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Biomedical subjects

S E Attwood

Publications and source records attributed to S E Attwood.

At least 19 recordsLinked to original sources

Prevention of the neoplastic progression of Barrett's oesophagus by endoscopic argon beam plasma ablation.

BACKGROUND: Patients with Barrett's oesophagus have a risk of approximately 1 per 100 patient-years for the development of oesophageal adenocarcinoma. Endoscopic ablation of Barrett's oesophagus has been shown to lead to the regrowth of a 'neo' squamous epithelium if gastro-oesophageal reflux is controlled, but the incidence of subsequent tumour formation is unknown. METHODS: The follow-up of 55 patients who underwent endoscopic ablation of Barrett's oesophagus by argon beam plasma coagulation (ABPC) is reported. Of the 55 patients, nine had low-grade dysplasia, nine had high-grade dysplasia and the remainder had non-dysplastic Barrett's metaplasia. Twelve patients had reflux control by antireflux surgery and the remainder received proton pump inhibitor therapy. Barrett's metaplasia was ablated by ABPC to within 2 cm of the gastro-oesophageal junction. RESULTS: To date, one patient has died and one patient was unable to complete treatment. The remaining patients were followed by regular endoscopic surveillance for a mean of 38.5 months to give a total follow-up of 173.5 patient-years. No malignancy has developed in any patient during follow-up. CONCLUSION: The absence of malignant complications in this study of prophylactic ablation of long-segment Barrett's oesophagus strengthens the argument for endoscopic ablation in the prevention of oesophageal adenocarcinoma.

Adenocarcinoma↗

Who defines Barrett's oesophagus: endoscopist or pathologist?

The diagnosis of Barrett's oesophagus has traditionally relied on the identification of a 3-cm segment of endoscopically abnormal epithelium (columnar) in the distal oesophagus. More recently, the presence of intestinal metaplasia has become essential. The importance of the definition relates to the identification of the risk of cancer development. These factors are discussed in the context of the rising incidence of adenocarcinoma, and the relative contributions of endoscopists and pathologists in determining likely progression are explored. We also discuss the advances in endoscopic technology that may aid the endoscopist in predicting malignant progression.

Barrett Esophagus↗

Cyclooxygenase-2 expression in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.

OBJECTIVE: Increased expression of the inducible cyclooxygenase 2 (COX-2) enzyme has been detected in esophageal and colonic adenocarcinoma, and intake of aspirin and non-steroidal anti-inflammatory drugs, known COX-2 inhibitors, have been associated with reduced tumor formation. Elevated COX-2 mRNA but variable protein expression has been demonstrated in Barrett's epithelium, and we have, therefore, sought to evaluate the expression of COX-2 protein throughout the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. METHODS: Paraffin-embedded esophageal biopsies from 56 different patients with Barrett's esophagus were analyzed for COX-2 expression by immunohistochemistry. Twenty contained nondysplastic intestinal and gastric metaplasia, 12 demonstrated low-grade dysplasia (LGD), 12 high-grade dysplasia (HGD), and 12 contained invasive adenocarcinoma. RESULTS: Epithelial expression of COX-2 protein was detected in 75% (15/20) of benign cases, 83% (10/12) of cases with LGD, and 100% of cases with HGD or adenocarcinoma. Using a semiquantitative analysis, median staining scores for the groups were 2, 3, 14, and 13, respectively (scale 0-16), with the expression being significantly higher in the HGD and cancer groups compared to benign and LGD groups (p < 0.001). CONCLUSIONS: This study demonstrates clear COX-2 expression in the epithelial cells in Barrett's metaplasia, confirms elevated expression in adenocarcinoma, and shows that the elevation in expression occurs in the progression from LGD to HGD.

Adenocarcinoma↗

Argon beam plasma coagulation in the management of cancers of the esophagus and stomach.

