Radiofrequency ablation in Barrett's esophagus with dysplasia. Endoscopic ablation of dysplastic Barrett's oesophagus comparing argon plasma coagulation and photodynamic therapy: a randomized prospective trial assessing efficacy and cost-effectiveness. Photodynamic therapy for dysplastic Barrett's oesophagus: a prospective, double blind, randomised, placebo controlled trial. Failure of Nd-YAG photocoagulation therapy as treatment for Barrett's oesophagus--a pilot study. Randomized trial of argon plasma coagulation versus endoscopic surveillance for barrett esophagus after antireflux surgery: late results. Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett's esophagus: international, partially blinded, randomized phase III trial. Endoscopic regression of Barrett's oesophagus during omeprazole treatment; a randomised double blind study. Endoscopic ablation of Barrett's oesophagus: a randomized-controlled trial of photodynamic therapy vs. argon plasma coagulation. Long-term results of a randomized prospective study comparing medical and surgical treatment of Barrett's esophagus. A randomised controlled trial of ablation of Barrett's oesophagus with multipolar electrocoagulation versus argon plasma coagulation in combination with acid suppression: long term results. Randomized trial of argon plasma coagulation vs. multipolar electrocoagulation for ablation of Barrett's esophagus. Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction. Cryosurgical ablation and radiofrequency ablation for unresectable hepatic malignant neoplasms: a proposed algorithm.
Barrett's 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 Barrett's esophagus and decrease the rate of neoplastic progression.
                In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barrett's 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 Barrett's esophagus. Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia.
                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.
                In patients with dysplastic Barrett's 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.)
                2009 Massachusetts Medical Society Endoscopic mucosal ablation is a promising technique that is used to treat dysplastic Barrett's oesophagus. The purpose of this study was to investigate the efficacy and cost-effectiveness of two promising techniques, argon plasma coagulation (APC) and photodynamic therapy (PDT), in the ablation of dysplastic Barrett's oesophagus.
                Twenty-six patients with dysplastic Barrett's oesophagus (21 M, median age 60 years, median length 4 cm, 23 low-grade dysplasia (LGD), 3 high-grade dysplasia (HGD)) were randomized to APC: 13 patients, PDT: 13 patients. APC was performed at a power setting of 65 W and argon gas flow at 1.8 l/min in 1-6 sessions (mean 5). PDT was performed 48 h after intravenous injection of Photofrin 2 mg/kg with a 630 nm red laser light, 200 J/cm through a PDT balloon in one session. All patients received treatment with high-dose proton pump inhibitors. Cost analysis was undertaken and the results were assessed by endoscopy and biopsies at 4 months and 12 months after therapy.
                All patients in both groups showed a reduction in the length of Barrett's oesophagus. The median length of Barrett's oesophagus eradicated at the 4-month follow-up: APC 65%, PDT 57% and at the 12-month follow-up: APC 56%, PDT 60%. Dysplasia eradication at 4 months: APC 62%, PDT 77%, p = 0.03 (95% CI 0.66-0.96) and at 12 months APC 67%, PDT 77%. Buried columnar glands with intestinal metaplasia were seen in both groups, with one patient in the PDT arm developing adenocarcioma under the neo-squamous epithelium. Severe adverse events included APC 2/13 (15%) stricture, 1/13 (8%) odynophagia, chest pain and fever; PDT 2/13 (15%) photosensitivity, 2/13 (15%) stricture. PDT would cost an additional 266 pounds sterling for every percentage reduction in Barrett's length and 146 pounds sterling per percentage reduction in dysplasia compared with APC treatment.
                APC and PDT are equally effective in eradicating Barrett's mucosa, with PDT being the more expensive treatment. However, PDT is more effective in eradicating dysplasia and the extra benefits of PDT are generated at an extra cost. The occurrence of buried columnar glands and carcinoma warrants caution. Long-term follow-up is needed to assess cancer prevention and the durability of the neo-squamous epithelium to justify these interventions. Photodynamic therapy (PDT) is a treatment in which cell damage is achieved by the action of light on a photosensitizing agent. We have assessed the potential use of PDT in the ablation of Barrett's oesophagus.
