Endoscopic ultrasound fine needle aspiration vs fine needle biopsy for pancreatic masses,subepithelial lesions,and lymph nodes

Endoscopic ultrasound tissue acquisition,in the form of both fine needle aspiration(EUS-FNA)and fine needle biopsy(EUS-FNB),is utilized for pancreatic mass lesions,subepithelial lesions,and lymph node biopsy.Both procedures are safe and yield high diagnostic value.Despite its high diagnostic yield,EUS-FNA has potential limitations associated with cytological aspirations,including inability to determine histologic architecture,and a small quantitative sample for further immunohistochemical staining.EUS-FNB,with its larger core biopsy needle,was designed to overcome these potential limitations.However,it remains unclear which technique should be used and for which lesions.Comparative trials are plagued by heterogeneity at every stage of comparison;including variable needles used,and different definitions of endpoints,which therefore limit generalizability.Thus,we present a review of prospective trials,systematic reviews,and meta-analyses on studies examining EUS-FNA vs EUSFNB.Prospective comparative trials of EUS-FNA vs EUS-FNB primarily focus on pancreatic mass lesions,and yield conflicting results in terms of demonstrating the superiority of one method.However,consistent among trials is the potential for diagnosis with fewer passes,and a larger quantity of sample achieved for next generation sequencing.With regard to subepithelial lesions and lymph node biopsy,fewer prospective trials exist,and larger prospective studies are necessary.Based on the available literature,we would recommend EUS-FNB for peri-hepatic lymph nodes.

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.

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 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.

Endoscopic ultrasound fine needle aspiration vs fine needle biopsy in solid lesions:A multi-center analysis

BACKGROUND While endoscopic ultrasound(EUS)-guided fine needle aspiration(FNA)is considered a preferred technique for tissue sampling for solid lesions,fine needle biopsy(FNB)has recently been developed.AIM To compare the accuracy of FNB vs FNA in determining the diagnosis of solid lesions.METHODS A retrospective,multi-center study of EUS-guided tissue sampling using FNA vs FNB needles.Measured outcomes included diagnostic test characteristics(i.e.,sensitivity,specificity,accuracy),use of rapid on-site evaluation(ROSE),and adverse events.Subgroup analyses were performed by type of lesion and diagnostic yield with or without ROSE.A multivariable logistic regression was also performed.RESULTS A total of 1168 patients with solid lesions(n=468 FNA;n=700 FNB)underwent EUS-guided sampling.Mean age was 65.02±12.13 years.Overall,sensitivity,specificity and accuracy were superior for FNB vs FNA(84.70%vs 74.53%;99.29%vs 96.62%;and 87.62%vs 81.55%,respectively;P<0.001).On subgroup analyses,sensitivity,specificity,and accuracy of FNB alone were similar to FNA+ROSE[(81.66%vs 86.45%;P=0.142),(100%vs 100%;P=1.00)and(88.40%vs 85.43%;P=0.320].There were no difference in diagnostic yield of FNB alone vs FNB+ROSE(P>0.05).Multivariate analysis showed no significant predictor for better accuracy.On subgroup analyses,FNB was superior to FNA for non-pancreatic lesions;however,there was no difference between the techniques among pancreatic lesions.One adverse event was reported in each group.CONCLUSION FNB is superior to FNA with equivalent diagnostic test characteristics compared to FNA+ROSE in the diagnosis of non-pancreatic solid lesions.Our results suggest that EUS-FNB may eliminate the need of ROSE and should be employed as a first-line method in the diagnosis of solid lesions.

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.

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.

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.

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.

Cytopathologic diagnosis of fine needle aspiration biopsies of thyroid nodules

Fine-needle aspiration(FNA) cytology is an important diagnostic tool in patients with thyroid lesions.Several systems have been proposed for the cyropathologic diagnosis of the thyroid nodules.However cases with indeterminate cytological findings still remain a matter of debate.In this review we analyze all literature regarding Thyroid Cytopathology Reporting systems trying to identify the most suitable methodology to use in clinical practice for the preoperative diagnosis of thyroid nodules.A review of the English literature was conducted,and data were analyzed and summarized and integrated from the authors' perspective.The main purpose of thyroid FNA is to identify patients with higher risk for malignancy,and to prevent unnecessary surgeries for benign conditions.The Bethesda System for Reporting Thyroid Cytopathology is the most widely used system for the diagnosis of thyroid FNA specimens.This system also contains guidelines for the diagnosis and treatment of indeterminate or suspicious for malignancy cases.In conclusion,patients who require repeated FNAs for indeterminate diagnoses will be resolved by repeat FNA in a percentage of 72%-80%.

