Individualized treatment guided by endoscopic ultrasound-guided fine-needle aspiration for adrenocortical oncocytoma:A case report

BACKGROUND Adrenocortical oncocytoma is a rare,mostly benign,nonfunctional tumor that is typically detected incidentally.Its diagnosis is challenging because of the absence of distinctive imaging characteristics,necessitating pathological validation.CASE SUMMARY We present a case report of a 35-year-old woman with an adrenal mass located on the left side,where endoscopic ultrasound-guided fine-needle aspiration(EUSFNA)was performed after comprehensive diagnostic assessment.Our results are consistent with those of previously documented cases regarding tumor demographics and anatomical location.Given the limited number of reports on this condition,long-term follow-up is crucial to enhance our understanding of its prognosis.CONCLUSION For patients with adrenocortical oncocytoma,EUS-FNA can enables collection of preoperative tissue specimens leading to suitable treatment strategies.

Preoperative diagnosis of gastrointestinal stromal tumor by endoscopic ultrasound-guided fine needle aspiration

AIM： to evaluate the role of endoscopic ultrasonographyguided fine needle aspiration （EUS-FNA） in the preoperative diagnosis of gastrointestinal stromal tumor （GIST）.METHODS： From September 2002 to June 2006, Fiftythree consecutive EUS-FNAs of GI tract subepithelial hypoechoic tumors with continuity to proper muscle layer suspected as GIST by standard EUS were evaluated prospectively. The reference standards for the final diagnosis were surgery （n = 31）, or clinical follow-up （n = 22）. Additionally, immunophenotyping of specimens obtained by EUS-FNA and surgical resection specimens were compared.RESULTS： In 2 cases puncture was not performed because of anatomical problems. The collection rate of adequate specimens from the GI tract subepithelial hypoechoic tumor with continuity to proper muscle layer was 82% （42/51）. The diagnostic rate for the tumor less than 2 cm, 2 to 4 cm, and 4 cm or more were 71% （15/21）, 86% （18/21）, and 100% （9/9）,respectively. In 29 surgically resected cases, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of EUS-FNA using immunohistochemical analysis of GIST were 100%（24/24）, 80% （4/5）, 96% （24/25）, 100% （4/4）, and 97% （28/29）, respectively. No major complications were encountered.CONCLUSION： EUS-FNA with immunohistochemical analysis is a safe and accurate method in the pretherapeutic diagnosis of GIST. It should be taken into consideration in decision making, especially in early diagnosis following minimal invasive surgery for GIST.

Slow-pull and different conventional suction techniques in endoscopic ultrasound-guided fine-needle aspiration of pancreatic solid lesions using 22-gauge needles

AIM To evaluate the cytological diagnostic capacity and sample quality of the slow-pull technique and compare them with different suction techniques.METHODS From July 2010 to December 2015, 102 patients with pancreatic solid lesions who underwent endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA) with 22-gauge needles were retrospectively evaluated. EUS-FNA diagnosis was based on a cytological examination, and final diagnosis was based on a comprehensive standard of cytological diagnosis, surgical pathology and clinical or imaging follow-up. Cytological specimens were characterized for cellularity and blood contamination. The cytological diagnostic capacity and sample quality of the slow-pull technique and suction techniques with 5-m L/10-m L/20-m L syringes were analyzed.RESULTS Of all of the EUS-FNA procedures, the slow-pull technique and suction techniques with 5-m L/10-m L/20-m L syringes were used in 31, 19, 34 and 18 procedures, respectively. There were significant differences between these four suction techniques in terms of cytological diagnostic accuracy(90.3% vs 63.2% vs 58.8% vs 55.6%, P = 0.019), sensitivity(88.2% vs 41.7% vs 40.0% vs 36.4%, P = 0.009) and blood contamination(score ≥ 2 for 29.0% vs 52.6% vs 70.6% vs 72.2%, P = 0.003). The accuracy and sensitivity of the slow-pull technique were significantly higher than those of the suction techniques using 5-m L(P = 0.03, P = 0.014), 10-m L(P = 0.005; P = 0.006) and 20-mL syringes(P = 0.01, P = 0.01). Blood contamination was significantly lower in the slow-pull technique than in the suction techniques with 10-m L(P = 0.001) and 20-mL syringes(P = 0.007).CONCLUSION The slow-pull technique may increase the cytological diagnostic accuracy and sensitivity with slight blood contamination during EUS-FNA when using 22-gauge needles for solid pancreatic masses.

