EUS-guided fine-needle aspiration cytodiagnosis of hilar cholangiocarcinoma: a case series

BACKGROUND: Improved methods of tissue diagnosis for obstruction at the hilum of the liver (porta hepatis) have contributed substantially to the preoperative diagnosis of cholangiocarcinoma. Endoscopic brushing during endoscopic retrograde cholangiopancreatography (ERCP), with sensitivity of 20% to 100%, is the preferred technique for obtaining accurate pathologic results. Extensive hepatic resection with curative intent as well as modern approaches to palliative treatment are based on definitive diagnosis. This is a study involving endosonography-guided, fine-needle aspiration (EUS-FNA) for cytodiagnosis of potentially operable hilar cholangiocarcinoma when brush cytology was negative or unavailable. METHODS: Ten consecutive patients (7 men, 3 women; age 47 to 78 years, median 59 years) with bile duct strictures at the hepatic hilum, diagnosed by CT and/or ERCP, underwent EUS-FNA using linear echoendoscopes and 22-gauge needles. RESULTS: Adequate material was obtained in nine patients. Cytology revealed cholangiocarcinoma in seven and hepatocellular carcinoma in one. One benign inflammatory lesion identified on cytology proved to be a false-negative finding by frozen section. Metastatic locoregional hilar lymph nodes were detected in two patients, and in one patient the celiac and para-aortic lymph nodes were aspirated to obtain tissue proof of distant metastasis. There were no complications. CONCLUSIONS: When standard methods of tissue diagnosis are inconclusive, EUS-guided FNA may have a potential role in the diagnosis of primary cholangiocarcinoma of the hepatic hilum. As a new, minimally invasive approach, it proved to be technically feasible without significant risks.     

Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma

AIM： To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS： Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography （ERCP） including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS： Positive results for malignancy were obtained in 24/58 patients （41.4%） by brush cytology and in 31/58 patients （53.4%） by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% （35/58 patients）. In 20/58 patients （34.5%）, diagnosis were obtained by both positive cytology and positive histology, in 11/58 （19%） by positive histology （negative cytology） and only 4/58 patients （6.9%） were confirmed by positive cytology （negative histology）.CONCLUSION： Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.     

Comparison between EUS-guided fine-needle aspiration cytology and EUS-guided fine-needle biopsy histology for the evaluation of pancreatic neuroendocrine tumors

Background/objectivesStudies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens.MethodsPatients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed.ResultsThree-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (<500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p < 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482).ConclusionOur study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.     

EUS-guided FNA of regional lymph nodes in patients with unresectable hilar cholangiocarcinoma

BACKGROUND: The clinical impact of EUS-guided FNA (EUS-FNA) in regional lymph-node staging in patients with unresectable hilar cholangiocarcinoma before liver transplantation has yet to be determined. OBJECTIVES: To determine the frequency of regional lymph-node detection, identify EUS features predictive of benign or malignant lymph nodes, compare EUS lymph-node detection rates to CT/magnetic resonance imaging and exploratory laparotomy, and evaluate the impact of EUS-FNA on patient selection for liver transplantation. DESIGN: Retrospective case series. SETTING: Tertiary referral EUS unit. PATIENTS: Clinical, radiographic, EUS, cytologic, and surgical data of 47 patients with unresectable hilar cholangiocarcinoma before liver transplantation were evaluated. INTERVENTIONS: EUS-FNA. MAIN OUTCOME MEASUREMENTS: Lymph-node morphology and echo features. RESULTS: EUS identified lymph nodes in all patients. FNA of 70 lymph nodes identified metastases in 9 nodes of 8 patients (17%), who were then precluded from transplantation before a staging laparotomy. Identified lymph nodes, irrespective of malignant involvement, were typically oval and geographic in shape, of mixed echogenicity, with a hypoechoic border. There were no morphologic criteria or echo features to correlate with nodal malignancy. The EUS finding of absent regional lymph-node metastases was confirmed in 20 of 22 by a subsequent exploratory staging laparotomy. LIMITATIONS: Single institution, retrospective analysis. CONCLUSIONS: EUS identified lymph nodes in all patients, and confirmation of malignant lymph nodes detected by FNA precluded 17% of patients from transplantation. EUS-FNA of visualized lymph nodes irrespective of appearance is advised because morphology and echo features do not predict malignant involvement.     

