Kathleen McGreevy

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

EUS-guided ethanol versus saline solution lavage for pancreatic cysts: a randomized, double-blind study

BACKGROUND Surgery for pancreatic cysts is associated with significant morbidity. A pilot study previously demonstrated the safety of EUS-guided ethanol lavage of pancreatic cysts. OBJECTIVE To determine whether EUS-guided ethanol lavage would decrease pancreatic cyst size more than saline solution lavage. DESIGN Prospective, multicenter, randomized trial. SETTING Two tertiary referral hospitals in the United States. PATIENTS Patients referred for EUS with a 1- to 5-cm unilocular pancreatic cyst were randomized to blinded ethanol or saline solution lavage. Three months later, the cyst diameter was remeasured by EUS, and a second unblinded ethanol lavage was performed. INTERVENTIONS EUS-guided pancreatic cyst lavage. MAIN OUTCOME MEASUREMENTS Cyst ablation based on size changes from follow-up EUS, CT, and histology of resected specimens. RESULTS Of 58 patients randomized, 16 were excluded and 42 underwent initial ethanol (n = 25) or saline solution (n = 17) lavage. Ethanol lavage resulted in a greater mean percentage of decrease in cyst surface area (-42.9; 95% CI, -58.4 to -27.4) compared with saline solution alone (-11.4; 95% CI, -25.0 to 2.2; P = .009). Nineteen (76.0%) of 25 and 14 (82.3%) of 17 patients randomized to ethanol and saline solution, respectively, underwent a second ethanol lavage. A follow-up CT scan demonstrated resolution in 12 (33.3%) of 36 cysts. Histology of 4 resected cysts demonstrated epithelial ablation ranging from 0% (saline solution alone) to 50% to 100% (1 or 2 ethanol lavages). Complication rates were similar in all groups. LIMITATION Short-term follow-up. CONCLUSIONS EUS-guided ethanol lavage results in a greater decrease in pancreatic cyst size compared with saline solution lavage with a similar safety profile. Overall CT-defined complete pancreatic cyst ablation was 33.3%.

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.

Nurse-administered propofol sedation compared with midazolam and meperidine for EUS: a prospective, randomized trial

BACKGROUND The utility of nurse-administered propofol sedation (NAPS) compared with midazolam and meperidine (M/M) for EUS is not known. OBJECTIVE To compare recovery times, costs, safety, health personnel, and patient satisfaction of NAPS and M/M for EUS. DESIGN Prospective, randomized, single-blinded trial. SETTING Tertiary-referral hospital in Indianapolis, Indiana. PATIENTS Outpatients referred for EUS. INTERVENTIONS Sedation with M/M or NAPS. The patient and recovery nurse were blinded; however, the sedating nurse, endoscopist, and recording research nurse were unblinded to the sedatives used. A capnography, in addition to standard monitoring, was used. A questionnaire and visual analog scale assessed patient, endoscopist, and sedating nurse satisfaction. MAIN OUTCOME MEASUREMENTS Recovery times, costs, safety, health personnel, and patient satisfaction in both groups. RESULTS Eighty consecutive patients were randomized to NAPS (n = 40) or M/M (n = 40). More patients in the propofol group were current tobacco users; patient demographics, procedures performed, mean procedure length, and the overall frequency of adverse events were otherwise similar. Compared with M/M, NAPS was associated with a faster induction of sedation (2.3 vs 5.7 minutes, respectively; P = .001) and full recovery time (29 vs 49 minutes, respectively; P = .001), higher postprocedure patient satisfaction, and quicker anticipated return to baseline function. At discharge, total costs (recovery plus medications) were similar between the propofol (

EUS-guided Trucut biopsy of suspected nonfocal chronic pancreatitis

406) and M/M groups (

A prospective, randomized study of EUS-guided celiac plexus neurolysis for pancreatic cancer: one injection or two?

