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Colorectal cancer is the second leading cause of cancer death in the United States, with over 130,000 new cases diagnosed each year. Most colon cancers arise from preexisting adenomatous polyps. Screening for colorectal cancer by detecting and removing these precursor lesions in asymptomatic individuals can be expected to impact the death rate from this largely preventable cancer, which currently claims over 50,000 American lives annually. Screening methods previously relied on fecal occult blood testing, sigmoidoscopy, and barium enema, or some combination thereof. After the publication of studies that indicate that flexible sigmoidoscopy can miss over 50% of proximal neoplastic lesions, complete colonic examination with colonoscopy now is considered to be the most effective and desirable screening option. In addition, colonoscopy offers the singular advantage of allowing detection and removal of polyps during the same procedure. The choice of colonoscopy as the primary screening modality for colorectal cancer is not without controversy. Colonoscopy is an invasive test and, hence, carries the risk for potential complications, albeit low. More importantly, there are the negative patient perceptions of the procedure, based partly on fear of invasive procedures, poor acceptability of the bowel-preparation process, and fear of discomfort during the procedure. All of these factors may lead to patients underutilizing the opportunity to undergo screening. Data from the late 1990s indicated that only 32% of adults reported having undergone a flexible sigmoidoscopy or colonoscopy in the preceding 5 years. In addition to patient factors, there are higher initial costs associated with colonoscopy, although the cost-effectiveness may be superior to earlier screening modalities. Finally, colonoscopy may be incomplete in 5% to 15% of examinations and may have a miss rate for polyps of up to 24%, even when performed by experienced colonoscopists at tertiary care centers. Therefore, there is an opportunity for an alternative colon cancer screening test that is accurate, safe, rapid, cost effective, and more acceptable to patients. CT colonography (CTC) is a new imaging modality that has been generating increasing interest and attention as a possible

Background The aim of this study was to determine the frequency and the severity of pancreatitis after EUS-guided FNA of solid pancreatic masses. A survey of centers that offer training in EUS in the United States was conducted. Methods A list of centers in which training in EUS is offered was obtained from the Web site of the American Society for Gastrointestinal Endoscopy. Designated program directors were contacted via e-mail. The information requested included the number of EUS-guided FNA procedures performed for solid pancreatic masses, the number of cases of post-procedure pancreatitis, and the method for tracking complications. For each episode of pancreatitis, technical details were obtained about the procedure, including the location of the mass, the type of fine needle used, the number of needle passes, and the nature of the lesion. Results Nineteen of the 27 programs contacted returned the questionnaire (70%). In total, 4909 EUS-guided FNAs of solid pancreatic masses were performed in these 19 centers over a mean of 4 years (range 11 months to 9 years). Pancreatitis occurred after 14 (0.29%): 95% CI[0.16, 0.48] procedures. At two centers in which data on complications were prospectively collected, the frequency of acute pancreatitis was 0.64%, suggesting that the frequency of pancreatitis in the retrospective cohort (0.26%) was under-reported ( p =0.22). The odds that cases of pancreatitis would be reported were 2.45 greater for the prospective compared with the retrospective cohort (95% CI[0.55, 10.98]). The median duration of hospitalization for treatment of pancreatitis was 3 days (range 1-21 days). The pancreatitis was classified as mild in 10 cases, moderate in 3, and severe in one; one death (proximate cause, pulmonary embolism) occurred after the development of pancreatitis in a patient with multiple comorbid conditions. Conclusions EUS-guided FNA of solid pancreatic masses is infrequently associated with acute pancreatitis. The procedure appears to be safe when performed by experienced endosonographers. The frequency of post EUS-guided FNA pancreatitis may be underestimated by retrospective analysis.

