Kenneth J. Chang

Endosonography-guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment.

BACKGROUND & AIMS Endosonography-guided fine-needle aspiration biopsy (EUS-FNA) permits cytological confirmation of EUS findings. A multicenter prospective evaluation of EUS-FNA for primary diagnosis, staging, and/or follow-up purposes was undertaken. METHODS EUS-FNA was performed in 457 patients with 554 lesions. Clinical (n = 218) or histopathologic (n = 256) confirmation was available in 192 lymph nodes, 145 extraluminal masses, 115 gastrointestinal wall lesions, and 22 cystic lesions. RESULTS EUS-FNA sensitivity, specificity, and accuracy was 92%, 93%, and 92% for lymph nodes, 88%, 95%, and 90% for extraluminal masses, and 61%, 79%, and 67% for gastrointestinal wall lesions, respectively. The sensitivity and accuracy for lymph nodes and extraluminal masses was superior to that for gastrointestinal wall lesions. When EUS-FNA was compared with EUS size criteria in lymph node evaluation, specificity (93% vs. 24%) and accuracy (92% vs. 69%) were superior, whereas sensitivity (92% vs. 86%) was similar. The accuracy of EUS-FNA in patients with previously failed biopsy procedures was 81% (73 of 90). Five nonfatal complications occurred for a rate of 0.5% (95% confidence interval, 0.1%-0.8%) in solid lesions vs. 14% (95% confidence interval, 6%-21%) in cystic lesions. CONCLUSIONS EUS-FNA accurately and safely evaluates solid peri-intestinal lesions and improves lymph node staging accuracy.

Radiofrequency Ablation in Barrett's Esophagus with Dysplasia

BACKGROUND Barretts esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barretts esophagus and decrease the rate of neoplastic progression. METHODS In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barretts esophagus in a 2:1 ratio to receive either radiofrequency ablation (ablation group) or a sham procedure (control group). Randomization was stratified according to the grade of dysplasia and the length of Barretts esophagus. Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia. RESULTS In the intention-to-treat analyses, among patients with low-grade dysplasia, complete eradication of dysplasia occurred in 90.5% of those in the ablation group, as compared with 22.7% of those in the control group (P<0.001). Among patients with high-grade dysplasia, complete eradication occurred in 81.0% of those in the ablation group, as compared with 19.0% of those in the control group (P<0.001). Overall, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, as compared with 2.3% of those in the control group (P<0.001). Patients in the ablation group had less disease progression (3.6% vs. 16.3%, P=0.03) and fewer cancers (1.2% vs. 9.3%, P=0.045). Patients reported having more chest pain after the ablation procedure than after the sham procedure. In the ablation group, one patient had upper gastrointestinal hemorrhage, and five patients (6.0%) had esophageal stricture. CONCLUSIONS In patients with dysplastic Barretts esophagus, radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression. (ClinicalTrials.gov number, NCT00282672.)

The clinical utility of endoscopic ultrasound–guided fine-needle aspiration in the diagnosisand staging of pancreatic carcinoma

BACKGROUND Endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) of pancreatic lesions is being increasingly used. Our aim was to determine the safety, accuracy, and clinical utility of EUS-guided FNA in both the diagnosis and staging of pancreatic cancer. METHODS Forty-four patients (24 men/20 women) had EUS-guided FNA of pancreatic lesions (39 head/neck, 5 body, 3 tail) and/or associated lymph nodes. The mean age was 61 (range, 28 to 88 years). The indication for EUS-guided FNA was a pancreatic lesion seen initially on CT (39%), ERCP (43%), or EUS (18%). Follow-up data were collected on all patients for mean of 14.5 months (range 1 to 33 months). RESULTS CT detected only 15 of 61 (25%) focal lesions seen by EUS, Adequate specimens were obtained by EUS-guided FNA in 44 of 47 (94%) pancreatic lesions and 14 of 14 (100%) associated lymph nodes (overall adequacy was 95%). Of the 46 lesions in which specimens were adequate and a final diagnosis was available (32 malignant, 14 benign), EUS-guided FNA had a sensitivity of 92%, specificity of 100%, and diagnostic accuracy of 95% for pancreatic lesions and 83%, 100%, and 88% for lymph nodes, respectively. Six percent of pancreatic cases had inadequate specimens and, if included, lowered the sensitivity to 83%, specificity to 80%, and diagnostic accuracy to 88% for pancreatic lesions. In 3 patients with enlarged celiac nodes on EUS, EUS-guided FNA was able to make a tissue diagnosis of metastasis, which changed the preoperative staging and precluded surgery. EUS in combination with EUS-guided FNA precluded surgery in 12 of 44 (27%) and may have precluded surgery in an additional 6 of 44 (14%). EUS-guided FNA avoided the need for further diagnostic tests, thus expediting therapy in a total of 25 (57%) patients and influenced clinical decisions in 30 of 44 (68%) patients. The estimated cost savings based on surgeries avoided was approximately

Pretreatment Assessment of Resectable and Borderline Resectable Pancreatic Cancer: Expert Consensus Statement

3300 per patient. There was only one complication (2%), a post-FNA fever. CONCLUSION EUS-guided FNA of the pancreas appears to be a safe and effective method that increases both the diagnostic and staging capability of EUS in pancreatic cancer. The clinical impact of EUS-guided FNA includes avoiding surgery and additional imaging studies with a substantial cost savings.

