Microforceps Biopsy Research Articles

Jehlová konfokální laserová endomikroskopie v diferenciální diagnostice cystických lézí pankreatu

Summary: Background: Pancreatic cystic lesions are relatively common findings, and their prevalence continues to rise, which is also related to the expansion of imaging methods. Up to 15% of pancreatic cancers arise from mucinous cystic tumours of the pancreas, primarily from intraductal papillary mucinous neoplasia (IPMN). Needle-based confocal laser endomicroscopy (nCLE) represents an advanced diagnostic method with the potential to improve the accuracy of diagnosing focal pancreatic lesions. Aim: The aim of the work is to provide a recent overview of the position of nCLE in the diagnosis of pancreatic cystic lesions and some of our own experiences. The nCLE method is based on so-called real-time optical biopsy, which brings better diagnostic results compared to traditional methods such as CT, MRI/MRCP, and EUS, as confirmed by the authors‘ own data. Although nCLE offers certain advantages, its wider use in clinical practice is limited by the high costs of equipment, technical difficulties during examination, and the need for thorough training of endoscopists. The integration of all diagnostic procedures (EUS, cytology, nCLE, and next-generation sequencing) into artificial intelligence algorithms could minimize the disadvantages of individual methods and increase the overall efficiency of diagnosing pancreatic cystic lesions. Conclusion: nCLE represents an innovative method for diagnosing pancreatic cystic lesions, which, in combination with other procedures (microforceps biopsy, next-generation sequencing, assessment of nCLE findings, and overall malignancy risk using artificial intelligence), can further enhance its diagnostic accuracy in this context. Key words: needle-based confocal laser endomicroscopy – pancreatic cystic lesion – optical biopsy – endoscopic ultrasound – artificial intelligence

EUS-guided through-the-needle microforceps biopsy for pancreatic cysts: Why no widespread adoption?

EUS-guided through-the-needle microforceps biopsy for pancreatic cysts: Why no widespread adoption?

Diagnosis and Management of Pancreatic Cysts: A Comprehensive Review of the Literature.

The prevalence of pancreatic cysts has been rising due to the widespread use of cross-sectional imaging (CT scan and MRI) of the abdomen. While most pancreatic cysts are benign and do not require treatment or surveillance, a significant minority are premalignant and rarely malignant. The risk stratification of these lesions is not straightforward, and individual risk assessment, cyst size, distribution, and alarming morphologic features (when present) can guide the next steps in management. Neoplastic pancreatic cysts are mucinous or non-mucinous. Endoscopic ultrasound with fine-needle aspiration is often required to classify pancreatic cysts into mucinous and non-mucinous cysts and to assess the malignant potential. Advances in endoscopic techniques (confocal laser endomicroscopy, microforceps biopsy) can provide a definitive diagnosis of pancreatic cysts in some cases; however, the use of these techniques involves a higher risk of adverse events.

EUS-guided through-the-needle microforceps biopsy for diagnosis of tubercular lymphadenitis mimicking pancreatic cystic lesion (with video).