CASE REPORT A 56-year-old woman was found to have a 2-cm subepithelial mass in the sigmoid colon at 35 cm from the anal verge at screening sigmoidoscopy. There was no “naked fat” sign,1 and biopsy specimens revealed normal colonic mucosa. The lesion was thought to represent a lipoma or leiomyoma and endoscopic removal was deemed unnecessary. One year later at sigmoidoscopy there was no change in size and it was elected to simply observe the lesion endoscopically. Two years later sigmoidoscopy revealed the texture of the lesion to be “firm” although the size had not changed (Fig. 1). This change in texture raised the possibility that the tumor was undergoing malignant transformation and EUS was performed with a 20 MHz catheter probe. The lesion was hypoechoic and appeared to arise within the muscularis propria. It involved the submucosa and penetrated into the subserosal adipose tissue (Fig. 2). The patient’s history included diet-controlled diabetes mellitus, hypertension, hypothyroidism, a Morton’s neuroma of the foot treated with corticosteroid injection, total abdominal hysterectomy for uterine fibroid tumors, and a cholecystectomy for gallstones. Her brother had myelofibrosis diagnosed at age 49 years. A maternal uncle had polycythemia vera. There was no family history of neurofibromatosis type 1 or 2. Examination was unremarkable except for obesity and a single cafe-au-lait spot on the thigh. No subcutaneous nodules were appreciated. Ophthalmologic examination was normal. The EUS finding of extension of the tumor into the subserosal adipose suggested the possibility of malignant transformation of a leiomyoma, atypical behavior for a benign stromal tumor. The patient therefore underwent a segmental sigmoid colectomy. The gross specimen included 2 well-circumscribed subepithelial tumors measuring 0.5 cm and 1.7 cm, respectively. Histologically, both masses were composed of multiple nodules with dense cellularity, and the findings appeared to be consistent with a peripheral nerve sheath tumor. Nodules from both masses were present extensively within the muscularis propria (Fig. 3A) and were contiguous with the myenteric plexus. The larger mass also extended into the pericolonic adipose tissue (Fig. 3B). The majority of the neoplasm was composed of densely packed spindle cells in interweaving short fascicles and whorls. Palisading nuclei and numerous Verocay bodies (Fig. 3C) were easily identified. A lymphocytic infiltrate was scat

Background: The endoscopically placed enteral stent has emerged as a reasonable alternative to palliative surgery for malignant intestinal obstruction. This is a report of our experience with the use of enteral stents for nonesophageal malignant upper GI obstruction. Methods: Data on all patients who had undergone enteral stent placement were reviewed. Those with a diagnosis of pancreatic cancer were compared with another similar cohort of patients who underwent palliative gastrojejunostomy. Results: Thirty-one procedures were performed on 29 patients (mean age 67.7 years). Thirteen (45%) were men and 16 (55%) women. The diagnoses were gastric (13.8%), duodenal (10.3%), pancreatic (41.4%), metastatic (27.6%), and other malignancies (6.9%). Malignant obstruction occurred at the pylorus (20.7%), first part of duodenum (37.9%), second part of duodenum (27.6%), third part of duodenum (3.5%), and anastomotic sites (10.3%). Twenty-nine (93.5%) procedures were successful and good clinical outcome was achieved in 25 (80.6%). Re-obstruction by tumor ingrowth occurred in 2 patients after a mean of 183 days. The median survival time for patients with pancreatic cancer who underwent enteral stent placement compared with those who underwent surgical gastrojejunostomy was 94 and 92 days, charges were $9921 and $28,173, and duration of hospitalization was 4 and 14 days, respectively (latter 2 differences with p value Conclusion: Endoscopic enteral stent placement of nonesophageal malignant upper GI obstruction is a safe, efficacious, and cost-effective procedure with good clinical outcome, lower charges, and shorter hospitalization period than the surgical alternative. (Gastrointest Endosc 2001;53:329-32.)

Background: Incomplete endoscopic ultrasound (EUS) staging procedures in patients with esophageal cancer due to obstructing malignant strictures are prone to underestimate T stage and cannot detect celiac adenopathy. EUS staging in the setting of stenotic malignancies using the large caliber echoendoscope has been complicated by esophageal perforation. We report on the clinical utility of a newly developed, wire-guided echoendoscope for the complete staging of patients with esophageal cancer. Methods: Pretreatment EUS examinations performed for esophageal cancer staging were evaluated and the ability to traverse the esophagus and examine the celiac axis were documented. Outcomes before and after the availability of the wire-guided echoendoscope were compared. Results: One hundred thirty consecutive examinations were evaluated—100 before and 30 after the introduction of the wire-guided echoendoscope. Complete staging was accomplished in 60 of 100 (60%) cases before and 27 of 30 (90%) after its introduction ( p = 0.002). The wire-guided echoendoscope was used in 14 of the 30 cases. Despite a trend toward fewer stage T4 tumors, metastatic disease was documented significantly more frequently after the introduction of the esophagoprobe (34% vs. 11%, p = 0.002). There were no complications. Conclusions: The introduction of the wire-guided echoendoscope markedly reduced the occurrence of incomplete esophageal cancer staging and improved the detection of metastatic disease. (Gastrointest Endosc 1999;50:53-7.)