Durability of Radiofrequency Ablation in Barrett's Esophagus With Dysplasia

Preoperative Staging and Defining Resectability From a surgical perspective, the first objective in the management of suspected or confirmed pancreatic cancer is to determine the potential for resection. Routine exploratory laparotomy for the purpose of operatively determining resectability has been diminished by modern 3-D radiographic imaging, along with effective and sustainable nonoperative methods of palliation. Careful correlation between preoperative CT findings and surgical results has better-defined CT criteria for resectability. The critical aspects that need be evaluated in a thorough radiographic assessment are the presence or absence of peritoneal or hepatic metastases; the potential involvement of the SMV and portal vein and the relationship of these vessels and their tributaries to the tumor; the relationship of the tumor to the SMA, celiac axis, hepatic artery, and gastroduodenal artery; and the presence of any aberrant vascular anatomy. Unequivocal radiographic findings contraindicating resection include distant metastases, major venous thrombosis of the portal vein or SMV extending for several centimeters, and circumferential encasement of the SMA, celiac axis or proximal hepatic artery. Recent revisions of the National Comprehensive Cancer Network (NCCN) guidelines were an attempt to distinguish locally advanced unresectable tumors from potentially resectable tumors.22 Ambiguity exists in these guidelines because of the lack of clarity in defining clearly resectable situations from “borderline resectable” tumors and because of the subjective criteria used to define “borderline” tumors relative to locally advanced, unresectable lesions. The NCCN guidelines do offer a definition of what should be considered a radiographically resectable tumor. Patients without distant metastases and no evidence of tumor extension to the SMV and portal vein and clear fat planes around the celiac axis, the hepatic artery, and SMA should be categorized as having localized and resectable cancers. More refined and objective criteria have been proposed by the M. D. Anderson Cancer Center Pancreas Cancer Group in an attempt to better define the term “borderline resectable” and to guide treatment decisions regarding the use of neoadjuvant therapy and the high likelihood of vein resection and reconstruction as a means to improve the rate of a complete and margin-negative resection.23 Radiographic findings of tumor abutment on the portal vein or SMV with or without venous deformity, and limited encasement of the mesenteric vein and portal vein (i.e., short segment occlusion with suitable vessel for anastomosis above and below) represent the extent of venous involvement that would categorize a tumor as borderline resectable. Radiographic findings suggesting borderline arterial involvement as defined by M. D. Anderson Cancer Center include encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis and/or tumor abutment of the SMA involving < 180° of the artery circumference. In patients without clinically important major comorbidities, and in the absence of radiographic findings to suggest metastatic disease or locally advanced unresectable disease as outlined above, surgical resection should be considered feasible and likely to be achievable. Whether these resections would result in a higher-than-expected rate of margin-positive resections, and whether such resections would affect survival would best be determined by careful examination of outcomes relative to extent of vascular involvement using objective criteria to determine categorization of extent of disease. Consensus Statement 1. Tumors considered localized and resectable should demonstrate the following: a. No distant metastases. b. No radiographic evidence of SMV and portal vein abutment, distortion, tumor thrombus, or venous encasement. c. Clear fat planes around the celiac axis, hepatic artery, and SMA. 2. Tumors considered borderline resectable include the following: a. No distant metastases. b. Venous involvement of the SMV/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction. c. Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis. d. Tumor abutment of the SMA not to exceed >180° of the circumference of the vessel wall.

Circumferential ablation of Barrett's esophagus that contains high-grade dysplasia: a U.S. multicenter registry

BACKGROUND & AIMS Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barretts esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE. METHODS We performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events. RESULTS After 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years). CONCLUSIONS In subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years.

Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.

BACKGROUND The management strategies for Barretts esophagus (BE) that contains high-grade dysplasia (HGD) include intensive endoscopic surveillance, photodynamic therapy, thermal ablation, EMR, and esophagectomy. OBJECTIVE To assess the safety and effectiveness of endoscopic circumferential balloon-based ablation by using radiofrequency energy for treating BE HGD. DESIGN Multicenter U.S. registry. SETTING Sixteen academic and community centers; treatment period from September 2004 to March 2007. PATIENTS Patients with histologic evidence of intestinal metaplasia (IM) that contained HGD confirmed by at least 2 expert pathologists. A prior EMR was permitted, provided that residual HGD remained in the BE region for ablation. INTERVENTION Endoscopic circumferential ablation with follow-up esophageal biopsies to assess the histologic response to treatment. OUTCOMES Histologic complete response (CR) end points: (1) all biopsy specimen fragments obtained at the last biopsy session were negative for HGD (CR-HGD), (2) all biopsy specimens were negative for any dysplasia (CR-D), and (3) all biopsy specimens were negative for IM (CR-IM). RESULTS A total of 142 patients (median age 66 years, interquartile range [IQR] 59-75 years) who had BE HGD (median length 6 cm, IQR 3-8 cm) underwent circumferential ablation (median 1 session, IQR 1-2). No serious adverse events were reported. There was 1 asymptomatic stricture and no buried glands. Ninety-two patients had at least 1 follow-up biopsy session (median follow-up 12 months, IQR 8-15 months). A CR-HGD was achieved in 90.2% of patients, CR-D in 80.4%, and CR-IM in 54.3%. LIMITATIONS A nonrandomized study design, without a control arm, a lack of centralized pathology review, ablation and biopsy technique not standardized, and a relatively short-term follow-up. CONCLUSIONS Endoscopic circumferential ablation is a promising modality for the treatment of BE that contains HGD. In this multicenter registry, the intervention safely achieved a CR for HGD in 90.2% of patients at a median of 12 months of follow-up.

