Clinical performance of custom-milled polyetherketoneketone (PEKK) posts and cores: A 12-month follow-up randomized controlled pilot study.

OBJECTIVES: Comparing the survival rate and the cumulative success rates of custom-milled polyetherketone ketone posts and cores (MPP) with prefabricated fiber posts (PFP) in restoring compromised endodontically treated premolars. MATERIAL AND METHODS: This was a randomized, double-blind, parallel, two-arm controlled pilot study. A total of 24 patients (12 males, 12 females), each had a compromised lower premolar, needed a root canal treatment and to be restored with post and core. Patients were randomly allocated into two groups, MPP-group: restored with MPP, and PFP-group: restored with PFP and composite cores. After that, premolars were restored with single porcelain fused to metal (PFM) crowns. Clinical and radiographic follow-ups were conducted after 3, 6, and 12 months. The Kaplan-Meier, log-Rank, and χ2 tests were used to investigate differences between the two groups at the 0.05 significance level. RESULTS: The survival rate after 12 months in the MPP and PFP groups was 66.7% and 100%, respectively. Meanwhile, the cumulative success rates were 63.6% and 100% in the same order. The log-rank test showed a significant difference between the two groups (p = .031). The difference in cumulative success rates was also significant, as the χ2 test revealed (p = .011). CONCLUSION: The PFP group showed a higher success rate than the MPP group and according to the failure types, PEKK posts seem to be inferior to PFP in terms of the mechanical properties and bonding to resin mechanism. TRIAL REGISTRATION: ISRCTN, ISRCTN13456471. October, 14, 2019. (https://doi.org/10.1186/ISRCTN13456471ISRCTN13456471).

Population Pharmacokinetics of Fasinumab in Healthy Volunteers and Patients With Pain Due to Osteoarthritis of the Knee or Hip.

Osteoarthritis (OA) pain management options are currently limited. Fasinumab, an anti-nerve growth factor monoclonal antibody, has been investigated in healthy volunteers and patients with OA-related pain, among other conditions. Data from 12 Phase I-III clinical trials of 92 healthy volunteers and 7430 patients with OA were used to develop a population pharmacokinetic model to characterize fasinumab concentration-time profiles and assess the covariates' effect on fasinumab pharmacokinetic parameters. Participants received single or repeated fasinumab doses intravenously (IV)/subcutaneously (SC), based on body weight (0.03-1 mg/kg IV or 0.1-0.3 mg/kg SC)/fixed dose (9-12 mg IV or 1-12 mg SC). Fasinumab concentration-time data following IV and SC administration in healthy volunteers and patients with OA-related pain were adequately described by a 2-compartment model. Bioavailability increased with higher doses; estimated at 55.1% with 1 mg SC dose, increasing in a greater-than-proportional manner above this. Body weight had the largest predicted impact on fasinumab steady-state exposures, participants at the 5th and 95th percentiles had a 43%-45% higher/22%-23% lower exposure versus reference, respectively. Other covariates had small but clinically irrelevant impacts.

Subcutaneous Administration of Monoclonal Antibodies: Pharmacology, Delivery, Immunogenicity, and Learnings From Applications to Clinical Development.

Subcutaneous (s.c.) administration of monoclonal antibodies (mAbs) can reduce treatment burden for patients and healthcare systems compared with intravenous (i.v.) infusion through shorter administration times, made possible by convenient, patient-centric devices. A deeper understanding of clinical pharmacology principles related to efficacy and safety of s.c.-administered mAbs over the past decade has streamlined s.c. product development. This review presents learnings from key constituents of the s.c. mAb development pathway, including pharmacology, administration variables, immunogenicity, and delivery devices. Restricted mAb transportation through the hypodermis explains their incomplete absorption at a relatively slow rate (pharmacokinetic (PK)) and may impact mAb-cellular interactions and/or onset and magnitude of physiological responses (pharmacodynamic). Injection volumes, formulation, rate and site of injection, and needle attributes may affect PKs and the occurrence/severity of adverse events like injection-site reactions or pain, with important consequences for treatment adherence. A review of immunogenicity data for numerous compounds reveals that incidence of anti-drug antibodies (ADAs) is generally comparable across i.v. and s.c. routes, and complementary factors including response magnitude (ADA titer), persistence over time, and neutralizing antibody presence are needed to assess clinical impact. Finally, four case studies showcase how s.c. biologics have been clinically developed: (i) by implementation of i.v./s.c. bridging strategies to streamline PD-1/PD-L1 inhibitor development, (ii) through co-development with i.v. presentations for anti-severe acute respiratory syndrome-coronavirus 2 antibodies to support rapid deployment of both formulations, (iii) as the lead route for bispecific T cell engagers (BTCEs) to mitigate BTCE-mediated cytokine release syndrome, and (iv) for pediatric patients in the case of dupilumab.