A 40-year-old male presented with upper abdominal discomfort and ultrasound abdomen revealed a cystic lesion in the uncinate process. Contrast-enhanced computed tomography revealed a thick-walled cystic lesion measuring 4.2 cm in the uncinate process [Figure 1]. Positron emission computed tomography revealed flouro-deoxyglucose avidity in the wall of this cystic lesion [Figure 2]. EUS-guided fine-needle biopsy from the cystic lesion done elsewhere was inconclusive on two separate occasions. EUS done at our center revealed a complex cystic lesion posterior to the head of the pancreas and closely abutting the inferior vena cava with normal uncinate process [Figure 3; arrows]. Contrast-enhanced harmonic EUS using Sonovue (Bracco, Milan, Italy) at low mechanical index of 0.12 revealed nonhomogenous enhancement of the cystic lesion with solid areas showing enhancement [arrows; Figure 4] and anechoic areas not enhancing. EUS-guided fine-needle biopsy form the solid as well as liquid areas was inconclusive and revealed necrosis only. Thereafter, tissue sampling was done from the solid area of the lesion under EUS guidance using through the needle forceps device (Moray Micro Forceps, US Endoscopy, United States) [Figure 5 and Video 1]. To improve the visualization of opening of forceps in the lesion, biopsy was performed using both B mode and harmonic EUS [Video 1]. The use of harmonic EUS led on to better visualization of the tip of Microforceps. Two passes were taken and crush smear was prepared with one specimen and the other specimen was sent in formalin vial. The cytopathological examination revealed lymphoid tissue with the presence of loose collection of epitheloid cells and necrosis [Figure 6]. No acid fast bacilli could be detected. The rapid nucleic acid amplification test (Xpert MTB/RIF; Cepheid, Sunnyvale, CA, USA) performed on the aspirated specimen was negative. The Mantoux test was positive (induration of 16 mm), C-reactive protein was elevated (16 mg/L), and the patient was started on anti-tubercular therapy (ATT). The patient responded to ATT and the abdominal discomfort subsided after 1 month of initiating ATT. Serum CRP normalized at 2 months and ultrasound of the abdomen done three months after initiation of ATT revealed reduction in size of the lesion (2.3 cm).Figure 1: Contrast enhanced computed tomography: thick walled cystic lesion in the uncinate process of pancreasFigure 2: Positron emission computed tomography: flouro-deoxyglucose avidity in the wall of cystic lesionFigure 3: EUS: Complex cystic lesion (arrows) posterior to the head of pancreas and closely abutting the inferior vena cava with normal uncinate processFigure 4: Contrast-enhanced harmonic EUS: Nonhomogenous enhancement of the cystic lesion with solid areas showing enhancement (arrows) and anechoic areas not enhancingFigure 5: EUS-guided biopsy using through the needle forceps deviceFigure 6: Microphotograph of microbiopsy specimen: a loose collection of epithelioid cells (arrows) with necrosis in the background (H and E, ×40)To improve the diagnostic yield of EUS-guided tissue sampling, through-the-needle micro-forceps device has been introduced and studies have reported high diagnostic yield in pancreatic cystic lesions.[1,2] It can also be used for tissue diagnosis in difficult to diagnose lesions as in the index case. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest Surinder Singh Rana is an Editorial Board Member of the journal. This article was subject to the journal’s standard procedures, with peer review handled independently of this editor and his research group.

Endoscopic Ultrasound Through-The-Needle Biopsy of Pancreatic Cysts: Toward Procedure Standardization

Background and Aims: EUS-guided through-the-needle microforceps biopsy (EUS-TTNB) was introduced as a new diagnostic tool to establish pancreatic cyst histotype and help to better risk stratify the patients. The aim of this study was to describe the technical success, diagnostic yield, and adverse events of through-the-needle biopsy and discuss the technique variations, focusing on future procedure standardization. Methods: We performed a prospective single-center study including patients with presumed mucinous cysts harboring worrisome features or indeterminate cyst type on imaging, submitted to EUS-TTNB using Moray® microforceps between March 2018 and September 2021. Specimens were processed as a cell-block. Results: We included 40 patients. Technical success was 97.5%. The diagnostic yield was 72.5% for TTNB whereas for cyst fluid cytology/analysis it was 27.5%. Moreover, without TTNB 5 mucinous lesions would not have been diagnosed. TTNB had a sensitivity of 76% and a specificity of 91%, while FNA cytology had a sensitivity and specificity of 35% and 91%, respectively. Moreover for IPMN lesions, subtyping was possible in 63% of cases. TTNB resulted in change in clinical management in 20% of patients. We registered three adverse events: 2 self-limited intracystic bleeding and 1 patient with abdominal pain not associated with pancreatitis. Conclusion: TTNB proved superior to cyst fluid analysis and cytology for the definition of cyst histotype and mucinous cyst diagnosis with acceptable risk profile. Further studies should explore the best steps for procedure standardization.

Endoscopic ultrasound-guided through-the-needle microforceps biopsy and needle-based confocal laser-endomicroscopy increase detection of potentially malignant pancreatic cystic lesions: A single-center study

Endoscopic ultrasound-guided through-the-needle microforceps biopsy and needle-based confocal laser-endomicroscopy increase detection of potentially malignant pancreatic cystic lesions: A single-center study

Endoscopic ultrasound-guided through-the-needle microforceps biopsy and needle-based confocal laser-endomicroscopy increase detection of potentially malignant pancreatic cystic lesions: A single-center study.

