Andrea May

Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett's esophagus

BACKGROUND & AIMS In view of the mortality and morbidity rates of esophagectomy and the relatively large group of inoperable patients, local therapeutic techniques are required for high-grade dysplasia and early Barretts cancer. METHODS A prospective investigation of endoscopic mucosal resection was conducted in 64 patients (mean age, 65 +/- 10 years) who had early carcinoma (61 patients) or high-grade dysplasia (3 patients) in Barretts esophagus. Thirty-five patients met the criteria for low risk: macroscopic types I, IIa, IIb, and IIc; lesion diameter up to 20 mm; mucosal lesion; and histological grades G1 and G2 and/or high-grade dysplasia (group A). The remaining 29 patients were included in group B (high risk). RESULTS A total of 120 resections were performed, with no technical problems encountered. The mean number of treatment sessions per patient was 1. 3 +/- 0.6 in group A and 2.8 +/- 2.0 in group B (P < 0.0005). Only one major complication occurred, a case of spurting bleeding, which was managed endoscopically. Complete local remission was achieved significantly earlier (P = 0.008) in group A than in group B. In May 1999, complete remission had been achieved in 97% of the patients in group A and in 59% of those in group B; however, 1 patient in group A and 9 in group B are still undergoing treatment or awaiting the first check-up. During a mean follow-up of 12 +/- 8 months, recurrent or metachronous carcinomas were found in 14%. CONCLUSIONS Endoscopic mucosal resection of early carcinoma in Barretts esophagus is associated with promisingly low morbidity and mortality rates. The procedure may offer a new minimally invasive therapeutic alternative to esophagectomy, especially in low-risk situations. Comparisons with surgical results will need to be done when the long-term results of this procedure become available.

Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus.

Objective: Endoscopic therapy is increasingly being used in the treatment of high-grade intraepithelial neoplasia (HGIN) and mucosal adenocarcinoma (BC) in patients with Barrett’s oesophagus. This report provides 5 year follow-up data from a large prospective study investigating the efficacy and safety of endoscopic treatment in these patients and analysing risk factors for recurrence. Design: Prospective case series. Setting: Academic tertiary care centre. Patients: Between October 1996 and September 2002, 61 patients with HGIN and 288 with BC were included (173 with short-segment and 176 with long-segment Barrett’s oesophagus) from a total of 486 patients presenting with Barrett’s neoplasia. Patients with submucosal or more advanced cancer were excluded. Interventions: Endoscopic therapy. Main outcome measures: Rate of complete remission and recurrence rate, tumour-associated death. Results: Endoscopic resection was performed in 279 patients, photodynamic therapy in 55, and both procedures in 13; two patients received argon plasma coagulation. The mean follow-up period was 63.6 (SD 23.1) months. Complete response (CR) was achieved in 337 patients (96.6%); surgery was necessary in 13 (3.7%) after endoscopic therapy failed. Metachronous lesions developed during the follow-up in 74 patients (21.5%); 56 died of concomitant disease, but none died of BC. The calculated 5 year survival rate was 84%. The risk factors most frequently associated with recurrence were piecemeal resection, long-segment Barrett’s oesophagus, no ablative therapy of Barrett’s oesophagus after CR, time until CR achieved >10 months and multifocal neoplasia. Conclusions: This study showed that endoscopic therapy was highly effective and safe, with an excellent long-term survival rate. The risk factors identified may help stratify patients who are at risk for recurrence and those requiring more intensified follow-up.

Photodynamic ablation of high-grade dysplasia and early cancer in Barrett's esophagus by means of 5-aminolevulinic acid

Abstract Background & Aims: The first therapeutic experiences with the conventional photosensitizer dihematoporphyrinester in the treatment of Barretts esophagus show the curative potential of photodynamic therapy (PDT). The aim of this study was to test 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX, a photosensitizer with a high mucosa specificity without phototoxic side effects on the skin, as a new form of PDT. Methods: Thirty-two patients (mean age, 68.5 years) with histologically proven high-grade dysplasia (n = 10) and mucosal cancer (n = 22) in Barretts esophagus were treated. Four to 6 hours after oral ingestion of 5-ALA (dose, 60 mg/kg body wt), irradiation was conducted with a dye laser system (635 nm) with a light dose of 150 J/cm 2 . The patients received 20–80 mg omeprazole daily after PDT. Results: High-grade dysplasia was eradicated in all patients (10 of 10), and mucosal cancer was eliminated in 17 of 22 patients (77%) at a mean follow-up of 9.9 months (range, 1–30 months). All tumors ≤2 mm in thickness were completely ablated (17 of 17). The method-related mortality and morbidity was 0%. Conclusions: Severe dysplasia and thin (≤2 mm) mucosal cancer of Barretts esophagus can be completely ablated. PDT might offer a minimally invasive treatment modality as an alternative to esophagectomy. GASTROENTEROLOGY 1998;114:448-455

Local endoscopic therapy for intraepithelial high-grade neoplasia and early adenocarcinoma in Barrett's oesophagus: acute-phase and intermediate results of a new treatment approach.