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.

Influence of the safety and diagnostic accuracy of preoperative endoscopic ultrasound-guided fine-needle aspiration for resectable pancreatic cancer on clinical performance

AIM: To evaluate the safety and diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in a cohort of pancreatic cancer patients.

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.

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.

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.

Peritoneal dissemination of pancreatic cancer caused by endoscopic ultrasound-guided fine needle aspiration:A case report and literature review

BACKGROUND Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)is a biopsy technique widely used to diagnose pancreatic tumors because of its high sensitivity and specificity.Although needle-tract seeding caused by EUS-FNA has been recently reported,dissemination of pancreatic cancer cells is generally considered to be a rare complication that does not affect patient prognosis.However,the frequency of dissemination and needle-tract seeding appears to have been underestimated.We present a case of peritoneal dissemination of pancreatic cancer due to preoperative EUS-FNA.CASE SUMMARY An 81-year-old man was referred to the Department of Surgery of our hospital in Japan owing to the detection of a pancreatic mass on computed tomography during medical screening.Trans-gastric EUS-FNA revealed that the mass was an adenocarcinoma;hence laparoscopic distal pancreatectomy with lymphadenectomy was performed.No intraoperative peritoneal dissemination and liver metastasis were visually detected,and pelvic lavage cytology was negative for carcinoma cells.The postoperative surgical specimen was negative for carcinoma cells at the dissected margin and the cut end margin;however,pathological findings revealed adenocarcinoma cells on the peritoneal surface proximal to the needle puncture site,and the cells were suspected to be disseminated via EUSFNA.Hence,the patient received adjuvant therapy with S-1(tegafur,gimeracil,and oteracil potassium);however,computed tomography performed 5 mo after surgery revealed liver metastasis and cancerous peritonitis.The patient received palliative therapy and died 8 mo after the operation.CONCLUSION The indications of EUS-FNA should be carefully considered to avoid iatrogenic dissemination,especially for cancers in the pancreatic body or tail.

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.

Endoscopic ultrasound-guided fine-needle aspiration for diagnosing a rare extraluminal duodenal gastrointestinal tumor

Duodenal gastrointestinal stromal tumors(GISTs) are extremely rare disease entities, and the extraluminal type is difficult to diagnose. These tumors have been misdiagnosed as pancreatic tumors; hence, pancreaticoduodenectomy has been performed, although partial duodenectomy can be performed if accurately diagnosed. Developing a diagnostic methodology including endoscopic ultrasonography(EUS) and fine-needle aspiration(FNA) has allowed us to diagnose the tumor directly through the duodenum. Here, we present a case of a 50-year-old woman with a 27-mm diameter tumor in the pancreatic uncus on computed tomography scan. EUS showed a well-defined hypoechoic mass in the pancreatic uncus that connected to the duodenal proper muscular layer and was followed by endoscopic ultrasoundguided fine-needle aspiration(EUS-FNA). Histological examination showed spindle-shaped tumor cells positively stained for c-kit. Based on these findings, the tumor was finally diagnosed as a duodenal GIST of the extraluminal type, and the patient underwent successful mass resection with partial resection of the duodenum. This case suggests that EUS and EUS-FNA are effective for diagnosing the extraluminal type of duodenal GISTs, which is difficult to differentiate from pancreatic head tumor, and for performing the correct surgical procedure.