EUS-guided FNA of proximal biliary strictures after negative ERCP brush cytology results

BACKGROUND: Accurate nonoperative diagnosis of proximal biliary strictures (PBSs) is often difficult. OBJECTIVE: To report our experience with EUS-guided FNA (EUS-FNA) of PBSs following negative or unsuccessful results with brush cytology during ERCP. DESIGN: Retrospective cohort study. SETTING: Single, tertiary referral hospital in Indianapolis, Indiana. PATIENTS: Consecutive subjects from January 2001 to November 2004 who underwent EUS-FNA of a PBS documented by ERCP. INTERVENTIONS: EUS-FNA of PBS. MAIN OUTCOME MEASURES: Performance of EUS-FNA, with the final diagnosis determined by surgical pathology study or the results of EUS-FNA and follow-up. RESULTS: A total of 291 biliary strictures undergoing EUS were identified. Of these, 26 (9%) had PBSs and 2 were excluded. EUS-FNA was not attempted in 1 because no mass was visualized. The second had a PBS seen on magnetic resonance cholangiopancreatography, but no ERCP was performed. Twenty-four patients (14 men; mean age, 68 years) underwent EUS-FNA of a PBS following ERCP brush cytology studies that were either negative/nondiagnostic (20) or unable to be performed (4). EUS visualized a mass in 23 (96%) patients, including 13 in whom previous imaging detected no lesion. EUS-FNA (median, 4 passes; range, 1-11) demonstrated malignancy in 17 of 24 (71%) patients with findings showing adenocarcinoma (15), lymphoma (2), atypical cytology (3), or benign cells (4). No complications were noted. Pathology results from 8 of 24 (33%) patients who underwent surgery showed hilar cholangiocarcinoma (6), gallbladder cancer (1), and a benign, inflammatory stricture (1). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS-FNA were 77% (95% confidence interval [CI], 54%-92%), 100% (95% CI, 15%-100%), 100% (95% CI, 83%-100%), 29% (95% CI, 4%-71%), and 79% (95% CI, 58%-93%), respectively. LIMITATIONS: Histopathologic correlation of EUS-FNA findings was limited to 8 of 24 (33%) patients who underwent surgery. CONCLUSIONS: EUS-FNA is a sensitive method for the diagnosis of PBSs following negative results or unsuccessful ERCP brush cytology. The low negative predictive value does not permit reliable exclusion of malignancy following a negative biopsy.     

Assessment of complications of EUS-guided fine-needle aspiration

BACKGROUND: EUS-guided fine-needle aspiration (EUS-FNA) permits both morphologic and cytologic analysis of lesions within or adjacent to the GI tract. Despite increasing use of this technique, the safety and overall complication rates remain poorly defined. METHODS: During a period of 20 months, 322 consecutive patients underwent EUS-FNA in 2 centers. All procedures were performed with the patients under general anesthesia. All complications (including local complications resulting from endoscopy/aspiration or clinical complications after the procedure) were evaluated. Potential risk factors for the development of complications were also analyzed including site and nature of the lesion, presence of portal hypertension, and number of needle passes. RESULTS: A total of 345 lesions were aspirated in 322 patients. EUS-FNA involved the pancreas in 248 cases. Pancreatic lesions included solid (134) and cystic (114) types, which required a mean of 2.5 and 1.4 needle passes, respectively. Complications were observed in 4 (1.2%) patients after aspiration of pancreatic cystic lesions (acute pancreatitis, n = 3; aspiration pneumonia, n = 1) and all cases of pancreatitis resulted from FNA of lesions in the head/uncinate process. No complications resulted from FNA of solid pancreatic lesions. Complications were not observed after FNA of lymph nodes (n = 62) and one case of aspiration pneumonia was observed after FNA of a stromal tumor. EUS-FNA was performed without complication in 16 patients (5%) with portal hypertension. The number of needle passes was not predictive of complications. CONCLUSIONS: Because the overall risk of complications from EUS-FNA was relatively low (1.6%) with no severe or fatal incidents and although the risk appears slightly higher than that for standard EUS alone, the safety of EUS-FNA appears acceptable based on this analysis from an experienced center.     

