Endoscopic ultrasound-guided fine-needle aspiration pancreatic adenocarcinoma samples yield adequate DNA for next-generation sequencing:A cohort analysis

BACKGROUND Genetic tests are increasingly performed for the management of unresectable pancreatic cancer.For genotyping aimed samples current guidelines recommend using core specimens,although based on moderate quality evidence.However,in clinical practice among the endoscopic ultrasound(EUS) guided tissue acquisition methods,fine needle aspiration(FNA) is the most widely performed.AIM To assess the adequacy for next generation sequencing(NGS) of the DNA yielded from EUS-FNA pancreatic adenocarcinoma(PDAC) samples.METHODS Between November 2018 and December 2021,105 patients with PDAC confirmed by EUS-FNA were included in the study at our tertiary gastroenterology center.Either 22 gauge(G) or 19G FNA needles were used.One pass was dedicated to DNA extraction.DNA concentration and purity(A260/280,A260/230) were assessed by spectrophotometry.We assessed the differences in DNA parameters according to needle size and tumor characteristics(size,location) and the adequacy of the extracted DNA for NGS(defined as A260/280 ≥ 1.7,and DNA yield:≥ 10 ng for amplicon based NGS,≥ 50 ng for whole exome sequencing [WES],≥ 100 ng for whole genome sequencing [WGS]) by analysis of variance and ttest respectively.Moreover,we compared DNA purity parameters across the different DNA yield categories.RESULTS Our cohort included 49% male patients,aged 67.02 ± 8.38 years.The 22G needle was used in 71%of the cases.The DNA parameters across our samples varied as follows:DNA yield:1289 ng(inter quartile range:534.75-3101),A260/280 = 1.85(1.79-1.86),A260/230 = 2.2(1.72-2.36).DNA yield was > 10 ng in all samples and > 100 ng in 93% of them(one sample < 50 ng).There were no significant differences in the concentration and A260/280 between samples by needle size.Needle size was the only independent predictor of A260/230 which was higher in the 22G samples(P =0.038).NGS adequacy rate was 90% for 19G samples regardless of NGS type,and for 22G samples it reached 89% for WGS adequacy and 91% for WES and amplicon based NGS.Samples with DNA yield > 100 ng had significantly higher A260/280(1.89 ± 0.32 vs 1.34 ± 0.42,P = 0.013).Tumor characteristics were not corelated with the DNA parameters.CONCLUSION EUS-FNA PDAC samples yield DNA adequate for subsequent NGS.DNA amount was similar between 22G and 19G FNA needles.DNA purity parameters may vary indirectly with needle size.

Ultrasound-guided vs endoscopic ultrasound-guided fine-needle aspiration for pancreatic cancer diagnosis

AIM: To clarify the effectiveness and safety of endo- scopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis of pancreatic cancer (PC). METHODS: Patients who were diagnosed with unresectable, locally advanced or metastatic PC between February 2006 and September 2011 were selected for this retrospective study. FNA biopsy for pancreatic tumors had been performed percutaneously under extracorporeal ultrasound guidance until October 2009; then, beginning in November 2009, EUS-FNA has been performed. We reviewed the complete medical records of all patients who met the selection criteria for the following data: sex, age, location and size of the targeted tumor, histological and/or cytological findings, details of puncture procedures, time from day of puncture until day of definitive diagnosis, and details of severe adverse events. RESULTS: Of the 121 patients who met the selection criteria, 46 had a percutaneous biopsy (Group A) and 75 had an EUS-FNA biopsy (Group B). Adequate cytological specimens were obtained in 42 Group A patients (91.3%) and all 75 Group B patients (P=0.0192), and histological specimens were obtained in 41 Group A patients (89.1%) and 65 Group B patients (86.7%). Diagnosis of malignancy by cytology was positive in 33 Group A patients (78.6%) and 72 Group B patients (94.6%) (P=0.0079). Malignancy by both cytology and pathology was found in 43 Group A (93.5%) and 73 Group B (97.3%) patients. The mean period from the puncture until the cytological diagnosis in Group B was 1.7 d, which was significantly shorter than that in Group A (4.1 d) (P < 0.0001). Severe adverse events were experienced in two Group A patients (4.3%) and in one Group B patient (1.3%). CONCLUSION: EUS-FNA, as well as percutaneous needle aspiration, is an effective modality to obtain cytopathological confirmation in patients with advanced PC.

