In vivo characterization of pancreatic and lymph node tissue by using EUS spectrum analysis: a validation study.

BACKGROUND: Quantitative spectral analysis of the radiofrequency (RF) signals that underlie grayscale EUS images can be used to provide additional, objective information about tissue state. OBJECTIVE: Our purpose was to validate RF spectral analysis as a method to distinguish between (1) benign and malignant lymph nodes and (2) normal pancreas, chronic pancreatitis, and pancreatic cancer. DESIGN AND SETTING: A prospective validation study of eligible patients was conducted to compare with pilot study RF data. PATIENTS: Forty-three patients underwent EUS of the esophagus, stomach, pancreas, and surrounding intra-abdominal and mediastinal lymph nodes (19 from a previous pilot study and 24 additional patients). MAIN OUTCOME MEASUREMENTS: Midband fit, slope, intercept, and correlation coefficient from a linear regression of the calibrated RF power spectra were determined. RESULTS: Discriminant analysis of mean pilot-study parameters was then performed to classify validation-study parameters. For benign versus malignant lymph nodes, midband fit and intercept (both with t test P < .058) provided classification with 67% accuracy and area under the receiver operating curve (AUC) of 0.86. For diseased versus normal pancreas, midband fit and correlation coefficient (both with analysis of variance P < .001) provided 93% accuracy and an AUC of 0.98. For pancreatic cancer versus chronic pancreatitis, the same parameters provided 77% accuracy and an AUC of 0.89. Results improved further when classification was performed with all data. LIMITATIONS: Moderate sample size and spatial averaging inherent to the technique. CONCLUSIONS: This study confirms that mean spectral parameters provide a noninvasive method to quantitatively discriminate benign and malignant lymph nodes as well as normal and diseased pancreas.

Characterization of pancreatic cancer and intra-abdominal lymph node malignancy using spectrum analysis of endoscopic ultrasound imaging.

This study assessed the ability of spectral analysis of endoscopic ultrasound (EUS) RF signals acquired in humans in vivo to distinguish between (1) benign and malignant intraabdominal and mediastinal lymph nodes and (2) pancreatic cancer, chronic pancreatitis, and normal pancreas. Mean midband fit, slope, intercept, and correlation coefficient from a linear regression of the calibrated RF power spectra were computed over regions of interest defined by the endoscopist. Linear discriminant analysis was then performed to develop a classification of the resulting spectral parameters. For lymph nodes, classification based on the midband fit and intercept provided 67% sensitivity, 82% specificity, and 73% accuracy for malignant vs. benign nodes. For pancreas, classification based on midband fit and correlation coefficient provided 95% sensitivity, 93% specificity, and 93% accuracy for diseased vs. normal pancreas and 85% sensitivity, 71% specificity, and 85% accuracy for pancreatic cancer vs. chronic pancreatitis. These promising results suggest that mean spectral parameters can provide a non-invasive method to quantitatively characterize pancreatic cancer and lymph malignancy in vivo.

Creation of an effective and reproducible nonsurvival porcine model that simulates actively bleeding peptic ulcers.

BACKGROUND: Efforts to develop improved endoscopic therapeutic methods for upper GI bleeding require an effective animal model. OBJECTIVE: To develop a nonsurvival porcine model that simulates acute peptic ulcer bleeding. DESIGN: Prospective animal (porcine) study. SETTING: Animal laboratory. INTERVENTIONS: A surgical seromyotomy was created along the external surface of the greater curvature of the stomach in anesthesized pigs. A submucosal plane was developed and the gastroepiploic bundle, in continuity, was placed adjacent to the mucosa, and the seromuscular tissues were re-approximated over the vascular bundle. By using EGD, a needle-knife with electrocautery was then used to incise the mucosal tissue overlying the vascular bundle. Standard endoscopic methods for bleeding control were then tested in this animal model. MAIN OUTCOME MEASUREMENTS: To evaluate whether successful bleeding that simulates submucosal arterial bleeding from peptic ulcer disease could be achieved in a porcine animal model. RESULTS: Successful simulation of active peptic ulcer bleeding was achieved with this nonsurvival porcine model in a total of 5 sequential pigs. Other porcine models for bleeding were tested and found to be unsatisfactory. Hemoclips and combination injection-thermal therapy were used to stop bleeding over Doppler-positive areas, with subsequent endoscopic nonimaging Doppler US probe examination of the ulcer bed revealing a negative Doppler signal. LIMITATIONS: This was an animal laboratory study. Further human studies would be ideal once any future endoscopic interventions are proven to be safe in animals. CONCLUSIONS: This active bleeding ulcer model can be used to develop future endoscopic therapies and for training purposes.