Background: Limitations in the technical capabilities of the fiberoptic echoendoscope often necessitate concurrent diagnostic endoscopy at the time of an endosonographic (EUS) examination. Our aim was to determine whether a new video echoendoscope would allow the performance of EUS without diagnostic endoscopy. Methods: EUS examinations on all patients at two centers were initiated with a fiberoptic echoendoscope (period of 5 weeks) or a video echoendoscope (period of 6 weeks). Note was made of need for concurrent diagnostic endoscopy. The endosonographer also rated the mechanical, optical, and sonographic performance of the video instrument using a 9-point comparative scale (1 = much worse, 5=equal to, and 9=much better than fiberoptic echoendoscope). Results: A total of 103 patients including 40 and 28 with mural lesions and 22 and 15 with retroperitoneal lesions were examined with the fiberoptic and video echoendoscopes, respectively. Mean values for parameters rating the video echoendoscope's mechanical performance ranged between 5.0 and 5.9, optical performance ranged between 6.6 and 7.5, and sonographic performance ranged between 4.6 and 4.9. Concurrent diagnostic endoscopy was required less frequently when patients with mural lesions (18% vs. 70%, p p = no significance) were examined with the video echoendoscope compared with the fiberoptic echoendoscope. Conclusions: Moderately improved optics and slightly better mechanical characteristics of the new video echoendoscope allow the performance of EUS without concurrent diagnostic endoscopy in the majority of patients. (Gastrointest Endosc 1999;49:695-9.)

Background: Some patients are admitted following outpatient therapeutic ERCP because of adverse events. This study aimed to identify factors that may predict such admissions. Methods: We prospectively studied admissions for post-ERCP adverse events in 415 consecutive patients undergoing outpatient therapeutic ERCP. Potentially relevant predictors of admission were assessed by univariate analysis and in case of significance included in a multivariate analysis. Results: Admission was necessary in 41 patients (9.9%) because of complications and in 63 (15.2%) for observation of adverse events that did not progress to definable complications. Potential predictors of admission were evaluated comparing patients who required more than an overnight admission (n = 63) with those who did not (n = 352). Multivariate analysis identified three factors that were significant: pain during the procedure (odds ratio 3.8: 95% CI [1.8, 7.9]), history of pancreatitis (odds ratio 2.3: 95% CI [1.1, 4.7]) and performance of sphincterotomy (odds ratio 2.2: 95% CI [1.1, 4.3]). The presence of all these features was associated with a 66.7% likelihood of admission, whereas the absence of pain during the procedure, history of pancreatitis and performance of sphincterotomy made admission likely in only 11.0%, 9.8% and 10.7%, respectively, of the cases. Conclusions: The occurrence of pain during the procedure, a history of pancreatitis and the performance of sphincterotomy were independent predictors of admission following outpatient therapeutic ERCP. (Gastrointest Endosc 1999;49:587-92.)

Background: Previous in vitro studies showed that autofluorescence images of colonic mucosa collected endoscopically can be used to detect dysplasia with high sensitivity. This method is extended to the collection of fluorescence images of adenomatous polyps in vivo. Methods: Fluorescence images were collected during colonoscopy in 30 patients. A total of 12 adenomatous and 6 hyperplastic polyps were identified. A fiberoptic excitation probe, located in the instrument channel of the colonoscope, delivered 300 mW of near-ultraviolet light at λex = 351 and 364 nm. Mucosal fluorescence in the spectral bandwidth between 400 and 700 nm was imaged, processed, and displayed with various likelihoods of associated dysplasia. Results: Adenomatous polyps exhibited decreased fluorescence intensity compared with adjacent mucosa with normal appearance. With the fluorescence threshold set to 80% of the average intensity of normal mucosa, a sensitivity of 83% for dysplasia identification was achieved. All hyperplastic polyps were correctly identified as being non-dysplastic. Optimal identification of dysplastic regions was obtained with the colonoscope oriented at a near-normal angle of incidence to the polyps. At higher angles of incidence, artifacts caused by illumination shadows were introduced. Conclusions: The dysplasia associated with adenomatous polyps can be identified in vivo by fluorescence imaging with high sensitivity, thus demonstrating the potential to guide endoscopic procurement of biopsy specimens. (Gastrointest Endosc 1999;49:447-55.)