Pancreatic cystic lesions:How endoscopic ultrasound morphology and endoscopic ultrasound fine needle aspiration help unlock the diagnostic puzzle

Cystic lesions of the pancreas are being diagnosed with increasing frequency,covering a vast spectrum from benign to malignant and invasive lesions.Numerous investigations can be done to discriminate between benign and non-evolutive lesions from those that require surgery.At the moment,there is no single test that will allow a correct diagnosis in all cases.Endoscopic ultrasound(EUS) morphology,cyst fluid analysis and cytohistology with EUS-guided fine needle aspiration can aid in this difficult diagnosis.

Endoscopic ultrasound guided fine needle aspiration and useful ancillary methods

The role of endoscopic ultrasound(EUS) in evaluating pancreatic pathology has been well documented from the beginning of its clinical use. High spatial resolution and the close proximity to the evaluated organs within the mediastinum and abdominal cavity allow detection of small focal lesions and precise tissue acquisition from suspected lesions within the reach of this method. Fine needle aspiration(FNA) is considered of additional value to EUS and is performed to obtain tissue diagnosis. Tissue acquisition from suspected lesions for cytological or histological analysis allows, not only the differentiation between malignant and non-malignant lesions, but, in most cases, also the accurate distinction between the various types of malignant lesions. It is well documented that the best results are achieved only if an adequate sample is obtained for further analysis, if the material is processed in an appropriate way, and if adequate ancillary methods are performed. This is a multi-step process and could be quite a challenge in some cases. In this article, we discuss the technical aspects of tissue acquisition by EUS-guided-FNA(EUS-FNA), as well as the role of an on-site cytopathologist, various means of specimen processing, and the selection of the appropriate ancillary method for providing an accurate tissue diagnosis and maximizing the yield of this method. The main goal of this review is to alert endosonographers, not only to the different possibilities of tissue acquisition, namely EUS-FNA, but also to bring to their attention the importance of proper sample processing in the evaluation of various lesions in the gastrointestinal tract and other accessible organs. All aspects of tissue acquisition(needles, suction, use of stylet, complications, etc.) have been well discussed lately. Adequate tissue samples enable comprehensive diagnoses, which answer the main clinical questions, thus enabling targeted therapy.

Resected tumor seeding in stomach wall due to endoscopic ultrasonography-guided fine needle aspiration of pancreatic adenocarcinoma

Endoscopic ultrasonography-guided fine needle aspiration(EUS-FNA) is a useful and relatively safe tool for the diagnosis and staging of pancreatic cancer. However, there have recently been several reports of tumor seeding after EUS-FNA of adenocarcinomas. A 78-year-old man was admitted to our hospital due to upper gastric pain. Examinations revealed a 20 mm mass in the pancreatic body, for which EUS-FNA was performed. The cytology of the lesion was adenocarcinoma, and the stage of the cancer was T3N0M0. The patient underwent surgery with curative intent, followed by adjuvant chemotherapy with S-1. An enlarging gastric submucosal tumor was found on gastroscopy at 28 mo after surgery accompanied by a rising level of CA19-9. Biopsy result was adenocarcinoma, consistent with a pancreatic primary tumor. Tumor seeding after EUS-FNA was strongly suspected. The patient underwent surgical resection of the gastric tumor with curative intent. The pathological result of the resected gastric specimen was adenocarcinoma with a perfectly matched mucin special stain result with the previously resected pancreatic cancer. This is the first case report of tumor seeding after EUS-FNA which was surgically resected and inspected pathologically.