EUS spectrum analysis for in vivo characterization of pancreatic and lymph node tissue: a pilot study.

BACKGROUND: EUS is limited by variability in the examiner's subjective interpretation of B-scan images to differentiate among normal, inflammatory, and malignant tissue. By using information otherwise discarded by conventional EUS systems, quantitative spectral analysis of the raw radiofrequency (RF) signals underlying EUS images enables tissue to be characterized more objectively. OBJECTIVE: Our purpose was to determine the feasibility of using spectral analysis of EUS data for characterization of pancreatic tissue and lymph nodes. DESIGN AND SETTING: A pilot study of eligible patients was conducted to analyze the RF data obtained during EUS by using spectral parameters. PATIENTS: Twenty-one subjects who underwent EUS of the esophagus, stomach, pancreas, and surrounding intra-abdominal and mediastinal lymph nodes. MAIN OUTCOME MEASUREMENTS: Linear regression parameters of calibrated power spectra of the RF signals were tested to differentiate normal pancreas from chronic pancreatitis and from pancreatic cancer as well as benign from malignant-appearing lymph nodes. RESULTS: The mean intercept, slope, and midband fit of the spectra differed significantly among normal pancreas, adenocarcinoma, and chronic pancreatitis when all were compared with each other (P < .01). On direct comparison, mean midband fit for adenocarcinoma differed significantly from that for chronic pancreatitis (P < .05). For lymph nodes, mean midband fit and intercept differed significantly between benign- and malignant-appearing lymph nodes (P < .01 and P < .05, respectively). LIMITATIONS: Small sample population and spatial averaging inherent to this technique. CONCLUSIONS: Mean spectral parameters in EUS imaging can provide a noninvasive method to discriminate normal from diseased pancreas and lymph nodes.

EUS-guided FNA diagnostic yield of malignancy in solid pancreatic masses: a benchmark for quality performance measurement.

BACKGROUND: The diagnostic yield of EUS-guided FNA (EUS-FNA) of solid pancreatic masses is a potential benchmark for EUS-FNA quality, because the majority of EUS-FNA of solid pancreatic masses should be diagnostic for malignancy. OBJECTIVES: To determine the cytologic diagnostic rate of malignancy in EUS-FNA of solid pancreatic masses and to determine if variability exists among endoscopists and centers. DESIGN: Multicenter retrospective study. PATIENTS: EUS centers provided cytology reports for all EUS-FNAs of solid, noncystic, >or=10-mm-diameter, solid pancreatic masses during a 1-year period. MAIN OUTCOME MEASUREMENT: Cytology diagnostic of pancreatic malignancy. RESULTS: A total of 1075 patients underwent EUS-FNA at 21 centers (81% academic) with 41 endoscopists. The median number of EUS-FNA of solid pancreatic masses performed during the year per center was 46 (range, 4-177) and per endoscopist was 19 (range, 1-97). The mean mass dimensions were 32 x 27 mm, with 73% located in the head. The mean number of passes was 3.5. Of the centers, 90% used immediate cytologic evaluation. The overall diagnostic rate of malignancy was 71%, 95% confidence interval 0.69%-0.74%, with 5% suspicious for malignancy, 6% atypical cells, and 18% negative for malignancy. The median diagnostic rate per center was 78% (range, 39%-93%; 1st quartile, 61%) and per endoscopist was 75% (range, 0%-100%; 1st quartile, 52%). LIMITATIONS: Retrospective study, participation bias, and varying chronic pancreatitis prevalence. CONCLUSIONS: (1) EUS-FNA cytology was diagnostic of malignancy in 71% of solid pancreatic masses and (2) endoscopists with a final cytologic diagnosis rate of malignancy for EUS-FNA of solid masses that was less than 52% were in the lowest quartile and should evaluate reasons for their low yield.

Endoscopic Doppler ultrasound versus endoscopic stigmata-directed management of acute peptic ulcer hemorrhage: a multimodel cost analysis.

