advanced pancreatic cancer - results from a population-based, prospective cohort study.

Objective: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS FNA/FNB) and potential endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression are indicated in patients with pancreatic cancer before initation of primary chemotherapy. This study aims to investigate the performance and safety of these two procedures in patients with borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC). Methods: Endoscopy and pathology reports, and hospital records of consecutive patients with a radiological diagnosis of BRPC/LAPC included in a population based, protocol-driven study (NORPACT-2) were reviewed. Results: Of 251 patients, 223 (88.9%) underwent EUS-FNA/FNB, and 133 (53%) underwent ERCP. Repeated EUS attempts were performed in 33 (14.8%), eight (3.6%), and four (1.8%) patients. FNA was performed in 155 procedures, FNB in 30, and combined EUS-FNA/FNB in 83. Diagnostic accuracy was 86.1% for first EUS-FNA/FNB. The cumulative diagnostic accuracy for all attempts was 96%. False positive rate for malignancy was 0.9%. Of a total of 149 ERCP procedures, 122 (81.9%) were successful, and 27 (18.1%) were unsuccessful. Success rate of first ERCP attempt was 80.5% (107/133). Sixteen patients (12%) underwent a second attempt with a success rate of 93.8% (15 of 16). Combined EUS and ERCP was performed in 41 patients. Complications occurred in eight procedures (3%) after EUS-FNA/FNB, 23 procedures (15.3%) after ERCP, and four (9.8%) patients after combined EUS-FNA/FNB and ERCP. Conclusion: EUS-FNA/FNB and ERCP with biliary stenting in patients with BRPC/LAPC demonstrated acceptable performance and safety. Repeat procedures were performed with high success rates. Same session EUS-FNA/FNB and ERCP for biliary decompression is safe.

The advent of the first electric driven EUS-guided 17 gauge core needle biopsy - A pilot study on subepithelial lesions.

BACKGROUND AND AIMS: This pilot study aimed to evaluate safety and tissue sampling from subepithelial lesions (SEL) in the upper gastrointestinal tract with a novel electric motor driven endoscopic ultrasonography (EUS)-guided 17-gauge (G) size core needle biopsy (CNB) instrument. METHODS: An investigator-led prospective open label, performance and safety control study, including seven patients (female n = 4, median 71 y, range 28-75) with a determined SEL (median size 30 mm, range 17-150 mm) in the upper digestive tract (stomach n = 6, duodenum n = 1) were eligible and later followed up 14 days after index procedure. All investigations were completed according to protocol with three FNB 22-G passes with four fanning strokes and two EndoDrill® 17-G passes with three fanning strokes. RESULTS: Quality of samples as 'visible pieces' (>5 mm): FNB (n = 5/7) (fragmented/blood imbibed n = 1, poor tissue quantity n = 1) compared with 17-G CNB (n = 7/7). Histological result which led to final diagnosis (leiomyoma n = 2, adenocarcinoma n = 1, schwannoma n = 1, neuroendocrine tumour n = 1, desmoid tumour n = 1 and gastrointestinal stromal tumour (GIST) n = 1) could be obtained with the 17-G CNB instrument in all seven patients. FNB technique reached correct diagnosis in six patients. No serious adverse event were recorded. CONCLUSIONS: By using an electric driven 17-G biopsy device, a true cylinder of core tissue can be obtained in one single puncture from the area of interest reducing the need for a second sampling. The absolute benefit of EUS-guided CNB is that the sample can be handled and histologically prepared in the same manner as standard percutaneous core needle sample, e.g., breast and prostate cancer.

Efficacy of endoscopic ultrasound-guided tissue acquisition using stereo-microscopic on-site evaluation for possible comprehensive genome profile in patients with advanced pancreatic cancer.