Identification of biomarkers of human pancreatic adenocarcinomas by expression profiling and validation with gene expression analysis in endoscopic ultrasound-guided fine needle aspiration samples

AIM： To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR （RT-QPCR） in endoscopic ultrasound-guided fine needle aspiration （EUS-guided FNA） specimens.METHODS： Commercially dedicated cancer cDNA macroarrays （Atlas Human Cancer 1.2） containing 1176 genes were used. Different statistical approaches （hierarchical clustering, principal component analysis （PCA） and SAM） were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results.RESULTS： RT-QPCR validated the increased expression of LCN2 （lipocalin 2） and for the first time PLAT （tissue-type plasminogen activator or tPA） in malignant pancreas as compared with normal pancreas. Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique.CONCLUSION： Expression profiling is a useful method to identify biomarkers and potential target genes. Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.

Endoscopic ultrasound-fine needle injection for oncological therapy

The minimal invasiveness and precision of endoscopicultrasound(EUS) has lead to both its widespread use as a diagnostic and staging modality for gastrointestinal and pancreaticobiliary malignancies, and to its expand-ing role as a therapeutic modality. EUS-guided celiac plexus neurolysis is now a well-accepted modality for palliation of pain in patients with pancreatic cancer. EUS-guided ablation, brachytherapy, fiducial marker placement, and antitumor agent injection have been described as methods of performing minimally invasive oncological therapy. EUS-fine needle injection may be performed as adjunctive, alternative, or palliative treatment. This review summarizes the studies to date that have described these methods. A literature search using the Pub Med/MEDLINE databases was performed. While most published studies to date are limited with disappointing outcomes, the concept of a role of EUS in oncological therapy seems promising.

Simultaneous endoscopic ultrasound fine needle aspiration and endoscopic retrograde cholangio-pancreatography:Evaluation of safety

AIM: To investigate the rate of complications of endoscopic retrograde cholangio-pancreatography (ERCP) performed immediately after endoscopic ultrasound fine needle aspiration (EUS-FNA) in a large series of patients. METHODS: Patients with the following conditions were considered candidates for EUS-FNA and ERCP: diagnosis of locally advanced or metastatic pancreatic lesion not eligible for surgery, and patients with pancreatic lesion of unknown nature causing jaundice. Data were prospectively collected on the following parameters: indication for FNA, EUS findings, pathological diagnosis, procedure duration of EUS-FNA and combined EUS-FNA and ERCP, and immediate and late complications. RESULTS: From January 2004 to October 2006, 72 patients were deemed eligible for combined EUS and ERCP. In 25/72 EUS-FNA was performed to obtain a pathology diagnosis of lesions causing biliary obstruction, and ERCP sequentially performed to drain the biliary system. No immediate complications occurred except for two mild bleeding episodes post sphincterotomy. No late complications were recorded except for one patient who experienced fever, promptly recovered with antibiotic therapy. CONCLUSION: Simultaneous approach appears to be feasible and safe. When possible, this can be considered the reference standard to avoid double sedation and reduce duration of the procedure and hospital stay.

Endoscopic ultrasound fine needle aspiration:Technique and applications in clinical practice

Since its initial report in 1992,endoscopic ultrasoundguided fine needle aspiration(EUS-FNA) has now been incorporated into the diagnostic and staging algorithm for the evaluation of benign and malignant diseases of the gastrointestinal tract and of adjacent organs.Its introduction constitutes a major breakthrough in the endoscopic field and has gradually transformed EUS from a pure imaging modality into a more interventional procedure.In addition,the possibility of collecting samples,providing a definitive cytological and/or histological evidence of the presence of malignancy,has strongly contributed to changing EUS from a subjective,highly operator dependant procedure into a more objective one.This article will review the instrumentation,technique and the most important clinical applications of EUS-FNA.

