William Tam

Endoscopic mucosal resection outcomes and prediction of submucosal cancer from advanced colonic mucosal neoplasia.

BACKGROUND & AIMS Large sessile colonic polyps usually are managed surgically, with significant morbidity and potential mortality. There have been few prospective, intention-to-treat, multicenter studies of endoscopic mucosal resection (EMR). We investigated whether endoscopic criteria can predict invasive disease and direct the optimal treatment strategy. METHODS The Australian Colonic Endoscopic (ACE) resection study group conducted a prospective, multicenter, observational study of all patients referred for EMR of sessile colorectal polyps that were 20 mm or greater in size (n=479, mean age, 68.5 y; mean lesion size, 35.6 mm). We analyzed data on lesion characteristics and procedural, clinical, and histologic outcomes. Multiple logistic regression analysis identified independent predictors of EMR efficacy and recurrence of adenoma, based on findings from follow-up colonoscopy examinations. RESULTS Risk factors for submucosal invasion were as follows: Paris classification 0-IIa+c morphology, nongranular surface, and Kudo pit pattern type V. The most commonly observed lesion (0-IIa granular) had a low rate of submucosal invasion (1.4%). EMR was effective at completely removing the polyp in a single session in 89.2% of patients; risk factors for lack of efficacy included a prior attempt at EMR (odds ratio [OR], 3.8; 95% confidence interval, 1.77-7.94; P=.001) and ileocecal valve involvement (OR, 3.4; 95% confidence interval, 1.20-9.52; P=.021). Independent predictors of recurrence after effective EMR were lesion size greater than 40 mm (OR, 4.37; 95% confidence interval, 2.43-7.88; P<.001) and use of argon plasma coagulation (OR, 3.51; 95% confidence interval, 1.69-7.27; P=.0017). There were no deaths from EMR; 83.7% of patients avoided surgery. CONCLUSIONS Large sessile colonic polyps can be managed safely and effectively by endoscopy. Endoscopic assessment identifies lesions at increased risk of containing submucosal cancer. The first EMR is an important determinant of patient outcome-a previous attempt is a significant risk factor for lack of efficacy.

Long-term adenoma recurrence following wide-field endoscopic mucosal resection (WF-EMR) for advanced colonic mucosal neoplasia is infrequent: results and risk factors in 1000 cases from the Australian Colonic EMR (ACE) study

Objective Wide-field endoscopic mucosal resection (WF-EMR) is an alternative to surgery for treatment of advanced colonic mucosal neoplasia up to 120 mm in size, but has been criticised for its potentially high recurrence rates. We aimed to quantify recurrence at 4 months (early) and 16 months (late) following successful WF-EMR and identify its risk factors and clinical significance. Design Ongoing multicentre, prospective, intention-to-treat analysis of sessile or laterally spreading colonic lesions ≥20 mm in size referred for WF-EMR to seven academic endoscopy units. Surveillance colonoscopy (SC) was performed 4 months (SC1) and 16 months (SC2) after WF-EMR, with photographic documentation and biopsy of the scar. Results 1134 consecutive patients were enrolled when 1000 successful EMRs were achieved, of whom 799 have undergone SC1. 670 were normal. Early recurrent/residual adenoma was present in 128 (16.0%, 95% CI 13.6% to 18.7%). One case was unknown. The recurrent/residual adenoma was diminutive in 71.7% of cases. On multivariable analysis, risk factors were lesion size >40 mm, use of argon plasma coagulation and intraprocedural bleeding. Of 670 with normal SC1, 426 have undergone SC2, with late recurrence present in 17 cases (4.0%, 95% CI 2.4% to 6.2%). Overall, recurrent/residual adenoma was successfully treated endoscopically in 135 of 145 cases (93.1%, 95% CI 88.1% to 96.4%). If the initial EMR was deemed successful and did not contain submucosal invasion requiring surgery, 98.1% (95% CI 96.6% to 99.0%) were adenoma-free and had avoided surgery at 16 months following EMR. Conclusions Following colonic WF-EMR, early recurrent/residual adenoma occurs in 16%, and is usually unifocal and diminutive. Risk factors were identified. Late recurrence occurs in 4%. Overall, recurrence was managed endoscopically in 93% of cases. Recurrence is not a significant clinical problem following WF-EMR, as with strict colonoscopic surveillance, it can be managed endoscopically with high success rates. Trial registration number: NCT01368289.