BACKGROUNDCurrently, there is insufficient data about the accuracy in the diagnosing of pancreatic cystic lesions (PCLs), especially with novel endoscopic techniques such as with direct intracystic micro-forceps biopsy (mFB) and needle-based confocal laser-endomicroscopy (nCLE).AIMTo compare the accuracy of endoscopic ultrasound (EUS) and associated techniques for the detection of potentially malignant PCLs: EUS-guided fine needle aspiration (EUS-FNA), contrast-enhanced EUS (CE-EUS), EUS-guided fiberoptic probe cystoscopy (cystoscopy), mFB, and nCLE.METHODSThis was a single-center, retrospective study. We identified patients who had undergone EUS, with or without additional diagnostic techniques, and had been diagnosed with PCLs. We determined agreement among malignancy after 24-mo follow-up findings with detection of potentially malignant PCLs via the EUS-guided techniques and/or EUS-guided biopsy when available (EUS malignancy detection). RESULTSA total of 129 patients were included, with EUS performed alone in 47/129. In 82/129 patients, EUS procedures were performed with additional EUS-FNA (21/82), CE-EUS (20/82), cystoscopy (27/82), mFB (36/82), nCLE (44/82). Agreement between EUS malignancy detection and the 24-mo follow-up findings was higher when associated with additional diagnostic techniques than EUS alone [62/82 (75.6%) vs 8/47 (17%); OR 4.35, 95%CI: 2.70-7.37; P < 0.001]. The highest malignancy detection accuracy was reached when nCLE and direct intracystic mFB were both performed, with a sensitivity, specificity, positive predictive value, negative predictive value and observed agreement of 100%, 89.4%, 77.8%, 100% and 92.3%, respectively (P < 0.001 compared with EUS-alone). CONCLUSIONThe combined use of EUS-guided mFB and nCLE improves detection of potentially malignant PCLs compared with EUS-alone, EUS-FNA, CE-EUS or cystoscopy.

Recent advances in the diagnostic evaluation of pancreatic cystic lesions.

Pancreatic cystic lesions (PCLs) are becoming more prevalent due to more frequent abdominal imaging and the increasing age of the general population. It has become crucial to identify these PCLs and subsequently risk stratify them to guide management. Given the high morbidity associated with pancreatic surgery, only those PCLs at high risk for malignancy should undergo such treatment. However, current diagnostic testing is suboptimal at accurately diagnosing and risk stratifying PCLs. Therefore, research has focused on developing new techniques for differentiating mucinous from non-mucinous PCLs and identifying high risk lesions for malignancy. Cross sectional imaging radiomics can potentially improve the predictive accuracy of primary risk stratification of PCLs at the time of detection to guide invasive testing. While cyst fluid glucose has reemerged as a potential biomarker, cyst fluid molecular markers have improved accuracy for identifying specific types of PCLs. Endoscopic ultrasound guided approaches such as confocal laser endomicroscopy and through the needle microforceps biopsy have shown a good correlation with histopathological findings and are evolving techniques for identifying and risk stratifying PCLs. While most of these recent diagnostics are only practiced at selective tertiary care centers, they hold a promise that management of PCLs will only get better in the future.

Efficacy and safety of EUS-guided through-the-needle microforceps biopsy sampling in categorizing the type of pancreatic cystic lesions

EUS-guided through-the-needle biopsy sampling (EUS-TTNB) using microbiopsy forceps is performed for the accurate diagnosis of pancreatic cystic lesions (PCLs). However, there are no standardized protocols for this procedure, and the amount of data on its efficacy is limited. Here, we evaluated the feasibility, efficacy, and safety of EUS-TTNB in categorizing the types of PCLs and identified the factors associated with diagnostic failure. The prospectively collected and maintained EUS-TTNB database at Asan Medical Center was reviewed to identify patients with PCLs who underwent EUS-TTNB between January 2019 and January 2021. The primary outcomes were technical success, diagnostic yield, and adverse events. Factors contributing to diagnostic failure and the discrepancies in the diagnosis made by conventional modalities (ie, EUS morphology, cross-sectional imaging, and cystic fluid analysis) were also evaluated. Forty-five patients were analyzed. EUS-TTNB was successfully performed in all patients (technical success, 100%). Histologic diagnosis of PCLs was made in 37 patients (diagnostic yield, 82%). When comparing EUS-TTNB with a presumptive diagnosis, EUS-TTNB changed the diagnosis in 10 patients in terms of the categorization of the types of PCLs. The diagnostic yield was significantly higher in those who had 4 or more visible biopsy specimens per session (93%) than in those with fewer than 4 visible biopsy specimens per session (67%; P= .045). During follow-up, 3 patients (7%) experienced adverse events (2 acute pancreatitis, 1 intracystic bleeding), and no life-threatening adverse event occurred. EUS-TTNB showed high technical feasibility, diagnostic yield, and good safety profile. EUS-TTNB may improve the categorization of the types of PCLs. Studies with standardized procedure protocols are needed to reduce the diagnostic failure for the types of PCLs.