Comparison of cytological and histological preparations in the diagnosis of pancreatic malignancies using endoscopic ultrasoundguided fine needle aspiration

BACKGROUND:Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) has become a crucial diagnostic technique for pancreatic malignancies.The specimen obtained by EUS-FNA can be prepared for either cytological or histological examinations.This study was to compare diagnostic performance of cytological and histological preparations using EUSFNA in the same lesions when pancreatic malignancies were suspected.METHODS:One hundred and eighteen patients who underwent EUS-FNA for suspected pancreatic malignancies were consecutively enrolled.All procedures were conducted by a single echoendoscopist under the same conditions.Four adequate preparations were obtained by 22-gauge needles with 20 to-and-fro movements for each pass.The 4 preparations included 2 cytological and 2 histological specimens.The pathologic reviews of all specimens were conducted independently by a single experienced cytopathologist.Sensitivity,specificity,and accuracy of the 2 preparations were compared.RESULTS:The enrolled patients consisted of 62 males(52.5%),with the mean age of 64.6±10.5 years.Surgery was performed in 23(19.5%) patients.One hundred and sixteen(98.3%) lesions were classified as malignant,while 2(1.7%) were benign.Sensitivity of cytology and histology were 87.9% and 81.9%,respectively,with no significant difference(P=0.190).Accuracy was also not significantly different.Cytological preparation was more sensitive when the size of lesion was <3 cm(86.7% vs 68.9%,P=0.033).CONCLUSIONS:Our results suggested that the diagnostic performances of cytological and histological preparations are not significantly different for the diagnosis of pancreatic malignancies.However,cytological preparation might be more sensitive for pancreatic lesions <3 cm.

Pancreatic paraganglioma diagnosed by endoscopic ultrasoundguided fine needle aspiration: A case report and review of literature

BACKGROUND Pancreatic paragangliomas(PPGL)are rare benign neuroendocrine neoplasms but malignancy can occur.PPGL are often misdiagnosed as pancreatic neuroendocrine tumor or pancreatic adenocarcinoma.CASE SUMMARY We reviewed 47 case reports of PPGL published in PubMed to date.Fifteen patients(15/47)with PPGL underwent endoscopic ultrasound-guided fine needle aspiration(EUS-FNA).Only six(6/15)were correctly diagnosed as PPGL.All patients with PPGL underwent surgical resection except three(one patient surgery was aborted because of hypertensive crisis,two patients had metastasis or involvement of major vessels).Our patient remained on close surveillance as she was asymptomatic.CONCLUSION Accurate preoperative diagnosis of PPGL can be safely achieved by EUS-FNA with immunohistochemistry.Multidisciplinary team approach should be considered to bring the optimal results in the management of PPGL.

Endoscopic ultrasound-guided sampling of solid pancreatic masses:the fine needle aspiration or fine needle biopsy dilemma. Is the best needle yet to come?

Fine needle aspiration (FNA) is currently the standard of care for sampling pancreatic solid masses by using endoscopic ultrasound (EUS).The accuracy of the technique is reported to be high,especially if coupled with the rapid on site evaluation (ROSE),and it has a high safety profile.However,FNA presents some limitations,such as the small amount of tissue that can be collected and the inability of obtaining a core tissue with intact histological architecture,which is relevant to perform immunohistochemical analysis,molecular profiling and,therefore,targeted therapies.Moreover,the presence of the ROSE by an expert cytopathologist is very important to maximize the diagnostic yield of FNA technique;however,it is not widely available,especially in small centers.Hence,the introduction of EUS fine needle biopsy (FNB) with a new generation of needles,which show a high safety profile too and a satisfying diagnostic accuracy even in the absence of ROSE,could be the key to overcome the limitations of FNA.However,FNB has not yet shown diagnostic superiority over FNA.Considering all the technical aspects of FNA and FNB,the different types of needle currently available,comparisons in term of diagnostic yield,and the different techniques of sampling,a tailored approach should be used in order to determine the needle that is most appropriate for the different specific scenarios.

22-gauge core vs 22-gauge aspiration needle for endoscopic ultrasound-guided sampling of abdominal masses