BACKGROUND AND AIM: Stereomicroscopic on-site evaluation (SOSE) is a rapid evaluation method for endoscopic ultrasound-guided tissue acquisition (EUS-TA) with a high diagnostic sensitivity when the stereomicroscopically visible white core (SVWC) cut-off value (≥ 11 mm) is met. We prospectively examined the association between SVWCs and the adequacy of tissue specimens, assuming subsequent comprehensive genome profiling (CGP). METHODS: This study included 66 consecutive patients with suspected unresectable pancreatic cancer who underwent EUS-TA. The primary endpoint was the frequency of combined samples with ≥ 20% tumor cell content that met over twice the SVWC (T-SVWC) cut-off value, achieved through multiple punctures. The secondary endpoints were the number of punctures, the percentage of SVWC cut-off values, adverse events, the positive diagnosis rate, and the tissue section area. RESULTS: The median number of EUS-TA punctures for suspected unresectable pancreatic cancer was 3 (range, 3-4); SVWC and T-SVWC cut-off values were obtained in 171/206 specimens and 65/66 patients, respectively. There were no EUS-TA-related adverse events. The positive diagnosis rate of EUS-TA was 95.5%. Among the 63 patients meeting the T-SVWC cut-off value in pathological diagnoses, the median tumor cell content was 40% (range, 5-80%), with 57 patients having tumor cell content ≥ 20%. The median tissue section area was 15 (range, 3-40) mm2. CONCLUSIONS: When performing EUS-TA for unresectable pancreatic cancer with the intention of subsequent CGP, obtaining a high tumor cell content (≥ 20%) by assessing the T-SVWC cut-off value via SOSE may serve as a novel indicator for on-site estimation of CGP suitability for EUS-TA specimens.

EBUS-TBNA for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer clinically staged with PET/CT.

BACKGROUND AND OBJECTIVE: To evaluate the diagnostic accuracy and clinical usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer (NSCLC) clinically staged with positron emission tomography/computed tomography (PET/CT). METHODS: We conducted a study that included patients with centrally located T1N0M0 NSCLC, clinically staged with PET/CT who underwent EBUS-TBNA for mediastinal staging. Patients with negative EBUS-TBNA underwent mediastinoscopy, video-assisted mediastinoscopic lymphadenectomy (VAMLA) and/or lung resection with systematic nodal dissection, that were considered the gold standard. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), overall accuracy of EBUS-TBNA for diagnosing mediastinal metastases (N2 disease) and the number needed to treat (NNT: number of patients needed to undergo EBUS-TBNA to avoid a case of pathologic N2 disease after resection) were calculated. RESULTS: One-hundred eighteen patients were included. EBUS-TBNA proved N2 disease in four patients. In the remaining 114 patients who underwent mediastinoscopy, VAMLA and/or resection there were two cases of N2 (N2 prevalence 5.1%). The sensitivity, specificity, NPV, PPV and overall accuracy for diagnosing mediastinal metastases (N2 disease) were of 66%, 100%, 98%, 100% and 98%, respectively. The NNT was 31 (95% CI: 15-119). CONCLUSION: EBUS-TBNA in patients with central clinically staged T1N0M0 NSCLC presents a good diagnostic accuracy for mediastinal staging, even in a population with low prevalence of N2 disease. Therefore, its indication should be considered in the management of even these early lung cancers.

Comparison of the specimen quality of endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized forceps versus mini forceps for lung cancer: A prospective study.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic procedure with adequate performance; however, its ability to provide specimens of sufficient quality and quantity for treatment decision-making in advanced-stage lung cancer may be limited, primarily due to blood contamination. The use of a 0.96-mm miniforceps biopsy (MFB) permits true histological sampling, but the resulting small specimens are unsuitable for the intended applications. Therefore, we introduced a 1.9-mm standard-sized forceps biopsy (SFB) and compared its utility to that of MFB. METHODS: We prospectively enrolled patients from three institutions who presented with hilar/mediastinal lymphadenopathy and suspected advanced-stage lung cancer, or those who were already diagnosed but required additional tissue specimens for biomarker analysis. Each patient underwent MFB followed by SFB three or four times through the tract created by TBNA using a 22-gauge needle on the same lymph node (LN). Two pathologists assessed the quality and size of each specimen using a virtual slide system, and diagnostic performance was compared between the MFB and SFB groups. RESULTS: Among the 60 enrolled patients, 70.0% were diagnosed with adenocarcinoma. The most frequently targeted sites were the lower paratracheal LNs, followed by the interlobar LNs. The diagnostic yields of TBNA, MFB and SFB were 91.7%, 93.3% and 96.7%, respectively. The sampling rate of high-quality specimens was significantly higher in the SFB group. Moreover, the mean specimen size for SFB was three times larger than for MFB. CONCLUSION: SFB is useful for obtaining sufficient qualitative and quantitative specimens.

