Transbronchial Cryobiopsy Using the Ultrathin 1.1-mm Cryoprobe with Ultrathin Bronchoscopy under Radial Endobronchial Ultrasound Guidance for Diagnosis of Peripheral Pulmonary Lesions.

INTRODUCTION: Today, the increasing number of incidentally detected peripheral pulmonary lesions (PPLs) within and outside lung cancer screening trials is a diagnostic challenge. This fact encourages further improvement of diagnostic procedures to increase the diagnostic yield of transbronchial biopsy, which has been shown to have a low complication rate. The purpose of this study was to evaluate the safety and feasibility of a new ultrathin 1.1 cryoprobe that can be placed through an ultrathin bronchoscope (UTB) using fluoroscopy and radial endobronchial ultrasonography (rEBUS) navigation for assessing PPLs. METHODS: Thirty-five patients with PPL less than 4 cm in diameter were prospectively enrolled to receive transbronchial cryobiopsies (TBCBs) using the ultrathin 1.1-mm cryoprobe. Navigation to the PPL was accomplished with the UTB. Under rEBUS and fluoroscopy guidance up to 4 cryobiopsies were obtained. The sample sizes of the biopsies were compared to a historic collective derived from a 1.9-mm cryoprobe and standard forceps. The feasibility and safety of the procedure, the cumulative and overall diagnostic yield, and the cryobiopsy sizes were evaluated. RESULTS: After detection with the rEBUS, TBCB was collected from 35 PPLs, establishing a diagnosis in 25 cases, corresponding to an overall diagnostic yield of 71.4%. There was no difference in diagnostic yield for PPL <20 mm or ≥20 mm. All cryobiopsies were representative with a mean tissue area of 11.9 ± 4.3 mm2, which was significantly larger compared to the historic collective (p = 0.003). Six mild and four moderate bleeding events and 1 case of pneumothorax were observed. CONCLUSIONS: Using the ultrathin 1.1-mm cryoprobe combined with an UTB for rEBUS-guided TBCB of PPL is feasible and safe. This diagnostic approach improves bronchoscopic techniques for diagnosing peripheral lung lesions and may contribute to improve diagnosis of lung cancer even in small PPL.

Early Pneumatocele Identification Post-Robotic Assisted Bronchoscopy Cryobiopsy: A Case Series Experience.

INTRODUCTION: The use of cryobiopsy in conjunction with robotic assisted bronchoscopy is on the rise due to the safety and increased diagnostic yield of cryobiopsy. The incorporation of 3D fluoroscopy in the procedure improves the workflow and helps confirm the accuracy of sampling of peripheral pulmonary nodules. METHODS: We describe an observational series of 12 patients comprising 14 nodules where cryobiopsy was performed during shape-sensing robot-assisted bronchoscopy cryobiopsy under general anesthesia. 3D fluoroscopy was used to confirm accurate placement of the cryoprobe. All these patients underwent a second spin with the 3D fluoroscopy either to sample a second lesion intraoperatively or to investigate suspected pneumothorax. RESULTS: The development of a pneumatocele was noted after cryobiopsy in each of the cases. The majority of these were in the upper lobe with the median size of a sampled nodule being 14 mm. The majority of patients were asymptomatic with 1 patient developing mild hemoptysis and 4 patients developing chest tightness or dyspnea. None of the patients required an intervention for the pneumatocele. CONCLUSION: The development of pneumatoceles appears to be a fairly frequent and benign occurrence following cryobiopsy, likely due to increased tissue destruction. The increased use of intraoperative 3D fluoroscopy is likely to highlight changes to the pulmonary parenchyma that were previously not known. The occurrence of pneumatoceles does not appear to adversely impact the safety or tolerability profile of cryobiopsy.

Molecular survey of Leishmania spp. in skin samples of capybaras (Hydrochoerus hydrochaeris) from different areas of Brazil / Investigação molecular de Leishmania spp. em amostras de pele de capivaras (Hydrochoerus hydrochaeris) de diferentes regiões do Brasil

Leishmaniases comprise a spectrum of diseases caused by protozoan parasites of the genus Leishmania, with some species of rodents being incriminated as reservoirs. The capybara is the largest extant rodent species in the world and is widely distributed in South America. The occurrence of infection by Leishmania spp. was investigated in capybaras captured in Brazil during 2015­2019 from established populations in five highly anthropic areas of the state of São Paulo and two natural areas of the states of Mato Grosso and Mato Grosso do Sul. A total of 186 individuals were captured and subjected to abdominal skin biopsy. All skin samples were Leishmania kDNA-negative, suggesting that capybaras have no role in the transmission cycles of Leishmania species in the studied areas despite the well-known role of other rodents in the life cycle of Leishmania spp.(AU)