399; P = .79). LIMITATION Low-risk patient population. CONCLUSIONS Compared with M/M, NAPS for an EUS offered a faster sedation induction and full recovery time, higher postprocedure patient satisfaction, and a quicker anticipated return to baseline function. Total costs were similar between the groups.

Utility of a repeated EUS at a tertiary-referral center

BACKGROUND The diagnosis of early chronic pancreatitis (CP) is difficult, and the role of EUS-FNA cytology for this indication remains unclear. The aim of this study is to determine the utility and the safety profile of EUS-guided Trucut biopsy (EUS-TCB) for the histologic diagnosis of suspected nonfocal CP. METHODS After radial EUS, patients with suspected CP (> or =3 EUS criteria) underwent attempted transgastric EUS-TCB of the pancreas. Histopathologic specimens were examined by one pathologist and were classified as nondiagnostic, normal pancreas, and probable or definite CP. Within 1 week after EUS, ERCP was performed by an endoscopist blinded to the EUS results. The severity of CP by ERCP was stratified by the Cambridge classification. Agreement between tests for the diagnosis of CP was evaluated by a kappa statistic. RESULTS Of 45 patients screened, 15 declined and 30 (12 men and 18 women, mean age 44 years) underwent diagnostic EUS. Of these, 18 (60%) had suspected CP and 16 underwent attempted biopsy. Calcific pancreatitis in two patients precluded EUS-TCB. EUS-TCB results were as follows: probable CP (1), normal pancreas (8), nondiagnostic (6), device malfunction (1). Complications after EUS-TCB occurred in two patients with normal pancreatic biopsies were the following: acute pancreatitis (1) and abdominal pain without pancreatitis (1), both of whom were hospitalized and discharged within 23 hours. Six patients refused ERCP and two (per protocol) did not undergo ERCP. For the remaining 22, agreement between diagnostic EUS and ERCP was moderate (kappa, 0.40). Agreement between EUS and ERCP with EUS-TCB were poor (kappa, 0) and fair (kappa, 0.25), respectively. CONCLUSIONS Transgastric EUS-TCB of suspected nonfocal CP infrequently demonstrates histologic CP in clinically suspected disease. Because of potential complications and limited diagnostic yield, this technique is not currently recommended for evaluation of these patients.

A prospective randomized trial of 1 versus 2 injections during EUS-guided celiac plexus block for chronic pancreatitis pain

BACKGROUND The technique of alcohol injection during EUS-guided celiac plexus neurolysis (CPN) in patients with pancreatic cancer-related pain has not been standardized. OBJECTIVE To compare pain relief and safety of alcohol given as 1 versus 2 injections during EUS-guided CPN (EUS-CPN). Secondary outcomes examined were characteristics that predict response and survival. DESIGN Single-blinded, prospective, randomized, parallel-group study. SETTING Tertiary-care center. PATIENTS This study involved patients with pancreatic cancer-related pain. INTERVENTION EUS-CPN done by injecting 20 mL of 0.75% bupivacaine and 10 mL 98% alcohol into 1 or 2 sites at the celiac trunk. Participants were interviewed by telephone at 24 hours and weekly thereafter. MAIN OUTCOME MEASUREMENTS Time until onset of pain relief, duration of pain relief, complications. RESULTS Fifty patients (mean age 63 years; 24 men) were enrolled and randomized (29 in 1-injection, 21 in 2-injections groups). Pain relief was observed in 37 (74%) patients: 20 (69%) in the 1-injection group and 17 (81%) in the 2-injection group (chi-square P = .340). Median onset of pain relief was 1 day for both 1-injection (range 1-28 days) and 2-injection (range 1-21 days) groups (Mann-Whitney P = .943). Median duration of pain relief in the 1-injection and 2-injection groups was 11 weeks and 14 weeks, respectively (log-rank P = .612). Complete pain relief was observed in 4 (8%) patients total, 2 in each group. There were no long-term complications. LIMITATIONS Single-blinded study. CONCLUSION There were no differences in onset or duration of pain relief when either 1 or 2 injections were used. There was no difference in safety or survival between the 2 groups.