Diagnostic Yield and Safety of the 19-Gauge versus 22-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Needle in Subjects with Sarcoidosis (GUESS).

INTRODUCTION: Observational data suggest that the 19-gauge (G) needle for endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) offers a higher diagnostic yield than the 22-G needle in sarcoidosis. No randomized trial has compared the yield of the two needles. METHODS: We randomized consecutive subjects with suspected sarcoidosis and enlarged thoracic lymph nodes to undergo EBUS-TBNA with either the 19-G or the 22-G needle. We compared the study groups for diagnostic sensitivity (primary outcome) assessed by the yield of granulomas in subjects finally diagnosed with sarcoidosis. We also compared the sample adequacy, difficulty performing the needle puncture assessed on a visual analog scale (VAS), the subject's cough intensity on an operator-rated VAS, and procedure-related complications (secondary outcomes). RESULTS: We randomized 150 (mean age, 43.0 years; 55% women) subjects and diagnosed sarcoidosis in 116 subjects. The diagnostic sensitivity of the 19-G needle (45/60, 75.0%) was not higher (p = 0.52) than the 22-G needle (39/56, 69.6%). We obtained adequate aspirates in 90.0% and 85.7% of subjects in the respective groups (p = 0.48). The operators had greater difficulty puncturing lymph nodes with the 19-G needle (p = 0.03), while the operator-assessed cough intensity was similar in the groups (p = 0.41). Transient hypoxemia was the only complication encountered during EBUS-TBNA (two subjects in either group). CONCLUSION: We did not find the 19-G needle superior to the 22-G in diagnostic sensitivity, specimen adequacy, or safety of EBUS-TBNA in sarcoidosis. Puncturing the lymph nodes was more difficult with the 19-G needle.

Endobronchial Ultrasound-Guided Transbronchial Mediastinal Cryobiopsy versus Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Mediastinal Disorders: A Meta-Analysis.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC), a novel technique, has been reported to improve the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lesions in recent studies. Current literature suggests that this procedure has greater diagnostic efficacy compared to conventional EBUS-TBNA. This systematic review and meta-analysis aimed to evaluate the diagnostic yield and complications associated with EBUS-TMC in comparison to EBUS-TBNA, thereby exploring the potential of this novel technique in enhancing the diagnostic utility for mediastinal lesions. METHODS: A comprehensive literature review was conducted by searching the PubMed, Embase, and Google Scholar databases for articles published from inception to December 31, 2023. The objective of this review was to evaluate the utilization of EBUS-TMC in diagnosing mediastinal disease, while also assessing the quality of each study using the QUADAS-2 tool. The diagnostic yield estimates were subjected to a meta-analysis utilizing inverse variance weighting. Furthermore, a comprehensive analysis of the complications associated with this procedure was performed. RESULTS: The meta-analysis included 10 studies involving a total of 538 patients. The findings of the meta-analysis demonstrated that EBUS-TMC yielded an overall diagnostic rate of 89.59% (482/538), while EBUS-TBNA yielded a rate of 77.13% (415/538). The calculated inverse variance-weighted odds ratio was 2.63 (95% confidence interval, 1.86-3.72; p < 0.0001), and I2 value was 11%, indicating a statistically significant difference between the two techniques. The associated complications consisted of pneumothorax, pneumomediastinum, mediastinitis, and bleeding, with an incidence of 0.74% (4/538), 0.37% (2/538), 0.0% (0/538), and 1.12% (6/538), respectively. Moreover, the funnel plot displayed no discernible publication bias. Further subgroup analysis revealed a notable improvement in the diagnosis value for lymphoma (86.36% vs. 27.27%, p = 0.0006) and benign disorder (87.62% vs. 60.00%, p < 0.0001). CONCLUSION: This review of the current available studies indicated that EBUS-TMC enhanced overall diagnostic yields compared to EBUS-TBNA, particularly for diagnosing benign disease and lymphoma. This procedure was not associated with any serious complications.

