Lee McHenry

Comparison of Endoscopic Ultrasonography and Multidetector Computed Tomography for Detecting and Staging Pancreatic Cancer

Context Clinicians often use multidetector computed tomography or endoscopic ultrasonography to detect and stage pancreatic cancer. Contribution This prospective study found that, among 80 adults with proven pancreatic cancer, the sensitivity of multidetector computed tomography and endoscopic ultrasonography for detecting a pancreatic mass was 86% (CI, 77% to 93%) and 98% (CI, 91% to 100%), respectively. Among 53 patients undergoing surgery, endoscopic ultrasonography was more accurate for staging local tumor spread, but both tests showed similar accuracy for nodal staging and detecting resectability. Cautions Optimal strategies to detect and stage pancreatic cancer may vary across sites depending on the expertise of radiologists and endosonographers. The Editors In the United States for the year 2003, it was estimated that pancreatic cancer would be diagnosed in approximately 30700 patients and contribute to 30000 deaths (1). Complete surgical removal with negative histologic margins (R0 resection) is an independent predictor of postoperative survival (2-4) and remains the only potential curative treatment for pancreatic cancer. At surgical exploration, however, only 5% to 25% of the tumors are amenable to resection (5-8). Therefore, the principle goal of preoperative evaluation is to identify patients with potentially resectable disease while avoiding surgical exploration in those with unresectable disease. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer. Because of widespread availability, helical computed tomography (CT) is usually the initial study for this indication (9, 10). Dual-phase helical CT, during which postinjection contrast image acquisition is obtained in both the pancreatic (arterial) and portal venous phases, has improved detection rate and assessment of resectability in patients with suspected pancreatic cancer (11, 12). Current state-of-the-art CT imaging uses a multiple-row detector with narrow detector collimation, wide x-ray beam, and rapid table translation; these features offer faster acquisition and thinner image slices compared with single-detector CT (13-15). Whether multidetector CT offers improved detection and staging of pancreatic cancer, however, is unknown. Endoscopic ultrasonography has been shown to be superior to conventional CT for the detection (16-20) and staging (19, 20) of pancreatic cancer. When compared with helical CT, however, endoscopic ultrasonography is reported to be either equivalent for detection (21, 22) or superior for detection or staging (23-25). To date, no comparative studies of multidetector CT with other imaging tests, including endoscopic ultrasonography, for suspected pancreatic cancer have been performed. Therefore, we conducted a prospective trial to compare endoscopic ultrasonography and multidetector CT for the detection, staging, and resectability of suspected locoregional pancreatic cancer. Methods Patients The institutional review board at Indiana University Medical Center approved this study, and all patients signed written informed consent. Eligible patients were referred to our hospital with clinically suspected or recently diagnosed solid or cystic pancreatic cancer within the previous 8 weeks. The referral base for our hospital consists of gastroenterologists and surgeons from Indiana and the surrounding contiguous states. Patients were eligible only if they agreed to undergo endoscopic ultrasonography, CT, and surgery (if necessary) at our institution. Patients were excluded if they had previously undergone endoscopic retrograde cholangiopancreatography or endoscopic ultrasonography at our institution for suspected pancreatic cancer; declined or remained undecided about potential surgical intervention; were referred to our institution by surgeons outside our hospital system. Patients were also excluded if they were pregnant, were incarcerated, could not independently provide informed consent, or were considered high surgical risk (American Society of Anesthesiology class III to V). In addition, we excluded patients with known or suspected periampullary masses, cholangiocarcinomas, or cancer with suspected locally advanced arterial (superior mesenteric, hepatic, or celiac) involvement or metastatic disease (ascites, suspicious liver or pulmonary lesions, distant enlarged lymph nodes) detected by previous imaging studies. Patients with suspected nonocclusive involvement of the superior mesenteric vein or portal vein were considered eligible for enrollment. Study Design This was a prospective, single-center, observational study. All enrolled patients had to respond to an initial health and medical questionnaire, which was followed by same-day endoscopic ultrasonography. Computed tomography was performed within 1 week. Within 3 weeks after CT, a surgeon examined the patient and reviewed the results of endoscopic ultrasonography