As leishmanioses compreendem um espectro de doenças causadas por protozoários do gênero Leishmania e algumas espécies de roedores são incriminadas como reservatórios de Leishmania spp. As capivaras compreendem a maior espécie de roedores existentes e são amplamente distribuídas na América do Sul. Para investigar a ocorrência de infecção por Leishmania spp. em capivaras, durante os anos de 2015-2019 capivaras foram capturadas em cinco áreas antrópicas do estado de São Paulo e em duas áreas naturais dos estados do Mato Grosso e do Mato Grosso do Sul, todos esses ambientes com populações de capivaras estabelecidas. Um total de 186 indivíduos foram capturados e submetidos à biópsia de pele abdominal. Todas as amostras de pele foram negativas para o alvo kDNA, assim, os dados sugerem que nas áreas estudadas as capivaras não têm papel no ciclo de transmissão de espécies de Leishmania spp., apesar do papel bem conhecido de outros roedores no ciclo de vida de Leishmania spp.(AU)

Acceptability and Adequacy of a Non-endoscopic Cell Collection Device for Diagnosis of Barrett's Esophagus: Lessons Learned.

BACKGROUND: Endoscopic screening for Barrett's esophagus (BE) is common, costly, and underperformed in at-risk people. A non-endoscopic cell collection device can be used to collect esophageal cells, enabling BE screening. AIMS: This study assessed the acceptability and adequacy of a commercial non-endoscopic cell collection device in a US population. METHODS: Six sites enrolled patients with confirmed BE or heartburn/regurgitation for ≥ 6 months. Patients underwent administration of the device, consisting of a sponge encapsulated in a capsule. The capsule dwelled in the stomach for 7.5 min and was retracted via an attached suture. An adequate sample was ≥ 1 columnar cell by H&E staining. Sample quality was rated using a 0-5 scale, with 0 = no columnar cells and 5 = plentiful groups. Trefoil Factor 3 (TFF3) staining was performed. Accuracy was assessed using esophagogastroduodenoscopy (EGD)/biopsy as the gold standard. RESULTS: Of 191 patients, 99.5% successfully swallowed the device. Overall sample adequacy was 91% (171/188), with 84% (158/188) high quality. The detachment rate was 2/190 (1%). Overall sensitivity, specificity, and accuracy of the assay with TFF3 staining were 76%, 77%, and 76%. Sensitivity, specificity, and accuracy for ≥ 3 cm BE were 86%, 77%, and 82%. Asked if willing to repeat the procedure, 93% would, and 65% indicated a preference for the device over EGD. CONCLUSIONS: This study demonstrated a high rate of sample adequacy and promising acceptability of this non-endoscopic sampling device in a US population. Diagnostic characteristics suggest that non-endoscopic assessment of BE deserves further development as an alternative to endoscopy.

Novel Method of Sampling the Gastrointestinal Muscle Layer: Feasibility of Endoscopic Muscular Resection with a Ligation Device in an in Vivo Porcine Model.

BACKGROUND: Gastrointestinal muscular sampling is useful in the histological assessment of functional gastrointestinal disorders. We devised a new sampling method to obtain a large volume of muscle tissues and then investigated the feasibility and safety of endoscopic muscular resection with a ligation device in an in vivo porcine model. METHODS: After establishing a submucosal tunnel, a rubber band was placed on the muscle tissue by sucking the exposed muscle layer. Thereafter, the established pseudopolyp was removed using an electrocautery snare, and the entry site of the submucosal tunnel was closed endoscopically. This procedure was performed at three sites in the esophagus and stomach of two pigs. The technical success, histology, and survival rate on postoperative day 7 were examined postoperatively. RESULTS: We successfully completed the mentioned procedure in 11 of the 12 sites (92%), without the occurrence of severe adverse events. The median diameters of obtained tissues from the esophagus and stomach, respectively, were 5 mm and 10 mm. Histologically, both the inner and outer muscle layers were included in all specimens. The postprocedural course was found uneventful in both pigs during the observatory period. CONCLUSIONS: Endoscopic muscular resection using a ligation device enabled us to obtain large and thick muscle tissue samples. This approach may facilitate more precise histological assessments of functional gastrointestinal disorders.