The rate of false-positive results with EUS-guided fine-needle aspiration

BACKGROUND: The aims of this study were to determine the rate of false-positive diagnosis with EUS-guided fine-needle aspiration and to identify factors contributing to this type of error. METHODS: The records of 577 patients undergoing EUS-guided fine-needle aspiration were reviewed and a subset of 188 patients with malignant cytology who underwent surgery was identified. Operative histopathology was compared with EUS-guided fine-needle aspiration cytopathology and false-positive cases were identified. An experienced cytopathologist, who was not involved with the original interpretation of the specimens, reviewed these cases to identify any factor(s) contributing to the errors. RESULTS: Three cases of false-positive diagnosis were identified (1.6%; 95% CI [0.3%, 4.6%]). By aspiration site, the false-positive rates were as follows: pancreas 2/39 (5.1%), 95% CI [0.6%, 17.3%]; lymph nodes 1/136 (0.7%), 95% CI [0.02%, 4.0%]; and other sites 0/13, 95% CI [0.0%, 24.7%]. In both instances of a false-positive diagnosis for a pancreatic aspiration cytologic specimen, interpretative errors were identified. The false-positive interpretation of cytologic material aspirated from a lymph node occurred in a patient without any evidence for malignancy at surgery. In 111 patients with confirmed esophageal, gastric, or rectal malignancy undergoing EUS-guided fine-needle aspiration of nonperitumoral lymph nodes, there was no false-positive diagnosis, suggesting that specimen contamination by luminal tumor is rare. CONCLUSION: The overall rate of false-positive diagnosis for EUS-guided fine-needle aspiration is similar to that reported for other modalities. Most false-positive diagnoses are caused by interpretation errors.     

Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma

BACKGROUND: Preoperative identification of lymph node metastases associated with esophageal carcinoma may influence treatment. EUS is the most accurate method for locoregional staging of these tumors. The impact of EUS-guided fine-needle aspiration (EUS-FNA) on lymph node staging in esophageal carcinoma is unclear. METHODS: From May 1996 to May 1999, 74 patients with esophageal carcinoma underwent preoperative EUS. After October 1998 EUS-guided FNA was performed on nonperitumoral lymph nodes greater than 5 mm in width. The results of EUS with and without FNA were retrospectively reviewed and compared. Final diagnosis was based on surgical results or EUS-guided FNA malignant cytology. Ten of the 74 patients had to be excluded for lack of lymph node stage confirmation. Final diagnosis was obtained in the remaining 64 patients (33 from the EUS only group and 31 from the EUS-FNA group). RESULTS: The results of EUS versus EUS-FNA for lymph node staging were sensitivity 63% versus 93% (p = 0.01), specificity 81% versus 100% (not significant), and accuracy 70% versus 93% (p = 0.02), respectively. Complications comprised 1 patient who developed self-limited bleeding after dilation that did not preclude completion of the EUS (1%, 95% CI [0%, 7%]). CONCLUSIONS: EUS-FNA is more sensitive and accurate than EUS alone for preoperative staging of locoregional and celiac lymph nodes associated with esophageal carcinoma. EUS-FNA of nonperitumoral lymph nodes in patients with esophageal carcinoma is safe and should be routinely performed when treatment decisions will be affected by nodal stage.     

Detection of pancreatic metastases by EUS-guided fine-needle aspiration

BACKGROUND: Metastases to the pancreas are usually found incidentally. Tissue diagnosis is imperative because imaging alone is incapable of differentiating them from primary pancreatic tumors. This study tested whether it is possible to differentiate metastases from other focal pancreatic lesions by using EUS-guided fine-needle aspiration (EUS-FNA) for cytodiagnosis. METHODS: One hundred fourteen consecutive patients (mean age 61 years) with focal pancreatic masses, detected on CT, underwent EUS-FNA by using a linear-array echoendoscope and 22-gauge needles. RESULTS: Adequate specimens were obtained from 112 lesions. Carcinomas were identified in 68 cases (60.7%), 56 (50%) of pancreatic origin and 12 (10.7%) from distant primary tumors. The metastases were all located in the head and body of the pancreas and measured 1.8 to 4.0 cm. The echo-texture was heterogeneous or hypoechoic in all cases and resembled that of primary tumors. Six of the 12 patients with metastatic disease had a prior diagnosis of cancer (breast, 3; renal cell, 2; salivary gland, 1), 4 of them with a recurrence and 2 with a second carcinoma metastasizing to the pancreas. Six patients without a prior diagnosis of cancer had metastases from renal cell, colonic, ovarian, and esophageal carcinomas; one metastasis was from an unknown primary and another was from a malignant lymphoma. These findings influenced the therapeutic strategy in 8 patients who underwent nonsurgical palliation. There were no complications. CONCLUSIONS: Pancreatic metastasis is an important cause of focal pancreatic lesions, but the EUS features are not diagnostic. Simultaneous EUS-FNA allows cytodiagnosis and can have a decisive influence on the selection of appropriate therapeutic strategies.     