and CT to determine eligibility for potential resection. After surgery or the decision to pursue nonoperative management, we telephoned patients to assess quality of life at 1 month, 3 months, and every 6 months until death or until 24 months if clinical disease remained stable. Endoscopic Ultrasonography Technique Conscious sedation was performed with various combinations of intravenously administered propofol, meperidine, fentanyl, or midazolam. Initially, we examined all patients with a radial echoendoscope (Olympus GF-UM130 [Olympus America Inc., Melville, New York]). We then examined patients with a linear echoendoscope (using either Pentax FG-36UX [Pentax Precision Instruments, Orangeburg, New York] or Olympus GF-UC140P [Olympus America Inc.]). Unless cancer had been definitively confirmed previously, endoscopic ultrasonographyguided fine-needle aspiration was performed with a 22-gauge needle (Wilson-Cook Medical Inc., Winston-Salem, North Carolina) in all patients, when applicable. A cytotechnologist or cytopathologist was on-site for preliminary interpretations of all aspirations. One of 3 experienced gastroenterologists, each of whom had performed at least 1000 pancreatic examinations, performed all procedures. The operator was not blinded to previous radiographic data. Recorded information included the presence or absence, size, echocharacteristics, location, or locoregional extension of any visualized pancreatic mass, lymph nodes, or distant metastases. Lymph nodes that were not accessible to endoscopic ultrasonographyguided fine-needle aspiration were considered malignant if 3 or more of the following criteria were present: diffuse hypoechoic echogenicity, short-axis diameter of 5 mm or greater, well-defined borders, round shape, or location within 5 mm of the tumor. Well-defined hypoechoic or hyperechoic lesions within the liver with a short-axis diameter of 10 mm or greater and not accessible to fine-needle aspiration were defined as metastases. We considered vascular involvement by the tumor to be present if any 1 of the following were noted: loss of the normal hyperechoic interface between tumor and vessel for at least 5 mm (adherence), irregular tumor and vessel interface, tumor within vessel lumen (invasion), vessel encasement, and perigastric or periduodenal collaterals with associated venous occlusion. Immediately after the examination, any visualized mass was designated by the endosonographer as surgically resectable or unresectable and assigned a tumor, node, metastasis (TNM) staging according to the 1997 American Joint Committee on Cancer (AJCC) classification (Appendix Table) for staging of pancreatic cancer (26). Multidetector CT Technique We performed multidetector CT with a quad-channel scanner (MX 8000 Quad, Philips Medical Systems, Cleveland, Ohio) by using 0.5-second gantry rotation time and acquisition of 4 sections per rotation. All patients drank 500 mL of tap water as nonopaque oral intraluminal contrast media. A total of 150 mL (300 mg of iodine/mL) of low-osmolar contrast media (Isovue-300, Bracco Diagnostics, Princeton, New Jersey) was injected with a power injector (CT Envision Injector, Medrad, Pittsburgh, Pennsylvania) at a rate of 4.0 mL/s into an antecubital vein by using either an 18- or 20-gauge cannula. Examination was performed in a dual-phase mode. Image acquisition was first done during the pancreatic phase (35 seconds after the start of contrast infusion) from the top to the bottom of the pancreas with 4.0-mm beam collimation (nominal section thickness, 1.0 mm; effective section thickness, 1.3 mm), 0.5-mm reconstruction interval, 120 kVp, 205 mAs, and a pitch of 1.0 during a single breath-hold of 15 to 20 seconds. The second phase was performed during the portal venous phase (65 seconds after the start of contrast infusion) from the top of the liver to the iliac crests with 10-mm beam collimation (nominal section thickness, 2.5 mm; effective section thickness, 3.2 mm), 1.3-mm reconstruction interval, 120 kVp, 250 mAs, and a pitch of 0.875 during a single breath-hold of 15 seconds. Multiplanar (2-dimensional) reformatting was not routinely performed; however, when it was used, the entire data set was transferred to a workstation (MX View, Philips Medical Systems) for evaluation. No 3-dimensional (volume rendering) postprocessing was used in this study. One of 3 experienced gastrointestinal radiologists who were blinded to the results of the previous endoscopic ultrasonography examination interpreted all scans. Patient information provided to the interpreting radiologist included presenting symptoms; the size, location, and vascular involvement (if known) of any visualized pancreatic mass from previous CT; and the results of any previous endoscopic retrograde cholangiopancreatography (for example, presence or absence of ductal strictures) or pathology (for example, endoscopic brush cytology). Locoregional and distant adenopathy were considered malignant if they were greater than 10 mm in