Delivery of radiofrequency energy to the lower oesophageal sphincter and gastric cardia inhibits transient lower oesophageal sphincter relaxations and gastro-oesophageal reflux in patients with reflux disease

Background and aims: Radiofrequency energy (RFe) treatment to the lower oesophageal sphincter (LOS) and gastric cardia is a new luminally delivered therapy proposed as an alternative treatment for gastro-oesophageal reflux disease (GORD). However, it is unclear how RFe achieves its antireflux effect. This study investigated the effects of RFe on mechanisms of spontaneous reflux in patients with GORD. Methods: Twenty patients with GORD underwent endoscopy, symptom evaluation, and combined postprandial oesophageal manometry and pH monitoring before and six months after RFe, and 24 hour ambulatory pH monitoring before and at six and 12 months after treatment. Results: RFe reduced the rate of postprandial transient LOS relaxations from 6.8 (5.7–8.1) (median (interquartile range) per hour to 5.2 (4.2–5.8) per hour (p<0.01), and increased mean basal LOS pressure from 5.2 (SEM 0.3) mm Hg to 8.0 (SEM 0.4) mm Hg (p<0.01). The number of reflux events was reduced from 10 (2–15.3)/3 hours to 5 (3.5–8.5)/3 hours (p<0.05) and there was an associated significant reduction in acid exposure time from 5.4% (0.4–14.7) to 3.9% (0.4–6.6) (p<0.05). RFe significantly reduced ambulatory oesophageal acid exposure from 10.6% (7.8–13.0) to 6.8% (3.1–9.1) (p<0.01) at six months and 6.3% (4.7–10.9) (p<0.05) at 12 months. All patients required acid suppressant medication for symptom control before RFe. Six months after treatment, 15 patients (75%) were in symptomatic remission and 13 (65%) at 12 months. Conclusions: RFe has significant effects on LOS function that are associated with improvement in the antireflux barrier. Uncontrolled clinical data also suggest a beneficial effect in the control of reflux symptoms in these patients.

Impacts and patterns of disturbed gastrointestinal function in critically ill patients

Disordered upper gastrointestinal tract motility occurs frequently in intensive care unit patients and often represents a substantial treatment challenge. In addition to specific complications such as pulmonary aspiration and diarrhea, abnormal gastrointestinal motility is a limiting factor for delivery and success of enteral nutrition. The pathophysiologies involved are incompletely understood because of the difficulties of making measurements of gastrointestinal function in critically ill patients. With the recent development of techniques that overcome some of these difficulties, the prospects are brighter for significant advances in this field.

Antro-pyloro-duodenal motor responses to gastric and duodenal nutrient in critically ill patients

Background: Gastric emptying is frequently delayed in critical illness which compromises the success of nasogastric nutrition. The underlying motor dysfunctions are poorly defined. Aims: To characterise antro-pyloro-duodenal motility during fasting, and in response to gastric and duodenal nutrient, as well as to evaluate the relationship between gastric emptying and motility, in the critically ill. Subjects: Fifteen mechanically ventilated patients from a mixed intensive care unit; 10 healthy volunteers. Methods: Antro-pyloro-duodenal pressures were recorded during fasting, after intragastric administration (100 ml; 100 kcal), and during small intestinal infusion of liquid nutrient (6 hours; 1 kcal/min). Gastric emptying was measured using a 13C octanoate breath test. Results: In healthy subjects, neither gastric nor small intestinal nutrient affected antro-pyloro-duodenal pressures. In patients, duodenal nutrient infusion reduced antral activity compared with both fasting and healthy subjects (0.03 (0–2.47) waves/min v 0.14 (0–2.2) fasting (p = 0.016); and v 0.33 (0–2.57)/min in healthy subjects (p = 0.005)). Basal pyloric pressure and the frequency of phasic pyloric pressure waves were increased in patients during duodenal nutrient infusion (3.12 (1.06) mm Hg; 0.98 (0.13)/min) compared with healthy subjects (−0.44 (1.25) mm Hg; p<0.02 after 120 minutes; 0.29 (0.15)/min; p = 0.0002) and with fasting (−0.06 (1.05) mm Hg; p<0.03 after 160 minutes; 0.49 (0.13)/min; (p = 0.0001). Gastric emptying was delayed in patients (gastric emptying coefficient 2.99 (0.2) v 3.47 (0.1); p = 0.015) and inversely related to the number of pyloric pressure waves (r = −0.563, p = 0.029). Conclusions: Stimulation of pyloric and suppression of antral pressures by duodenal nutrient are enhanced in the critically ill and related to decreased gastric emptying.

Prospective randomized controlled trial of argon plasma coagulation ablation vs. endoscopic surveillance of patients with Barrett's esophagus after antireflux surgery.