Predictors of malignancy and recommended follow-up for patients with negative endoscopic ultrasound-guided fine-needle aspiration of suspected pancreatic lesions

BACKGROUND:

Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) can characterize and diagnose pancreatic lesions as malignant, but cannot definitively rule out the presence of malignancy. Outcome data regarding the length of follow-up in patients with negative or nondiagnostic EUS-FNA of pancreatic lesions are not well-established.

OBJECTIVE:

To determine the long-term outcome and provide follow-up guidance for patients with negative EUS-FNA diagnosis of suspected pancreatic lesions based on imaging predictors.

METHODS:

A retrospective review of patients undergoing EUS-FNA for suspected pancreatic lesions, but with negative or nondiagnostic FNA results was conducted at a tertiary care referral medical centre. Patient demographics, EUS imaging characteristics and follow-up data were examined.

RESULTS:

Seventeen of 55 patients (30.9%) with negative/nondiagnostic FNA were subsequently diagnosed with pancreatic malignancy. The risk of cancer was significantly higher for patients who had associated lymph nodes on EUS (P<0.001) and vascular involvement on EUS (P=0.001). The mean time to diagnosis in the group with false-negative EUS-FNA diagnosis was 66 days. The true-negative EUS-FNA patients were followed for a mean of 403 days after negative EUS-FNA results without the development of malignancy.

CONCLUSION:

For patients undergoing EUS-FNA for a suspected pancreatic lesion, a negative or nondiagnostic FNA does not provide conclusive evidence for the absence of cancer. Patients for whom vascular invasion and lymphadenopathy are detected on EUS are more likely to have a true malignant lesion and should be followed closely. When a patient has been monitored for six months or more with no cancer being diagnosed, there appears to be much less chance that a pancreatic malignancy is present.     

Diagnosis of recurrent rectal carcinoma by EUS-guided fine-needle aspiration

BACKGROUND: Endoscopic mucosal resection has become a popular alternative for the treatment of early-stage neoplasia of the gastrointestinal tract. However, there are still no data on the frequency of bacteremia associated with this form of treatment. METHODS: We conducted a prospective study of 21 men and 17 women undergoing endoscopic mucosal resection with a cap-fitted panendoscope for upper gastrointestinal lesions. Blood cultures were performed before, 10 minutes after, and 4 hours after the procedure for both aerobic and anaerobic bacteria. RESULTS: Blood culture at baseline was negative in all the patients. Two of 38 patients (5.3 %) had positive blood culture at 10 minutes after the procedure. The isolated microorganisms were Streptococcus salivarius and Corynebacterium species. All patients had negative blood cultures 4 hours later. None of these 38 patients had any symptoms or signs associated with infection. CONCLUSIONS: Bacteremia associated with endoscopic mucosal resection is infrequent and transient.     

A prospective evaluation of the incidence of bacteremia associated with EUS-guided fine-needle aspiration

BACKGROUND: Endoscopic ultrasound (EUS)--guided fine-needle aspiration (FNA) is frequently performed for diagnostic evaluation of lesions in or near the gastrointestinal (GI) tract. Little data exist concerning possible infectious complications associated with EUS-guided FNA. This prospective evaluation was undertaken to determine the frequency of bacteremia and infectious complications associated with EUS-guided FNA. METHODS: All patients undergoing EUS-guided FNA for any indication were enrolled in this study. Patients who required antibiotic prophylaxis as per the American Heart Association or American Society for Gastrointestinal Endoscopy guidelines were excluded from the study as were patients with cystic lesions, patients with advanced liver disease/ascites and those with human immunodeficiency virus/acquired immune deficiency syndrome. Blood cultures were obtained 30 and 60 minutes after the EUS-FNA. Patients were monitored for evidence of infection after procedure including telephone follow-up of each subject 1 week after procedure. RESULTS: One hundred patients underwent EUS-FNA of 108 lesions. All blood cultures were negative except in 6 patients in whom 1 of 2 bottles were positive for coagulase negative Staphylococcus, which was considered a contaminant. There were no complications of acute febrile illness, abscess or other infections. CONCLUSION: EUS-guided FNA was not associated with bacteremia or infectious complications.     