                Thirty six patients with dysplastic Barrett's oesophagus receiving acid suppression medication with omeprazole were randomised to receive oral 5-aminolaevulinic acid (ALA) 30 mg/kg or placebo, followed four hours later by laser endoscopy. Follow up endoscopy was performed at one, six, 12, and 24 months.
                Of 18 patients in the ALA group, a response was seen in 16 (median decrease in area in the treated region 30%; range 0-60%). In the placebo group, a decrease in area of 10% was observed in two patients with no change in 16 (median 0%; range 0-10%; treatment v placebo, p<0.001). No dysplasia was seen in the columnar epithelium within the treatment area of any patient in the PDT group. However, in the placebo group, persistent low grade dysplasia was found in 12 patients (p<0.001). There were no short or long term major side effects. The effects of treatment were maintained for up to 24 months.
                This is the first randomised controlled trial of PDT for Barrett's oesophagus. It demonstrates that ALA induced PDT can provide safe and effective ablation of low grade dysplastic epithelium. Acid suppression therapy and surgical antireflux procedures have not consistently led to regression of Barrett's epithelium. We reasoned that laser photocoagulation in combination with powerful acid suppression might destroy the metaplastic columnar epithelium and allow the area to be replaced by normal squamous mucosa.
                Eight patients with endoscopic and histologically proven Barrett's oesophagus were recruited into the study. Four patients were randomized to receive omeprazole 40 mg daily and four patients received the same medical therapy plus repeated laser photocoagulation administered at 4-6 weekly intervals. Endoscopies were performed on entry and at 6 months. The extent of Barrett's epithelium was assessed and mapped on to a grid system and histological changes were assessed in blinded manner by a single histopathologist. One new quadrant of Barrett's segment was irradiated per treatment.
                Laser therapy was well tolerated and no complications occurred. After 6 months, the extent of Barrett's epithelium was unchanged in both groups. There was no appearance of squamous islands either endoscopically or microscopically in areas treated with laser.
                Nd-YAG laser is ineffective in ablating Barrett's epithelium. To determine the efficacy of endoscopic argon plasma coagulation (APC) for ablation of Barrett esophagus.
                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.
                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.
                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.
                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. Barrett's esophagus (BE) may lead to high-grade dysplasia (HGD) and adenocarcinoma. The objective was to examine the impact of treating patients with BE and with HGD by using porfimer sodium (POR) and photodynamic therapy (PDT) for ablating HGD and reducing the incidence of esophageal adenocarcinoma.
                The design was a multicenter, partially blinded (pathology), randomized clinical trial conducted in patients with BE who have HGD. There were 30 contributing centers. A total of 485 patients were screened, with 208 in the intent-to-treat population and 202 in the safety population. Patients were randomized on a 2:1 basis to compare PDT with POR plus omeprazole (PORPDT) with omeprazole only (OM). The main outcome measurement was complete HGD ablation occurring at any time during the study period.
                There was a significant difference (p < 0.0001) in favor of PORPDT (106/138 [77%]) compared with OM (27/70 [39%]) in complete ablation of HGD at any time during the study period. The occurrence of adenocarcinoma in the PORPDT group (13%) (n=18) was significantly lower (p < 0.006) compared with the OM group (28%) [corrected] (n=20). The safety profile showed 94% of patients in the PORPDT group and 13% of patients in the OM group had treatment-related adverse effects. The limitations of the study were that PDT therapy may have had to be applied more than once and that patients spent more time in treatment. The patients and the physicians were not blinded to the treatment.
                PORPDT in conjunction with omeprazole is an effective therapy for ablating HGD in patients with BE and in reducing the incidence of esophageal adenocarcinoma. Barrett's oesophagus, columnar metaplasia of the epithelium, is a premalignant condition with a 50-100-fold increased risk of cancer. The condition is caused by chronic gastro-oesophageal reflux. Regression of metaplasia may decrease the cancer risk.