Recurrent bleeding from acute peptic ulcer hemorrhage is problematic. Studies have shown that Doppler ultrasound (DOP-US) is useful in decreasing rebleeding. We analyzed associated costs and outcomes to better define the role of DOP-US versus Conventional (Forrest classification endoscopic stigmata) in the management of acute peptic ulcer bleeding. Two separate decision analyses were constructed. Recurrent bleeding, failed esophagogastroduodenoscopy (EGD) hemostasis, complications, and surgery rates were derived from medical literature. Costs were based on Medicare data. DOP-US is preferred over Conventional in acute peptic ulcer bleeding with average cost savings per patient ranging from 853 dollars (decision-tree modeling) to 1,160 dollars (Monte Carlo simulation). High-dose intravenous proton-pump inhibitors lowered rates of recurrent bleeding for both Conventional and DOP-US, resulting in a lower but still persistent average cost savings per patient for DOP-US (decision-tree modeling = 328 dollars, Monte Carlo simulation = 560 dollars). This decision analyses identified DOP-US as the preferred cost-minimizing strategy in acute peptic ulcer hemorrhage. Results of cost analyses were most dependent on hospitalization costs and recurrent bleeding rates.

A primer on natural orifice transluminal endoscopic surgery: building a new paradigm.

Access to the abdominal cavity is required for diagnostic and therapeutic endeavors for a variety of medical and surgical diseases. Historically, abdominal access has required a formal laparotomy to provide adequate exposure. Natural orifice transluminal endoscopic surgery (NOTES) is an emerging experimental alternative to conventional surgery that eliminates abdominal incisions and incision-related complications by combining endoscopic and laparoscopic techniques to diagnose and treat abdominal pathology. During NOTES, commercially available flexible video endoscopes are used to create a controlled transvisceral incision via natural orifice access to enter the peritoneal cavity. Common incision-related complications such as wound infections, incisional hernias, postoperative pain, aesthetic disdain, and adhesions could be minimized or eliminated by NOTES. NOTES has evolved from more than 2 centuries of technological innovations and continued growth in the field of surgical endoscopy. Innovative surgical endoscopists have slowly developed means to surpass the constraints of the gastrointestinal lumen by using a flexible endoscope. The future of surgical endoscopy may be the shared entity of NOTES, which further integrates endoscopy, gastroenterology, and minimally invasive and general surgery. Although the promise of NOTES is electrifying to surgeons and endoscopists, several key issues need to be characterized prior to the incorporation of NOTES into routine practice. This article reviews the status, contemporary body of literature, limitations, and potential future implications accompanying the development of NOTES.

Probabilistic reporting of EUS-FNA cytology: Toward improved communication and better clinical decisions.

BACKGROUND: The objectives of this study were to determine threshold probabilities needed to perform endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and those needed to treat patients suspected of having malignancy and then to compare these thresholds to the pre- and posttest probabilities of malignancy associated with benign, atypical, suspicious, and malignant diagnoses. The goal was to aid endoscopists in making appropriate clinical decisions based on both quantitative and qualitative approaches. METHODS: The study included 633 consecutive patients. A decision tree was constructed to estimate the "treatment" threshold. Using treatment threshold and likelihood ratios, the authors determined the "no-test-test" and "test-treatment" thresholds. Pretest probability was compared with no-test-test and test-treatment thresholds, and the post-EUS-FNA probability of malignancy for each diagnostic category with the treatment threshold. Results were stratified by lesion site, lesion size, and cytopathologist. RESULTS: EUS-FNA has a wide range of pretest probabilities within which it could be performed (0.06-0.98). The posttest probabilities for malignancy, 0.99 (95% confidence interval [CI], 0.967-0.996) and 0.09 (95% CI, 0.057-0.126), after a positive or a negative result, respectively, were significantly different from the treatment threshold but not those of suspicious, 0.92 (95% CI, 0.767-0.994) diagnosis. The posttest probability of atypical diagnosis, 0.60 (95% CI, 0.407-0.772), was not significantly different from that of pretest probability. Results did not vary by lesion size, organ site, or cytopathologist. CONCLUSION: The authors demonstrated the uncertainty associated with EUS-FNA diagnostic categories and used the threshold approach to qualify quantitatively the decision to perform EUS-FNA and the decision to treat patients suspected of having malignancy.

Expandable metal biliary stents before pancreaticoduodenectomy for pancreatic cancer: a Monte-Carlo decision analysis.