A Randomized Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis

BACKGROUND Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). METHODS In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights. RESULTS A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03). CONCLUSIONS Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).

Tissue sampling at ERCP in suspected malignant biliary strictures (Part 2)

Part I of this review in the previous issue of Gastrointestinal Endoscopy outlined the key points of tissue sampling at ERCP and considered intraductal bile aspiration cytology, cytologic/histologic analysis of retrieved plastic biliary stents and fine needle aspiration cytology. Specimen adequacy, slide preparation, and accuracy of slide interpretation, which is often influenced by the interpretation “philosophy” of individual cytopathologists, are fundamental to the effort to optimize cancer detection by using tissue sampling techniques at ERCP. Intraductal bile aspiration is simple and inexpensive but adds little to the other methods, which have higher rates of cancer detection. Therefore, bile aspiration is recommended only when other sampling techniques cannot be used. Cytologic evaluation of material from retrieved plastic biliary stents is relatively insensitive (32%) and impractical as a firstline approach to the diagnosis of malignant biliary obstruction because diagnosis is delayed until the stent is removed. However, it can be considered in patients undergoing stent exchange when other methods of tissue sampling fail to confirm the suspected diagnosis of malignancy. Endoscopic fineneedle aspiration (FNA) cytology has a lower rate of cancer detection (33%) than initially reported and is technically difficult. It is usually used to supplement other simpler methods. Part II of this review considers the remaining tissue sampling methods for use at ERCP: brush cytology, endobiliary forceps biopsy, and the multimodal tissue sampling. Methods for improving diagnostic yield are discussed. BRUSH CYTOLOGY

Large-diameter biliary orifice balloon dilation to aid in endoscopic bile duct stone removal: a multicenter series

BACKGROUND The utility and safety of endoscopic biliary orifice balloon dilation (EBD) for bile duct stone removal (with use of large-diameter balloons) after biliary endoscopic sphincterotomy (BES) is currently not well established. OBJECTIVE Our purpose was to evaluate the efficacy and complications of BES followed by > or = 12 mm diameter EBD for bile duct stone removal. DESIGN Retrospective, multicenter series. SETTING Five ERCP referral centers in the United States. PATIENTS AND INTERVENTIONS Patients who underwent attempted removal of bile duct stones by BES followed by EBD with > or = 12 mm diameter dilating balloons were identified by searching the prospectively recorded endoscopic databases from 1999 to 2007. Clinical parameters, endoscopic data, and outcomes were collected and analyzed. RESULTS One hundred three patients, mean age 70 +/- 17 years (range 23-98 years), with 56 (54%) women, underwent 107 procedures. Eleven patients (11%) had a prior history of acute pancreatitis. Pancreatogram was performed in 15 (14%) patients. Median stone size and median balloon diameter used was 13 mm. Complete stone removal in the first session of EBD was accomplished in 102 (95%) procedures, and mechanical lithotripsy was required in 29 (27%). Six patients (5.4%) had documented procedure-related complications including one patient with severe bleeding and one with severe cystic duct perforation. No acute pancreatitis occurred. CONCLUSION EBD with a large-diameter balloon in conjunction with BES for bile duct stone removal is effective and relatively safe. This technique appears to be a reasonable alternative option when standard BES and basket or balloon sweep are inadequate to remove bile duct stones.

Endoscopic snare papillectomy for tumors of the duodenal papillae

BACKGROUND Tumors of the major and the minor duodenal papillae can be malignant or premalignant, and traditionally are treated by surgical excision. This study evaluated the safety and the outcome of endoscopic snare resection of such tumors. METHODS All patients with tumors of the major or the minor papilla treated by endoscopic snare resection over a 10-year period (1994-2003) were identified from an ERCP database. Patients with tumors that had endoscopic features of malignancy and those proven to be cancerous by biopsy were excluded. Papillectomy was performed by electrosurgical snare resection. A pancreatic stent usually was placed before or after excision. Residual tumor was eradicated by repeated procedures. Endoscopic surveillance was at the discretion of the endoscopist. RESULTS Seventy snare resections were performed in 55 patients (mean age 59 years). Histopathologic diagnoses were the following: adenoma (45 patients; 7 with focal high-grade dysplasia, 6 with intraductal extension), adenocarcinoma (5), carcinoid tumor (2), gastric heterotopia (1), and normal histology (2). Fourteen patients had familial adenomatous polyposis. Of the 39 patients with isolated extraductal adenoma per cholangiogram, two underwent surgical resection because of persistent high-grade dysplasia, and 37 were successfully treated by endoscopic papillectomy alone. During follow-up (mean 30 months), 18 of 37 patients (49%) had no recurrence, 7 had recurrent adenoma (mean time interval to recurrence 27 months), two died of unrelated illnesses, and 10 are awaiting follow-up. Of the 6 patients with intraductal adenoma per cholangiogram, two underwent surgical resection, two had intraductal photodynamic therapy, and two had endoscopic snare resection. Intraductal tumor in the 4 latter patients was eliminated, although it recurred in one of the patients who had photodynamic therapy. Of the 7 patients with adenocarcinoma or carcinoid tumor, pancreaticoduodenectomy was performed in 3 and palliative papillectomy was performed in 4 unsuitable for surgery. One patient with carcinoid tumor of the minor papilla is alive, without recurrence, at 5 years after papillectomy. There were 10 procedure-related complications (14.5%), including pancreatitis (5), bleeding (4), and mild perforation (1). There was no procedure-related death. CONCLUSIONS Most adenomas of the duodenal papillae without intraductal extension can be fully resected by snare papillectomy. However, adenoma recurs in about a third of patients. Endoscopic therapy appears to be a reasonable alternative to surgery for management of papillary tumors. Longer follow-up is needed to determine the true recurrence rate and if endoscopic re-treatments are effective.