                To determine whether elimination of acid gastro-oesophageal reflux induces a regression of metaplastic epithelium.
                Sixty eight patients with acid reflux and proven Barrett's oesophagus were included in a prospective, randomised, double blind study with parallel groups, and were treated with profound acid secretion suppression with omeprazole 40 mg twice daily, or with mild acid secretion suppression with ranitidine 150 mg twice daily, for 24 months. Endoscopy was performed at 0, 3, 9, 15, and 24 months with measurement of length and surface area of Barrett's oesophagus; pH-metry was performed at 0 and 3 months. Per protocol analysis was performed on 26 patients treated with omeprazole, and 27 patients treated with ranitidine.
                Omeprazole reduced reflux to 0.1%, ranitidine to 9.4% per 24 hours. Symptoms were ameliorated in both groups. There was a small, but statistically significant regression of Barrett's oesophagus in the omeprazole group, both in length and in area. No change was observed in the ranitidine group. The difference between the regression in the omeprazole and ranitidine group was statistically significant for the area of Barrett's oesophagus (p=0. 02), and showed a trend in the same direction for the length of Barrett's oesophagus (p=0.06).
                Profound suppression of acid secretion, leading to elimination of acid reflux, induces partial regression of Barrett's oesophagus. Barrett's oesophagus is the major risk factor for oesophageal adenocarcinoma. 5-Aminlevulinic acid-induced photodynamic therapy and argon plasma coagulation have been shown to be effective for ablating Barrett's oesophagus, but a comparative trial of these two modalities has not been reported.
                To compare photodynamic therapy and argon plasma coagulation for the ablation of Barrett's oesophagus.
                A total of 68 patients (54 male, 14 female; median age 61) with Barrett's oesophagus were randomized to photodynamic therapy (n = 34) or argon plasma coagulation (n = 34). Photodynamic therapy was performed using 5-aminlevulinic acid (30 mg/kg) and red light. Argon plasma coagulation was administered at a power setting of 65 W. Multiple treatment sessions were performed, with follow-up to 24 months.
                All patients showed a macroscopic reduction in the area of Barrett's oesophagus. This was greatest in the argon plasma coagulation group with 33 of 34 (97%) ablated, compared with 17 of 34 (50%) in the photodynamic therapy group; in the remainder, there was a reduction in the length of Barrett's oesophagus (median 50%, range: 5-90). Buried glands were found in 24% of photodynamic therapy patients, and in 21% of argon plasma coagulation patients. The median follow-up is 12 months (range: 6-24).
                Photodynamic therapy and argon plasma coagulation are both effective for ablating Barrett's oesophagus. Argon plasma coagulation appears more effective than photodynamic therapy, but the impact of both on carcinoma development requires larger studies with long-term follow-up. To compare the results of medical treatment and antireflux surgery in patients with Barrett's esophagus (BE).
                The treatment of choice in BE is still controversial. Some clinical studies suggest that surgery could be more effective than medical treatment in preventing BE from progressing to dysplasia and adenocarcinoma. However, data from prospective comparative studies are necessary to answer this question.
                One hundred one patients were included in a randomized prospective study, 43 with medical treatment and 58 with antireflux surgery. All patients underwent clinical, endoscopic, and histologic assessment. Functional studies were performed in all the operated patients and in a subgroup of patients receiving medical treatment. The median follow-up was 5 years (range 1-18) in the medical treatment group and 6 years (range 1-18) in the surgical treatment group.
