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 One patient has withdrawn from the study.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.     

Review: Barrett's oesophagus in Taiwan

Barrett's oesophagus is the eponym applied to the columnar epithelium-lined lower oesophagus which is acquired as a complication of chronic gastro-oesophageal reflux (GER). Various complications seen in the Barrett's oesophagus, such as peptic ulcer, stricture, adenocarcinoma are named as Barrett's ulcer, Barrett's stricture-and Barrett's carcinoma, respectively. It is now generally accepted that Barrett's oesophagus is an acquired condition resulting from chronic repetitive GER. The frequency of Barrett's oesophagus seems to be higher in Caucasian than in Oriental or Negro populations. There is a tendency towards increasing prevalence rates all over the world, including Taiwan, due to the Westernization of diet, rapid growth in the elderly population, obesity etc. Almost 6% of the patients who manifest heartburn in GI clinics in Taiwan now suffer from GER, which is almost similar to the 7% reported by Nabel, (USA) in 1976. During the last 30 years, the incidence of esophageal adenocarcinoma has increased rapidly. Patients with Barrett's oesophagus have an increased risk of developing oesophageal adenocarcinoma and should be kept under surveillance. Regular follow-up, at least twice a year or preferably, every 2-3 months, for those patients with SCE using endoscopic surveillance and biopsy for those with severe dysphasia (oesophageal columnar intraepithelial neoplasia) in the surrounding area to detect Barrett's oesophagus cancer, is very important.     

Restoration of squamous mucosa after ablation of Barrett's esophageal epithelium

BACKGROUND: Antireflux therapy has generally failed to induce regression of Barrett's epithelium. It was hypothesized that squamous epithelium could be restored if the columnar tissue was ablated while gastric acid secretion was suppressed. METHODS: Ten white men with Barrett's esophagus received 40 mg of omeprazole daily. Thereafter, every 2-5 weeks they underwent videotaped endoscopies to argon laser photoablate columnar tissue, obtain biopsy specimens, and assess results. Squamous re-epithelialization was assessed by correlation of videotapes and directed biopsies. RESULTS: Patients had one to eight areas ablated, totaling 0.5-12.0 cm2. Videotape assessments were corroborated by biopsy in all but one instance. Thirty-eight of 40 treatment locations partially or completely re-epithelialized with squamous tissue. Squamous regrowth appeared to occur by spread from contiguous squamous borders and de novo from glandular tissue. Regrowth was influenced by the extent of squamous borders and completeness of ablations. Nonablated glandular tissue persisted beneath squamous epithelium. CONCLUSIONS: Ablation of Barrett's epithelium and suppression of acid secretion facilitated squamous re-epithelialization. A progenitor cell within the metaplastic tissue has the potential to differentiate normally.     

Eradication of Barrett''s mucosa with argon plasma coagulation and acid suppression: immediate and mid term results

Microcapsules are used for the formulation of drug controlled release and drug targeting dosage forms. Encapsulated hydrophobic drugs are often applied as their solutions in plant oils. The uptake of the oils in the complex coacervate microcapsules can be improved by the addition of surfactants. In this study, soybean, olive and peanut oils were chosen as the representatives of plant oils. The well characterized complex coacervation of gelatin and acacia has been used to produce the microcapsules. The amount of encapsulated oil has been determined gravimetrically. The encapsulation of the oils was high (75-80%). When the surfactants with HLB values from 1.8 to 6.7 were used, the amount of encapsulated oil was high (65-85%). A significant decrease of the oil content in the microcapsules was found when Tween 61 with HLB = 9.6 had been added into the mixture. No oil was found inside the microcapsules from the coacervate emulsion mixture containing Tween 81 (HLB = 10) and Tween 80 (HLB = 15), respectively. The results of the experiment confirm the dependence of hydrophobic substance encapsulation on the HLB published recently for Squalan.     