Successful Retrieval of a Broken Aspiration Needle Penetrated into the Right Pulmonary Artery: A Case Report with Experience Sharing.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration is increasingly used as a minimally invasive procedure in clinical settings. It is generally regarded as a safe procedure with high diagnostic accuracy. However, a complication involving a needle fracture that penetrated a nearby artery has not been reported during this procedure. CASE PRESENTATION: A male patient, 58 years of age, underwent endobronchial ultrasound-guided transbronchial needle aspiration for a mediastinal lymph node biopsy at a local hospital. The aspiration needle fractured and penetrated from the right middle segmental bronchus into the right pulmonary artery. The patient was then transferred to our hospital. After conducting repeated chest imaging examinations to confirm the presence of the foreign body and holding multidisciplinary team consultations, we first inserted a deflated balloon catheter near the puncture site in the right middle segmental bronchus. Following the needle retrieval through a flexible bronchoscope, the balloon catheter was inflated to ensure local hemostasis. Follow-up evaluations revealed no further complications for this patient. CONCLUSION: Intragenic vascular injury can occur during endobronchial ultrasound-guided transbronchial needle aspiration. Careful pre-procedure preparations should be planned to minimize complications. In patients experiencing complications due to needle penetration, consultation and coordination with a multidisciplinary team are essential to ensure the safe retrieval of the broken needle.

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and PD-L1 Yields.

PURPOSE: Immunotherapy is a leading approach for treating advanced non-small cell lung cancer (NSCLC) by targeting the PD-1/PD-L1 checkpoint signaling pathway, particularly in tumors expressing high levels of PD-L1 (Jug et al. in J Am Soc Cytopathol 9:485-493, 2020; Perrotta et al. in Chest 158: 1230-1239, 2020). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method to obtain tissue for molecular studies, including PD-L1 analysis, in unresectable tumors (Genova et al. in Front Immunol 12: 799455, 2021; Wang et al. in Ann Oncol 29: 1417-1422, 2018). This study aimed to assess the adequacy of PD-L1 assessment in EBUS-TBNA cytology specimens. METHODS: Data was collected retrospectively from patients who underwent EBUS-TBNA between 2017 and 2021 for suspected lung cancer biopsy. Samples positive for NSCLC were examined for PD-L1 expression. EBUS was performed by experienced practitioners, following institutional guidelines of a minimum of five aspirations from positively identified lesions. Sample adequacy for molecular testing was determined by the pathology department. RESULTS: The analysis involved 387 NSCLC cases (149 squamous cell, 191 adenocarcinoma, 47 unspecified). Of the 263 EBUS-TBNA specimens tested for PD-L1, 237 (90.1%) were deemed adequate. While 84% adhered to the protocol, adherence did not yield better results. Significantly higher PD-L1 adequacy was observed in squamous cell carcinomas (93.2%) compared to adenocarcinoma (87.6%). The number of aspirations and sedation type did not correlate with PD-L1 adequacy in either cancer type, but lesion size and location had a significant impact in adenocarcinomas. Adenocarcinoma exhibited higher PD-L1 expression (68%) compared to squamous cell carcinoma (48%). CONCLUSION: EBUS-TBNA offers high yields for assessing immunotherapy markers like PD-L1, with satisfactory adequacy regardless of NSCLC subtype, lesion size, or location.

Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and Next Generation Sequencing Yields.