                Satisfactory clinical results (excellent to good) were achieved in 39 of the 43 patients (91%) undergoing medical treatment and in 53 of the 58 patients (91%) following antireflux surgery. The persistence of added inflammatory lesions was significantly higher in the medical treatment group. The metaplastic segment did not disappear in any case. Postoperative functional studies showed a significant decrease in the median percentage of total time with pH below 4, although 9 of the 58 patients (15%) showed pathologic rates of acid reflux. High-grade dysplasia appeared in 2 of the 43 patients (5%) in the medical treatment group and in 2 of the 58 patients (3%) in the surgical treatment group. In the latter, both patients presented with clinical and pH-metric recurrence. There was no case of malignancy after successful antireflux surgery.
                These results show that there are no differences between the two types of treatment with respect to preventing BE from progressing to dysplasia and adenocarcinoma. However, successful antireflux surgery proved to be more efficient than medical treatment in this sense, perhaps because it completely controls acid and biliopancreatic reflux to the esophagus. Many modalities have been used to ablate Barrett's oesophagus (BO). However, long term results and comparative effectiveness are unknown.
                Our aim was to compare the long term efficacy of achieving complete reversal (endoscopic and histological) between multipolar electrocoagulation (MPEC) and argon plasma coagulation (APC) in BO patients and assess factors influencing successful ablation.
                Patients with BO, 2-6 cm long, underwent 24 hour pH testing on proton pump inhibitor (PPI) therapy. Patients were then randomised by BO length to undergo ablation with MPEC or APC every 4-8 weeks until endoscopic reversal or maximal of six treatment sessions.
                Thirty five BO patients have been followed for at least two years following endoscopic ablation, 16 treated with MPEC and 19 with APC. There was complete reversal of BO in 24 patients (69%); 75% with MPEC and 63% with APC (p = 0.49). There was no difference in the number of sessions required in the two groups. There was no difference in age, pH results, BO length, PPI dose, or hiatal hernia size between patients with and without complete reversal. One patient developed an oesophageal stricture but there were no major complications such as bleeding or perforation.
                In BO patients treated with MPEC or APC in combination with acid suppression, at long term follow up, complete reversal of BO can be maintained in approximately 70% of patients, irrespective of the technique. There are no predictors associated with achieving complete reversal of BO. Continued surveillance is still indicated in the post ablative setting. As yet, these techniques are not ready for clinical application (other than for high grade dysplasia or early oesophageal adenocarcinoma) and cannot be offered outside the research arena. Endoscopic ablation of Barrett's esophagus has been described in which various thermocoagulation modalities are used in combination with a high dose of a proton pump inhibitor. No randomized comparison of ablation strategies has been published.
                Referred patients were screened to identify those with Barrett's esophagus 2 to 7 cm in length, without high-grade dysplasia or cancer. Included patients received pantoprazole (40 mg twice a day), followed by randomization to treatment with argon plasma coagulation (APC) or multipolar electrocoagulation (MPEC). The primary outcome measure was the number of treatment sessions required for endoscopic ablation.
                Of 235 patients screened, 52 were randomized. The mean length of Barrett's esophagus was 3.1 cm in the MPEC group vs. 4.0 cm in the APC group (p = 0.03). Otherwise, the treatment groups were similar with regard to baseline characteristics. The mean number of treatment sessions required for endoscopic ablation was 2.9 for MPEC vs. 3.8 for APC (p = 0.04) in an intention-to-treat analysis (p = 0.249, after adjustment for the difference in length of Barrett's esophagus). The proportion of patients in which ablation was endoscopically achieved proximal to the gastroesophageal junction was 88% for the MPEC group vs. 81% for the APC group (p = 0.68) and histologically achieved in 81% for MPEC vs. 65% for APC (p = 0.21). The mean time required for the first treatment session was 6 minutes with MPEC vs. 10 minutes with APC (p = 0.01) in per protocol analysis. There was no serious adverse event, but transient moderate to severe upper-GI symptoms occurred after MPEC in 8% vs. 13% after APC (p = 0.64). Conclusions Although there were no statistically