Combination of diathermy and argon plasma coagulation in treatment of cicatricial esophageal stenoses

Scar stenoses of the esophagus are caused by peptic reflux or following surgery of the upper gastrointestinal tract. Short scar cicatricial stenoses are difficult to treat and have a high recurrence rate. Pneumatic dilatations show a short term success. We treated 5 patients with a short scar esophageal stenosis after esophagogastrostomy (n = 3) and after esophagojejunostomy (n = 2). The main symptom was dysphagia. X-ray shows the length of the stenosis (max. 1.5 cm). The stenosis was cutted by diathermy in a starshape. In all 5 cases it was possible to achieve the wide lumen. There were no complications. The combination of diathermy and argon-plasma-coagulation is a safe method, rare of complications in the treatment of short scar stenosis of the esophagus.     

Prospective long-term endoscopic and histological follow-up of short segment Barrett's esophagus: comparison with traditional long segment Barrett's esophagus

OBJECTIVES: Barrett's esophagus is associated with adenocarcinoma of the cardia and esophagus, regardless of its extent. The aim of this study was to compare the prevalence and incidence of dysplasia and adenocarcinoma in short segment and traditional long segment Barrett's esophagus. METHODS: Seventy-four patients with short segment Barrett's and 78 with traditional Barrett's entered the study. RESULTS: There were no significant differences in age or gender between the two groups of patients with Barrett's esophagus. A greater percentage of patients with short segment barrett's were black (p = 0.04). The prevalence of dysplasia at diagnosis in patients with short segment Barrett's was 8.1% versus 24.4% in patients with traditional Barrett's (p < 0.007). Adenocarcinoma was noted at diagnosis only in patients with traditional Barrett's (p < 0.0005). Twenty-six patients with short segment Barrett's and 29 with traditional Barrett's were followed prospectively for 12-40 months. Dysplasia developed during follow-up in two patients with short segment Barrett's and in six patients with traditional Barrett's (p < 0.05). Neither high grade dysplasia nor cancer developed in any patients with short segment Barrett's. High grade dysplasia did develop in two patients with traditional Barrett's esophagus, and mucosal adenocarcinoma developed in one. The frequency of dysplasia on the latest surveillance examination continued to be significantly higher for patients with traditional Barrett's (p = 0.03). Follow-up surveillance biopsy specimens of Barrett's mucosa frequently demonstrated an absence of goblet cells in patients with short segment Barrett's compared with patients with traditional Barrett's (p < 0.0001). CONCLUSIONS: The prevalence of dysplasia or adenocarcinoma and the incidence of dysplasia in patients with traditional Barrett's esophagus are significantly higher than in patients with short segment Barrett's esophagus. Further prospective surveillance is required to determine whether the incidence of adenocarcinoma in patients with short segment Barrett's esophagus is significantly lower.     

Association of high plasma antioxidant capacity with new lesion formation in carotid atherosclerosis: a prospective study

BACKGROUND: In atherosclerosis, both reductions and elevations in plasma levels of antioxidants have been reported. This study investigated total antioxidant capacity of plasma from subjects with atherosclerotic disease. MATERIALS AND METHODS: The study population consisted of 48 men with or without carotid atherosclerosis. At baseline (1990) carotid arteries were evaluated by duplex sonography and plasma samples were obtained for testing antioxidant capacity by two different test systems. One assay system used neutrophils from healthy volunteers as a source of oxygen free radicals activating the non-fluorescent dichlorofluorescin diacetate in the presence of antioxidant containing plasma from study subjects. In the other test system, total plasma antioxidants were detected colorimetrically by using 2,2'-azino-di-(3-ethylbenzthiazoline sulphonate), metmyoglobin and superoxide in the presence of plasma. Carotid arteries were re-evaluated for the development of new plaques 5 years later (1995). RESULTS: Increased baseline total antioxidant capacity of plasma was significantly associated with the development of new atherosclerotic lesions during a period of 5 years. CONCLUSIONS: Endogenous antioxidant capacity of plasma is increased in patients with active atherosclerotic disease. As scavenging of oxygen free radicals is thought to protect from atherogenesis, elevated antioxidative capacity may represent an adaptive mechanism.     