AIM To compare the aspiration needle(AN) and core biopsy needle(PC) in endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) of abdominal masses.METHODS Consecutive patients referred for EUS-FNA were included in this prospective single-center trial. Each patient underwent a puncture of the lesion with both standard 22-gauge(G) AN(Echo Tip Ultra; Cook Medical, Bloomington, Indiana, United States) and the novel 22 G PC(Echo Tip Pro Core; Cook Medical, Bloomington, Indiana, United States) in a randomized fashion; histology was attempted in the PC group only. The main study endpoint was the overall diagnostic accuracy, including the contribution of histology to the final diagnosis. Secondary outcome measures included material adequacy, number of needle passes, and complications.RESULTS Fifty six consecutive patients(29 men; mean age 68 years) with pancreatic lesions(n = 38), lymphadenopathy(n = 13), submucosal tumors(n = 4), or others lesions(n = 1) underwent EUS-FNA using both of the needles in a randomized order. AN and PC reached similar overall results for diagnostic accuracy(AN: 88.9 vs PC: 96.1, P = 0.25), specimen adequacy(AN: 96.4% vs PC: 91.1%, P = 0.38), mean number of passes(AN: 1.5 vs PC: 1.7, P = 0.14), mean cellularity score(AN: 1.7 vs PC: 1.1, P = 0.058), and complications(none). A diagnosis on the basis of histology was achieved in the PC group in 36(64.3%) patients, and in 2 of those as the sole modality. In patients with available histology the mean cellularity score was higher for AN(AN: 1.7 vs PC: 1.0, P = 0.034); no other differences were of statistical significance.CONCLUSION Both needles achieved high overall diagnostic yields and similar performance characteristics for cytological diagnosis; histological analysis was only possible in 2/3 of cases with the new needle.

Randomized controlled study of the safety and efficacy of nitrous oxide-sedated endoscopic ultrasound-guided fine needle aspiration for digestive tract diseases

AIM To evaluate the efficacy and safety of nitrous oxidesedated endoscopic ultrasound-guided fine needle aspiration. METHODS Enrolled patients were divided randomly into an experimental group(inhalation of nitrous oxide) and a control group(inhalation of pure oxygen) and heart rate, blood oxygen saturation, blood pressure, electrocardiogram(ECG) changes, and the occurrence of complications were monitored and recorded. All patients and physicians completed satisfaction questionnaires about the examination and scored the process using a visual analog scale. RESULTS There was no significant difference in heart rate, blood oxygen saturation, blood pressure, ECG changes, or complication rate between the two groups of patients(P > 0.05). However, patient and physician satisfaction were both significantly higher in the nitrous oxide compared with the control group(P < 0.05).CONCLUSION Nitrous oxide-sedation is a safe and effective option for patients undergoing endoscopic ultrasound-guided fine needle aspiration.

Diagnostic utility of endoscopic ultrasound-guided fineneedle aspiration biopsy for glomus tumor of the stomach

A 52-year-old man was referred for further investigation of a gastric submucosal tumor on the greater curvature of the antrum. Endoscopic ultrasonography demonstrated a hypoechoic solid mass, which was primarily connected to the muscular layer of the stomach. We performed endoscopic ultrasoundguided fine-needle aspiration biopsy. The pathological examination showed proliferation of oval-shaped cells with nest formation, which stained strongly positive for muscle actin, and negative for c-kit, CD34, CD56,desmin, S-100, chromogranin, and neuron-specific enolase. Therefore, we performed laparoscopy and endoscopy cooperative surgery based on the preoperative diagnosis of glomus tumor of the stomach. The final histological diagnosis confirmed the preoperative diagnosis. Although preoperative diagnosis of glomus tumor of the stomach is difficult with conventional images and endoscopic biopsy, endoscopic ultrasoundguided fine-needle aspiration biopsy is an essential tool to gain histological evidence of glomus tumor of the stomach for early diagnosis.

Usefulness of endoscopic ultrasound-guided fine needle aspiration in the diagnosis of hepatic, gallbladder and biliary tract Lesions

Endoscopic ultrasound(EUS)-guided fine needle aspira-tion(FNA) of the liver is a safe procedure in the diag-nosis and staging of hepatobiliary malignancies with a minimal major complication rate. EUS-FNA is useful for liver lesions poorly accessible to other imaging modali-ties of the liver. EUS-guided FNA of biliary neoplasia and malignant biliary stricture is superior to the con-ventional endoscopic brushing and biopsy.