PURPOSE: The use of endobronchial ultrasound (EBUS) is standard practice for lung cancer diagnosis and staging. Next generation sequencing (NGS) for detection of genetic alterations is recommended in advanced, non-squamous, non-small-cell lung cancer (NSCLC). Existing protocols for NGS testing are minimal and reported yields vary. This study aimed to determine the yield of EBUS samples obtained for NGS using a sampling protocol at our institution and assess predictive factors to form collection protocols. METHODS: We reviewed EBUS bronchoscopies from 2016 to 2021 with non-squamous NSCLC diagnoses. For target lesions suspected to be malignant, the sampling protocol was: (a) two slides for on-site evaluation, (b) three to five fine needle aspirations rinsed into saline for immunohistochemical staining and in-house molecular markers, and (c) additional three to five rinses for NGS. Sufficiency for NGS processing was determined by the pathology department. RESULTS: Two hundred and seventy-eight non-squamous NSCLC samples were obtained by EBUS (205 adenocarcinoma; 73 not otherwise specified). EBUS was performed under general anesthesia in 75.5% of cases. The overall sample adequacy for NGS testing was 57.5%. Higher adequacy rates were observed when protocol was adhered to 66.0% versus 37.2% (p < 0.001). There was no statistically significant difference based on the size of the lesion or location of the sample. CONCLUSION: When a protocol of three to five dedicated needle rinses for NGS was followed, we nearly doubled our sample adequacy rate for NSG as compared to standard care. Studies are needed to determine the ideal collection and processing modality to preserve tissue samples for genetic sequencing.

Adenocarcinoma originating in the anterior mediastinum diagnosed by endobronchial ultrasound-guided transbronchial cryobiopsy: a case report.

BACKGROUND: Endobronchial ultrasound-guided transbronchial cryobiopsy (EBUS-cryobiopsy) is advantageous for collecting larger specimens with minimal crushing; however, it has not been widely used for mediastinal tumors. CASE PRESENTATION: A 73-year-old woman with a history of left breast cancer underwent surgery followed by radiotherapy. Computed tomography showed a mass in the anterior mediastinum that was in extensive contact with the sternum on the ventral side and partly with the trachea on the dorsal side. Two computed tomography-guided needle biopsies (CTNBs) were performed on the mass; however, a definitive diagnosis was not made because of severe crush artifacts. Subsequently, we performed EBUS-cryobiopsy and safely obtained sufficient specimen volume with minimal crushing. The histopathological diagnosis was adenocarcinoma, with immunobiological features distinct from those of previous breast cancers. Her overall diagnosis was a rare tumor originating in the anterior mediastinum. CONCLUSIONS: EBUS-cryobiopsy can be safely performed in narrow areas surrounded by major blood vessels, and the obtained specimens may be superior to CTNBs for histopathological diagnosis.

A prospective, open-label, randomized clinical trial to evaluate the efficacy and safety of remimazolam in patients undergoing EBUS-TBNA: REST trial design.

BACKGROUND: Remimazolam is safe and effective for moderate sedation during flexible bronchoscopy, but its safety and efficacy during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains undetermined. The REST trial (NCT06275594) will be a prospective randomized study of remimazolam in patients undergoing EBUS-TBNA with conscious sedation. The primary aim is to evaluate whether remimazolam is safe and effective for moderate sedation during EBUS-TBNA compared to real-world midazolam and on-label midazolam. METHODS: The REST trial will recruit 330 patients from four university hospitals with mediastinal lesions suspected of being lung cancer who are eligible for EBUS-TBNA under moderate sedation. The participants will be randomized into groups using remimazolam, real-world midazolam, and on-label midazolam (US prescribing information dosage) to perform EBUS-TBNA for procedural sedation. The primary endpoint will be procedural success using composite measures. DISCUSSION: The REST trial will prospectively evaluate the efficacy and safety of remimazolam during EBUS-TBNA under moderate sedation. It will provide information for optimizing sedation modalities and contribute to practical benefits in patients undergoing EBUS-TBNA. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06275594). Prospectively registered on 15 February 2024.