BACKGROUND: Esophagogastric cancer often presents at an advanced stage, or in patients unfit for resection. These patients may benefit from local ablation to provide both symptom and disease control. METHODS: A series of 48 consecutive patients with esophagogastric cancer were treated with endoscopic argon beam plasma coagulation (ABPC) at a specialist unit. RESULTS: Of 16 unfit patients who presented with early cancers, four are disease-free and all are asymptomatic at a median of 21 months after treatment. In 13 of 14 patients with occluded esophageal stents, the esophageal lumen was restored. In 18 patients with advanced cancers, ABPC was employed to debulk two gastric outlet and eight esophageal tumors. Argon was employed successfully to control bleeding in three of five patients. In advanced disease, dysphagia was relieved in only one of three patients. CONCLUSIONS: Endoscopic ABPC controls symptoms and may control early esophageal and gastric cancers in unfit patients. ABPC allows restoration of the lumen in stent overgrowth and control of bleeding from advanced gastric neoplasms; however, its role in debulking large tumors is less clear.

Aged↗

Duodenogastric reflux of bile in health: the normal range.

Duodenogastric reflux (DGR) is suspected to be an aetiological factor in the pathogenesis of foregut disease. The 'Bilitec' bile probe allows continuous detection of bilirubin, based on spectrophotochemical properties. We aimed to describe duodenogastric bile reflux in healthy, normal volunteers in a Western European population, as a basis for the future study of DGR in disease. An international multicentre study was established. DGR was measured using 24 h ambulatory bile and pH monitoring in the proximal stomach, in 43 normal volunteers from the third to the seventh decades. Subjects adhered to a standard protocol. The total test period, supine and upright components, were analysed. The 90th percentile values for absorbance thresholds of 0.14, 0.25, 0.3, 0.4 and 0.5 were 40.5%, 20.9%, 19.6%, 11.6% and 4.6% of the total time respectively. There was a wide range of absorbance within each threshold. Supine DGR was greater than upright, and associated with an alkaline tide. The upright phase was further subdivided into upright fasting, prandial and post prandial phases, and ranges for these periods are also described. No relationship between age, weight, or body mass index and duodenogastric reflux was seen. The results of this study form a range which allows further investigation into the contribution of duodenogastric bile reflux in the pathogenesis of foregut disease.

Adult↗

Comparative study of intestinal metaplasia and mucin staining at the cardia and esophagogastric junction in 225 symptomatic patients presenting for diagnostic open-access gastroscopy.

OBJECTIVE: Adenocarcinoma around the esophagogastric junction (EGJ) is increasing in incidence, and is frequently associated with areas of macroscopic or microscopic intestinal metaplasia (IM). The aim of this study was to define the incidence and type of metaplastic changes in the cardia and at the EGJ in symptomatic patients in whom there was no endoscopic columnar segment. METHODS: Patients attending for open-access gastroscopy had three sets of endoscopic biopsies taken at 3-cm intervals, from cardia, EGJ, and distal esophagus. Hematoxylin and eosin, Alcian blue/PAS (AB/PAS), and high-iron diamine/Alcian blue (AB/HID) were used to define and characterize IM. RESULTS: Of 225 patients, eight (4%) had carcinoma, eight (4%) had conventional long-segment Barrett's esophagus, 15 (7%) showed endoscopic short-segment Barrett's change, with no endoscopic Barrett's in 194 (86.2%). Of the latter, 34 (17.5%) had IM at the EGJ, and nine (4.6%) had IM at the cardia on hematoxylin and eosin. Acid mucin stains were positive at the EGJ in 135 (69.6%) and at the cardia in 75 (38.7%). Metaplasia at the EGJ was associated with sulphomucins (p < 0.0001) and involved the surface glandular epithelium (p < 0.0001) more frequently than the cardia. Metaplasia was not related to reflux symptoms, hiatus hernia, or endoscopic esophageal inflammation. Ninety percent of those with IM detectable by hematoxylin and eosin were taking acid suppression, compared with 72.8% overall. CONCLUSIONS: Intestinal metaplasia is very common at the esophagogastric junction and gastric cardia, with marked differences in incidence and characteristics of mucin staining between the two sites. The relationship of intestinal metaplasia to the development of carcinoma is yet to be determined.

Adolescent↗

Simple laparoscopic gastropexy as the initial treatment of paraoesophageal hiatal hernia.