Accuracy of endoscopic ultrasound-guided needle aspiration specimens for molecular diagnosis of non-small-cell lung carcinoma

BACKGROUND Endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)and endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)are highly sensitive for diagnosing and staging lung cancer.In recent years,targeted therapy has shown great significance in the treatment of non-small cell lung carcinoma(NSCLC).Using these minimally invasive techniques to obtain specimens for molecular testing will provide patients with a more convenient diagnostic approach.AIM To evaluate the feasibility and accuracy of tissue samples obtained using EUSFNA and EBUS-TBNA for molecular diagnosis of NSCLC.METHODS A total of 83 patients with NSCLC underwent molecular testing using tissues obtained from EUS-FNA or EBUS-TBNA at the Tianjin Medical University Cancer Hospital from January 2017 to June 2019.All enrolled patients underwent chest computed tomography or positron emission tomography/computed tomography prior to puncture.We detected abnormal expression of EGFR,KRAS,MET,HER2,ROS1 and anaplastic lymphoma kinase protein.Two patients failed to complete molecular testing due to insufficient tumor tissue.The clinical features,puncture records,molecular testing results and targeted treatment in the remaining 81 patients were summarized.RESULTS In a total of 99 tissue samples obtained from 83 patients,molecular testing was successfully completed in 93 samples with a sample adequacy ratio of 93.9%(93/99).Biopsy samples from two patients failed to provide test results due to insufficient tumor tissue.In the remaining 81 patients,62 cases(76.5%)were found to have adenocarcinoma,11 cases(13.6%)had squamous cell carcinoma,3 cases(3.7%)had adenosquamous carcinoma and 5 cases(6.2%)had NSCLC-not otherwise specified.The results of molecular testing showed EGFR mutations in 21 cases(25.9%),KRAS mutations in 9 cases(11.1%),ROS-1 rearrangement in 1 case(1.2%)and anaplastic lymphoma kinase-positive in 5 cases(6.2%).Twentyfour patients with positive results received targeted therapy.The total effectiveness rate of targeted therapy was 66.7%(16/24),and the disease control rate was 83.3%(20/24).CONCLUSION Tissue samples obtained by EUS-FNA or EBUS-TBNA are feasible for the molecular diagnosis of NSCLC and can provide reliable evidence for clinical diagnosis and treatment.

Diagnostic value of liquid-based cytology and smear cytology in pancreatic endoscopic ultrasound-guided fine needle aspiration: A meta-analysis

BACKGROUND Smear cytology(SC)using endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)is the established and traditional choice for diagnosing pancreatic lesions.Liquid-based cytology(LBC)is a novel alternative cytological method,however,the comparative diagnostic efficacy of LBC remains inconclusive.AIM To examine the diagnostic efficacy of LBC and SC for pancreatic specimens obtained through EUS-FNA via a systematic review and meta-analysis.METHODS A systematic literature search was performed using PubMed,EMBASE,the Cochrane Library,and Web of Science.The numbers of true positives,false positives,true negatives,and false negatives for each cytological test(LBC and CS)were extracted from the included studies.The pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve(AUC)were calculated,and the AUC was compared by Tukey's multiple comparisons test.The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies II tool.RESULTS A total of 1656 patients in eight studies were included.The pooled sensitivity and specificity and the AUC for LBC were 0.76(95%CI:0.72-0.79),1.00(95%CI:0.98-1.00),and 0.9174,respectively,for diagnosing pancreatic lesions.The pooled estimates for SC were as follows:Sensitivity,0.68(95%CI:0.64-0.71);specificity,0.99(95%CI:0.96-100.00);and AUC,0.9714.Similarly,the corresponding values for LBC combined with SC were 0.87(95%CI:0.84-0.90),0.99(95%CI:0.96-1.00),and 0.9894.Tukey’s multiple comparisons test was used to compare the sensitivities and AUCs of the three diagnostic methods;statistically significant differences were found between the three methods,and LBC combined with SC was superior to both LBC(P<0.05)and SC(P<0.05).The pooled sensitivity and AUC did not change significantly in the sensitivity analysis.CONCLUSION LBC may be sensitive than SC in the cytological diagnosis of pancreatic lesions,however,the superior diagnostic performance of their combination emphasizes their integrated usage in the clinical evaluation of pancreatic lesions.