BACKGROUND & AIMS: Endoscopic placement of plastic or self-expandable metal biliary stents (SEMS) relieves obstructive jaundice from pancreatic cancer. Short-length, distally placed SEMS do not preclude subsequent pancreaticoduodenectomy. We sought to determine whether SEMS placement in patients whose surgical status is uncertain is cost-effective for management of obstructive jaundice. METHODS: A Markov model was constructed to evaluate costs and outcomes associated with endoscopic biliary stenting for obstructive jaundice. Strategies evaluated were: (1) initial plastic stent with plastic stents for subsequent occlusions in nonsurgical candidates after staging (plastic followed-up by [f/u] plastic), (2) initial plastic with subsequent SEMS (plastic f/u metal), (3) initial short-length SEMS with subsequent plastic (metal f/u plastic), and (4) initial short-length SEMS with subsequent expandable metal stent (metal f/u metal). Published stent occlusion rates, ERCP complication rates and outcomes, cholangitis rates and outcomes, pancreatic cancer mortality rates, and Whipple complication rates were used. Costs were based on 2004 Medicare standard allowable charges and were accrued until all patients reached an absorbing health state (death or pancreaticoduodenectomy) or 24 cycles (24 mo) ended. RESULTS: Average costs per patient from Monte Carlo simulation were: (1) metal f/u metal, $19,935; (2) plastic f/u metal, 20,157 dollars; (3) metal f/u plastic, 20,871 dollars; and (4) plastic f/u plastic, 20,878 dollars. For initial plastic stents to be preferred over short-length metal stents, 70% or more of pancreatic cancers would need to be potentially resectable by pancreaticoduodenectomy. CONCLUSIONS: In patients undergoing ERCP before definitive cancer staging, short-length SEMS is the preferred initial cost-minimizing strategy.

Endoscopic ultrasound-guided fine-needle aspiration in patients with non-small cell lung cancer and prior negative mediastinoscopy.

BACKGROUND: Mediastinoscopy and endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) are complementary for staging non-small cell lung cancer (NSCLC) patients. We assessed (1) the yield of EUS-FNA of malignant lymph nodes in NSCLC patients with combined anterior and posterior lymph nodes that had already undergone mediastinoscopy and (2) the cost implications associated with alternative initial strategies. METHODS: All patients underwent chest computed tomography (CT) and/or positron emission tomography (PET), and mediastinoscopy. Then, the posterior mediastinal stations (7, 8, and 9) or station 5 were targeted with EUS-FNA. The reference standard included thoracotomy with complete thoracic lymphadenectomy, repeat clinical imaging, or long-term clinical follow-up. A Monte Carlo cost-analysis model evaluated the expected costs and outcomes associated with staging of NSCLC. RESULTS: Thirty-five NSCLC patients met inclusion criteria (median age 65 years; 80% men). Endoscopic ultrasound-guided FNA was performed in 53 lymph nodes in various stations, the subcarinal station (7) being the most common (47.3%). Of the 35 patients who had a prior negative mediastinoscopy, 13 patients (37.1%) had malignant N2 or N3 lymph nodes. Accuracy of EUS-FNA (98.1%) was significantly higher than that of CT (41.5%; p < 0.001) and PET (40%; p < 0.001). Initial EUS-FNA resulted in average costs per patient of 1,867 dollars (SD +/- 4,308 dollars) while initial mediastinoscopy cost 12,900 dollars (SD +/- 4,164.40 dollars). If initial EUS-FNA is utilized rather than initial mediastinoscopy, an average cost saving of 11,033 dollars per patient would result. CONCLUSIONS: In patients with NSCLC and combined anterior and posterior lymph nodes, starting with EUS-FNA would preclude mediastinoscopy in more than one third of the patients. Endoscopic ultrasound-guided FNA is a safe outpatient procedure that is less invasive and less costly than mediastinoscopy.

Endoscopic ultrasound-guided fine needle aspiration of mediastinal lymph node in patients with suspected lung cancer after positron emission tomography and computed tomography scans.

BACKGROUND: The treatment of patients with non-small cell lung cancer (NSCLC) depends on the stage. Positron emission and computed tomography (CT) scans can identify suspicious lymph nodes that require biopsy. We prospectively evaluated the yield and accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in sampling mediastinal lymph nodes and compared its accuracy to that of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and CT in staging NSCLC. METHODS: A consecutive series of patients with suspicious nodes on PET or CT scan in the posterior mediastinal lymph node stations (#5, 7, 8, or 9) were prospectively evaluated by EUS-FNA. The reference standard included thoracotomy with complete lymphadenectomy in patients with lung cancer or if EUS-FNA was benign, repeat clinical imaging, or long-term follow-up. RESULTS: There were 104 patients (63 men) with 125 lesions (117 lymph nodes, 8 left adrenal glands) who underwent EUS-FNA. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS-FNA were 92.5%, 100%, 100%, 94%, and 97%, respectively. EUS-FNA was more accurate and had a higher positive predictive value than the PET or CT (p < 0.001) scan in confirming cancer in the posterior mediastinal lymph nodes. EUS-FNA documented metastatic cancer to the left adrenal in all 4 patients with advanced disease. No deaths resulted from EUS-FNA. One patient experienced self-limited stridor. CONCLUSIONS: EUS-FNA is a safe, accurate, and minimally invasive technique that improves the staging of patients with NSCLC. It is more accurate and has a higher predictive value than either the PET scan or CT scan for posterior mediastinal lymph nodes.