New chemical biopsy tool for spatially resolved profiling of human brain tissue in vivo.

It is extremely challenging to perform chemical analyses of the brain, particularly in humans, due to the restricted access to this organ. Imaging techniques are the primary approach used in clinical practice, but they only provide limited information about brain chemistry. Solid-phase microextraction (SPME) has been presented recently as a chemical biopsy tool for the study of animal brains. The current work demonstrates for the first time the use of SPME for the spatially resolved sampling of the human brain in vivo. Specially designed multi-probe sampling device was used to simultaneously extract metabolites from the white and grey matter of patients undergoing brain tumor biopsies. Samples were collected by inserting the probes along the planned trajectory of the biopsy needle prior to the procedure, which was followed by metabolomic and lipidomic analyses. The results revealed that studied brain structures were predominantly composed of lipids, while the concentration and diversity of detected metabolites was higher in white than in grey matter. Although the small number of participants in this research precluded conclusions of a biological nature, the results highlight the advantages of the proposed SPME approach, as well as disadvantages that should be addressed in future studies.

Tao brush endometrial cytology is a sensitive diagnostic tool for cancer and hyperplasia among women presenting to clinic with abnormal uterine bleeding.

BACKGROUND: Abnormal uterine bleeding requires the investigation of the endometrium. Histology is typically used but there remains room for the improvement and use of cytology. METHODS: Women presenting for clinically indicated office endometrial biopsy were prospectively enrolled. Tao endometrial brushing and office endometrial biopsy were performed, and surgical procedure if clinically indicated. Tao brush cytology specimens were blindly reviewed by up to three pathologists, consensus obtained, and scored as: benign, atypical (favor benign), suspicious, positive for malignancy, or non-diagnostic. Cytology and histology were compared to surgical pathology to determine sensitivity, specificity, positive, and negative predictive values to detect AH (atypical hyperplasia) or EC (endometrial cancer). RESULTS: Clinical indications of 197 enrolled patients included postmenopausal bleeding (90, 45.7%), abnormal uterine bleeding (94, 47.7%), and abnormal endometrium on ultrasound without bleeding (13, 6.6%). Of the 197 patients, 185 (93.9%) had cytology score consensus and a total of 196 (99.5%) had consensus regarding cytology positivity. Surgical pathology diagnoses (N = 85) were 13 (15.3%) FIGO grade 1 or 2 EC, 3 (3.5%) AH, and 69 (81.2%) benign endometrium. Sensitivity and specificity to detect EC or AH were 93.7% and 100%, respectively, via endometrial biopsy; 87.5% and 63.8%, respectively, via endometrial cytology when scores of malignancy, suspicious, or atypical were considered positive. CONCLUSIONS: In a high-risk population, Tao brush endometrial cytology showed high sensitivity to detect AH and EC comparable to biopsy histology when considering scores of malignancy, suspicious, atypical, and non-diagnostic. Revisiting the potential value of endometrial cytology in the contemporary era of endometrial diagnostic workup is warranted.

The accuracy of dry surgical field sublabial biopsy in the diagnosis of sicca syndrome.

BACKGROUND: Sublabial gland biopsy is the 'gold standard' in establishing the diagnosis of primary Sjögren's syndrome. Bleeding and nerve damage are complications. Our centre has adopted the use of the chalazion clamp to provide a dry surgical field to address these challenges. This study aimed to assess the accuracy of minor salivary gland harvest rate using this technique. METHOD: A retrospective review of all minor salivary gland biopsies was carried out in a single tertiary referral centre over a five-year period. RESULTS: Forty-one biopsy patients were identified, with a mean age of 56.1 years. There was 100 per cent accuracy in harvest rate in our series. Twelve patients (29 per cent) were positive for primary Sjögren's syndrome. No patients had a complication immediately or at one month follow up. CONCLUSION: Dry surgical field sublabial gland biopsy is a safe and highly effective technique in the diagnosis of primary Sjögren's syndrome. Initial results indicate it may provide a higher harvest rate with fewer complications than traditional non-ischaemic techniques.

Utility of Radial Probe Endobronchial Ultrasound Guided Transbronchial Lung Biopsy in Bronchus Sign Negative Peripheral Pulmonary Lesions.