BACKGROUND Argon plasma coagulation is one of several techniques used to ablate Barretts esophagus. This study assessed the efficacy and safety of argon plasma coagulation in the ablation of Barretts esophagus in patients who have undergone antireflux surgery. METHODS A total of 40 patients with Barretts esophagus who had undergone a fundoplication were entered into a prospective, randomized, unblinded study comparing argon plasma coagulation with endoscopic surveillance. Treatment was repeated until either no Barretts epithelium remained or a maximum of 6 treatment sessions. RESULTS One month after the final treatment, complete ablation was achieved in 12 patients. In the remaining 8, a reduction of over 95% was observed. One patient died at 9 months of an unrelated cause. At 1 year, one patient with residual Barretts epithelium regressed completely, while relapse of Barretts esophagus was seen in another because of fundoplication failure. Buried glands were observed in 35% patients at 1 month, but only 5% at 1 year. Dysplasia was never seen. In the surveillance group, partial regression was observed in 11 patients, and, in 3 with short-segment Barretts esophagus, regression was complete. The length of Barretts esophagus increased in two patients. Two had low-grade dysplasia initially, but this was not evident at 1 year. Overall, complete ablation was achieved in 12 of 19 (63%) patients in the ablation group and 3 of 20 (15%) in the surveillance group (p<0.01). CONCLUSIONS Argon plasma coagulation of Barretts esophagus is safe and effective. The effects are durable, and buried glands may resolve with time. Long-term follow-up is required to assess the impact of argon plasma coagulation on cancer risk.

Risk Factors for Intraprocedural and Clinically Significant Delayed Bleeding After Wide-field Endoscopic Mucosal Resection of Large Colonic Lesions

BACKGROUND & AIMS Wide-field endoscopic mucosal resection (WF-EMR) of large sessile colonic polyps is a safe and cost-effective outpatient treatment. Bleeding is the main complication. Few studies have examined risk factors for bleeding during the procedure (intraprocedural bleeding [IPB]) or after it (clinically significant post-endoscopic bleeding [CSPEB]). We investigated factors associated with IPB and CSPEB in a large prospective study. METHODS We analyzed data from WF-EMRs of sessile colorectal polyps ≥ 20 mm in size (mean size, 35.5 mm), which were performed on 1172 patients (mean age, 67.8 years) from June 2008-March 2013 at 7 tertiary hospitals as part of the Australian Colonic Endoscopic Resection Study. Data were collected on characteristics of patients and lesions, along with outcomes of procedures and clinical and histologic analyses. Independent predictors of IPB and CSPEB were identified by multiple logistic regression analysis. RESULTS Of the patients studied, 133 (11.3%) had IPB. Independent predictors included increasing lesion size (odds ratio, 1.24/10 mm; P < .001), Paris endoscopic classification of 0-IIa + Is (odds ratio, 2.12; P = .004), tubulovillous or villous histology (odds ratio, 1.84; P = .007), and study institutions that performed the procedure on fewer than 75 patients (odds ratio, 3.78; P < .001). All IPB was successfully controlled endoscopically. IPB prolonged procedures and was associated with early recurrence (relative risk, 1.68; P = .011). Seventy-three patients (6.2%) had CSPEB. On multivariable analysis, CSPEB was associated with proximal colon location (odds ratio, 3.72; P < .001), use of an electrosurgical current not controlled by a microprocessor (odds ratio, 2.03; P = .038), and IPB (odds ratio, 2.16; P = .016). Lesion size and comorbidities did not predict CSPEB. CONCLUSIONS In a prospective study of patients undergoing WF-EMR of large sessile colonic polyps, IPB is associated with larger lesions, lesion histology, and Paris endoscopic classification of type 0-IIa + Is. IPB prolongs the duration of the procedure, is a marker for recurrence, and is associated with CSPEB. CSPEB occurs most frequently in the proximal colon and less when current is controlled by a microprocessor.

Impact of Endoscopic Suturing of the Gastroesophageal Junction on Lower Esophageal Sphincter Function and Gastroesophageal Reflux in Patients with Reflux Disease

