Treatment of clinical T2N0M0 esophageal cancer.

BACKGROUND: Management of clinical T2N0M0 (cT2N0M0) esophageal cancer remains controversial. We reviewed our institutional experience over 21 years (1990-2011) to determine clinical staging accuracy, optimal treatment approaches, and factors predictive of survival in this patient population. METHODS: Patients with cT2N0M0 esophageal cancer determined by endoscopic ultrasound (EUS) were identified through a prospectively collected database. Demographics, perioperative data, and outcomes were examined. Cox regression model and Kaplan-Meier plots were used for statistical survival analysis. RESULTS: A total of 731 patients underwent esophagectomy, of whom 68 cT2N0M0 patients (9 %) were identified. Fifty-seven patients (84 %) had adenocarcinoma. Thirty-three patients (48.5 %) were treated with neoadjuvant chemoradiation followed by surgery, and 35 underwent surgical resection alone. All resections except one included a transthoracic approach with two-field lymph node dissection. Thirty-day operative mortality was 2.9 %. Only 3 patients (8.5 %) who underwent surgery alone had T2N0M0 disease identified by pathology: the disease of 15 (42.8 %) was found to be overstaged and 17 (48.5 %) understaged after surgery. Understaging was more common in poorly differentiated tumors (p = 0.03). Nine patients (27.2 %) had complete pathologic response after chemoradiotherapy. Absence of lymph node metastases (pN0) was significantly more frequent in the neoadjuvant group (29 of 33 vs. 21 of 35, p = 0.01). Median follow-up was 44.2 months. Overall 5-year survival was 50.8 %. On multivariate analysis, adenocarcinoma (p = 0.001) and pN0 after resection (p = 0.01) were significant predictors of survival. CONCLUSIONS: EUS was inaccurate in staging cT2N0M0 esophageal cancer in this study. Poorly differentiated tumors were more frequently understaged. Adenocarcinoma and absence of lymph node metastases (pN0) were independently predictive of long-term survival. pN0 status was significantly more common in patients undergoing neoadjuvant therapy, but long-term survival was not affected by neoadjuvant therapy. A strategy of neoadjuvant therapy followed by resection may be optimal in this group, especially in patients with disease likely to be understaged.

Performance characteristics of molecular (DNA) analysis for the diagnosis of mucinous pancreatic cysts.

BACKGROUND: Diagnosis of mucinous pancreatic cysts (MPCs) is challenging due to the poor sensitivity of cytology provided by EUS-guided-FNA (EUS-FNA). OBJECTIVE: To quantify the test characteristics of molecular (DNA) analysis in suspected low-risk MPCs. DESIGN: A prospective cohort study performed in between 2008 and 2011. SETTING: Academic referral center. PATIENTS: Consecutive patients who underwent EUS-FNA of suspected MPCs. INTERVENTION: EUS-FNA and molecular (DNA) analysis of cyst fluid. MAIN OUTCOME MEASUREMENTS: The sensitivity and specificity of molecular analysis in the diagnosis of MPCs using the criterion standard of surgical pathology in resected cysts. RESULTS: Patients with suspected MPCs underwent EUS-FNA and cyst fluid DNA analysis. Surgical resection was performed in 48 patients (17%), confirming a mucinous pathology in 38 (79%). In this group, molecular analysis had a sensitivity of 50% and a specificity of 80% in identifying MPCs (accuracy of 56.3%). The combination of molecular analysis with cyst fluid carcinoembryonic antigen (CEA) and cytology resulted in higher MPC diagnostic performance than either one of its individual components, with a sensitivity, specificity, and accuracy of 73.7%, 70%, and 72.9%, respectively. There was no significant difference in accuracy between molecular analysis and CEA/cytology in this group. LIMITATIONS: Single-center experience. CONCLUSION: Molecular analysis aids in the diagnosis of MPCs when cytology is nondiagnostic or cyst fluid is insufficient for CEA or its level is indeterminate. Our results do not support the routine use of molecular analysis, which should be used selectively after review of imaging findings and cyst fluid studies. Further studies are needed to assess DNA's performance in malignant cysts.

Utility of EUS-guided biopsy of extramural pelvic masses.