Background: The accuracy and complication rates of brush cytology obtained from pancreaticobiliary strictures have not been fully defined. In this study we compared the accuracy and complications of brush cytology obtained from bile versus pancreatic ducts. Methods: We identified 148 consecutive patients for whom brush cytology was done during an ERCP from a database with prospectively collected data. We compared cytology results with the final diagnosis as determined by surgical pathologic examination or long-term clinical follow-up. We followed all patients and recorded ERCP-related complications. Results: Forty-two pancreatic brush cytology samples and 101 biliary brush cytology samples were obtained. The accuracy rate of biliary cytology was 65 of 101 (64.3%) and the accuracy rate of pancreatic cytology was 30 of 42 (71.4%). Overall sensitivity was 50% for biliary cytology and 58.3% for pancreatic cytology. Of 67 patients with pancreatic adenocarcinoma, sensitivity for biliary cytology was 50% versus 66% for pancreatic cytology. Concurrent pancreatic and biliary cytology during the same procedure increased the sensitivity in only 1 of 10 (10%) patients. Pancreatitis occurred in 11 (11%) patients (9 mild cases, 2 moderate cases) after biliary cytology and in 9 (21%) patients (6 mild cases, 3 moderate cases) after pancreatic cytology ( p = 0.22). In 10 patients who had pancreatic brush cytology, a pancreatic stent was placed. None of these patients developed pancreatitis versus 9 of 32 (28%) patients in whom a stent was not placed (p = 0.08). Pancreatic cytology samples obtained from the head of the pancreas were correct in 13 of 18 (72%) cases, from the genu in 7 of 7 (100%) cases, from the body in 5 of 9 (55%) cases, and from the tail in 4 of 7 (57%) cases. Conclusion: The accuracy of biliary brush cytology is similar to the accuracy of pancreatic brush cytology. The yield of the latter for pancreatic adenocarcinoma is similar to that of the former. Complication rates for pancreatic cytology are not significantly higher than the rates for biliary cytology. The placement of a pancreatic stent after pancreatic brushing appears to reduce the risk of postprocedure pancreatitis. (Gastrointest Endosc 1999;49:322-7.)

Background: Laser-induced fluorescence spectroscopy has the potential to detect colonic dysplasia in vivo. However, previous studies have limited their analyses to multivariate regression techniques and unblinded retrospective evaluation. The purpose of this study was to develop a probability-based algorithm to detect colonic dysplasia using laser-induced fluorescence spectroscopy and to evaluate it in a blinded manner. Methods: Fluorescence spectra were collected from normal mucosa and colonic polyps during colonoscopy using 370 nm excitation. Tissue was classified as normal, hyperplastic, or adenomatous by histologic examination. Preliminary data was used to devise an algorithm to differentiate tissue type based on probability distributions of the fluorescence intensity at 460 nm and the ratio of the intensity at 680 nm to that at 600 nm. The algorithm was then tested in a blinded fashion. Results: The algorithm correctly determined the tissue type in 88% of cases, equal to the agreement of independent pathologists. Sensitivity, specificity, and positive predictive value for the detection of dysplasia was 90%, 95%, and 90%, respectively. Conclusions: Dysplasia was detected in vivo using fluorescence spectroscopy and a probability-based algorithm. This method may form the basis for a new surveillance technique for patients with increased risk for dysplastic transformation. (Gastrointest Endosc 1996;44:168-76.)