A cost-minimization analysis of alternative strategies in diagnosing pancreatic cancer.

BACKGROUND: Several modalities currently exist for tissue confirmation of suspected pancreatic cancer prior to therapy. Since there is a paucity of cost-minimization studies comparing these different biopsy modalities, we analyzed costs and examined effectiveness of four alternative strategies for diagnosing pancreatic cancer. METHODS: A decision analysis model of patients with suspected pancreatic cancer was constructed. We analyzed costs, failure rate, testing characteristics, and complication rates of four commonly employed diagnostic modalities: 1) computerized tomography or ultrasound-guided fine-needle aspiration (CT/US-FNA), 2) endoscopic retrograde cholangiopancreatography with brushings (ERCP-B), 3) Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA), and 4) laparoscopic surgical biopsy. If the first attempt with a particular modality failed, a different modality was employed to identify the most preferable secondary biopsy strategy. RESULTS: This analysis identifies EUS-FNA as the preferred initial modality for the diagnosis of pancreatic cancer. Resultant expected costs and strategies in decreasing optimality include: 1) EUS-FNA (1,405 dollars), 2) ERCP-B (1,432 dollars), 3) CT/US-FNA (3,682 dollars), and 4) surgery (17,711 dollars). If a patient presents with obstructive jaundice, decision analysis modeling resulted in a total expected costs of 1,970 dollars if ERCP-B is successful at the time of biliary stent placement. Additional analyses to identify the preferred follow-up modality after a failed alternative method showed that EUS-FNA is the preferred secondary modality if any of the other three modalities failed first, in both the setting of and absence of obstructive jaundice. One- and two-way sensitivity analysis of the variables shows unchanged results over an acceptable range. CONCLUSIONS: This cost-minimization study illustrates that EUS-FNA is the best initial and the preferred secondary alternative method for the diagnosis of suspected pancreatic cancer. In addition to local expertise and availability, costs and diagnostic yield should be considered when choosing an optimal diagnostic strategy.

Diagnosis of gastrointestinal tract lesions by endoscopic ultrasound-guided fine-needle aspiration biopsy.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) allows detailed imaging of both intramural and extramural structures of the gastrointestinal (GI) tract and also allows tissue samples to be obtained from masses and lesions in the GI tract. The objective of the current study was to determine the diagnostic utility of EUS-FNA in evaluating intramural and extramural GI tract lesions. METHODS: The authors evaluated all EUS-FNA specimens of GI tract lesions obtained over a 30-month period (from August 2000 to February 2003). Samples of pancreatic and intrabdominal/mediastinal lymph nodes were excluded from the study. A single endosonographer performed all procedures. An attending cytopathologist also was present on site to assess specimen adequacy. Cytologic diagnoses were analyzed for correlations with final diagnoses, which were based on histologic examination of biopsied/resected pathology materials and/or clinical follow-up findings. RESULTS: Sixty-two EUS-FNA specimens of intramural and extramural GI tract lesions were obtained from a total of 60 patients. The mean patient age was 58.8 years (standard deviation, 15.3 years). Thirty-six patients (60%) were male, and 24 (40%) were female. Twenty-eight patients had surgical pathologic evaluation of the corresponding lesions. The remaining 32 patients were followed clinically for a mean duration of 9.5 months (standard deviation, 7.7 months). The anatomic sites of the lesions were as follows: esophagus in 23 patients (37%), stomach in 13 patients (21%), duodenum in 15 patients (24%), and rectum/sigmoid in 11 patients (18%). It is noteworthy that 29 patients (43%) previously had experienced unsuccessful attempts at tissue diagnosis by endoscopic forceps biopsy. Of the 62 EUS-FNA specimens, 43, 4, and 15 were reported as being positive for a neoplasm, suspicious, and benign, respectively. Neoplastic lesions included carcinoma (n = 24), gastrointestinal stromal tumor (GIST; n = 18), neuroendocrine neoplasm (n = 2), and lymphoma (n = 1). There were two cases of endometriosis, three foregut duplication cysts, and one case of diverticulosis. There were two lesions that yielded false-negative findings (one gastric lymphoma and one GIST) secondary to sampling or interpretive error. There also were three cases that yielded false-positive findings (one case of endometriosis, one case of duodenal diverticula with smooth muscle hyperplasia, and one case of normal pancreas, which presented as a periduodenal mass). The sensitivity, specificity, and diagnostic accuracy of EUS-FNA in diagnosing GI tract neoplastic lesions were 89%, 88%, and 89%, respectively. CONCLUSIONS: EUS-FNA provides accurate tissue diagnosis in a wide variety of extraintestinal mass lesions and intramural GI tumors, particularly in patients for whom previous endoscopic forceps biopsy was unsuccessful in establishing a diagnosis.