BACKGROUND: Paraoesophageal hiatal hernia is relatively rare compared with sliding hernia but it is associated with serious complications. Its clinical management presents a major challenge since many patients are elderly and unfit for a formal repair. This paper describes a laparoscopic method aimed at reducing the complications of open repair. METHODS: Thirteen patients treated for symptomatic paraoesophageal hernia were included in the study. Eleven patients successfully underwent a simple laparoscopic modification of the Boerema anterior gastropexy. Two patients required an open anterior gastropexy through a minilaparotomy because of incomplete reduction of the hernia. A five-puncture technique was used. The stomach and any other contents of the sac were reduced into the abdomen and the stomach was firmly fixed to the fascia of the anterior abdominal wall with GORE-TEX sutures tied extracorporeally. RESULTS: There was one postoperative death due to spontaneous intrathoracic perforation of the posterior aspect of the stomach in an elderly woman with severe cardiac disease. There was no postoperative morbidity. Eight of the ten patients who went home following laparoscopic gastropexy have remained asymptomatic on follow-up. In three patients, two in the laparoscopic group and one in the open group, symptoms recurred. CONCLUSION: While anterior gastropexy has a significant incidence of recurrent herniation, the clinical results of this simple procedure in a high-risk population support its use as the initial surgical option.

Aged↗

Restoration of the normal squamous lining in Barrett's esophagus by argon beam plasma coagulation.

OBJECTIVE: Barrett's esophagus is associated with significantly increased risk of development of esophageal adenocarcinoma. Replacing columnar epithelium with the normal squamous lining in this condition offers the possibility of decreasing the risk of degeneration to invasive adenocarcinoma. This study aimed to establish the feasibility of argon beam plasma coagulation (ABPC), in conjunction with control of gastroesophageal reflux, to restore the squamous lining. METHODS: Thirty patients with Barrett's esophagus (four low-grade dysplasia, three high-grade) were recruited from our surveillance program, and underwent endoscopic ABPC. RESULTS: Twenty-seven patients completed treatment, with macroscopic replacement of their columnar lining by squamous epithelium, histologically confirmed in all 27, and followed up for a median of 9 months (range, 6-18 months). Two patterns of squamous replacement were identified: 70% of patients showed squamous epithelium with no persistent intestinal metaplasia, and in 30% the new squamous epithelium covered areas of underlying intestinal metaplasia. One patient has withdrawn from the study. Two esophageal perforations, with one death, occurred early in the study. CONCLUSION: ABPC, in conjunction with control of gastroesophageal reflux, allows squamous regrowth in both benign and dysplastic Barrett's esophagus. Despite the theoretical safety advantages of ABPC over techniques such as laser, esophageal perforation may occur with this technique. It is too soon to recommend ABPC for dysplastic or nondysplastic Barrett's because follow-up is too short to show a decreased incidence of and mortality from adenocarcinoma.

Adenocarcinoma↗

The management of impalement injury.

Four cases of impalement injury are described. The principles of management are discussed, these being minimal manipulation of the object before and during transport, preoperative planning, a multidisciplinary approach, and wound care.

Abdominal Injuries↗

Adhesions after laparoscopic inguinal hernia repair. A comparison of extra versus intra peritoneal placement of a polypropylene mesh in an animal model.

Prosthetic mesh for laparoscopic inguinal hernia repair has become popular but the method of its placement is controversial. Mesh placed within the peritoneum may cause adhesion formation and further complications. The aim of this study was to examine the laparoscopic placement of a mesh, comparing intraperitoneal vs extraperitoneal insertion. In a porcine model (n = 15) a polypropylene mesh was placed laparoscopically over the anterior abdominal wall. On the left side the mesh was stapled on the parietal peritoneum. On the right side the peritoneum was incised, an extraperitoneal space was dissected, the mesh was inserted, and the peritoneum was closed over it. The animals were maintained for 2 weeks. At postmortem there were adhesions in two of those placed extraperitoneally and five of those placed intraperitoneally (P = 0.19, Fisher's exact test). The adhesions comprised fibrous peritoneal bands to loops of small intestine. Both methods of laparoscopic mesh placement were associated with a small but significant incidence of adhesion formation.

Animals↗

An ambulatory bile reflux monitoring system: an in vitro appraisal.