Background: The usefulness of endoscopic ultrasonography (EUS) in the preoperative staging of esophageal carcinoma is well established. Alternatively, the role of EUS in the early diagnosis of anastomotic recurrence is less well accepted. Methods: EUS was used to evaluate 30 asymptomatic and 10 symptomatic patients (i.e., with dysphagia) who had previously undergone resection of esophageal carcinoma. Results: There were 3 (10%) unsuspected anastomotic recurrences in the asymptomatic group. EUS correctly identified locally recurrent cancer in all cases, whereas endoscopy confirmed the presence of only one anastomotic recurrence. Computed tomography was not diagnostic in any of the three recurrences. Sensitivity of EUS for recurrence of esophageal carcinoma was 100% compared with 33% for endoscopic diagnosis while the specificity was 96% for EUS compared with 100% for endoscopic biopsy. There was one false positive diagnosis of recurrence by EUS because of postoperative fibrosis resulting in concentric hypertrophy of the esophageal wall near the surgical anastomosis. Of the 10 symptomatic patients, 4 were diagnosed with tumor recurrence. EUS correctly predicted recurrences in all symptomatic patients (100% sensitivity and specificity), as did upper endoscopy with biopsy. Conclusions: EUS is more sensitive than upper endoscopy and CT scan for the evaluation of anastomotic recurrence of esophageal carcinoma and should be considered as an adjunctive modality to conventional endoscopy for the postoperative surveillance of these patients. (Gastrointest Endosc 1995;42:540-4.)

To investigate interobserver variation and reproducibility of endosonographic findings, both experienced and inexperienced endosonographers evaluated depth of tumor invasion (T stage) and presence of lymph node metastasis (N stage) in 50 patients with nonobstructing esophageal carcinoma. Results were compared with the findings by surgical pathology of the resected specimens. The kappa statistic (kappa) was used to assess interobserver and intraobserver agreement and consistency of accurate interpretation (reproducibility) for the two groups. Agreement between the experienced endosonographers was excellent (kappa =.75) for T1 and T4 lesions, good (kappa = .61) for T3 lesions, but only poor (kappa =.46) for T2 lesions. The overall agreement between the experienced endosonographers was equally good for both T and N stages. Agreement between the inexperienced endosonographers was poor for all T stages but was good for lymph node metastasis (kappa = .52). For experienced endosonographers, endosonographic reproducibility of histologically confirmed T4 lesions was excellent, followed closely by T3 and T2 lesions; T1 tumors were frequently interpreted differently by the same endosonographer. Reproducibility of N stage determinations was excellent for N0 lymph nodes and good for N1 nodes. Thus, for experienced endosonographers, interobserver agreement was excellent for all T stages except T2, whereas reproducibility of determination of depth of tumor invasion was good to excellent for T2, T3, and T4 lesions but poor for T1 lesions. As yet poorly defined operator and machine-dependent factors that cause misinterpretation of T1 and T2 tumors will require additional study.

Endosonography, which provides high-resolution images of the esophageal wall, could potentially detect carcinoma not visible endoscopically in patients with Barrett's esophagus and high-grade dysplasia. We studied the ability of endosonography to detect early esophageal carcinoma in 9 patients with Barrett's esophagus and high-grade dysplasia who were candidates for esophagectomy. Pre-operative endoscopy and biopsy revealed high-grade dysplasia without evidence of carcinoma in all patients. Pre-operative endosonographic evaluations were compared to the pathologic diagnoses of resected specimens. Post-operatively, 3 of the 9 patients were found to have intra-mucosal carcinoma. Endosonography identified a tumor in only 1 of these 3 patients and over-staged it as invasive carcinoma (T2, N1). In 2 of the 6 patients without intra-mucosal carcinoma, endosonography predicted invasive carcinoma (T2, N0). Endoscopy revealed mucosal nodularity in each of the 3 over-staged patients. We conclude that recommendation of the routine use of endosonography to determine the need for surgery in patients with Barrett's esophagus and high-grade dysplasia would be premature, because the current generation of echo-endoscopes does not reliably differentiate between benign and malignant wall thickening. (Gastrointest Endosc 1994;40:207-12.)

Background Image-guided radiation therapy (IGRT) accurately delivers a high dose of potentially tumoricidal radiation to its target while sparing adjacent healthy tissue. Application of IGRT to unresectable pancreatic cancer requires the use of fiducials to track the precise location of the tumor. Fiducial markers have been successfully placed endoscopically. Objective To determine the feasibility of EUS-guided gold fiducial placement for IGRT. Design Prospective case series. Setting Tertiary medical center. Patients Consecutively referred patients with locally advanced unresectable pancreatic adenocarcinoma for EUS–guided insertion of gold fiducials from December 2006 to February 2009. Interventions Under only EUS guidance, fiducial markers were deployed into or near the tumor by using a 19-gauge needle. In most cases, a sterile water injection technique was used to insert the fiducials. Fluoroscopy was not used in any case. Main Outcome Measurements Successful placement of an adequate number of fiducials to proceed with IGRT as determined by CT. Results Fifty-seven consecutive patients were included. Fifty cases (88%) were successful. Of the cases in which fiducial placement was attempted and follow-up was adequate, 94% (50 of 53) of cases were successful. Limitations Single-center, nonrandomized study. Conclusions EUS-guided fine-needle insertion was safe and effective in delivering gold fiducial markers for image-guided radiation therapy. Fluoroscopy was not required for successful fiducial placement.