Improved stent characteristics for prophylaxis of post-ERCP pancreatitis

BACKGROUND & AIMS Pancreatic stenting is an effective method to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in high-risk patients. This retrospective study evaluated the impact of modified stent characteristics on the rate of post-ERCP pancreatitis, spontaneous stent dislodgment, and stent-related sequelae. METHODS A total of 2283 patients underwent 2447 ERCPs over a 6-year period with placement of 3-4F diameter, unflanged pancreatic stents. The indication for stenting was pancreatitis prophylaxis predominantly in suspected sphincter of Oddi dysfunction (SOD), pancreas divisum therapy, and precut sphincterotomy. An abdominal radiograph was obtained 10-14 days later to assess spontaneous stent passage. Post-ERCP pancreatitis was defined according to established criteria. A total of 479 patients underwent repeat ERCPs after an initial ERCP with pancreatic stent placement. The prestenting pancreatogram was then compared with follow-up studies. RESULTS The pancreatitis rate with 3F, 4F, 5F, and 6F stents was 7.5%, 10.6%, 9.8%, and 14.6%, respectively (3F vs. 4F, 5F, 6F: P = 0.047). Spontaneous stent dislodgment was 86%, 73%, 67%, and 65%, respectively (3F vs. 4F, 5F, 6F: P < 0.0001). The frequency of ductal changes was 24% in patients with 3-4F stents compared with 80% with 5-6F stents. Ductal perforation from the stents occurred in 3 patients (0.1%). CONCLUSIONS Small diameter (3-4F), unflanged pancreatic stents are more effective than the traditionally used stents (5-6F) in preventing post-ERCP pancreatitis. Stent-induced ductal changes and the need for endoscopic removal are also significantly less with 3-4F stents. The 3F stent appears to be superior in all aspects studied. Additional studies are needed to define the ideal method to eliminate post-ERCP pancreatitis.

EUS-guided FNA of pancreatic metastases: a multicenter experience

BACKGROUND Metastatic lesions of the pancreas are a rare but important cause of focal pancreatic lesions. The purpose of this study is to describe the EUS features, cytologic diagnoses, and clinical impact of a cohort of patients with pancreatic metastases diagnosed by EUS-guided FNA (EUS-FNA). METHODS Over a 6-year period, in a retrospective, multicenter study, patients had the diagnosis of pancreatic metastases confirmed with EUS-FNA. All examinations were performed by one of 5 experienced endosonographers. The EUS and the clinical findings of pancreatic metastases were compared with those of a cohort with primary pancreatic malignancy. RESULTS Thirty-seven patients with possible metastases were identified, and 13 were excluded because of diagnostic uncertainty. The remaining 24 underwent EUS-FNA (mean passes 4.1) of a pancreatic mass without complications. Diagnoses included metastases from primary kidney (10), skin (6), lung (4), colon (2), liver (1), and stomach (1) cancer. In 4 (17%), 16 (67%), and 24 (100%) patients, EUS-FNA provided the initial diagnosis of malignancy, tumor recurrence, and pancreatic metastases, respectively. Four (17%) metastases initially were discovered by EUS after negative (n = 3) or inconclusive (n = 1) CT scans. Compared with primary cancer, pancreatic metastases were more likely to have well-defined margins (46% vs. 4%) compared with irregular (94% vs. 54%; p < 0.0001) margins. No statistically significant difference between the two populations was noted for tumor size, echogenicity, consistency, location, lesion number, or number of FNA passes performed. CONCLUSIONS Pancreatic metastases are an important cause of focal pancreatic lesions and may occasionally be discovered during EUS examination after previously negative or inconclusive CT. Use of immunocytochemistry, when available, may help to confirm a suspected diagnosis. These lesions are more likely to have well-defined EUS margins compared with primary pancreatic cancer.

Role of EUS for preoperative evaluation of cholangiocarcinoma: a large single-center experience.