Background Radical oesophageal resection has until now been regarded as the gold standard for treatment in intraepithelial high-grade neoplasia or early adenocarcinoma of the oesophagus. However, the mortality and morbidity rates are substantial. Design A new therapeutic approach involving low-risk endoscopic therapy modalities was examined in the framework of a prospective study. Patients A total of 115 patients with intraepithelial high-grade neoplasia (19) and early adenocarcinoma (96) in Barretts oesophagus. Methods Endoscopic mucosal resection (EMR) was used in 70 patients, and photodynamic therapy (PDT) was used in 32 patients. The two procedures were combined in ten patients. Three patients underwent primary treatment with argon plasma coagulation (APC). The average follow-up was 34 ± 10 months (range 24–60 months). Results Complete local remission was achieved in 98%. The overall complication rate was 9.5%. Major complications, such as perforation and severe bleeding, did not occur. Minor complications included not haemoglobin relevant bleeding (drop of haemoglobin less than 2 g/dl) (5) and stenosis (3) after EMR, and long-lasting odynophagia (1) and sunburn (2) after PDT. In all, 13 patients have died so far, but in only one case due to the underlying disease. The calculated overall 3-year survival rate is 88%. During the follow-up period, a 30% rate of metachronous lesions was observed; endoscopic therapy was performed successfully in all but one of these patients. Conclusions These good acute-phase and intermediate results, along with low morbidity rates and no mortality, suggest that the organ-preserving local endoscopic procedure including EMR and PDT is an attractive alternative to oesophageal resection. Therefore, endoscopic therapy might replace radical oesophageal resection in future in cases of intraepithelial high-grade neoplasia and early mucosal adenocarcinoma in Barretts oesophagus.

Endoscopic interventions in the small bowel using double balloon enteroscopy: feasibility and limitations.

BACKGROUND:Double-balloon enteroscopy (DBE) is a new endoscopic tool that not only allows diagnostic workup of small bowel diseases, but also makes it possible to carry out therapeutic interventions. However, for a variety of reasons, endoscopic therapy appears to be more difficult to carry out deep in the small bowel than in the upper or lower gastrointestinal tract.AIM:The purpose of this study was to evaluate the acute technical success and acute complication rate of DBE.PATIENTS:Between June 2003 and July 2006, 353 patients (152 women, 201 men; mean age 60.3 ± 17.1 yr) with suspected or known small bowel disease underwent 635 consecutive DBE procedures. The majority of the patients were suffering from midgastrointestinal bleeding (N = 210, 60%). The overall diagnostic yield was 75% (265/353) for relevant lesions in the small bowel. The overall therapeutic yield was 67% (236/353).METHODS:Endoscopic therapy was performed in 59% of these patients (139/236). All therapeutic interventions were done in an inpatient manner. The majority of the procedures were carried out with the patients under conscious sedation (N = 130, 73%); sedation with propofol was administered in 37 (20.8%) and with a combination of propofol and meperidine in 11 (6.2%) investigations.RESULTS:A total of 178 therapeutic procedures was carried out. A median of 270 cm of the small bowel was visualized using the oral route and a median of 150 cm using the anal route. The investigation time averaged 78 ± 30 minutes. The endoscopic treatments included argon plasma coagulation (APC, 102 treatment sessions), injection therapy (N = 2), a combination of APC and injection (N = 6), polypectomies (N = 46), dilation therapy (N = 18), and foreign-body extraction (N = 3). In 6/178 cases (3.4%), polypectomy (N = 2), dilation (N = 3), and implantation of a self-expanding metal stent (N = 1) could not be performed successfully for technical or anatomical reasons. Severe treatment-associated complications occurred in six of the 178 therapeutic procedures (3.4%) and 4/139 patients (2.9%), consisting of bleeding (N = 2) and perforation (N = 3) during and after polypectomy of large polyps (>3 cm in size), as well as one case of segmental enteritis after APC.CONCLUSIONS:Endoscopic therapeutic interventions can be performed safely even in the more difficult conditions of the small bowel in the majority of patients. Polypectomy of large polyps appears to be the procedure associated with the highest risk.

Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett's cancer and high-grade intraepithelial neoplasia

BACKGROUND Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has proven to be safe and effective in patients with early neoplasia in Barretts esophagus. However, long-term results in patients with high-grade intraepithelial neoplasia (HGIN) or with early cancer are still lacking. METHODS The aim of the study was to evaluate the efficacy of ALA-PDT and the survival of patients with early Barretts neoplasia. ALA-PDT was carried out in 66 patients. Protoporphyrin IX induced by oral administration of ALA (60 mg/kg body weight orally applied 4-6 hours before PDT) was used as the photosensitizer. Acid suppression was maintained in all patients. RESULTS Between September 1996 and September 2002, 667 patients with early neoplasia in Barretts esophagus were referred for local endoscopic therapy. A total of 558 patients fulfilled the criteria for local endoscopic therapy, and 66 patients (mean [standard deviation] age 61.4 [10.2] years) with HGIN (group A; n = 35) and early adenocarcinoma (group B; n = 31) were treated by PDT. A total of 82 ALA-PDT were performed. A total of 34 of the 35 patients in group A (97%) and all patients in group B (100%) achieved a complete response during a median follow-up period of 37 months (interquartile range 23-55) (not significant). One local recurrence was observed in group A and 10 in group B (p < 0.005). Seven patients died during follow-up; but, all deaths were not tumor related. No major complications were observed. Disease-free survival in patients with HGIN was 89%, and, in patients with mucosal cancer, it was 68%. The calculated 5-year survival was 97% in group A and 80% in group B, but there occurred no death related to Barretts neoplasia. CONCLUSIONS The excellent long-term results of PDT with ALA in patients with HGIN or mucosal cancer might offer PDT with ALA as an alternative to surgical esophagectomy and endoscopic resection, especially in cases with multifocal Barretts neoplasia.

Early Barrett's Carcinoma With “Low-Risk” Submucosal Invasion: Long-Term Results of Endoscopic Resection With a Curative Intent

BACKGROUND: Endoscopic therapy (ET) has become a less risky alternative to open surgery in mucosal Barretts cancer (BC) because of the very low risk of lymph node (LN) metastasis. Recently published surgical series demonstrated that even in case of minimal submucosal invasion of BC, the risk for LN metastasis is very low. In consequence, also these patients might be eligible for curative ET. The aim of this study was to prospectively evaluate the efficacy and safety of endoscopic resection (ER) in these patients.METHODS: From September 1996 to September 2003, the suspicion or definite diagnosis of submucosal BC was made in 80 patients referred to our department. Of those, 21 patients (20 male [95.2%], mean age 62 ± 9 yr, range 47–78) fulfilled the definition of “low-risk” submucosal cancer: invasion of the upper submucosal third (sm1), absence of infiltration into lymph vessels/veins, histological grade G1/2, and macroscopic type I/II. ET was carried out using ER with the suck-and-cut technique with or without an additive ablation of non-neoplastic remnants of Barretts esophagus.RESULTS:One of the 21 patients was referred to surgery directly after the detection of sm1 invasion at the beginning of the study. One patient died (not tumor-related) before completion of ET. Using definitive ET, complete remission (CR) was achieved in 18 of 19 patients (95%) after a mean of 5.3 months (range 1–18) and a mean of 2.9 resections (range 1–9). Only one minor complication (bleeding without drop in hemoglobin level >2 g/dL) occurred (5% of patients). During a mean follow-up (FU) of 62 months (range 45–89), recurrent or metachronous carcinomas were found in 5 patients (28%). Repeat ET was carried out successfully using ER (4 patients) and argon plasma coagulation (1 patient). In one of the 19 patients (5%), tumor freedom had not been achieved after a total of 2 ER. This patient died of a heart attack before surgery could be performed. The calculated 5-yr survival rate of all 21 patients was 66%. No tumor-related death occurred.CONCLUSIONS: As in mucosal BC, ER is associated with favorable outcomes even in case of “low-risk” submucosal BC. Further and larger clinical trials are required before a general recommendation for ER as the treatment of choice in “low-risk” submucosal BC can be given.

Cardiac rather than intestinal-type background in endoscopic resection specimens of minute Barrett adenocarcinoma

Many publications focusing on the background or original mucosa of Barrett adenocarcinoma have maintained that adenocarcinoma arises in intestinal-type mucosa with goblet cells in the columnar-lined esophagus, and this has become a central dogma. The mucosa on each side of a series of 141 minute esophageal adenocarcinomas (almost all of which were mucosal carcinomas) resected by endoscopic mucosal resection was recorded as the background mucosa. All 141 cases had endoscopic evidence of an esophageal origin, and for 113 of them, histologic evidence of an esophageal origin was also available. The mucosae were classified into 4 types--squamous, cardiac, fundic, and intestinal--based on routine histology and immunohistochemical staining. The present joint pathologic examination of the background mucosa of Barrett adenocarcinoma conducted by Japanese and German pathologists and gastroenterologists found that more than 70% of primary small adenocarcinomas (<2 cm) of the esophagus were adjacent to cardiac/fundic-type rather than intestinal-type mucosa. Moreover, intestinal metaplasia was not observed in any areas of the endoscopic mucosal resection specimens in 64 (56.6%) of the 113 cases. In other words, there was no evidence to support the previously held view that Barrett adenocarcinoma is nearly always accompanied and preceded by intestinal-type mucosa. Our study has demonstrated a close relationship between esophageal adenocarcinoma and cardiac-type mucosa. Therefore, it is not proven histogenetically that the background mucosa of esophageal adenocarcinoma is the intestinal type. Also, it seems better to define Barrett esophagus as metaplastic columnar-lined esophagus alone, without requiring the presence of goblet cells, in accordance with histogenetic and practical standpoints.