Assessment of duodenogastric bile reflux has hitherto been unsatisfactory. An ambulatory system which utilizes the optical properties of bilirubin is examined. Test readings are correlated with the laboratory values for bilirubin in each of a number of physiological solutions. For dilutions of pure bile there was a linear correlation between absorbance and bilirubin concentration (r = 0.93, p < 0.001). In the more acidic environment of gastric juice there was also a linear correlation between absorbance and bilirubin concentration (r = 0.65, p < 0.001), but absorbance values were significantly higher than those of pure bile solutions (F ratio = 130, p < 0.0001). Normal gastric secretions and saliva give low absorbance values (0.02-0.04). Common foodstuffs such as soups, tea and coffee give higher readings and may interfere with bile reflux assessment in a clinical setting. Bilitec 2000 has potential for use as an ambulatory bile reflux monitoring system but consideration should be given to a standard diet or attention must focus on the fasting period.

Ambulatory Care↗

Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome.

Small numbers of intraepithelial esophageal eosinophils (IEE) may be seen in 50% of patients with gastroesophageal reflux disease and occasionally in normal volunteers. High concentrations of IEE are rarely seen in either setting. During a two-year period we identified 12 adult patients with very dense eosinophil infiltrates in esophageal biopsies (defined as > 20 IEE/high-power field). Dysphagia was the presenting complaint in each, but no evidence of anatomical obstruction could be found. Endoscopic esophagitis was absent, but biopsy showed marked squamous hyperplasia and many IEE. Eleven patients had normal esophageal acid exposure on 24-hr pH monitoring. Esophageal manometry showed a nonspecific motility disturbance in 10 patients. For comparison, 90 patients with excess esophageal acid exposure on 24-hr pH monitoring were studied. Thirteen (14%) had motility disturbance, and 21 (23%) had dysphagia. Esophageal biopsies were devoid of IEE in 47 patients; none of the 43 with IEE had infiltrates as dense as those seen in the 12 study patients. The presence of high concentrations of IEE in esophageal biopsies from patients with dysphagia, normal endoscopy, and normal 24-hr esophageal pH monitoring represents a distinctive clinicopathologic syndrome not previously described.

Adult↗

Role of intragastric and intraoesophageal alkalinisation in the genesis of complications in Barrett's columnar lined lower oesophagus.

Patients with Barrett's columnar lined lower oesophagus have severe acid gastrooesophageal reflux and may develop complications, including ulceration, stricture, and carcinoma. The aim of this study was to establish if a relationship exists between the pH profile in the oesophagus and stomach and the development of complications in patients with Barrett's columnar lined lower oesophagus. Twenty four hour ambulatory oesophageal pH monitoring was performed in 26 patients with Barrett's columnar lined lower oesophagus and combined with 24 hour ambulatory gastric pH monitoring in 16. Ten of the 26 with Barrett's columnar lined lower oesophagus had complications including stricture (eight), deep ulceration (one), and carcinoma (one). Oesophageal acid exposure (% time < pH 4) was similar in patients with or without complications (19.2% v 19.3% p > 0.05). Oesophageal alkaline exposure (% time > pH 7) was greater in patients with complications (24.2% v 8.4% p > 0.05). Of the 16 patients who underwent gastric pH monitoring there was a clear relationship between gastric and oesophageal alkalinisation in 13. These results support the hypothesis that complications in Barrett's columnar lined lower oesophagus develop in association with increased exposure of the oesophagus to an alkaline environment which appears to be secondary to duodenogastric reflux. The routine use of 24 hour ambulatory gastric pH monitoring in conjunction with oesophageal pH monitoring can help identify those patients at risk.

Alkalies↗

Barrett's esophagus.

A new stimulus for research into the etiology and pathogenesis of Barrett's columnar-lined lower esophagus has been provided by the discovery that Barrett's esophagus has a very high prevalence in the general population and that adenocarcinoma of the esophagus and cardia is the fastest-growing cancer in the United States. Gastroesophageal reflux disease is the single most important factor in the pathogenesis of Barrett's esophagus, and duodenal juices may play a key role in the development of complications of stricture, ulceration, and possibly even malignant degeneration. Treatment is, therefore, aimed at abolishing all forms of reflux. Acid suppression, if used, needs to be given in massive doses to be effective in gastric hypersecretion and has no effect on other constituents of the refluxed material. Antireflux surgery has been shown to be superior to all forms of medical treatment. Regression is rare after any therapy, but continued surveillance is essential, with increased vigilance in patients with dysplasia or DNA abnormalities on flow cytometry. The role of cigarettes and alcohol in malignant degeneration is refuted.

Adenocarcinoma↗