Through-the-needle microforceps biopsy: a powerful tool but for selected patients

Through-the-needle microforceps biopsy: a powerful tool but for selected patients

Endoscopic ultrasound-guided through-the-needle microforceps biopsy improves diagnostic yield for pancreatic cystic lesions: a systematic review and meta-analysis.

Background and study aims Given variable diagnostic yield of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) for pancreatic cystic lesions (PCLs), a through-the-needle (TTN) microforceps biopsy device passed through a 19-gauge FNA needle has been devised to improve tissue sampling. This was a systematic review and meta-analysis to evaluate the feasibility, diagnostic yield, and safety of EUS-guided TTN microforceps biopsy for diagnosis of PCLs. Methods Individualized searches were developed in accordance with PRISMA and MOOSE guidelines. This was a cumulative meta-analysis performed by calculating pooled proportions with rates estimated using random effects models. Measured outcomes included pooled technical success, diagnostic yield, accuracy, and procedure-associated adverse events (AEs) as well as comparison to conventional FNA. Results Eleven studies (n = 518 patients; mean age 64.13 ± 5.83 years; 58.19 % female) were included. Mean PCL size was 33.39 ± 3.72 mm with the pancreatic head/uncinate (35.50 %) being the most common location. A mean of 2.47 ± 0.92 forceps passes were performed with a mean of 2.79 ± 0.81 microbiopsies obtained per lesion. Pooled technical success was 97.12 % (95 % CI, 93.73–98.71; I 2 = 34.49) with a diagnostic yield of 79.60 % (95 % CI, 72.62–85.16; I 2 = 56.00), and accuracy of 82.76 % [(95 % CI, 77.80–86.80; I 2 = 0.00). The pooled serious adverse event rate was 1.08 % (95 % CI, 0.43–2.69; I 2 = 0.00). Compared to conventional FNA, TTN microforceps biopsy resulted in significant improvement in diagnostic yield [OR 4.79 (95 % CI: 1.52–15.06; P = 0.007)] and diagnostic accuracy [OR 8.69 (95 % CI, 1.12–67.12; P = 0.038)], respectively. Conclusions EUS-guided TTN microforceps biopsy appears to be safe and effective for diagnosis of PCLs with improvement in diagnostic yield and accuracy when compared to FNA alone.

EUS-through-the-needle microbiopsy forceps in pancreatic cystic lesions: A systematic review.

Pancreatic cystic lesions (PCLs) are being increasingly encountered in clinical practice, and sometimes, they can represent a diagnostic challenge. Recently, a through-the-needle micro forceps biopsy (MFB) device was introduced in the endosonography practice to facilitate EUS-guided sampling of PCLs. The aim was to perform a systematic review of studies evaluating the technical aspects, safety, and efficacy of the EUS-guided MFB for PCLs. A literature search was performed in three major databases, PubMed, Embase, and Web of Science in September 2019 using the search terms: “through-the-needle,” “biopsy forceps,” “microforceps,” “endoscopic ultrasound,” and “endosonography.” Case reports and case series with <10 patients were excluded from the analysis. Altogether nine studies reporting on 463 patients were included in our systematic review. The mean age of the patients was 68.3 years, with a slight female predominance (60.9%). Most of the cysts were located in the body/tail of the pancreas (61.2%), with an overall mean size of 33 mm. The technical success of EUS-guided MFB was reported in 98.5%. The tissue acquisition yield reported was 88.2%, and the diagnostic accuracy was 68.6%. Adverse events were reported in 9.7%. EUS-guided MFB is technically feasible, safe, and has a high diagnostic accuracy for PCLs.

Endosonographic diagnosis of advanced neoplasia in intraductal papillary mucinous neoplasms.