Endoscopic ultrasound-guided fine needle aspiration is superior to lymph node echofeatures: a prospective evaluation of mediastinal and peri-intestinal lymphadenopathy.

BACKGROUND AND OBJECTIVE: The additional diagnostic value of endoscopic ultrasound-fine needle aspiration (EUS-FNA) over lymph node (LN) echofeatures alone in evaluating lymphadenopathy is unknown. The objectives of this study are (1) to prospectively evaluate the utility of EUS-FNA in evaluating mediastinal or peri-intestinal lymphadenopathy and to compare its yield to that of echofeatures alone and (2) to determine clinical and endosonographic features predictive of malignant involvement of LNs. METHODS: All consecutive patients who underwent EUS-FNA of a LN over a 22-month period were prospectively evaluated. Reference standard for final diagnosis included: surgery (n = 76), long-term clinical and/or imaging follow-up (n = 74), or death from disease (n = 26). RESULTS: One hundred and eighty-three EUS-FNAs of LNs were performed in 137 patients with no major complications. Locations of the biopsied LNs included 31% subcarinal, 21% celiac, 21% peripancreatic, 13% periesophageal, 4.4% aortopulmonary window, 3.2% perigastric, and 3.3% perirectal. Mean LN size was 20.5 mm (SD +/- 11.1) x 13.2 mm (SD +/- 7.97). The mean number of EUS-FNA passes was three (range 1-7). The sensitivity, specificity, PPV, and NPV of EUS-FNA of LNs were 98.3%, 100%, 100%, and 98.4%, respectively. EUS-FNA was more accurate compared to LN echofeatures alone (99.4%vs 75.4%, p < 0.001). Mediastinal LNs were 2.77 times less likely to be malignant as compared to other LN locations. In multivariable analysis, the number of LN echofeatures, site of LN, and patient's age were associated with malignant involvement (p= 0.001). CONCLUSIONS: EUS-FNA is superior to LN echofeatures in evaluating lymphadenopathy. Endosonographic LN features alone are particularly unreliable in the mediastinum, necessitating tissue confirmation. EUS-FNA can safely, reliably, and accurately sample mediastinal and peri-intestinal LNs obviating the need for more invasive testing or surgical intervention.

EUS-guided FNA of the left adrenal gland in patients with thoracic or GI malignancies.

BACKGROUND: The diagnostic yield and safety of trans-gastric EUS-guided FNA of the left adrenal gland are not well defined. METHODS: All patients with an enlarged left adrenal gland on abdominal imaging and known or suspected malignancy referred to two EUS centers over a 3-year period were included in this study. EUS-guided FNA was performed on an outpatient basis by one of 4 experienced endosonographers. RESULTS: Thirty-one consecutive patients (21 men, 10 women; mean age 64.8 years) were evaluated. Tissue adequate for interpretation was obtained in all patients; no attempt to obtain tissue was unsuccessful. The median number of needle passes was 4.5 (range 1-8). No immediate complications were encountered. EUS-guided FNA confirmed malignant left adrenal involvement in 42% (13/31) of the patients. Patients with malignant left adrenal masses were more likely to have known cancer at another site (OR 12.0: 95% CI[1.6, 87.9]). Patients with benign masses were more likely to have preservation of the normal sonographic appearance of the adrenal gland ("seagull" configuration) compared with those with malignant masses (OR 9.8: 95% CI[1.9, 51.0]). The accuracy of EUS imaging based on size (> or =3 cm) alone was 81%: 95% CI[63, 93]). Of the patients with malignant adrenal masses, 85% (11/13) died or their clinical condition deteriorated during follow-up, while 15% (2/13) were being treated and were stable clinically. CONCLUSIONS: EUS-guided FNA of the left adrenal gland is a minimally invasive, safe, and highly accurate method that confirms or excludes malignant adrenal involvement in patients with thoracic or GI malignancies.