BACKGROUND: The diagnostic utility of EUS-guided FNA (EUS-FNA) and EUS-guided Trucut biopsy (EUS-TCB) of pelvic masses has not been well described. OBJECTIVE: To evaluate the utility of EUS in the diagnosis of pelvic masses. DESIGN: Retrospective cohort study. SETTING: Single tertiary referral hospital in Indianapolis, Indiana. PATIENTS: Consecutive patients referred for EUS evaluation of pelvic mass from January 2002 to July 2009. Patients with newly diagnosed rectal cancer or a known/suspected intramural mass were excluded. INTERVENTIONS: EUS-FNA and/or EUS-TCB. MAIN OUTCOME MEASUREMENTS: Endosonographic features and cytological and pathological findings were evaluated. The final diagnosis was confirmed by surgical pathology or cytology and clinical follow-up. The sensitivities and specificities of EUS-TCB were calculated in a subset of patients with available surgical pathology. RESULTS: A total of 69 patients were identified, and 40 with intramural lesions (n = 36) or incomplete follow-up (n = 4) were excluded. The remaining 29 patients (15 men, mean age 58.5 ± 10.8 years) with pelvic masses (mean size 40.8 ± 20.1 mm) were evaluated. EUS-FNA or EUS-TCB helped to make the diagnosis in 25 of 29 patients (86%). Compared with surgical pathology (available in 17 patients), EUS-FNA had a sensitivity of 88% (95% CI, 53%-98%) and specificity of 100% (95% CI, 65%-100%) for malignancy. EUS-TCB alone had a sensitivity of 67% (95% CI, 21%-94%) and specificity of 100% (95% CI, 34%-100%) for malignancy, but the combination of EUS-FNA and EUS-TCB had a sensitivity of 100% (95% CI, 68%-100%) and a specificity of 100% (95% CI, 68%-100%). Complications after EUS-FNA included a pelvic abscess in 2 patients (7%) with a cystic pelvic mass. LIMITATION: Single-center study. CONCLUSION: EUS-FNA and EUS-TCB are sensitive for the diagnosis of malignancy in pelvic masses. Sampling of cystic masses in this region is discouraged.

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

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.

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 Trucut biopsy of gastrointestinal mesenchymal tumor.

BACKGROUND: Data on the utility of endoscopic ultrasound-guided Trucut biopsy (EUS-TCB) for suspected gastrointestinal mesenchymal tumor (GIMT) are limited. This study aimed to determine the diagnostic yield and complications from EUS-TCB for GIMT. METHODS: Consecutive patients with suspected upper gastrointestinal or rectal GIMT from the muscularis propria with a maximal diameter of 20 mm or more were enrolled in a prospective, single-center cohort. An EUS-TCB was performed when on-site fine-needle aspiration (FNA) cytology review of the lesion was deemed suboptimal. Gastrointestinal stromal tumor (GIST) and leiomyoma were defined by the presence or absence of positive immunochemistry (IC) for c-kit, respectively. All GIMTs with a nondiagnostic IC were considered as unspecified. The outcomes assessed included diagnostic pathologic and IC yield (when tested) and procedural complications. RESULTS: In this study, 38 patients (24 women; median age, 62 years) with suspected GIMT (median maximal diameter, 42 mm; range, 20-120 mm) in the esophagus (n=6), stomach (n=28), duodenum (n=3), or rectum (n=1) underwent EUS-TCB without complications. Final diagnoses included GIST for 20 patients, leiomyoma for 13 patients, unspecified GIMT for 3 patients, and unknown disorder for 2 patients. An EUS-FNA was performed for 33 (87%) of the 38 patients, a diagnostic final cytology for 25 (76%) of 33 patients, and an FNA-IC for 12 (50%) of 24 patients. The EUS-TCB (median, 3 passes; range, 1-8 passes) obtained a visible tissue specimen in 37 (97%) of the 38 patients, with a median overall maximal fragment length of 3.5 mm (range, 0-15 mm). The diagnostic final TCB histology and TCB-IC were obtained, respectively, in 79 and 97% of the samples tested. CONCLUSIONS: In this cohort, EUS-TCB provided diagnostic histology and IC for 79 and 97% of the patients, respectively. For the initial biopsy of GIMT, EUS-TCB may be considered an acceptable alternative to EUS-FNA.