Pancreatic cancer has a high mortality rate with minimal proven interventions. Intraductal Papillary Mucinous Neoplasms (IPMNs) are known precursor lesions for pancreatic cancer. Identification of pancreatic cysts has improved from advances in abdominal imaging. Despite multiple revisions of the international consensus recommendations and various guidelines by other major societies, successful risk stratification of the malignant potential of mucinous pancreatic cysts remains challenging. Specifically, detection and accurate classification of advanced neoplasia (high-grade dysplasia and/or adenocarcinoma) in IPMNs is suboptimal with current diagnostic strategies. Development of interventional techniques utilizing endoscopic ultrasound include - through-the-needle microforceps biopsy, next-generation or whole genome molecular analysis of cyst fluid, and needle-based confocal laser endomicroscopy. These techniques suffer from a series of limitations in technical success, diagnostic yield, and clinical feasibility, but a combination approach may offer a solution that optimizes their cyst evaluation and risk stratification. Assessment and comparison of these techniques is restricted by lack of adequate surgical specimens for testing of diagnostic accuracy, resulting in a possible sample bias. Additional large-scale multicenter studies are needed to accumulate evidence for the utility and feasibility of their translation into clinical practice. Great strides have been made in pancreatic cyst evaluation, but further research is required to improve diagnostic accuracy and clinical management of IPMNs.

Diagnostic yield of EUS-guided through-the-needle microforceps biopsy versus EUS-FNA of pancreatic cystic lesions: a systematic review and meta-analysis.

Background and study aims Accurate diagnosis and risk stratification of pancreatic cysts (PCs) is challenging. The aim of this study was to perform a systematic review and meta-analysis to assess the feasibility, safety, and diagnostic yield of endoscopic ultrasound-guided through-the-needle biopsy (TTNB) versus fine-needle aspiration (FNA) in PCs. Methods Comprehensive search of databases (PubMed, EMBASE, Cochrane, Web of Science) for relevant studies on TTNB of PCs (from inception to June 2019). The primary outcome was to compare the pooled diagnostic yield and concordance rate with surgical pathology of TTNB histology and FNA cytology of PCs. The secondary outcome was to estimate the safety profile of TTNB. Results: Eight studies (426 patients) were included. The diagnostic yield was significantly higher with TTNB over FNA for a specific cyst type (OR: 9.4; 95 % CI: [5.7–15.4]; I 2 = 48) or a mucinous cyst (MC) (OR: 3.9; 95 % CI: [2.0–7.4], I 2 = 72 %). The concordance rate with surgical pathology was significantly higher with TTNB over FNA for a specific cyst type (OR: 13.5; 95 % CI: [3.5–52.3]; I 2 = 48), for a MC (OR: 8.9; 95 % [CI: 1.9–40.8]; I 2 = 29), and for MC histologic severity (OR: 10.4; 95 % CI: [2.9–36.9]; I 2 = 0). The pooled sensitivity and specificity of TTNB for MCs were 90.1 % (95 % CI: [78.4–97.6]; I 2 = 36.5 %) and 94 % (95 % CI: [81.5–99.7]; I 2 = 0), respectively. The pooled adverse event rate was 7.0 % (95 % CI: [2.3–14.1]; I 2 = 82.9). Conclusions TTNB is safe, has a high sensitivity and specificity for MCs and may be superior to FNA cytology in risk-stratifying MCs and providing a specific cyst diagnosis.

Diagnostic performance of endoscopic ultrasound through-the-needle microforceps biopsy of pancreatic cystic lesions: Systematic review with meta-analysis.

Endoscopic ultrasound through-the-needle biopsy (EUS-TTNB) is a useful tool for differential diagnosis among pancreatic cystic lesions (PCLs). Cystic fluid cytology (CFC) is recommended by guidelines, but its diagnostic accuracy is about 50%. The aim of this meta-analysis is to assess the clinical impact of EUS-TTNB in terms of technical success (TS), histological accuracy (HA) and diagnostic yield (DY). Original studies in English language on EUS-TTNB were searched in MEDLINE and EMBASE until October 2019. Diagnostic accuracy of EUS-TTNB for identification of mucinous PCLs was calculated using individual diagnostic data of patients who underwent CFC and surgery. Nine studies, including 454 patients who underwent EUS-TTNB, met the inclusion criteria for the meta-analysis. TS and HA of EUS-TTNB were, respectively, 98.5% (95% Confidence Interval [CI] 97.3%-99.6%) and 86.7% (95%CI 80.1-93.4). DY was 69.5% (95%CI 59.2-79.7) for EUS-TTNB and 28.7% (95%CI 15.7-41.6) for CFC. Heterogeneity persisted significantly high in most of subgroup analyses. In the multivariate meta-regression, cyst size was independently associated with higher DY. Sensitivity and specificity for mucinous PCLs were 88.6 and 94.7% for EUS-TTNB, and 40 and 100% for CFC. Adverse events rate was 8.6% (95%CI 4.0-13.1). This meta-analysis shows that EUS-TTNB is a feasible technique that allows a high rate of adequate specimens to be obtained for histology; in about two-thirds of patients a specific histotype diagnosis could be assessed. The number of adverse events is slightly higher respect to standard EUS-FNA, but complications are very rarely severe.