BACKGROUND: The presence of the bronchus sign on chest computed tomography is associated with an increased diagnostic yield of radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB). However, the utility of RP-EBUS-TBLB for bronchus sign negative peripheral pulmonary lesions (PPLs) remains unknown. We investigated the utility of RP-EBUS-TBLB in bronchus sign negative PPLs. METHODS: We retrospectively reviewed data from 109 patients who underwent RP-EBUS for bronchus sign negative PPLs from January 2019 to August 2020. TBLB was performed using RP-EBUS with a guide sheath and without fluoroscopy. The EBUS visualization and TBLB diagnostic yields were assessed. Multivariable logistic regression analyses were used to identify factors affecting the EBUS visualization and diagnostic yields. RESULTS: The EBUS visualization yield was 74.1% (68/109). Of the 109 lung lesions, 92 were definitively diagnosed. The overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 50.5% (55/109), 34.9% (29/83), 100% (26/26), 100% (29/29), and 32.5% (26/80), respectively. In multivariable analyses, the size of the lesion (≥ 20 mm; odds ratio [OR], 2.62; 95% confidence interval [CI], 1.16-5.93; P = 0.021) and the distance from the pleura (> 10 mm; OR, 2.37; 95% CI, 1.02-5.52; P = 0.045) were associated with EBUS visualization. Regarding diagnostic yield, having the probe within the lesion (OR, 28.50; 95% CI, 6.26-129.85; P < 0.001) and a solid lesion (OR, 14.58; 95% CI, 2.64-80.38; P = 0.002) were associated with diagnostic success. Pneumothorax and hemoptysis occurred in 3.7% (4/109) and 0.9% (1/109), respectively, of the patients. CONCLUSION: RP-EBUS-TBLB using a GS can be considered a diagnostic method in bronchus sign negative solid PPLs. Having the probe within the lesion and a solid lesion were important for diagnostic success. Complication rates were acceptable.

Quantifying procedural pain associated with office gynecologic tract sampling methods.

OBJECTIVE: Emerging technologies may enable detection of endometrial cancer with methods that are less invasive than standard biopsy methods. This study compares patient pain scores among 3 office gynecologic tract sampling methods and explores their potential determinants. METHODS: A prospective study including 3 sampling methods (tampon, Tao brush (TB), endometrial biopsy (EB)) was conducted between December 2015 and August 2017 and included women ≥45 years of age presenting with abnormal uterine bleeding, postmenopausal bleeding, or thickened endometrial stripe. Patients rated pain after each sampling procedure using a 100-point visual analog scale (VAS). RESULTS: Of 428 enrolled, 190 (44.39%) patients underwent all 3 sampling methods and reported a VAS score for each. Nearly half were postmenopausal (n = 93, 48.9%); the majority were parous (172, 90.5%) of which 87.8% had at least one vaginal delivery. Among the 190 patients, the median (IQR) pain score was significantly lower for sampling via tampon (0 [0,2]) compared to TB (28 [12, 52]) or EB (32 [15, 60]) (both p < 0.001, Wilcoxon signed rank test). Among women who underwent tampon sampling, age and pain scores showed a weak positive correlation (Spearman rank correlation, r = 0.14; p = 0.006); EB sampling was associated with a weak inverse correlation between parity and pain scores (r = -0.14; p = 0.016). CONCLUSION: Gynecologic tract sampling using a tampon had significantly lower pain than both EB and TB. Pain with tampon sampling was positively correlated with age and pain with EB sampling was inversely correlated with parity. Pain scores for TB and EB were not significantly related to age, menopausal status, or BMI.

A novel technique capable of taking 'protected' biopsies for reliable assessment of the distribution of microbiota along the colonic mucosa.

We evaluated a novel 'protected' biopsy method to reliably ascertain the spatial distribution of the mucosa-adherent colonic microbiota. Apart from minor differences at genus level, overall similarities along the colon were high between the various areas, irrespective of protected or unprotected sampling.

Miniature Flexible Instrument with Fibre Bragg Grating-Based Triaxial Force Sensing for Intraoperative Gastric Endomicroscopy.