Survival in patients with pancreatic cancer after the diagnosis of malignant ascites or liver metastases by EUS-FNA.

BACKGROUND: The expected survival after the EUS-FNA diagnosis of malignant ascites or liver metastases from pancreatic cancer is not known. OBJECTIVE: To report overall and 1-year survival in these patients. DESIGN: Retrospective cohort series. SETTING: Tertiary referral hospital. PATIENTS: Consecutive subjects with newly diagnosed pancreatic cancer from June 1998 and March 2008 in whom EUS-FNA of the liver or ascitic fluid confirmed hepatic metastases or malignant ascites. INTERVENTIONS: Calculation of survival after diagnosis by using the Social Security Death Index. MAIN OUTCOME MEASUREMENTS: Survival after EUS-FNA diagnosis of stage IV pancreatic cancer. RESULTS: EUS-FNA identified liver metastases and malignant ascites from primary pancreatic cancer in 75 and 13 patients, respectively, and all 88 died during follow-up. For all 88 patients, the 1-year survival rate and median survival were 3.4% (95% CI, 1.1%-10.4%) and 82 days (range 2-754 days), respectively. The 1-year survival rates for those with liver metastases (4.0% [95% CI, 1.3%-12.1%]) and for those with malignant ascites (0% [95% CI, 0-24.7%]) were similar (P = 1.0). The median survival for patients with liver metastases of 83 days (range 2-754 days) was similar to that for those with malignant ascites (64 days; range 2-153 days) (P = .13). No clinical variable considered predicted survival of more than, less than, or 3 months. LIMITATIONS: Retrospective series with variable treatment for malignancy. CONCLUSIONS: In patients with pancreatic cancer, identification of malignant ascites or liver metastases by EUS-FNA is associated with a very poor prognosis.

EUS-guided FNA of local recurrence of pancreatic cancer after surgical resection.

BACKGROUND: EUS-guided FNA (EUS-FNA) is a sensitive test for the preoperative diagnosis of pancreatic cancer. Its use for diagnosing local tumor recurrence after surgical resection has not been described. OBJECTIVE: To determine the sensitivity of EUS-FNA for this indication. DESIGN: Retrospective cohort study. SETTING: Tertiary referral hospital in the United States. PATIENTS: Consecutive patients referred for EUS with clinical and/or radiographic suspicion of pancreatic cancer recurrence. INTERVENTIONS: EUS ± FNA of retroperitoneal mass. MAIN OUTCOME MEASUREMENT: Sensitivity of EUS-FNA. RESULTS: Seventeen patients (9 male, median age 71 years) underwent EUS at a median of 17 months (range 7-46 months) after a classic Whipple procedure (n = 7), pylorus-sparing Whipple procedure (n = 7), or distal pancreatectomy (n = 3) for suspected local recurrence of pancreatic cancer. The primary tumor (median size 2.5 cm, range 1.5-7.9 cm) was located in the head in 14 patients, the body in 1, and the tail in 2. Final surgical margins at any site were positive in only 1 of 17 patients (+ retroperitoneal margin). At the time of suspected recurrence, 4 patients (24%) were asymptomatic. EUS disclosed a mass (median size 21 mm, range 12-30 mm) in 16 of 17 patients (94%). Transgastric EUS-FNA (n = 16, median 4.5 passes, range 2-10) disclosed recurrent malignancy in 13 of 16 (79%), atypical cells in 1 of 16 (7%), and benign cytology in 2 of 16 (14%). Subsequent radiographic evidence of increasing tumor burden was seen in 1 of 2 patients with benign cytology; however, follow-up for the 2 other patients with benign biopsy specimens was not available. Depending on the status of the 2 patients without available follow-up, the sensitivity, specificity, and accuracy of EUS-FNA for the diagnosis of recurrent cancer ranged from 81% to 93%, was 100%, and ranged from 81% to 93%, respectively. LIMITATIONS: Small, single-center retrospective cohort. CONCLUSIONS: EUS-FNA is sensitive for the diagnosis of retroperitoneal recurrence of pancreatic cancer after surgical resection.

EUS for pancreatic neuroendocrine tumors: a single-center, 11-year experience.