Efficacy of endoscopic ultrasonography-guided fine needle aspiration for pancreatic neuroendocrine tumor grading

AIM: To evaluate the efficacy of endoscopic ultrasonography-guided fine needle aspiration(EUS-FNA) for grading pancreatic neuroendocrine tumors(PNETs).METHODS: A total of 22 patients were diagnosed with PNET by EUS-FNA between October 2001 and December 2013 at Fukushima Medical University Hospital.Among these cases,we targeted 10 PNET patients who were evaluated according to the World Health Organization(WHO) 2010 classification.Surgery was performed in eight patients,and chemotherapy was performed in two patients due to multiple liver metastases.Specimens obtained by EUS-FNA were first stained with hematoxylin and eosin and then stained with chromogranin,synaptophysin,CD56,and Ki-67.The specimens were graded by the Ki-67 index according to the WHO 2010 classification.Specimens obtained by surgery were graded by the Ki-67 indexand mitotic count(WHO 2010 classification).For the eight specimens obtained by EUS-FNA,the Ki-67 index results were compared with those obtained by surgery.In the two cases treated with chemotherapy,the effects and prognoses were evaluated.RESULTS: The sampling rate for histological diagnosis by EUS-FNA was 100%.No adverse effects were observed.The concordance rate between specimens obtained by EUS-FNA and surgery was 87.5%(7/8).Fo r t h e t w o c a s e s t re a t e d w i t h c h e m o t h e ra p y,case 1 received somatostatin analog therapy and transcatheter arterial infusion(TAI) targeting multiple liver metastases.Subsequent treatment consisted of everolimus.During chemotherapy,the primary tumor remained unconfirmed,although the multiple liver metastases diminished dramatically.Case 2 was classified as neuroendocrine carcinoma(NEC) according to the Ki-67 index of a specimen obtained by EUS-FNA; therefore,cisplatin and irinotecan therapy was started.However,severe adverse effects,including renal failure and diarrhea,were observed,and the therapy regimen was changed to cisplatin and etoposide.TAI targeting multiple liver metastases was performed.Although the liver metastases diminished,the primary tumor remained unconfirmed.These chemotherapy regimens had immediate effects for both unresectable neuroendocrine tumor(NET) and NEC cases.These two subjects are still alive.CONCLUSION: EUS-FNA was effective for PNET diagnosis and Ki-67 index grading for WHO 2010 classification,enabling informed decisions on unresectable PNET treatment by identifying NET or NEC.

Endoscopic ultrasound-guided fine needle aspiration in the differentiation of type 1 and type 2 autoimmune pancreatitis

AIM:To investigate the usefulness of endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) in the differentiation of autoimmune pancreatitis(AIP).METHODS:We retrospectively reviewed 47 of 56 AIP patients who underwent EUS-FNA and met the Asian diagnostic criteria.On 47 EUS-FNA specimens,we evaluated the presence of adequate material and characteristic features of lymphoplasmacytic sclerosing pancreatitis(LPSP) and idiopathic duct-centric pancreatitis(IDCP) mentioned in the International Consensus Diagnostic Criteria and examined if these findings make a contribution to the differential diagnosis of type 1 and type 2 AIP.A disposable 22-gauge needle was used for EUS-FNA.RESULTS:Adequate specimens including pancreatic tissue for differentiating AIP from cancer were obtained from 43 of 47 patients who underwent EUSFNA.EUS-FNA was performed from the pancreatic head in 21 cases,which is known to be technically difficult when performed by core biopsy;there was no significant difference in the results compared with pancreatic body-tail.Nine of 47 patients met level 1 findings of LPSP and 5 patients met level 2 findings of LPSP.No one met level 1 findings of IDCP,but 3 patients met level 2 findings of IDCP.Of 10 seronegative cases,2 cases were diagnosed with "definitive type 1 AIP",and 3 cases were diagnosed with "probable type 2 AIP" when considering both the level 2 histological findings and response to steroids.CONCLUSION:EUS-FNA is useful in the differentiation of type 1 and type 2 AIP,particularly in seronegative cases.