Ultrasound-guided fine needle biopsy of intra- hepatic nodules and low elevation of AFP in early diagnosis of hepatocellular carcinoma

BACKGROUND: With the progress in early clinical treat- ment of hepatocellular carcinoma (HCC), early detection and diagnosis of HCC have been increasingly pressing. Combined alpha-fetoprotein ( AFP) determination and ul- trasonography has become the main method for the detec- tion of small HCC; but the relationship between low eleva- tion of AFP and pathologic findings of small HCC has not been well defined. The aim of this study was to assess the value of ultrasound-guided fine needle biopsy of intrahe- patic nodules and low elevation of serum AFP in the early diagnosis of HCC. METHODS; Fifty-nine patients with serum AFP exceeding 20 ng/ml and intrahepatic nodules varying from 0.8 cm to 5.0 cm in diameter who had been detected by ultrasonogra- phy underwent ultrasound-guided percutaneous fine needle biopsy, and cytological staining and histological sectioning were performed at the same time. RESULTS: Among the 59 patients, 11 patients (18.6%) showed AFP level above 400 ng/ml, 5 (8. 5%) from 200 ng/ml to 400 ng/ml, 18 (30. 5%) from 50 ng/ml to 200 ng/ml and 25 (42. 4% ) from 20 ng/ml to 50 ng/ml. Fol- low-up demonstrated that 53 patients (89.8%) had a pro- gressive increase of AFP level. In 58 patients (98.3%) cancer cells were found by cytological staining and/or his- tological sectioning. CONCLUSIONS: In those patients with slightly increased or continuously positive AFP, hepatic carcinoma should be highly suspected when AFP increases gradually and intrahe- patic nodules are detected by ultrasonography in follow-up. Once intrahepatic carcinoma nodules are suspected, ultra- sound-guided fine needle biopsy should be performed as early as possible for early diagnosis and treatment.

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.

Testicular fine needle aspiration as a diagnostic tool in nonobstructive azoospermia

Aim： To report the fine needle aspiration cytology （FNAC） of the testes used as a diagnostic tool in non-obstructive azoospermic patients. Methods： One hundred and twenty-five non-obstructive azoospermic male candidates to intracytoplasmic sperm injetion （ICSI） were analysed for follicle stimulating hormone （FSH）, luteinizing hormone （LH）, testosterone and inhibin B plasma levels. They were classified into three groups on the basis of FNAC： 1） Sertoli cell-only syndrome （SCOS） （70）; 2） severe hypospermatogenesis （42）; and 3） maturation arrest （13）, Then, all men underwent testicular sperm extraction （TESE） for sperm recovery for ICSI. Results： Mature spermatozoa were detected by FNAC in 24 of 42 men with severe hypospermatogenesis and nine of 13 men with maturation arrest; while they were retrieved by TESE in 29 of 70 men with SCOS, 35 of 42 men with severe hypospermatogenesis （including the 24 by FNAC） and 10 of 13 men with maturation arrest （including the nine by FNAC）. The sensitivity and specificity of FNAC were 44.6 % and 100 %, respectively. There was no difference on testicular volume and hormonal parameters in men with and without sperm retrieved. Conclusion： These findings suggest that FNAC may be a simple and valid diagnostic parameter in non-obstructive azoospermic men and it may represent a valid positive prognostic parameter for sperm recovery at TESE, （Asian J Androl 2005 Sep; 7： 289-294）

Impact of endoscopic ultrasound-guided fine needle biopsy for diagnosis of pancreatic masses

AIM: To evaluate the diagnostic accuracy of histologi- cal evaluation of pancreatic tissue samples obtained by a modified method for recovering and processing the endoscopic ultrasound (EUS)-guided fine needle aspira- tion (FNA) material in the differential diagnosis of pan- creatic solid masses. METHODS: Sixty-two consecutive patients with pan- creatic masses were prospectively studied. EUS was performed by the linear scanning Pentax FG-38UX ech- oendoscope. Three FNAs (22G needle) were carried out during each procedure. The materials obtained with first and second punctures were processed for cytological study. Materials of the third puncture were recovered into 10% formol solution by careful injection of saline so- lution through the needle, and processed for histological study. RESULTS: Length of the core specimen obtained for his- tological analysis was 6.5 ± 5.3 mm (range 1-22 mm). Cytological and histological samples were considered as adequate in 51 (82.3%) and 52 cases (83.9%), respec- tively. Overall sensitivity of both pancreatic cytology and histology for diagnosis of malignancy was 68.4%. Con- trary to cytology, histology was able to diagnose tumours other than adenocarcinomas, and all cases of inflamma- tory masses. Combination of cytology and histology al- lowed obtaining an adequate sample in 56 cases (90.3%), with a global sensitivity of 84.21%, specificity of 100% and an overall accuracy of 90.32%. The complication rate was 1.6%.CONCLUSION: Adequate pancreatic core specimens forhistological examination can be obtained by EUS-guided FNA. This technique is mainly useful for the diagnosis of different types of pancreatic tumours and evaluation of benign diseases.