BACKGROUND: Pancreatic neuroendocrine tumors (PNTs) are rare tumors with malignant potential. EUS and EUS-guided FNA (EUS-FNA) have been shown to be superior to other imaging methods in the preoperative localization and diagnosis of PNTs. OBJECTIVES: To evaluate the clinical presentation, EUS morphology, and sensitivity of EUS-FNA cytology in a large consecutive cohort with histologically and/or cytologically confirmed PNTs. DESIGN: Retrospective study of all consecutive patients from July 1995 to November 2006 who underwent EUS for a known or suspected PNT and had a subsequently histologically confirmed PNT. SETTING: Tertiary referral center. PATIENTS: Ninety-two patients with suspected PNT. INTERVENTIONS: EUS evaluation with or without EUS-FNA of PNTs. MAIN OUTCOME MEASUREMENTS: Clinical and EUS features of PNTs and sensitivity of EUS-FNA for the diagnosis of PNTs. RESULTS: Ninety-two patients underwent EUS; 76 patients had confirmed histopathology, of whom 69 (91%) were symptomatic. Patients with functional PNTs presented with diarrhea, peptic ulcer disease, and hypoglycemia. Tumor locations and echogenic features were similar except that nonfunctional PNTs tended to be larger and have cystic features. Patients with malignant PNTs were older (P = .03), presented with abdominal pain, and had larger tumors (P = .0006) with irregular margins. Eighty-nine percent of patients underwent EUS-FNA. Sensitivity of EUS-FNA for the diagnosis of a PNT was 87%. Sensitivity of EUS-FNA was similar in functional and nonfunctional PNTs. The sensitivity of EUS-FNA was higher for malignant PNTs (P = .008). LIMITATIONS: Retrospective single tertiary center. CONCLUSIONS: EUS and EUS-FNA are sensitive tools, especially in cases of suspected symptomatic PNTs in which other imaging modalities have failed.

Initial experience with EUS-guided Tru-cut biopsy of benign liver disease.

BACKGROUND: Histologic biopsy of the liver is often essential for diagnosing hepatic parenchymal disease. Tissue acquisition is traditionally obtained by a surgical, transvascular, or percutaneous route. OBJECTIVE: To describe our initial experience with EUS-guided Tru-cut biopsy (EUS-TCB) of benign liver disease. DESIGN: A prospective case series. SETTING: A tertiary-referral hospital in Indianapolis, Indiana. PATIENTS: Consecutive subjects undergoing EUS with suspected hepatic parenchymal disease. INTERVENTIONS: EUS-TCB of the liver. MAIN OUTCOME MEASUREMENTS: Liver biopsy specimen yield, diagnosis, and procedural complications. Specimens were routinely stained with hematoxylin and eosin and with special stains for reticulin, iron, and trichome. Each case was reviewed by a single experienced pathologist for the number of portal spaces, total specimen length, and final diagnosis. An adequate specimen was defined as 6 or more complete portal tracts. RESULTS: Between February 2007 and March 2008, 21 consecutive patients (mean age 45 years; 13 women) were evaluated. The most common indications for liver biopsy were suspected nonalcoholic steatohepatitis (n = 9), intrahepatic cholestasis (n = 4), and suspected cirrhosis (n = 3). Transgastric biopsy (median 3 passes, range 1-4) into the left lobe (n = 18) or both the left and caudate lobe (n = 3) yielded a median total specimen length of 9 mm (range 1-23 mm). The median total number of portal tracts in the specimen was 2 complete (range 0-10) plus 3 partial (range 0-8) tracts. Six or more complete portal tracts were present in 6 of 21 (29%). A histologic diagnosis was obtained in 19 of 21 (90%). There were no complications. LIMITATIONS: The small sample size and low-risk population. CONCLUSIONS: In our initial experience, transgastric EUS-TCB of suspected benign liver disease by using a 19-gauge needle appears safe and feasible. Samples obtained are usually smaller than those traditionally considered adequate for histologic assessment. Further refinement of this technique appears indicated.

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

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.

EUS-guided FNA aspiration of kidney masses: a multicenter U.S. experience.