Impact of EUS-guided microforceps biopsy sampling and needle-based confocal laser endomicroscopy on the diagnostic yield and clinical management of pancreatic cystic lesions

EUS-guided microforceps biopsy sampling (MFB) and needle-based confocal laser endomicroscopy (nCLE) are emerging diagnostic tools for pancreatic cystic lesions (PCLs). There is a paucity of data regarding their performance and impact. The aim of this study was to compare diagnostic outcomes and changes in clinical management resulting from MFB and nCLE use in PCLs. This was a single-center retrospective study of patients with PCLs who underwent combined EUS-guided FNA, MFB, and nCLE. Primary outcomes included diagnostic yield (specific PCL type) and change in clinical management for each modality compared with the current "composite standard" (CS) obtained by combining clinical, morphologic, cyst fluid cytology, and chemical analysis. Forty-four cysts were studied in 44 patients. Technical success was 100% for EUS-FNA, 88.6% for MFB, and 97.7% for nCLE. Of 44 procedures, there was 1 adverse event (2.3%, an infected pseudocyst). Diagnostic yield for each individual modality was 34.1% for CS, 75.0% for MFB (P< .05 vs CS), and 84.1% for nCLE (P< .05 vs CS). Diagnostic yield for combined tests was 79.5% for CS/MFB, 88.6% for CS/nCLE, and 93.2% for CS/MFB/nCLE (P= not significant). Compared with the CS, the use of MFB, nCLE, and their combination led to overall change in clinical management in 38.6%, 43.2%, and 52.3% of cases, respectively. MFB and nCLE led to an overall increase in discontinuation of surveillance (MFB, 34.1% [P< .05]; nCLE, 31.8% [P< .05]), led by a reduction in the indication for follow-up radiologic or endoscopic studies (MFB, 34.1% [P< .05]; nCLE, 38.6% [P< .05]). Based on MFB and nCLE, 2 of 28 (7.1%) and 3 of 28 (10.7%) patients who would have undergone further surveillance were referred for surgery. In the evaluation of PCLs, the use of combined EUS-guided FNA, MFB, and nCLE is safe. MFB and nCLE led to significant improvements in specific PCL diagnosis, which in turn has major impacts in clinical management.

880 EUS-Guided Through-The-Needle Microforceps Biopsy Versus EUS-FNA in the Evaluation of Pancreas Cysts: A Meta-Analysis

INTRODUCTION: Accurate diagnosis and risk stratification of pancreas cysts (PCs) is crucial for management. A through-the-needle microforceps was recently introduced for endoscopic ultrasound (EUS)-guided tissue sampling of PCs. We performed a meta-analysis to evaluate the efficacy and safety of microforceps biopsy (TTNB) and compare its diagnostic outcomes with EUS-guided fine-needle aspiration (FNA). METHODS: Comprehensive search of electronic databases (PubMed, EMBASE, Cochrane, Web of Science) from inception to May 2019 to identify studies that reported on EUS-guided TTNB. Main outcomes included comparison of pooled rates of specific diagnosis and that of mucinous PCs with TTNB vs FNA. Secondary outcomes included concordance between TTNB, FNA with available surgical histopathology. Pooling was conducted using either fixed- or random-effects model depending on heterogeneity across studies. RESULTS: Seven studies including 365 patients were included. TTNB was technically feasible in 98% of the cases. A specific PC diagnosis was more frequently obtained with TTNB vs EUS-FNA (OR: 6.35; 95% CI: 4.47-9.01, I2 = 0). Similarly, diagnosis of a mucinous PC was most commonly obtained with TTNB vs. EUS-FNA (OR: 3.01; 95% CI: 1.32-6.86, I2 = 80%). Sixty-four of the 365 patients with PC underwent surgery. TTNB histology was concordant with a specific surgical histopathology in 81.9% (95% CI: 72.7-89.5; I2 = 12.1%) and with a diagnosis of a mucinous PC in 84.5% (95% CI: 70.4-94.6, I2 = 41.8%) of the cases. Using surgical histopathology as reference standard, the pooled diagnostic accuracy for histological severity of mucinous PCs was higher with TTNB vs. EUS-FNA (OR: 7.76; 95% CI: 1.21-49.9, I2 = 39%). The most common adverse event with TTNB was self-limited intracystic bleed (4.3%), followed by acute pancreatitis (1.9%) and abdominal pain (1%). CONCLUSION: This meta-analysis demonstrates that in the evaluation of PCs, TTNB procures a specific diagnosis and identifies a higher proportion of mucinous PCs when compared to EUS-FNA. TTNB histology is highly concordant with surgical histopathology and was more accurate in grading mucinous PCs histological severity when compared to EUS-FNA. Future comparative randomized trials are needed to corroborate these findings.