Optical biopsy methods, such as probe-based endomicroscopy, can be used to identify early-stage gastric cancer in vivo. However, it is difficult to scan a large area of the gastric mucosa for mosaicking during endoscopy. In this work, we propose a miniaturised flexible instrument based on contact-aided compliant mechanisms and fibre Bragg grating (FBG) sensing for intraoperative gastric endomicroscopy. The instrument has a compact design with an outer diameter of 2.7 mm, incorporating a central channel with a diameter of 1.9 mm for the endomicroscopic probe to pass through. Experimental results show that the instrument can achieve raster trajectory scanning over a large tissue surface with a positioning accuracy of 0.5 mm. The tip force sensor provides a 4.6 mN resolution for the axial force and 2.8 mN for transverse forces. Validation with random samples shows that the force sensor can provide consistent and accurate three-axis force detection. Endomicroscopic imaging experiments were conducted, and the flexible instrument performed no gap scanning (mosaicking area more than 3 mm2) and contact force monitoring during scanning, demonstrating the potential of the system in clinical applications.

Endobronchial Balloon Blockers: A Retrospective Analysis of Their Implementation for Use in Transbronchial Cryobiopsy Under Conscious Sedation.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is a promising technique that is evolving as a standard diagnostic procedure in the diagnosis of interstitial lung disease. However, there are a variety of non-standardised techniques adopted for this procedure. We aim to describe our approach to TBLC with balloon blockade under conscious sedation (CS). METHODS: We performed a retrospective analysis of patients undergoing TBLC using flexible bronchoscopy under CS in our institution over the calendar years 2017-2018; before and after a transition to the use of endobronchial balloon blockers (EBB) in 2017. RESULTS: 25 patients underwent transbronchial cryobiopsy during the study period. Of these; 12 procedures used EBB. EBB subjects had significantly less moderate or severe airway bleeding (8.3% vs 38.5%) despite higher biopsy rates in the EBB group, 2.9 (2-4) vs 2.4 (1-4) in the non-EBB group. No severe airway bleeding occurred in the EBB group. A multidisciplinary meeting (MDM) confirmed diagnosis was achieved in 88% of patients. 10/12 subjects (83%) in the EBB group and 12/13 subjects (92%) in the non-EBB group (p = 0.5). CONCLUSION: Our institution is novel in using EBB as standard during TBLC specifically under CS with flexible bronchoscopy in the bronchoscopy suite. This retrospective analysis demonstrates that EBB enhances the safety profile of performing TBLC under CS and did not appear to impact diagnostic yield or patient safety.

Local anaesthetic transperineal (LATP) prostate biopsy using a probe-mounted transperineal access system: a multicentre prospective outcome analysis.

OBJECTIVES: To assess the feasibility of local anaesthetic transperineal (LATP) technique using a single-freehand transperineal (TP) access device, and report initial prostate cancer (PCa) detection, infection rates, and tolerability. PATIENTS AND METHODS: Observational study of a multicentre prospective cohort, including all consecutive cases. LATP was performed in three settings: (i) first biopsy in suspected PCa, (ii) confirmatory biopsies for active surveillance, and (iii) repeat biopsy in suspected PCa. All patients received pre-procedure antibiotics according to local hospital guidelines. Local anaesthesia was achieved by perineal skin infiltration and periprostatic nerve block without sedation. Ginsburg protocol principles were followed for systematic biopsies including cognitive magnetic resonance imaging-targeted biopsies when needed using the PrecisionPoint™ TP access device. Procedure-related complications and oncological outcomes were prospectively and consecutively collected. A validated questionnaire was used in a subset of centres to collect data on patient-reported outcome measures (PROMs). RESULTS: Some 1218 patients underwent LATP biopsies at 10 centres: 55%, 24%, and 21% for each of the three settings, respectively. Any grade PCa was diagnosed in 816 patients (67%), of which 634 (52% of total) had clinically significant disease. Two cases of sepsis were documented (0.16%) and urinary retention was observed in 19 patients (1.6%). PROMs were distributed to 419 patients, with a 56% response rate (n = 234). In these men, pain during the biopsy was described as either 'not at all' or 'a little' painful by 64% of patients. Haematuria was the most common reported symptom (77%). When exploring attitude to re-biopsy, 48% said it would be 'not a problem' and in contrast 8.1% would consider it a 'major problem'. Most of the patients (81%) described the biopsy as a 'minor or moderate procedure tolerable under local anaesthesia', while 5.6% perceived it as a 'major procedure that requires general anaesthesia'. CONCLUSION: Our data suggest that LATP biopsy using a TP access system mounted to the ultrasound probe achieves excellent PCa detection, with a very low sepsis rate, and is safe and well tolerated. We believe a randomised controlled trial comparing LATP with transrectal ultrasound-guided biopsy (TRUS) to investigate the relative trade-offs between each biopsy technique would be helpful.