The American perspective on the state of the art of EUS is humbly an international one. From the development of the science to the advancement of cutting edge applications, the advent of EUS has been one of international collaboration. Even this meeting, in its most successful 16th offering, combines the talents of clinicians, scientists, engineers, and researchers from every corner of the world. I first participated in this meeting in Bologna, Italy, in 1993 (the Ninth International Symposium on Endoscopic Ultrasonography). At that moment, EUS was considered a novelty by some researchers; however, those with a clear vision saw the possibilities that have become the current state of the art, and, with the advent of a maturing technology, unprecedented access, and an impressive array of therapeutic possibilities, today’s visionaries see an even brighter future. The state-of-the-art practice in EUS continues to include such important clinical applications as GI-tumor staging, tumor diagnosis via tissue acquisition, and the delineation of subepithelial lesions detected in the still expanding use of GI endoscopy. Among the most recent and most interesting developments in interventional EUS are a variety of tumor therapies facilitated by EUS and novel approaches to biliary-tract disease.

Background Colonoscopy is the "gold standard" for colorectal polyp and cancer detection, but important lesions may be missed on the proximal aspect of haustral folds, rectal valves, or flexures. Objective Our purpose was to evaluate a prototype auxiliary imaging device that extends beyond the colonoscope's tip, providing a continuous retrograde view to detect lesions missed by the forward-viewing colonoscope. Design Three anatomic models of the colon were prepared with simulated polyps, 32% in obvious locations and 68% on the proximal aspect of folds. Six endoscopists examined each model with two methods. Method A used a standard video colonoscope. Method B involved an identical colonoscope with a retrograde-viewing auxiliary device positioned within its instrument channel. Order of testing was randomized and blinded. Setting Laboratory bench. Main Outcome Measurements Detection rates for simulated polyps. Results Of 78 "obvious" polyps, 69 (88%) and 70 (90%) were detected by methods A and B, respectively ( P > .9). In contrast, of 162 polyps on proximal aspects of folds, 20 (12%) and 131 (81%) were detected by methods A and B, respectively ( P Limitations Limitations resulted from (1) use of commercially available anatomic models in which haustral folds are less prominent and more rigid than in humans and (2) evaluation of a prototype device that had larger size and narrower angle of view than the planned production model and that was fixed in relation to the colonoscope. Conclusions In simulated testing, a retrograde-viewing auxiliary imaging device used with a standard video colonoscope significantly improves detection rates of simulated polyps and promises to enhance the diagnostic yield of colonoscopy in humans.

The differential diagnosis for cystic lesions of the pancreas is broad and the role of EUS is becoming more clearly defined. Pancreatic cysts may be inflammatory, such as pseudocysts, in which the cyst wall lacks an epithelium. Inflammatory cells line the fluid collection, which may often be located adjacent to an area of acute or chronic pancreatitis. Other types of pancreatic cysts may be broadly classified as benign or malignant. Benign cysts include serous cystadenomas (microcystic cystadenoma), lymphangioma, cystic teratoma, hemangioma, or paraganglioma. Malignant cysts include mucinous cystic neoplasms (mucinous cystadenoma or cystadenocarcinoma). These are lined by mucinous epithelium. Cystadenocarcinomas are believed to arise from cystadenomas. The latter are therefore considered premalignant. Other mucinous cystic lesions include mucinous ductal ectasia (MDE), now more correctly referred to as intraductal papillary mucinous tumor (IPMT). A rare form of islet cell tumor may include a cystic component, that is, cystic islet cell tumor. Occasionally, other neoplasms may be of mixed origin and are called solid cystic tumors.1 One possible etiology for mixed tumors is ossification of a cystic tumor.