Endoscopic diagnosis of pancreatic cysts.

Pancreatic cystic lesions (PCLs) are increasingly identified on abdominal imaging. Given the malignant potential of certain cyst subtypes and the poor survival rates of pancreatic cancer, accurate diagnosis and appropriate management of these cysts are critical. Advances in endoscopic ultrasound (EUS)-guided diagnostics have increased the accuracy of differentiating PCLs. These include cyst fluid molecular analysis, EUS-guided needle-based confocal laser endomicroscopy, and EUS-guided through the needle microforceps biopsy. This review encapsulates recent advances in the endoscopic management of PCLs with a specific focus on EUS-guided diagnosis. It is important to accurately diagnose pancreatic cystic lesions with malignant potential where the definitive management is surgical resection. Misdiagnosis can result in inadvertent surgery of an otherwise benign lesion or malignant progression of a precancerous cyst. Moreover, pancreatic surgery is associated with significant morbidity and mortality. Recent advances in EUS-guided tissue acquisition, imaging, and molecular biomarkers have resulted in improved diagnostic accuracy of pancreatic cystic lesions. Future studies need to define efficient and accurate diagnostic algorithms for improved management of pancreatic cysts.

Interobserver agreement among expert pathologists on through-the-needle microforceps biopsy samples for evaluation of pancreatic cystic lesions

The recent development of microforceps for EUS through-the-needle biopsy (TTNB) sampling of the wall of pancreatic cystic lesions (PCLs) allows the collection of histologic specimens never handled and evaluated before by pathologists. We aimed to estimate the interobserver agreement among pathologists in evaluating such samples. TTNB specimen slides from 40 PCLs with worrisome features were retrieved and independently evaluated for specimen adequacy, presence of lining epithelium, grade of epithelial dysplasia, presence of ovarian type stroma, and specific diagnosis by 6 expert pathologists from 6 different tertiary care centers. The Gwet's AC1 was used to assess interobserver agreement. An almost perfect agreement was observed for specimen adequacy (AC1, .82; 95% confidence interval [CI], .79-.98), presence of lesional epithelium (AC1, .90; 95% CI, .86-.92), epithelial dysplasia (AC1, .97; 95% CI, .95-.99), and ovarian-like stroma (AC1, .90; 95% CI, .86-.93). When considering all diagnoses separately, a moderate to substantial agreement was observed (AC1, .62; 95% CI, .57-.67), similarly to mucinous cysts versus serous adenoma versus other diagnoses (AC1, .65; 95% CI, .59-.70) and for mucinous cysts versus all other diagnoses (AC1,.74; 95% CI, .68-.84). The agreement for diagnosis of mucinous cystic neoplasm versus intraductal mucinous papillary neoplasm was almost perfect (AC1, .88; 95% CI, .81-.95). Interobserver agreement between expert pathologists in the evaluation of TTNB samples from PCLs with worrisome features was close to perfection for all evaluated parameters, except definitive diagnosis. When mucinous cystic lesions were compared versus all other diagnoses, the agreement became substantial, thus indicating that TTNB specimens can provide important information for PCL management decisions.

The role of endoscopic ultrasound-guided through-the-needle microforceps biopsy in the diagnosis of pancreatic cystic lesions

The role of endoscopic ultrasound-guided through-the-needle microforceps biopsy in the diagnosis of pancreatic cystic lesions