Nurse-Administered Propofol Sedation for Upper Endoscopic Ultrasonography

BACKGROUND The utility of a repeated EUS by experts is not known. OBJECTIVE To define the utility of a repeated EUS for the same indication. DESIGN A retrospective case series. SETTING Tertiary-referral hospital in Indianapolis, Indiana. PATIENTS Consecutive subjects, with and without cancer, who, between January 2000 and September 2006, underwent an initial EUS elsewhere within 6 and 12 weeks of a repeated EUS at our hospital. INTERVENTIONS A repeated EUS. MAIN OUTCOME MEASUREMENTS Clinical impact of a repeated EUS. RESULTS Of 8936 EUS examinations, 73 repeated procedures (0.8%) were identified, and 24 were excluded. The 49 initial EUS procedures (26 men, median age 59 years) were done in Indiana (n = 44) or another state (n = 5) by one of 15 physicians in private practice (n = 48) or at a teaching hospital (n = 1). An EUS-guided FNA (EUS-FNA) was performed during an initial EUS in 21 patients (no biopsy diagnostic for cancer) and was not attempted in 14 patients. The principle indication for a repeated EUS (n = 35) was for an EUS-FNA after the initial tissue sampling was benign, nondiagnostic, or not done. A second EUS had no clinical impact in 18 patients (37%). In the remaining 31 patients (63%), a repeated EUS provided a new or changed clinical diagnosis (n = 12), the initial diagnosis of primary pancreatic cancer (n = 5) or GI stromal tumor (GIST) (n = 1) after a previous nondiagnostic biopsy; or the initial diagnosis of primary (n = 4) or metastatic (n = 2) pancreatic cancer, metastatic esophageal cancer (n = 1), hilar cholangiocarcinoma (n = 1), GIST (n = 1), or pancreatic neuroendocrine tumor (n = 1), or an initial aspiration of a pancreatic cyst (n = 3) after a previous EUS-FNA was not able to be performed. LIMITATIONS A retrospective design; a small number of nonpancreatic indications. CONCLUSIONS In this study, a repeated EUS at a tertiary-referral center had a clinical impact in 63% of patients when performed by experts for a similar clinical indication.

EUS-FNA of Recurrent Postoperative Extraluminal and Metastatic Malignancy

BACKGROUND The efficacy of 1-injection versus a 2-injections method of EUS-guided celiac plexus block (EUS-CPB) in patients with chronic pancreatitis is not known. OBJECTIVE To compare the clinical effectiveness and safety of EUS-CPB by using 1 versus 2 injections in patients with chronic pancreatitis and pain. The secondary aim is to identify factors that predict responsiveness. DESIGN A prospective randomized study. INTERVENTIONS EUS-CPB was performed by using bupivacaine and triamcinolone injected into 1 or 2 sites at the level of the celiac trunk during a single EUS-CPB procedure. MAIN OUTCOME MEASUREMENTS Duration of pain relief, onset of pain relief, and complications. RESULTS Fifty [corrected] subjects were enrolled (23 received 1 injection, 27 [corrected] received 2 injections). The median duration of pain relief in the 31 responders was 28 days (range 1-673 days). [corrected] Fifteen [corrected] of 23 (65%) [corrected] subjects who received 1 injection [corrected] had relief from pain compared with 16 of 27 (59%) [corrected] subjects who received 2 injections [corrected] (P = .67). [corrected] The median times to onset in the 1-injection and 2-injections groups were 21 and 14 days, respectively (P = .99). No correlation existed between duration of pain relief and time to onset of pain relief or onset within 24 hours. Age, sex, race, prior EUS-CPB, and smoking or alcohol history did not predict duration of pain relief. LIMITATION Telephone interviewers were not blinded. CONCLUSIONS There was no difference in duration of pain relief or onset of pain relief in subjects with chronic pancreatitis and pain when the same total amount of medication was delivered in 1 or 2 injections during a single EUS-CPB procedure. Both methods were safe.