OBJECTIVES:Plication of the gastroesophageal junction by endoscopic suturing has been reported to improve symptoms and reduce acid exposure in patients with gastroesophageal reflux disease (GERD). The mechanisms underlying these effects are not well defined. The aims of our study were to determine the impact of endoscopic suturing of the gastroesophageal junction on lower esophageal sphincter (LES) function in patients with GERD.METHODS:In 15 patients (7 males) with GERD (heartburn, % time esophageal pH < 4 greater than 4%, ± history of erosive esophagitis within 6 months), two plications were performed circumferentially 1 cm below the gastroesophageal junction. Endoscopy and combined postprandial esophageal manometry and pH monitoring were performed before and 6 months after treatment; 24-h ambulatory pH monitoring and symptom assessment were also performed before, and at 6 and 12 months after treatment.RESULTS:Six months after treatment, the rate of transient LES relaxations (tLESRs) was decreased by 37% (p < 0.05) and basal LES pressure had increased from 4.3 ± 2.2 mmHg to 6.2 ± 2.1 mmHg (p < 0.05). The rate of postprandial reflux events and acid exposure time were not altered. Endoscopic suturing significantly reduced 24-h esophageal acid exposure from 9.6% (9.0–12.1) to 7.4% (3.9–10.1) at 6 months, due predominantly to a reduction in upright acid exposure. The reduction in total 24-h acid exposure was sustained to 12 months. At repeat endoscopy, only one plication was evident in 6 patients (40%) at 6 months. Seven patients (47%) remained off medications at 6 and 12 months follow-up.CONCLUSIONS:In patients with GERD, endoscopic suturing of the gastroesophageal junction results in a reduction in the rate of tLESRs, and an increase in basal LES pressure. These changes in LES function result in only a modest reduction in gastroesophageal reflux.

Radial Distribution of Dilated Intercellular Spaces of the Esophageal Squamous Epithelium in Patients with Reflux Disease Exhibiting Discrete Endoscopic Lesions

Introduction: Dilatation of intercellular spaces of the esophageal squamous epithelium has been suggested as a marker of early acid reflux-induced damage. This change is a potentially useful addition to histomorphological changes that represent so called minimal endoscopic lesions. We have assessed dilatation of intercellular spaces with regard to: (1) interobserver variability, and (2) whether the incidence of this varies between ‘red streaks’ and the adjacent normal looking squamous epithelium. Methods: Esophageal biopsies from 44 patients with chronic gastro-esophageal reflux (GERD) were evaluated. At endoscopy, these patients had one or more red streaks on the tops of the mucosal folds in the distal esophagus. Biopsies were taken from the red streaks and from the normal-appearing mucosa 1 cm lateral to the red streaks. Biopsies were assessed in a blinded fashion by two independent pathologists (MV & RF). Criteria for assessing intercellular space dilatation were evaluated and agreed on prior to the study. Results: Good interobserver agreement was recorded (kappa = 0.82 at the streaks and 0.77 for the control tissues) for absence/presence of intercellular space dilatation. Red streak and control biopsies differed significantly (p = 0.0001), with respect to presence of dilated intercellular spaces, with 90.5 % of the former demonstrating this as present compared to 56.1% in the controls. Conclusion: This study supports the concept that esophageal mucosal minimal changes due to reflux is localised and that dilatation of intercellular spaces is an early sign of reflux-induced epithelial damage. The low interobserver variability in the assessment of intercellular space dilatation suggests that this may be a useful variable for assessment of early signs of acid-reflux induced damage to the squamous epithelium of the esophagus by use of light microscopy.

Randomized Trial of Argon Plasma Coagulation Versus Endoscopic Surveillance for Barrett Esophagus After Antireflux Surgery : Late Results

Objective:To determine the efficacy of endoscopic argon plasma coagulation (APC) for ablation of Barrett esophagus. Summary Background Data:APC has been used to ablate Barrett esophagus. However, the long-term outcome of this treatment is unknown. This study reports 5-year results from a randomized trial of APC versus surveillance for Barrett esophagus in patients who had undergone a fundoplication for the treatment of gastroesophageal reflux. Methods:Fifty-eight patients with Barrett esophagus were randomized to undergo either ablation using APC or ongoing surveillance. At a mean 68 months after treatment, 40 patients underwent endoscopy follow-up. The efficacy of treatment, durability of the neosquamous re-epithelialization, and safety of the procedure were determined. Results:Initially, at least 95% ablation of the metaplastic mucosa was achieved in all treated patients. At the 5-year follow-up, 14 of 20 APC patients continued to have at least 95% of their previous Barrett esophagus replaced by neosquamous mucosa, and 8 of these had complete microscopic regression of the Barrett esophagus. Five of the 20 surveillance patients had more than 95% regression of their Barrett esophagus, and 4 of these had complete microscopic regression (1 after subsequent APC treatment). The length of Barrett esophagus shortened significantly in both study groups, although the extent of regression was greater after APC treatment (mean 5.9–0.8 cm vs. 4.6–2.2 cm). Two patients who had undergone APC treatment developed a late esophageal stricture, which required endoscopic dilation, and 2 patients in the surveillance group developed high-grade dysplasia during follow-up. Conclusions:Regression of Barrett esophagus after fundoplication is more likely, and greater in extent, in patients who undergo ablation with APC. In most patients treated with APC the neosquamous mucosa remains stable at up to 5-year follow-up. The development of high-grade dysplasia only occurred in patients who were not treated with APC.