Can the wet suction technique change the efficacy of endoscopic ultrasound-guided fine-needle aspiration for diagnosing autoimmune pancreatitis type 1? A prospective single-arm study

BACKGROUND Other than surgery,endoscopic ultrasound-guided fine-needle aspiration(EUSFNA)is the only procedure for histologically diagnosing autoimmune pancreatitis(AIP).However,adequate specimens are difficult to obtain.Recently,more adequate specimens were reported to be obtained with EUS-FNA with a wet suction technique(WEST)than with conventional EUS-FNA.AIM To histologically diagnose AIP by EUS-FNA with a WEST.METHODS Eleven patients with possible type 1 AIP between February 2016 and August 2018 underwent EUS-FNA with a WEST(WEST group),with four punctures by 19 or 22 G needles.As a historical control,23 type 1 AIP patients who underwent no fewer than four punctures with 19 or 22 G needles were enrolled(DRY group).Patient characteristics and histological findings were compared between the two groups.RESULTS Three histopathological factors according to the International Consensus Diagnostic Criteria were significantly greater in the WEST group than the DRY group[lymphoplasmacytic infiltrate without granulocytic infiltration:9(81.8%)vs 6(26.1%),P=0.003,storiform fibrosis:5(45.5%)vs 1(4.3%),P=0.008,abundant(>10 cells/HPF)IgG4-positive cells:7(63.6%)vs 5(21.7%),P=0.026].Level 1 or level 2 histopathological findings were observed more often in the WEST group than in the DRY group[8(72.7%)vs 3(13.0%),P=0.001].CONCLUSION EUS-FNA with a WEST was more successful than standard EUS-FNA in histologically diagnosing AIP.

Endoscopic ultrasound-guided fine-needle aspiration cytology in pancreaticobiliary carcinomas:diagnostic efficacy of cell-block immunocyto-chemistry

BACKGROUND： Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic le- sions. Nonetheless, the diagnostic value of this procedure may be limited by low cellularity of the specimen, contamination of intestinal cells and unfeasibility of ancillary immunocy- tochemical procedures. The present study was to evaluate its usefulness in the diagnosis of neoplastic lesions.

Endoscopic ultrasound-guided fine-needle aspiration cytology diagnosis of solid pseudopapillary tumor of the pancreas: A case report and literature review

We describe the clinical, imaging and cytopathological features of solid pseudopapillary tumor of the pancreas (SPTP) diagnosed by endoscopic ultrasound- guided (EUS-guided) fine-needle aspiration (FNA). A 17-year-old woman was admitted to our hospital with complaints of an unexplained episodic abdominal pain for 2 mo and a short history of hypertension in the endocrinology clinic. Clinical laboratory examinations revealed polycystic ovary syndrome, splenomegaly and low serum amylase and carcinoembryonic antigen (CEA) levels. Computed tomography (CT) analysis revealed a mass of the pancreatic tail with solid and cystic consistency. EUS confirmed the mass, both in body and tail of the pancreas, with distinct borders, which caused dilation of the peripheral part of the pancreatic duct (major diameter 3.7 mm). The patient underwent EUS-FNA. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform malignant cells, forming microadenoid structures, branching, papillary clusters with delicate fibrovascular cores and nuclear overlapping. Naked capillaries were also seen. The nuclei of malignant cells were round or oval, eccentric with fine granular chromatin, small nucleoli and nuclear grooves in some of them. The malignant cells were periodic acid Schiff (PAS)-Alcian blue (+) and immunocytochemically they were vimentin (+), CA 19.9 (+), synaptophysin (+), chromogranin (-), neuro-specific enolase (-), a1- antitrypsin and a1-antichymotrypsin focal positive. Cytologic findings were strongly suggestive of SPTP. Biopsy confirmed the above cytologic diagnosis. EUS- guided FNA diagnosis of SPTP is accurate. EUS findings,cytomorphologic features and immunostains of cell block help distinguish SPTP from pancreatic endocrine tumors, acinar cell carcinoma and papillary mucinous carcinoma.

Endoscopic ultrasound-guided fine-needle aspiration biopsy-Recent topics and technical tips

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is a useful procedure that enables reliable pathological diagnoses of pancreatobiliary diseases, subepithelial lesions, and swollen lymph nodes. In recent years, a pathological diagnosis based on EUS-FNA has made it possible to provide accurate treatment methods not only in these fields, but also in respiratory organs and otorhinolaryngology. This review discusses the latest topics pertaining to EUS-FNA as well as procedural tips.