Tissue amount and diagnostic yield of a novel franseen EUS-FNB and a standard EUS-FNA needle-A randomized controlled study in solid pancreatic lesions.

Background and Objectives: Several types of needles are available for EUS-guided tissue sampling of pancreatic lesions. Whereas fine-needle aspiration (FNA) needles typically provide cytological samples, fine-needle biopsy (FNB) needles are designed to obtain microcores with preserved tissue architecture. The aim of this study was to compare tissue amount and diagnostic yield between a modified Franseen-type FNB needle (TopGain; Medi-Globe GmbH, Grassau, Germany) and a standard FNA needle. Methods: We performed a prospective, multicenter randomized controlled study between June 2020 and September 2021, including patients with a solid pancreatic lesion referred for EUS-guided tissue sampling at 3 centers in Denmark. The patients were randomized 1:1 to either FNA needle or the novel FNB needle. Primary outcomes included the number of obtained tissue microcores and total and diagnostic tissue area. Results: Sixty-four patients were included. The median number of tissue microcores procured per pass was significantly higher in the FNB group compared with FNA (3 vs. 2, P < 0.001). Similarly, the mean total tissue area (2.74 vs. 0.44 mm2, P < 0.001) and mean diagnostic tissue area (1.74 vs. 0.28 mm2, P < 0.001) were more than 6-fold larger in the FNB samples compared with FNA. The median number of passes needed for a diagnostic sample was 1 for the FNB needle and 2 for FNA needle (P = 0.12). The novel FNB needle provided a higher percentage of samples of excellent quality (P = 0.002). Conclusions: The novel Franseen-type FNB needle seems to be significantly superior to a conventional FNA needle. The results of this study underline excellent performance of crown-cut needles.

Validation of a Novel EUS-FNB-Derived Organoid Co-Culture System for Drug Screening in Patients with Pancreatic Cancer.

Cancer-associated fibroblasts (CAFs) have been shown to impact the chemosensitivity of patient-derived tumor organoids (PDTOs). However, the published literature comparing PDTO response to clinical outcome does not include CAFs in the models. Here, a co-culture model was created using PDTOs and CAFs derived from endoscopic ultrasound-guided fine-needle biopsies (EUS-FNBs) for potential use in drug screening applications. Co-cultures were established, and growth was compared to monocultures using image metrics and a commercially available assay. We were able to establish and expand validated malignant PDTOs from 19.2% of adenocarcinomas from EUS-FNBs. CAFs could be established from 25% of the samples. The viability of PDTOs in the mixed cell co-culture could be isolated using image metrics. The addition of CAFs promoted PDTO growth in half of the established co-cultures. These results show that co-cultures can be established from tiny amounts of tissue provided by EUS-FNB. An increased growth of PDTOs was shown in co-cultures, suggesting that the present setup successfully models CAF-PDTO interaction. Furthermore, we demonstrated that standard validation techniques may be insufficient to detect contamination with normal cells in PDTO cultures established from primary tumor core biopsies.

Digital technologies: Innovations that transform the face of drug development.