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.

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

瞄准：在胃肠的基质肿瘤(大意) 的外科手术前的诊断评估内视镜的指导 ultrasonography 的好针渴望(EUS-FNA ) 的角色。方法：从 2002 年 9 月到 2006 年 6 月，有到合适的肌肉层的连续性的上皮的低亚硫酸钠拟声肿瘤由标准 EUS 作为大意怀疑了的官方补给的道潜水艇的 53 连续 EUS-FNAs 有希望地被评估。为最后的诊断的参考标准是外科(n = 31 ) ，或临床的后续(n = 22 ) 。另外，标本的免疫 phenotyping 由 EUS-FNA 获得了，外科的切除术标本被比较。结果：因为解剖问题，没在 2 情况刺被执行。从官方补给的道的足够的标本的收集率与连续性代替上皮的低亚硫酸钠拟声肿瘤到合适的肌肉层是 82%(42/51 ) 。为肿瘤的诊断的率不到 2 厘米， 2 ～ 4 厘米，和 4 厘米或更多是 71%(15/21 ) ， 86%(18/21 ) ，并且 100%(9/9 ) 分别地。在 29 通过手术用免疫的 EUS-FNA 的 resected 盒子，敏感，特性，积极预兆的价值，否定预兆的价值，和诊断精确性大意的组织化学的分析是100%( 24/24 )，80%( 4/5 )，96%( 24/25 )，100%( 4/4 )，并且97%( 28/29 )分别地。没有主要复杂并发症被遇到。结论：有免疫的 EUS-FNA 组织化学的分析是在大意的 prethera-peutic 诊断的一个安全、精确的方法。它应该在决策被考虑，特别在跟随为大意的最小的侵略外科的早诊断。

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.

Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer

AIM: To establish an optimum combination of molecular markers resulting in best overall diagnostic sensitivity and specificity for evaluation of suspicious pancreatic mass. METHODS: Endoscopic ultrasound (EUS)-guided fine needle aspiration cytology (FNA) was performed on 101 consecutive patients (63 males, 38 females, 60 ± 12 years; 81 with subsequently diagnosed pancreatic cancer, 20 with chronic pancreatitis) with focal pancreatic mass. Samples were evaluated on-site by an experienced cytopathologist. DNA was extracted from Giemsa stained cells selected by laser microdissection and the presence of K-ras, p53 and p16 somatic mutations was tested by cycling-gradient capillary electrophoresis (CGCE) and single-strand conformation polymorphism (SSCP) techniques. In addition, allelic losses of tumor suppressor genes p16 (INK4, CDKN2A) and DPC4 (MADH4, SMAD4) were detected by monitoring the loss of heterozygosity (LOH) at 9p and 18q, respectively. RESULTS: Sensitivity and specificity of EUS-guided FNA were 75% and 85%, positive and negative predictivevalue reached 100%. The remaining 26% samples were assigned as inconclusive. Testing of molecular markers revealed sensitivity and specificity of 70% and 100% for K-ras mutations (P < 0.001), 24% and 90% for p53 mutations (NS), 13% and 100% for p16 mutations (NS), 85% and 64% for allelic losses at 9p (P < 0.001) and 78% and 57% for allelic losses at 18q (P < 0.05). When tests for different molecular markers were combined, the best results were obtained with K-ras + LOH at 9p (92% and 64%, P < 0.001), K-ras + LOH at 18q (92% and 57%, P < 0.001), and K-ras + LOH 9q + LOH 18q (96% and 43%, P < 0.001). When the molecular markers were used as complements to FNA cytology to evaluate inconclusive samples only, the overall sensitivity of cancer detection was 100% in all patients enrolled in the study. CONCLUSION: EUS-guided FNA cytology combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy. Molecular markers may find its use particularly in cases where FNA cytology has been inconclusive.

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.

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.