Endoscopic ultrasound-guided fine needle aspiration biopsy of suspected cholangiocarcinoma.

BACKGROUND AND AIMS: Despite advances in endoscopic techniques for sampling bile duct strictures, the diagnosis of cholangiocarcinoma remains a challenge. The purpose of this study was to evaluate the yield of EUS-FNA and its impact on patient management for patients with suspected cholangiocarcinoma. METHODS: All patients undergoing EUS for the evaluation of suspected malignant biliary strictures were prospectively evaluated over a 23-month period. A single gastroenterologist performed all EUS-FNAs in the presence of a cytopathologist. Reference standard for final diagnosis included surgery, death from disease, and clinical and/or imaging follow-up. RESULTS: Twenty-eight patients (mean age 67 years [SD +/- 11], 72% male) were evaluated. Most patients (91%) presented with obstructive jaundice, and all except 1 had nondiagnostic sampling of the biliary lesions either at ERCP (88%), percutaneous transhepatic cholangiogram (n = 2), and/or computed tomography-guided biopsy (n = 1). Sixty-seven percent (14/21) had no definitive mass seen on prior abdominal imaging studies. The mean tumor size by EUS was 19 mm x 16 mm with a median number of passes to diagnosis of 3 (range 1-7). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 86%, 100%, 100%, 57%, and 88%, respectively. EUS-FNA had a positive impact on patient management in 84% of patients: preventing surgery for tissue diagnosis in patients with inoperable disease (n = 10), facilitating surgery in patients with unidentifiable cancer by other modalities (n = 8), and avoiding surgery in benign disease (n = 4). CONCLUSIONS: Given the apparent accuracy and safety of EUS with FNA for imaging bile duct mass lesions and for obtaining a tissue diagnosis in patients with suspected cholangiocarcinoma, this technology may represent a new approach to diagnosis especially when other methods fail. The ability to obtain a definite diagnosis has a significant impact on patient management.

Comparison of ThinPrep and conventional preparations in pancreatic fine-needle aspiration biopsy.

Use of ThinPrep preparation for fine-needle aspiration biopsy (FNA) is gaining popularity. However, there may be a difference in the morphology and the operating characteristics between ThinPrep and conventional methods. The objective of this study was to compare the accuracy of the two methods and to address the pitfalls of ThinPrep preparation in pancreatic FNA. A computer search identified 67 pancreatic FNAs with both conventional smears and ThinPrep preparation during a 19-mo period. These cases, obtained under endoscopic ultrasound-guidance, consisted of 47 malignant neoplasms (44 ductal carcinomas, two mucinous neoplasms, and one islet cell tumor) and 20 benign lesions. Direct smears were prepared first and the remaining material was then put into PreservCyt Solution for ThinPrep slides. All slides were reviewed and the cytologic diagnoses were correlated with histologic and clinical follow-up. Five conventional and 16 ThinPrep specimens were unsatisfactory due to insufficient cellularity. These cases were excluded from the analysis. Among the 62 cases evaluated by conventional preparation, 77% (34) were diagnosed as positive and 14% (seven) atypical/suspicious by conventional smears. For the 51 ThinPrep specimens, 58% (22) were interpreted as positive and 31% (12) atypical/suspicious. The sensitivity, specificity, and accuracy of diagnosing a malignancy were 77%, 100%, and 84% for conventional smears and 58%, 100%, and 67% for ThinPrep preparation, respectively. There were no false positives with either method. However, three benign lesions were interpreted as atypical/suspicious with ThinPrep preparation because of the presence of single atypical cells with distinct nucleoli. One of the two mucinous neoplasms was incorrectly diagnosed with ThinPrep preparation because of lack of mucin. The diagnostic accuracy of pancreatic FNA using ThinPrep is inferior to that of conventional smears. This may be partly due to the use of split sample technique resulting in scant cellularity in ThinPrep preparation and partly due to the differences in morphology between the two preparations. Therefore, the current morphologic criteria may need modification for ThinPrep preparation in pancreatic FNA.

Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with suspected pancreatic cancer: diagnostic accuracy and acute and 30-day complications.