EUS-guided fine-needle aspiration combined with flow cytometry and immunocytochemistry in the diagnosis of lymphoma

BACKGROUND: Limited information is available regarding the use of EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of lymphoproliferative disorders. The aim of this study was to evaluate the yield of this technique in the primary diagnosis of lymphoma. METHODS: The records were reviewed of 38 consecutive patients with GI lesions and/or enlarged lymph nodes identified on imaging studies that raised a suspicion of lymphoma who underwent EUS-FNA of lymph nodes or the gut wall. Final diagnosis was based on clinical follow-up, imaging studies, or surgical findings. RESULTS: Twenty-three patients with lymphoma and 15 patients with benign disease or reactive lymphadenopathy were identified. The overall sensitivity, specificity, and accuracy of EUS-FNA cytology with flow cytometry/immunocytochemistry (FC/IC) for the diagnosis of lymphoma were, respectively, 74%, 93%, and 81%. When comparing patients who had EUS-FNA with FC/IC versus those who had EUS-FNA without FC/IC, sensitivity was 86% versus 44% (p = 0.04), specificity was 100% versus 90% (not significant), and accuracy was 89% versus 68% (not significant). CONCLUSION: EUS-FNA can provide cytology specimens diagnostic for lymphoma. Selective use of FC/IC in patients with suspected lymphoma improves the yield of EUS-FNA and may guide diagnostic evaluation and treatment decisions.     

Endoscopic ultrasound-guided fine-needle aspiration in patients with lymphadenopathy suspected of recurrent malignancy after curative treatment

Background  The diagnosis of lymphadenopathy after treatment of malignancy is sometimes difficult, especially in patients whose treatment was deemed curative and without local recurrence or those who have increased serum levels of related tumor markers. We aimed to evaluate the effectiveness of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a diagnostic tool in patients with lymphadenopathy after curative treatment of malignancy. Methods  Consecutive patients with mediastinal, intraabdominal, or pelvic lymphadenopathy after curative treatment of malignancy who were referred to our hospital between October 2003 and September 2007 were enrolled in this study. Results  A total of 62 patients were included. The lymph nodes were located at the mediastinum in 22 patients, intraabdomen in 38 patients, and intrapelvis in 2 patients. From the pathological findings of the FNA sample, 31 patients (50%) were confirmed to have recurrence of the prior malignancy, and 9 patients (15%) were diagnosed as having a different new malignancy. The remaining 22 patients (35%) were shown to have no recurrence or no other malignancies. However, 1 of them was later diagnosed with recurrence by open laparotomy. The overall sensitivity, specificity, accuracy, and positive and negative predictive values of the EUS-FNA were 97%, 100%, 98%, 100%, and 97%, respectively. Conclusions  Lymphadenopathy after treatment of malignancy is not a definitive sign of recurrence. Therefore, pathological sampling and diagnosis are essential for determining the appropriate treatment. For this purpose, EUS-FNA is a safe, convenient, and minimally invasive procedure with high diagnostic value.     

Diagnosis of granulocytic sarcoma by fine-needle aspiration cytology

Granulocytic sarcoma (GS) occurs in patients with chronic myeloproliferative disorders as well as in patients with acute myeloid leukemia (AML). These tumorous masses can occur anywhere in the body and have to be differentiated from lymphoma, carcinoma or infectious processes. We report the results of fine-needle aspiration cytology (FNAC) in 26 patients with GS. Seventeen patients suffered from AML and 9 from chronic myeloid leukemia (CML) blast crisis. In 5 patients with AML, GS was the initial presentation of hematological malignancy, in the remaining 21 patients, FNAC confirmed relapse of AML or extramedullary blast crisis of CML. In 8 patients, GS was located in the skin, in 17 in the lymph node and in another patient in the spinal canal. This study demonstrates the clinical utility and diagnostic accuracy of FNAC in the evaluation of GS from multiple sites.