KTP laser destruction of dysplasia and early cancer in columnar-lined Barrett's esophagus

BACKGROUND The rising incidence of esophageal adenocarcinoma in western countries requires a new strategy in the management of dysplasia in Barretts esophagus. Esophagectomy, which has high morbidity and mortality rates, has been recommended to treat patients with severe dysplasia. Strictly superficial laser coagulation with tissue ablation therefore is a desirable option for the management of dysplasia in Barretts esophagus because the tissue to be ablated is only about 2 mm thick. Potassium-titanyl-phosphate (KTP) laser light with a wavelength of 532 nm is preferentially absorbed by hemoglobin and therefore combines excellent coagulation with limited tissue penetration. We report first clinical results with KTP laser superficial vaporization of dysplasia and early cancer in Barretts esophagus. METHODS Eight men and 2 women 43 to 84 years of age with short segments of Barretts esophagus or traditional Barretts esophagus and histologically proved low-grade (n = 4) and high-grade (n = 4) dysplasia or early adenocarcinoma (n = 2) were selected for this pilot study. For all patients thermal endoscopic destruction was conducted with a frequency-doubled neodymium:yttrium-aluminum-garnet (Nd:YAG) KTP laser system. Laser therapy was performed by means of the free-beam method with coaxial insufflation of gas. An average of 2.4 sessions per patient were required for ablation of the Barretts mucosa. RESULTS Two to three days after laser treatment the response of the ablated mucosa was assessed with endoscopy and biopsy. Samples taken showed fibrinoid necrosis of the mucosal layer. A complete response was obtained for all 10 patients. Replacement by normal squamous cell epithelium was induced in combination with acid suppression therapy of up to 80 mg omeprazole daily. No complications occurred. In two patients biopsy showed specialized mucosa beneath the restored squamous cell epithelial layer. Follow-up times were as long as 15 months (mean value 10.6 months). CONCLUSIONS KTP laser destruction of Barretts esophagus induced mucosal regeneration with normal squamous cell epithelium in combination with acid suppression. Limitation of the depth of thermal destruction in Barretts esophagus minimizes risk for perforation or stricture formation. KTP laser ablation of Barretts esophagus seems to be feasible and safe in short segments of Barretts esophagus with dysplasia or early cancer.

Prospective Comparison of Push Enteroscopy and Push-and-Pull Enteroscopy in Patients with Suspected Small-Bowel Bleeding

BACKGROUND AND AIMS:The management of patients with suspected mid-gastrointestinal bleeding has in the past been difficult, as push enteroscopy (PE) only allows limited endoscopic access for diagnosis and treatment. Recently published uncontrolled data on push-and-pull enteroscopy (PPE) using the double-balloon technique suggest that this new method has a high diagnostic yield and therapeutic efficacy. A prospective controlled study was therefore carried out to compare PPE with PE as the common nonsurgical gold standard method.METHODS:The diagnostic yield, complications, and various examination parameters were compared in 52 consecutive patients with suspected mid-gastrointestinal bleeding who were evaluated with both enteroscopy methods.RESULTS:No relevant complications were observed with either method. Sedoanalgesia, examination times, and X-ray exposure were lower with PE. The insertion depth was significantly greater with PPE than with PE (230 cm vs 80 cm, p < 0.0001). The overall diagnostic yield with PPE (38 of 52 patients, 73%) and the results of oral PPE only (33 of 52 patients, 63%) were superior to those with PE (23 of 52 patients, 44%; p < 0.0001). PPE identified additional lesions in deeper parts of the small bowel in PE-positive patients in 78% of cases (18 of 23 patients).CONCLUSIONS:For endoscopic examination of the small bowel in patients with suspected mid-gastrointestinal bleeding, PPE is superior to PE with regard to the length of small bowel visualized, as well as the diagnostic yield. As the method also allows endoscopic treatment to be carried out, PPE should always be considered before open surgery and intraoperative endoscopy in patients with mid-gastrointestinal bleeding.