OBJECTIVES: The aims of this study were to evaluate the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with suspected pancreatic cancer, and to assess immediate, acute, and 30-day complications related to EUS-FNA. METHODS: All patients with suspected pancreatic cancer were prospectively evaluated. A single gastroenterologist performed all EUS-FNAs in the presence of a cytopathologist. Immediate complications were evaluated in all patients. An experienced nurse called patients 24-72 h and 30 days after the procedure. Reference standard for the classification of the final diagnosis included: surgery (n = 48), clinical or imaging follow-up (n = 63), or death from the disease (n = 47). RESULTS: A total of 158 patients (mean age 62.3 yr) underwent EUS-FNA during the study period. The mean tumor size was 32 x 26 mm. The median number of passes was three (range one to 10). Of these patients, 44% had at least one failed attempt at tissue diagnosis before EUS-FNA. The sensitivity, specificity, PPV, NPV, and accuracy of EUS-FNA in solid pancreatic masses were 84.3%, 97%, 99%, 64%, and 84%, respectively. Immediate self-limited complications occurred in 10 of the 158 EUS-FNAs (6.3%). Of 90 patients contacted at 24-72 h, 78 patients (87%) responded. Of the 90 patients, 20 (22%) reported at least one symptom, all of which were minor except in three cases (one self-limited acute pancreatitis and two emergency room visits, one of which led to admission). In all, 83 patients were contacted at 30 days, and 82% responded. No additional or continued complications were reported. CONCLUSIONS: EUS-FNA is highly accurate in identifying patients with suspected pancreatic cancer, especially when other modalities have failed. Major complications after EUS-FNA are rare, and minor complications are similar to those reported for upper endoscopy. It seems that follow-up at 1 wk might capture all of the adverse events related to EUS-FNA.

Yield of endoscopic ultrasound-guided fine-needle aspiration biopsy in patients with suspected pancreatic carcinoma.

BACKGROUND: Although atypical or suspicious cytology may support a clinical diagnosis of a malignancy, it is often not sufficient for the implementation of therapy in patients with pancreatic carcinoma. Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is a relatively new method for obtaining cytology samples, and one that may decrease the number of atypical/suspicious diagnoses. The goals of the current study were to prospectively evaluate the yield of EUS-FNAB in the diagnosis of patients presenting with solid pancreatic lesions and to evaluate the significance of atypical, suspicious, and false-negative aspirates. METHODS: All patients who presented with a solid pancreatic lesion and underwent EUS-FNAB over a 13-month period were included in the current study. One endoscopist performed all EUS-FNABs. On-site evaluation of specimen adequacy by a cytopathologist was available for each case. Follow-up included histologic correlation (n = 21) and clinical and/or imaging follow-up (n = 80), including 38 patients who died of the disease. RESULTS: EUS-FNABs were obtained from 101 patients (mean age, 62 +/- 11.8 years; age range, 34-89 years). The male-to-female ratio was 2:1. Sixty-five percent of the lesions were located in the head of the pancreas, 12% were located in the uncinate, 17% were located in the body, and 6% were located in the tail. The mean size of the tumors was 3.3 cm (range, 1.3-7 cm). A median of 4 needle passes were performed (range, 1-11 needle passes). Sixty-two biopsies (61.4%) were interpreted as malignant on cytologic evaluation, 5 (5%) as suspicious for a malignancy, 6 (5.9%) as atypical/indeterminate, and 26 (25.7%) as benign processes. Of the 76 malignant lesions, 71 were adenocarcinomas, 3 were neuroendocrine tumors, 1 was a lymphoma, and 1 was a metastatic renal cell carcinoma. All except one of the suspicious/atypical aspirates were subsequently confirmed to be malignant. Agreement was complete for the atypical cases. Among the suspicious cases, 2 of the 5 were identified as carcinoma by one cytopathologist and as suspicious lesions by the other, yielding a 40% disagreement rate between the 2 cytopathologists. Therefore, for the 10 atypical or suspicious cases that later were confirmed to be malignant, the final diagnosis of malignant disease was not made due to scant cellularity that could be attributed to sampling error in 8 cases and to interpretative disagreement in 2 cases (20%). All four false-negative diagnoses were attributed to sampling error. Two percent of all biopsies were inadequate for interpretation. Of the 99 adequate specimens, 72 yielded true-positive results, 23 yielded true-negative results, and 4 yielded false-negative results. No false-positives were encountered. Therefore, the sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNAB for solid pancreatic masses were 94.7% (95% confidence interval [CI], 89.7-99.8%), 100%, 100%, and 85.2% (95% CI, 71.8-98.6%), respectively. CONCLUSIONS: EUS-FNAB is a safe and highly accurate method for tissue diagnosis of patients with solid pancreatic lesions. Patients with suspicious and atypical EUS-FNAB aspirates deserve further clinical evaluation.