Recently, digital health technologies (DHTs) and digital biomarkers have gained a lot of traction in clinical investigations, motivating sponsors, investigators, and regulators to discuss and implement integrated approaches for deploying DHTs. These new tools present new and unique challenges for optimal technology integration in clinical trial processes, including operational, ethical, and regulatory issues. In this paper, we gathered different perspectives to discuss challenges and perspectives from three different stakeholders: industry, US regulators, and a public-private partnership consortium. The complexities of DHT implementation, which include regulatory definitions, defining the scope of validation experiments, and the need for partnerships between BioPharma and the technology sectors, are highlighted. Most of these challenges are related to translation of DHT-derived measures into endpoints that are meaningful to clinicians and patients, participant safety, training, and retention and privacy of data. The example of the Wearable Assessments in the Clinic and Home in PD (WATCH-PD) study is discussed as an example that demonstrated the advantages of pre-competitive collaborations, which include early regulatory feedback, data sharing, and multistakeholder alignment. Future advances in DHTs are expected to spur device-agnostic measured development and incorporate patient reported outcomes in drug development. More efforts are needed to define validation experiments for a defined context of use, incentivize data sharing and development of data standards. Multistakeholder collaborations via precompetitive consortia will help facilitate broad acceptance of DHT-enabled measures in drug development.

In Vitro-In Vivo Correlation of Buprenorphine Transdermal Systems Under Normal and Elevated Skin Temperature.

PURPOSE: Application of external heat using a heating pad over buprenorphine transdermal system, Butrans® has been shown to increase systemic levels of buprenorphine in human volunteers. The purpose of this study was to perform in vitro permeation studies at normal as well as elevated temperature conditions to evaluate the correlation of in vitro data with the existing in vivo data. METHODS: In vitro permeation tests (IVPT) were performed on human skin from four donors. The IVPT study design was harmonized to a previously published clinical study design and skin temperature was maintained at either 32 ± 1 °C or 42 ± 1 °C to mimic normal and elevated skin temperature conditions, respectively. RESULTS: IVPT studies on human skin were able to demonstrate heat induced enhancement in flux and cumulative amount of drug permeated from Butrans® which was reasonably consistent with the corresponding enhancement observed in vivo. Level A in vitro-in vivo correlation (IVIVC) was established using unit impulse response (UIR) based deconvolution method for both baseline and heat arms of the study. The percent prediction error (%PE) calculated for AUC and Cmax values was less than 20%. CONCLUSIONS: The studies indicated that IVPT studies performed under the same conditions as those of interest in vivo may be useful for comparative evaluation of the effect of external heat on transdermal delivery system (TDS). Further research may be warranted to evaluate factors, beyond cutaneous bioavailability (BA) assessed using an IVPT study, that can influence plasma exposure in vivo for a given drug product.

Targeted next-generation sequencing of EUS-guided through-the-needle-biopsy sampling from pancreatic cystic lesions.

BACKGROUND AND AIMS: Recent advances have introduced molecular subtyping of pancreatic cystic lesions (PCLs) as a possible amendment to the diagnostic algorithm. The study evaluated the feasibility and diagnostic accuracy of molecular analysis and subtyping of PCLs using the recently introduced EUS-guided through-the-needle-biopsy (TTNB) sampling. METHODS: We prospectively included 101 patients in the study who presented with PCLs >15 mm in the largest cross-section. EUS-guided TTNB samples were obtained by a micro-biopsy forceps introduced through a 19-gauge needle. The TTNB samples were analyzed by next-generation sequencing (NGS) for point mutations in tumor suppressors and oncogenes using a 51-gene customized hotspot panel. Sensitivity and specificity were calculated with the histologic diagnosis as reference. RESULTS: After initial microscopic evaluation of the samples, 91 patients had residual TTNB samples available for NGS. Of these, 49 harbored mutations, most frequently in KRAS and GNAS, reflecting an excess frequency of intraductal papillary mucinous neoplasms (IPMNs) in the study population. A sensitivity and specificity of 83.7% (95% confidence interval [CI], 70.3-92.7) and 81.8% (95% CI, 48.2-97.7), respectively, were demonstrated for the diagnosis of a mucinous cyst and 87.2% (95% CI, 74.2-95.2) and 84.6% (95% CI, 54.5-98.1) for the diagnosis of an IPMN. CONCLUSIONS: Thus, molecular analysis of TTNB samples by NGS has high sensitivity and specificity for diagnosing mucinous cysts and IPMNs. Although the procedure comes with a risk of adverse events of 9.9%, TTNB samples are a robust alternative to cyst fluid for a combined histologic and molecular diagnosis of PCLs. (Clinical trial registration number: NCT03578445.).

Overview of Clinical Pharmacology Packages of New Drug Applications Approved for the Treatment of Rare Diseases.