A multispecialty approach to the diagnosis and management of pancreatic cancer

BACKGROUND AND STUDY AIMS The AIM-II Trial included patients with nondysplastic Barretts esophagus (NDBE) treated with radiofrequency ablation (RFA). Complete eradication of NDBE (complete response-intestinal metaplasia [CR-IM]) was achieved in 98.4 % of patients at 2.5 years. We report the proportion of patients demonstrating CR-IM at 5-year follow-up. PATIENTS AND METHODS Prospective, multicenter US trial (NCT00489268). After endoscopic RFA of NDBE up to 6 cm, patients with CR-IM at 2.5 years were eligible for longer-term follow-up. At 5 years, we obtained four-quadrant biopsies from every 1 cm of the original extent of Barretts esophagus. All specimens were reviewed by one expert gastrointestinal pathologist, followed by focal RFA and repeat biopsy if NDBE was identified. Primary outcomes were (i) proportion of patients demonstrating CR-IM at 5-year biopsy, and (ii) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA. RESULTS Of 60 eligible patients, 50 consented to participate. Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue (per patient, mean 30 , standard deviation [SD] 13). CR-IM was demonstrated in 92 % (46 / 50) of patients, while 8 % (4 / 50) had focal NDBE; focal RFA converted all these to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 (95 % confidence interval [CI] 0.77 - 0.97) and mean duration of CR-IM was 4.22 years (standard error [SE] 0.12). CONCLUSIONS In patients with NDBE treated with RFA, CR-IM was demonstrated in the majority of patients (92 %) at 5-year follow-up, biopsy depth was adequate to detect recurrence, and all failures (4 / 4, 100 %) were converted to CR-IM with single-session focal RFA.

Minimally Invasive Esophagectomy : Lessons Learned From 104 Operations

This article reviews recent developments in pancreatic cancer research and offers a multispecialty perspective on the diagnosis and management of this challenging disease. Current findings in the molecular biology of the disease and their implications for management are examined, as well as development in diagnostic techniques, including helical computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangio-pancreatography (MRCP), and, particularly, endoscopic ultrasound–guided fine-needle aspiration. Surgical management, the role of adjuvant/neoadjuvant chemoradiation therapy, and the critical importance of accurate preoperative imaging are also addressed in this review. Palliative techniques, including endoscopic stenting for malignant obstructive jaundice and chemotherapy for locally advanced and metastatic disease, are discussed, and results of recent clinical trials in pancreatic cancer are summarized. Finally, future directions for research are identified.

Negative predictive value of endoscopic ultrasound in a large series of patients with a clinical suspicion of pancreatic cancer.

Objectives:To review the outcomes of 104 consecutive minimally invasive esophagectomy (MIE) procedures for the treatment of benign and malignant esophageal disease. Summary Background Data:Although minimally invasive surgical approaches to esophagectomy have been reported since 1992, MIE is still considered investigational at most institutions. Methods:This prospective study evaluates 104 MIE procedures performed between August 1998 and September 2007. Main outcome measures include operative techniques, operative times, blood loss, length of stay, conversion rates, morbidities, and mortalities. Results:Indications for surgery were esophageal cancer (n = 80), Barrett esophagus with high-grade dysplasia (n = 6), recalcitrant stricture (n = 8), gastrointestinal stromal tumor (n = 3), and gastric cardia cancer (n = 7). Surgical approaches included thoracoscopic/laparoscopic esophagectomy with a cervical anastomosis (n = 47), minimally invasive Ivor Lewis esophagectomy (n = 51), laparoscopic hand-assisted blunt transhiatal esophagectomy (n = 5), and laparoscopic proximal gastrectomy (n = 1). There were 77 males. The mean age was 65 years. Three patients (2.9%) required conversion to a laparotomy. The median ICU and hospital stays were 2 and 8 days, respectively. Major complications occurred in 12.5% of patients and minor complications in 15.4% of patients. The incidence of leak was 9.6% and of anastomotic stricture was 26%. The 30-day mortality was 1.9% with an in-hospital mortality of 2.9%. The mean number of lymph nodes retrieved was 13.8. Conclusions:Minimally invasive esophagectomy is feasible with a low conversion rate, acceptable morbidity, and low mortality. Our preferred operative approach is the laparoscopic\thoracoscopic Ivor Lewis resection, which provides a tension-free intrathoracic anastomosis.