BACKGROUND: Tissue sampling of renal lesions is traditionally performed with percutaneous US or CT guidance. To date, only 3 known cases of EUS-guided FNA (EUS-FNA) of a renal mass have been reported. OBJECTIVE: To describe a multicenter experience with the indications, yield, and complications from attempted EUS-FNA of a kidney mass. DESIGN: Retrospective case series. SETTING: Six tertiary referral hospitals in the United States. PATIENTS: Consecutive subjects undergoing attempted EUS-FNA of a kidney mass. Endosonographers at 15 other teaching hospitals were contacted regarding EUS findings and follow-up of any EUS-guided renal biopsies previously attempted or considered at that institution. INTERVENTIONS: EUS-FNA of a kidney mass. MAIN OUTCOME MEASUREMENTS: Biopsy indications, yield, diagnosis, and complications. RESULTS: Fifteen procedures in 15 patients (9 men; median age 67 years) were performed at 6 (37%) of 16 hospitals (Indiana University plus 15 other hospitals). Kidney masses (median diameter 32 mm; range 11-60 mm) were located in the upper (n = 12) and lower (n = 3) poles of the left (n = 10) and right (n = 5) kidneys, respectively. Initial mass detection was by previous imaging in 13 (87%) patients or by EUS in 2 (13%) patients. Results of EUS-FNA (median 3 passes; range 2-4 passes) in 13 (87%) procedures were diagnostic of (n = 7) or highly suspicious for (n = 1) renal cell carcinoma (RCC), atypical cells (n = 2), oncocytoma (n = 1), benign cyst (n = 1), and nondiagnostic (n = 1). No complications were encountered. Surgical resection confirmed RCC in 7 patients in whom preoperative EUS-FNA demonstrated RCC (n = 5) or oncocytoma (n = 1) or was not performed (n = 1). LIMITATIONS: Retrospective series, small number of patients. CONCLUSIONS: EUS-FNA of renal masses is rarely performed at the U.S. teaching hospitals surveyed. This technique appears safe and feasible and should be considered when results would affect patient management.

Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study.

BACKGROUND: The role of pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts remains unclear. OBJECTIVE: Our purpose was to evaluate the utility of a detailed DNA analysis of pancreatic cyst fluid to diagnose mucinous and malignant cysts. DESIGN: Prospective, multicenter study. PATIENTS: Patients with pancreatic cysts presenting for EUS evaluation. INTERVENTION: EUS-guided pancreatic cyst aspirates cytology evaluation, carcinoembryonic antigen (CEA) level determination, and a detailed DNA analysis; incorporating DNA quantification, k-ras mutation and multiple allelic loss analysis, mutational amplitude, and sequence determination. MAIN OUTCOME MEASUREMENTS: Cyst fluid analysis compared with surgical pathologic or malignant cytologic examination. RESULTS: The study cohort consisted of 113 patients with 40 malignant, 48 premalignant, and 25 benign cysts. Cyst fluid k-ras mutation was helpful in the diagnosis of mucinous cysts (odds ratio 20.9, specificity 96%), whereas receiver-operator characteristic curve analysis indicated optimal cutoff points for allelic loss amplitude (area under the curve [AUC] 0.79; optimal value > 65%) and CEA (AUC 0.74; optimal value >148 ng/mL). Components of DNA analysis detecting malignant cysts included allelic loss amplitude over 82% (AUC 0.9) and high DNA amount (optical density ratio >10, AUC 0.79). The criteria of a high amplitude k-ras mutation followed by allelic loss showed maximum specificity (96%) for malignancy. All malignant cysts with negative cytologic evaluation (10/40) could be diagnosed as malignant by using DNA analysis. LIMITATIONS: Limited follow-up, selection bias. CONCLUSIONS: Elevated amounts of pancreatic cyst fluid DNA, high-amplitude mutations, and specific mutation acquisition sequences are indicators of malignancy. The presence of a k-ras mutation is also indicative of a mucinous cyst. DNA analysis should be considered when cyst cytologic examination is negative for malignancy.

Prospective evaluation of the performance and interobserver variation in endoscopic ultrasound staging of rectal cancer.