There are more than 7000 rare diseases affecting approximately 30 million people in the United States. More than 90% of these diseases lack approved therapies. Several challenges face the development of "orphan drugs", such as the small populations of patients, high development costs, and long development timelines. This study evaluates clinical pharmacology assessments conducted during the development of drugs to treat rare diseases approved by the United States Food and Drug Administration in 2020 and 2021. Thirty-nine new drug applications (NDAs) have been identified and the associated regulatory reviews, approved labels, and approval letters were reviewed. Approximately, 95%, 74%, and 77% of these submissions contained at least one type of drug-drug interaction, the effect of organ impairment (hepatic and renal) on drug exposure, and QT liability assessment, respectively. Modeling and simulation approaches were utilized to address many clinical pharmacology questions, with population pharmacokinetic analyses used extensively in the evaluation of the effect of organ impairment on drug exposure and with physiologically based pharmacokinetic analyses used mainly in assessing drug interaction risks. In general, the clinical pharmacology packages in the NDAs of orphan drugs are not optimal and more work is needed to obtain a complete clinical pharmacology package at the time of initial approval to ensure the safe and effective use of these drugs across the spectrum of the target patient population. This study provides insights into the clinical pharmacology studies needed for drugs to treat rare diseases and would help both the regulators and drug developers to identify challenges and opportunities in conducting clinical pharmacology assessments for drugs developed to treat rare diseases.

Assessing the Combined Public Health Impact of Pharmaceutical Interventions on Pandemic Transmission and Mortality: An Example in SARS CoV-2.

To assess the combined role of anti-viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission and mortality in the United States, an agent-based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID-19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April-August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non-pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID-19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment-as-prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS-CoV-2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness.

Trends in FDA Transporter-Based Post-Marketing Requirements and Commitments Over the Last Decade.

Characterizing interactions between new molecular entities (NMEs) and drug transporters is a critical element of drug development that helps in assessing potential transporter-based drug-drug interactions (DDIs). However, not all NME new drug applications (NDAs) include a full characterization of NMEs transporter-based DDIs, which necessitates the issuance of post-marketing requirement (PMR)/post-marketing commitment (PMC) by the US Food and Drug Administration (FDA) to characterize these potential interactions. The objective of this analysis is to identify trends in transporter-based PMRs/PMCs issued by the FDA between 2012 and 2021. A decrease in the number of transporter-based PMRs/PMCs was observed from 2012 to 2016 and an increasing trend in the number of PMRs/PMCs was observed after 2017. The majority of these transporter-based PMRs/PMCs requested clinical evaluation (48%), some requested in vitro assessment (38%), and 2.5% requested modeling and simulation assessment. Most of the PMRs/PMCs requested evaluation of NMEs as perpetrator with the efflux transporters, P-gp and/or BCRP (53%). Forty-eight percent of the PMRs/PMCs were fulfilled with 67% resulted in labeling updates. On average, 2.5 years were needed for the information related to PMRs/PMCs to show in NMEs labeling. In conclusion, this analysis highlights the increased emphasis from the FDA on proper characterization of transporter-based DDI and call for the need of early characterization of NMEs-transporters interaction before initial NDA approval.

Comparative study of phenolic profile, antioxidant and antimicrobial activities of aqueous extract of white and green tea.

The sole difference between white tea (WT) and green tea (GT) is the former that made only from the buds and young leaves of the Camelia sinensis plant, whilst the latter is made from matured tea leaves. The phytochemical profiles, phenolic compounds, antioxidant, and antimicrobial activity of two varieties of Camellia sinensis teas, white and green, were compared in this study. Total antioxidant capacity, reducing power, DPPH radical scavenging, and Fe+2 chelating activities were used to determine antioxidant activities in water extract of GT and WT. The largest level of phenolic content was discovered in WGTE compared with the lowest amount was found in WWTE (290.67 mg/100 g tea and 185.96 mg/100 g tea, respectively). Phenoilc acids (gallic, benzoic, chlorogenic, ellagic, and ρ-coumaric acids) and flavonoids (rutin and kampherol) were found in the two extracts. The findings of DPPH radical scavenging assays were 84.06 and 82.37% inhibition. In vitro antimicrobial activity was indicated that (WWTE and WGTE) had a high level of activity against Staphylococcus aureus, and gave negative activity against Salmonella typhimurium, and Aspergillus Niger. The WT and GT extracts are a great source of natural antioxidants with biological effects on human health.