BACKGROUND Accurate preoperative diagnosis and staging of cholangiocarcinoma (CCA) remain difficult. OBJECTIVE To evaluate the utility of EUS in the diagnosis and preoperative evaluation of CCA. DESIGN Observational study of prospectively collected data. SETTING Single tertiary referral hospital in Indianapolis, Indiana. PATIENTS Consecutive patients with CCA from January 2003 through October 2009. INTERVENTIONS EUS and EUS-guided FNA (EUS-FNA). MAIN OUTCOME MEASUREMENTS Sensitivity of EUS for the detection of a tumor and prediction of unresectability compared with CT and magnetic resonance imaging (MRI); sensitivity of EUS-FNA to provide tissue diagnosis, by using surgical pathology as a reference standard. RESULTS A total of 228 patients with biliary strictures undergoing EUS were identified. Of these, 81 (mean age 70 years, 45 men) had CCA. Fifty-one patients (63%) had distal and 30 (37%) had proximal CCA. For those with available imaging, tumor detection was superior with EUS compared with triphasic CT (76 of 81 [94%] vs 23 of 75 [30%], respectively; P < .001). MRI identified the tumor in 11 of 26 patients (42%; P = .07 vs EUS). EUS identified CCA in all 51 (100%) distal and 25 (83%) of 30 proximal tumors (P < .01). EUS-FNA (median, 5 passes; range, 1-12 passes) was performed in 74 patients (91%). The overall sensitivity of EUS-FNA for the diagnosis of CCA was 73% (95% confidence interval, 62%-82%) and was significantly higher in distal compared with proximal CCA (81% vs 59%, respectively; P = .04). Fifteen tumors were definitely unresectable. EUS correctly identified unresectability in 8 of 15 and correctly identified the 38 of 39 patients with resectable tumors (53% sensitivity and 97% specificity for unresectability). CT and/or MRI failed to detect unresectability in 6 of these 8 patients. LIMITATION Single-center study. CONCLUSION EUS and EUS-FNA are sensitive for the diagnosis of CCA and very specific in predicting unresectability. The sensitivity of EUS-FNA is significantly higher in distal than in proximal CCA.

Endoscopic ultrasound–guided fine needle aspiration cytology of solid liver lesions: a large single-center experience

OBJECTIVES:The aim of this study was to report the sensitivity, cytological diagnoses, endoscopic ultrasound (EUS) features, complications, clinical impact, and long term follow-up of a large single-center experience with endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) of benign and malignant solid liver lesions.METHODS:A database of cytologic specimens from EUS-FNA was reviewed to identify all hepatic lesions aspirated between January, 1997, and July, 2002. Procedural indications, prior radiographic data, patient demographics, EUS examination results, complications, and follow-up data were obtained and recorded.RESULTS:EUS-FNA of 77 liver lesions in 77 patients was performed without complications. Of these 77 lesions, 45 (58%) were diagnostic for malignancy, 25 (33%) were benign, and seven (9%) were nondiagnostic. A total of 22 lesions were confirmed as negative for malignancy by follow-up (mean 762 days, range 512–1556 days) or intraoperative examination; however, seven lesions could not be classified as benign or malignant. Depending on the status of the seven unclassified lesions, sensitivity of EUS-FNA for the diagnosis of malignancy ranged from 82 to 94%. When compared with benign lesions, EUS features predictive of malignant hepatic masses were the presence of regular outer margins (60% vs 27%; p = 0.02) and the detection of two or more lesions (38% vs 9%; p = 0.03). Of the 42 patients with malignancy identified by EUS-FNA and other available imaging records, EUS detected the malignancy in 41% of patients with previously negative examinations. For the 45 subjects with cytology positive for malignancy, EUS-FNA changed management in 86% of subjects.CONCLUSION:EUS-FNA of the liver is a safe and sensitive procedure that can have a significant impact on patient management. Prospective studies comparing the accuracy and complication rate of EUS-FNA and percutaneous fine needle aspiration (P-FNA) for the diagnosis of liver tumors are needed.

Efficacy of venous reconstruction in patients with adenocarcinoma of the pancreatic head

Pancreaticoduodenectomy is often avoided in patients with portal or superior mesenteric venous involvement due to the perception that venous resection is complex, morbid, and carries a poor longterm survival. Our recent experience using state-of-the-art imaging and strict resection criteria show that venous reconstruction increases operative time, transfusion requirements, intensive care unit stay, and total hospital length of stay, but has no significant impact on operative morbidity rates, mortality rates, or the incidence of positive histologic margins. Kalpan-Meier life table analysis shows similar survival curves when compared to a contemporary cohort of patients who do not undergo venous reconstruction.