BACKGROUND: Treatment and prognosis of patients with rectal adenocarcinoma (RAC) are dependent on accurate locoregional staging. OBJECTIVES: The aim of this study was to measure the performance characteristics of rectal endoscopic ultrasound (EUS) compared with surgical pathology, and to assess the interobserver variation of rectal EUS in the staging of RAC. PATIENTS AND METHODS: Patients referred for rectal EUS staging of a recently diagnosed RAC were prospectively enrolled between 2012 and 2016. Tandem EUS exams were performed by two independent endosonographers (ES1 and ES2) blinded to each other's findings. RESULTS: Ninety-five patients were enrolled. Seventy-five (79%) underwent curative intent tumor resection, including 30 without neoadjuvant therapy. In this latter group, the sensitivity, specificity, and accuracy of transrectal ultrasonography staging were 75, 83, and 82% for uT1; 50, 65, and 58% for uT2; 56, 81, and 73% for T3; 72, 44, and 63% for N0, and 38, 75, and 63% for N1, respectively. Experienced operators rendered a more accurate N stage and were less likely to overstage compared with less experienced ones (P=0.01 and 0.02, respectively). Overall, T staging agreement between endosonographers was substantial (κ=0.61) and N stage agreement was moderate (κ=0.45). CONCLUSION: Rectal EUS is more accurate in staging T1 and T3 tumors compared with T2 tumors. Interobserver agreement of rectal EUS in rectal cancer staging is generally good.

Role of endoscopic ultrasound in the diagnosis of intraductal papillary mucinous neoplasms: correlation with surgical histopathology.

BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are precancerous tumors characterized by dilation of the main pancreatic duct, its side branches, or both. The purpose of this study was to evaluate the role of endoscopic ultrasound (EUS) in differentiating benign and malignant IPMNs. METHODS: We identified all patients between July 1996-November 2005 who underwent preoperative EUS for IPMNs. Malignancy was defined as the presence of invasive carcinoma; all other neoplasms were considered benign. The results of EUS and EUS-guided fine-needle aspiration (EUS-FNA) were compared with corresponding histopathology. RESULTS: Seventy-four patients (38 male; mean age, 65 years) with 21 (28%) malignant and 53 (72%) benign IPMNs were identified. Sixty-five (88%) underwent EUS-FNA. Compared with benign tumors, patients with malignant IPMNs were more likely to be older (P = .011), present with jaundice (P = .03) or weight loss (P = .03), and have EUS features of a dilated main pancreatic duct (P = .0001), solid lesion (P = .0001), pancreatic ductal filling defects (P = .03), or thickened septa within any cyst (P = .02). The sensitivity, specificity, and accuracy of EUS-FNA for the diagnosis of malignancy were 75% (95% confidence interval [CI], 53%-89%), 91% (95% CI, 79%-97%), and 86% (95% CI, 76%-93%), respectively. Cyst or pancreatic duct fluid carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 did not differ between groups. CONCLUSIONS: Older age, jaundice and weight loss, and EUS features of a solid lesion, dilated main pancreatic duct, ductal filling defects, and thickened septa are predictive of malignancy in patients with IPMNs. EUS-FNA cytology is helpful, but cyst fluid CEA and CA 19-9 are of limited value to differentiate malignant from benign IPMNs.

Prospective Cross-Sectional Study of the Prevalence of Incidental Pancreatic Cysts During Routine Outpatient Endoscopic Ultrasound.

OBJECTIVE: Incidental pancreatic cysts are often detected during abdominal imaging and require follow-up since some have malignant potential. Endoscopic ultrasound (EUS) is highly sensitive for pancreatic diseases, yet the prevalence of incidental pancreatic cysts discovered with EUS is unknown. The objective of the study was to determine its prevalence by EUS. METHODS: A prospective cross-sectional study was conducted. Patients undergoing EUS for nonpancreatic indications and without known pancreatic abnormality were recruited to assess the prevalence of pancreatic cysts and its characteristics. Risk factors were determined by logistic regression. RESULTS: We enrolled 341 patients (mean age, 59 years; 187 females) and found 46 incidental pancreatic cysts (median [range], 5 [2-80] mm) in 32 patients (9.4%). Branch duct intraductal papillary mucinous neoplasm was the most common finding. Seven cysts were larger than 1 cm and 1 adenocarcinoma was discovered. Multivariate logistic regression showed an association between pancreatic cysts and older age (odds ratio, 1.04 per year; 95% confidence interval, 1.01-1.08) and female sex (odds ratio, 3.08; 95% confidence interval, 1.25-7.45). CONCLUSIONS: In our population, the prevalence of incidental pancreatic cyst discovered on EUS was 9.4% and the majority were less than 1 cm. Increasing age and female sex were associated with the development of pancreatic cysts.