Investigator Impact on Reproducibility of Drug Bioavailability in Stratum Corneum Sampling by Tape Stripping.

PURPOSE: Skin sampling by tape stripping measures the local bioavailability of topical drug products in the stratum corneum (SC). The goal of the current study was to evaluate the impact of different investigators in studies that utilize a tape stripping protocol designed to minimize investigator variability. METHODS: Two open-label clinical studies compared two lidocaine patches and a diclofenac patch and solution in twelve healthy volunteers. The mass of drug was determined in SC samples collected on tape strips at three time points following product removal in duplicate by two investigators. Investigator results were compared with each other and with results for the diclofenac solution measured by another laboratory using a similar protocol. RESULTS: For drug mass, the geometric mean ratio comparing two investigators is within the acceptable bioequivalence interval for most measurement times and drug products. Drug uptake into the SC from the diclofenac solution was not statistically different from that determined in another laboratory. The average flux from the SC over the clearance intervals for the four drug products correspond well with flux measurements from in vitro permeation tests. CONCLUSIONS: Results from different investigators are reproducible within the limitations of measurement variability, which can be managed by increasing volunteer numbers.

Evaluation of in vitro/in vivo correlations for three fentanyl transdermal delivery systems using in vitro skin permeation testing and human pharmacokinetic studies under the influence of transient heat application.

The value of developing an in vitro/in vivo correlation (IVIVC) is substantial in biopharmaceutical drug development because once the model is developed and validated, an in vitro method may be used to efficiently assess and predict drug product performance in vivo. In this study, three bioequivalent, matrix-type, fentanyl transdermal delivery systems (TDS) were evaluated in vitro using an in vitro permeation test (IVPT) and dermatomed human skin, and in vivo in human pharmacokinetic (PK) studies under harmonized study designs to evaluate IVIVC. The study designs included 1 h of transient heat application (42 ± 2°C) at either 11 h or 18 h after TDS application to concurrently investigate the influence of heat on drug bioavailability from TDS and the feasibility of IVPT to predict the effects of heat on TDS in vivo. Level A (point-to-point) and Level C (single point) IVIVCs were evaluated by using PK-based mathematical equations and building IVIVC models between in vitro fraction of drug permeation and in vivo fraction of drug absorption. The study results showed that the three differently formulated fentanyl TDS have comparable (p > 0.05) heat effects both in vitro and in vivo. In addition, the predicted steady-state concentration (Css) from in vitro flux data and the observed Css in vivo showed no significant differences (p > 0.05). However, the effects of heat on enhancement of fentanyl bioavailability observed in vivo were found to be greater compared to those observed in vitro for all three drug products, resulting in a weak prediction of the impact of heat on bioavailability from the in vitro data. The results from the current work suggest that while IVPT can be a useful tool to evaluate the performance of fentanyl TDS in vivo with a relatively good predictability at a normal temperature condition and to compare the effect of heat on drug delivery from differently formulated TDS, additional testing measures would enhance the ability to predict the heat effects in vivo with a lower prediction error.

Evaluation of head and cervical spine posture after functional therapy with Twin­Block and Bionator appliances: A pilot randomized controlled trial.

OBJECTIVE: Evaluation of head and cervical spine posture and estimation of sample size. METHODS: Thirty eligible participants who required functional therapy were randomly assigned to the Control group (C), Twin Block group (TB), or the Bionator group (B). Randomization was accomplished by means of blocks of fixed size stratified by sex and age, with the allocations concealed in opaque and sealed envelopes. RESULTS: Significant differences were identified between the pre -and post-functional SNB (p = 0.024) and ANB (p = 0.034) angles in the Twin Block group and SNA (p = 0. 019) and ANB (p = 0. 028) angles in the Bionator group. No statistically significant changes were seen in the head or cervical variables in the three groups. CONCLUSION: The functional appliance did not cause any statistical change in head posture or cervical spinal column in comparison with the non-treatment group.