Ultrasound-guided fine needle aspiration biopsy in differential diagnosis of portal vein tumor thrombosis

BACKGROUND: Portal vein tumor thrombosis(PVTT) is a serious complication and a major metastatic way of hepa- tocellular carcinoma (HCC). But portal vein benign throm- bosis(PVBT) always appears in patients with hepatocirrho- sis, and PVTT should be differentiated from PVBT. The aim of this study was to probe the value of ultrasound- guided fine needle aspiration biopsy in differential diagnosis of PVTT. METHODS: Twenty-two HCC patients with portal vein thrombosis and 8 hepatocirrhosis patients with portal vein thrombosis were studied by ultrasound-guided fine needle aspiration biopsy. Twelve portal vein thrombosis filling portal vein embranchment of the 30 portal vein thrombosis patients were examined by 18G automatic biopsy. The positive rates of aspiration biopsy cytology and histology were calculated and compared with those of automatic biopsy. RESULTS: The positive rates of fine needle aspiration biop- sy cytology and histology were 93.3% (28/30) and 90.0% (27/30), respectively. They were not different markedly from that of automatic biopsy 91.7% (11/12). In aspira- tion biopsy of 22 HCC patients with PVTT, HCC cellular was found in 19 portal vein thrombosis patients (86.4%) by cytology examination and in 18 portal vein thrombosis patients (81.8%) by histology examination. In total, 20 tumor thrombi were detected. The other two were diag- nosed as benign thrombosis. No HCC cell and/or tissue was observed in 8 patients with hepatocirrhosis associated with portal vein thrombosis. CONCLUSIONS: Ultrasound-guided fine needle biopsy in detecting PVTT shows a high positive rate and is of diag- nostic value. The positive rate is not apparently different from that of automatic biopsy. Hence the case that fails to be diagnosed by color Doppler flow imaging ( CDFI) and pulsed Doppler can be detected early by ultrasound-guided fine needle aspiration biopsy.

Rapid on-site evaluation of endoscopic-ultrasound-guided fine-needle aspiration diagnosis of pancreatic masses

Endoscopic ultrasound (EUS) has become an essential tool for the study of pancreatic diseases. Specifically, EUS plays a pivotal role evaluating patients with a known or suspected pancreatic mass. In this setting, differential diagnosis remains a clinical challenge. EUS-guided fine-needle aspiration (FNA) and fine-needle biopsy (FNB) have been proven to be safe and useful tools in this setting. EUS-guided FNA and FNB, by obtaining cytological and/or histological samples, are able to diagnose pancreatic lesions with high sensitivity and specificity. In this context, several methodological features, trying to increase the diagnostic yield of EUS-guided FNA and FNB, have been evaluated. In this review, we focus on the role of rapid on-site evaluation (ROSE). From data reported in the literature, ROSE may increase diagnostic yield of EUS-FNA specimens by 10%-30%, and thus, diagnostic accuracy. However, we should point out that many recent studies have reported adequacy rates of &#x0003e; 90% without ROSE, indicating that, perhaps, at high-volume centers, ROSE may not be indispensable to achieve excellent results. The use of ROSE can be considered important during the learning curve of EUS-FNA, and also in hospital with diagnostic accuracy rates &#x0003c; 90%.

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-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.

Concise review on the comparative efficacy of endoscopic ultrasound-guided fine-needle aspiration vs core biopsy in pancreatic masses, upper and lower gastrointestinal submucosal tumors

Endoscopic ultrasound(EUS)-guided fine needle aspiration with or without biopsy(FNA/FNB) are the primary diagnostic tools for gastrointestinal submucosal tumors. EUS-guided fine needle aspiration(EUS-FNA) is considered a first line diagnostic method for the characterization of pancreatic and upper gastrointestinal lesions, since it allows for the direct visualization of the collection of specimens for cytopathologic analysis. EUSFNA is most effective and accurate when immediate cytologic assessment is permitted by the presence of a cytopathologist on site. Unfortunately, the accuracy and thus the diagnostic yield of collected specimens suffer without this immediate analysis. Recently, a EUS-FNB needle capable of obtaining core samples(fine needle biopsy, FNB) has been developed and has shown promising results. This new tool adds a new dimension to the diagnostic and therapeutic utility of this technique. The aim of the present review is to compare the efficacy of EUS-FNA to that afforded by EUS-FNB in the characterization of pancreatic masses and of upper and lower gastrointestinal submucosal tumors.