Utility of EUS following endoscopic polypectomy of high-risk rectosigmoid lesions.

BACKGROUND: The utility of endoscopic ultrasound (EUS) compared with standard white light endoscopy (WLE) following recent polypectomy of high-risk colorectal polyps is unknown. OBJECTIVE: To assess the incremental yield of EUS after endoscopic polypectomy of a high-risk rectal lesion. DESIGN: Retrospective cohort. SETTING: Tertiary referral center. MATERIALS AND METHODS: Patients referred for EUS following attempted endoscopic resection of a high-risk rectal neoplasm, defined as a tubulovillous adenoma, tubular adenoma with high-grade dysplasia, carcinoid, carcinoma in-situ or adenocarcinoma (CA). INTERVENTIONS: Sigmoidoscopy ± mucosal biopsy and EUS ± fine-needle aspiration (FNA) to evaluate for: (1) Residual polyp/tumor in the rectal wall or (2) peritumoral adenopathy. MAIN OUTCOME: Sensitivity and specificity for detection of residual neoplasia for WLE ± biopsy (WLE/BX) and EUS ± FNA for cancer (CA group) or benign disease (non-CA group). The incremental yield of EUS defined as: (1) Residual intramural neoplasia not present on WLE ± BX and; (2) abnormal peritumoral adenopathy. RESULTS: A total of 70 patients (mean age 64 ± 11 years, 61% male) with a final diagnosis of CA (n = 38) and non-CA (n = 32) were identified. There was no difference between the sensitivity and specificity of WLE alone (65% and 84%), WLE with biopsy (71% and 95%), and EUS (59% and 84%), for the detection of residual neoplasia (P > 0.05 for all). EUS identified 3 masses missed by WLE, all in the CA group. A malignant (n = 2) or benign (n = 3) node was identified in 5 (13%) CA patients; EUS-FNA in two showed residual malignancy in one and a reactive lymph node (LN) in one. No LNs were identified in the non-CA patients. LIMITATIONS: Retrospective design, incomplete follow-up in some patients. CONCLUSION: Following endoscopic polypectomy of high-risk rectal neoplasia, the incremental yield of EUS compared with WLE/BX for evaluation of residual disease appears limited, especially in patients with benign disease.

Effectiveness and safety of serial endoscopic ultrasound-guided celiac plexus block for chronic pancreatitis.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound - guided celiac plexus block (EUS-CPB) is an established treatment for pain in patients with chronic pancreatitis (CP), but the effectiveness and safety of repeated procedures are unknown. Our objective is to report our experience of repeated EUS-CPB procedures within a single patient. PATIENTS AND METHODS: A prospectively maintained EUS database was retrospectively analyzed to identify patients who had undergone more than one EUS-CPB procedure over a 17-year period. The main outcome measures included number of EUS-CPB procedures for each patient, self-reported pain relief, duration of pain relief, and procedure-related adverse events. RESULTS: A total of 248 patients underwent more than one EUS-CPB procedure and were included in our study. Patients with known or suspected CP (N = 248) underwent a mean (SD) of 3.1 (1.6) EUS-CPB procedures. In 76 % of the patients with CP, the median (range) duration of the response to the first EUS-CPB procedure was 10 (1 - 54) weeks. Lack of pain relief after the initial EUS-CPB was associated with failure of the next EUS-CPB (OR 0.17, 95 %CI 0.06 - 0.54). Older age at first EUS-CPB and pain relief after the first EUS-CPB were significantly associated with pain relief after subsequent blocks (P = 0.026 and P = 0.002, respectively). Adverse events included peri-procedural hypoxia (n = 2) and hypotension (n = 1) and post-procedural orthostasis (n = 2) and diarrhea (n = 4). No major adverse events occurred. CONCLUSIONS: Repeated EUS-CPB procedures in a single patient appear to be safe. Response to the first EUS-CPB is associated with response to subsequent blocks.