Clinical impact of endoscopic ultrasound-guided through-the-needle microbiopsy in patients with pancreatic cysts.

BACKGROUND: The limited data on the utility of endoscopic ultrasound (EUS)-guided through-the-needle biopsies (TTNBs) in patients with pancreatic cystic lesions (PCLs) originate mainly from retrospective studies. Our aim was to determine the clinical impact of TTNBs, their added diagnostic value, and the adverse event rate in a prospective setting. METHODS: This was a prospective, single-center, open-label controlled study. Between February 2018 and August 2019, consecutive patients presenting with a PCL of 15 mm or more and referred for EUS were included. Primary outcome was a change in clinical management of PCLs following TTNB compared with cross-sectional imaging and cytology. Adverse events were defined according to the ASGE lexicon. RESULTS: 101 patients were included. TTNBs led to a change in clinical management in 11.9 % of cases (n = 12). Of these, 10 had serous cysts and surveillance was discontinued, while one of the remaining two cases underwent surgery following diagnosis of a mucinous cystic neoplasm. The diagnostic yield of TTNBs for a specific cyst diagnosis was higher compared with FNA cytology (69.3 % vs. 20.8 %, respectively; P < 0.001). The adverse event rate was 9.9 % (n = 10; 95 % confidence interval 5.4 % - 17.3 %), with the most common event being acute pancreatitis (n = 9). Four of the observed adverse events were severe, including one fatal outcome. CONCLUSIONS: TTNBs resulted in a change of clinical management in about one in every 10 patients; however, the associated adverse event risk was substantial. Further studies are warranted to elucidate in which subgroups of patients the clinical benefit outweighs the risks.

Cutaneous Pharmacokinetics of Acyclovir Cream 5% Products: Evaluating Bioequivalence with an In Vitro Permeation Test and an Adaptation of Scaled Average Bioequivalence.

PURPOSE: The in vitro permeation test (IVPT) with a new statistical approach was investigated to evaluate the utility of an IVPT methodology as a sensitive tool to support a demonstration of bioequivalence (BE) for topical dermatological drug products. METHODS: IVPT experiments were performed utilizing ex vivo human skin. The initial screening tests involved four differently formulated acyclovir 5% creams: the U.S. Zovirax® as the reference product and the U.K. Zovirax®, Aciclovir 1A Pharma® and Aciclostad® as test products. Subsequently, a pivotal BE study was conducted comparing the two Zovirax® creams. The resulting data was used to evaluate BE of test (T) versus reference (R), T versus T, and R versus R, with an adaption of scaled average BE approach to address high variability in IVPT data. RESULTS: More acyclovir permeated into and through the skin from the two Zovirax® creams compared to the two non-Zovirax® creams. The U.S. Zovirax® cream showed a significantly higher Jmax and total amount permeated over 48 h, compared to the U.K. Zovirax® cream. The statistical analysis indicated that the test and reference products were not bioequivalent, whereas each product tested against itself was shown to be bioequivalent. CONCLUSIONS: The current study demonstrated that the IVPT method, with an appropriate statistical analysis of the results, is a sensitive and discriminating test that can detect differences in the rate and extent of acyclovir bioavailability in the skin from differently formulated cream products.

EUS-guided through-the-needle microbiopsy of pancreatic cysts: Technical aspects (with video).

Pancreatic cystic lesions are frequently encountered and diagnostically challenging as some of the cysts may have malignant potential (mucinous) while others are completely benign (serous). EUS-guided through-the-needle biopsy (EUS-TTNB) of the cyst wall has recently been introduced as an alternative to cyst fluid cytology. Several studies have shown that microbiopsies outperform cytology in terms of distinction between mucinous and nonmucinous lesions, but also in determining the specific cyst diagnosis. However, little is known about the technical aspects of tissue sampling with TTNB. Herein, we summarize our experience with the procedure in a tertiary referral center and discuss indications, technical aspects, and safety of the procedure. Most adverse events (AEs) associated with the procedure are mild, but there is emerging evidence that the rate of postprocedural pancreatitis is higher compared to standard fine-needle aspiration. The added diagnostic yield should therefore be placed in perspective with an increased risk of AEs. Prospective studies are warranted to fully identify which patient groups could benefit from EUS-TTNB.