significant differences, ablation of Barrett's esophagus with pantoprazole and MPEC required numerically fewer treatment sessions, and endoscopic and histologic ablation was achieved in a greater proportion of patients compared with treatment with pantoprazole and APC. A prospective controlled randomized trial was performed in order to assess the effectiveness and safety of photodynamic therapy versus laser resection in 31 patients with partial or complete tracheobronchial obstruction due to inoperable non-small cell lung cancer. Fourteen patients received dihaematoporphyrin ether and argon dye laser photoradiation, and 17 patients received Nd-YAG laser resection. Endoluminal obstruction of >75% was found in 77.4% of the patients. Among the symptoms, cough was more severe in the Nd-YAG group (p=0.02). Patients in both groups experienced symptomatic relief after treatment (p=0.003). Patients in the photodynamic therapy (PDT) group showed a significantly longer time until treatment failure (p=0.03) and longer median survival (p=0.007). Bronchitis and photosensitization (both in the PDT group) were the most common adverse effects. There was one death, probably related to treatment, in the PDT group. Photodynamic therapy and neodymium-yttrium aluminium garnet laser resection showed similar effectiveness and safety in the palliation of symptoms. The more prolonged survival in the photodynamic therapy group may have been due to differences in tumour stage between the groups. The degree of obstruction improved after treatment in both groups. In conclusion, photodynamic therapy is a valid method of palliation in partially or totally obstructing non-small cell lung carcinoma. Thermal ablation of unresectable hepatic tumors can be achieved by cryosurgical ablation (CSA) or radiofrequency ablation (RFA). The relative advantages and disadvantages of each technique have not yet been determined.
                Radiofrequency ablation of malignant hepatic neoplasms can be performed safely, but is currently limited by size. Cryosurgical ablation, while associated with higher morbidity, is more effective for larger unresectable hepatic malignant neoplasms.
                Retrospective analysis of prospective patient database.
                Between July 1992 and September 1999, 308 patients with liver tumors not amenable to curative surgical resection were treated with CSA and/or RFA (percutaneous, laparoscopic, celiotomy). No patient had preoperative evidence of extrahepatic disease. All patients underwent laparoscopy with intraoperative ultrasound if technically possible. Both RFA and CSA were performed under ultrasound guidance. Resection, as an adjunctive procedure, was combined with ablation in certain patients.
                Laparoscopy identified extrahepatic disease in 12% of patients, and intraoperative hepatic ultrasound identified additional lesions in 33% of patients, despite extensive preoperative imaging. Radiofrequency ablation alone or combined with resection or CSA resulted in reduced blood loss (P<.05), thrombocytopenia (P<.05), and shorter hospital stay compared with CSA alone (P<.05). Median ablation times for lesions greater than 3 cm were 60 minutes with RFA and 15 minutes with CSA (P<.001). Local recurrence rates for lesions greater than 3 cm were also greater with RFA (38% vs 17%).
                Laparoscopy and intraoperative ultrasound are essential in staging patients with hepatic malignant neoplasms. Radiofrequency ablation when combined with CSA reduces the morbidity of multiple freezes. Although RFA is safer than CSA and can be performed via different approaches (percutaneously, laparoscopically, or at celiotomy), it is limited by tumor size (<3 cm). Percutaneous RFA should be considered in high-risk patients or those with small local recurrences.
Despite their failure to eradicate Barrett's oesophagus, the role of medical and surgical interventions to reduce the troubling symptoms and sequelae of GORD is not questioned. Whether therapies for GORD reduce the cancer risk is not yet known. Ablative therapies have an increasing role in the management of dysplasia within Barrett's and current data would favour the use of radiofrequency ablation compared with photodynamic therapy. Radiofrequency ablation has been shown to yield significantly fewer complications than photodynamic therapy and is very efficacious at eradicating both dysplasia and Barrett's itself. However, long-term follow-up data are still needed before radiofrequency ablation can be used in routine clinical care without the need for very careful post-treatment surveillance. More clinical trial data and in particular randomised controlled trials are required to assess whether or not the cancer risk is reduced in routine clinical practice.