K-ras point mutations are rare events in premalignant forms of Barrett's oesophagus

OBJECTIVE: In Barrett's adenocarcinomas, in contrast to squamous oesophageal carcinomas, K-ras point mutations are thought to be a frequent event. The frequency of K-ras point mutations in premalignant forms of Barrett's oesophagus (metaplasia, dysplasia) leading to adenocarcinoma with increased risk is currently not known. To establish the frequency of K-ras mutations in premalignant forms of Barrett's oesophagus, we investigated oesophageal biopsy specimens with Barrett's metaplastic and dysplastic epithelium for point mutations in the K-ras gene/codons 12, 13. DESIGN: A total of 412 biopsies from patients with Barrett's oesophagus were histologically classified into biopsies with metaplasia (n = 252), dysplasia (n = 105) and adenocarcinoma (n = 11), as well as biopsies distant from disease (normal, n = 37 and hyperplastic squamous epithelium, n = 7). METHODS: DNA from biopsy specimens was amplified by polymerase chain reaction (PCR) with a modified primer for generating a restriction site in the case of wild type in codon 12. Wild-type or point mutations in the K-ras gene/codons 12, 13 were detected by restriction fragment length analysis of the PCR products. RESULTS: Point mutations in K-ras/codon 12 were found in 9 biopsies (n = 1 in metaplasia, n = 4 in dysplasias, n = 4 in adenocarcinomas). All the other biopsies showed the wild type of K-ras/codon 12. No K-ras/codon 13 mutation (GGCgly-->GACasp) was observed. CONCLUSION: Mutations in K-ras/codon 12 were rarely found in premalignant forms of Barrett's oesophagus. Whereas the screening for K-ras point mutations in metaplastic sites of Barrett's epithelium seems not to be of practical value, the screening for mutations in dysplastic lesions might be helpful to estimate the individual risk for progression of Barrett's epithelium to adenocarcinoma. A further evaluation in larger numbers of patients is needed.     

Experiences with endoscopic surgery in treatment of carpal tunnel syndrome. Preliminary results of a prospective study

We evaluated the association between coronary spasm and hyperinsulinemia (high immunoreactive insulin, IRI) in patients with angina pectoris. The study cohort comprised 30 patients with spastic angina pectoris, 30 patients with angina pectoris showing fixed-obstructive coronary sclerosis and 30 control subjects who were matched for body mass index, age and sex. A 75-gram oral glucose test was performed, and blood sugar and IRI were serially measured concomitant with serum total cholesterol, triglyceride and HDL cholesterol. The IRI level at 60 min, the peak IRI during the test, sigma IRI and sigma IRI/sigma blood sugar were significantly higher in the patients than in the controls. Total cholesterol and LDL cholesterol levels were significantly increased in patients showing fixed-obstructive coronary sclerosis compared to controls.     

Comparative evaluation of therapeutic approaches in stage III and IV squamous cell carcinoma of the thoracic esophagus with conventional radiotherapy and endoscopic treatment in combination and endoscopic treatment alone: a randomized prospective trial

The expression of a cloned Drosophila octopamine/tyramine receptor (OctyR99AB) is described in Xenopus oocytes. Agonist stimulation of OctyR99AB receptors increased intracellular Ca2+ levels monitored as changes in the endogenous inward Ca2+-dependent chloride current. The receptor is preferentially sensitive to biogenic amines with a single hydroxyl on the aromatic ring. The G-protein, Galphai, appears to be involved in the coupling of the receptor to the production of intracellular calcium signals, since the effect is pertussis-toxin sensitive and is blocked or substantially reduced in antisense knockout experiments using oligonucleotides directed against Galphai but not by those directed against Galphao, Galphaq and Galpha11. The increase in intracellular calcium levels induced by activation of the OctyR99AB receptor can potentiate the ability of activation of a co-expressed beta2-adrenergic receptor to increase oocyte cyclic AMP levels. A comparison of the pharmacological coupling of OctyR99AB to different second messenger systems when expressed in Xenopus oocytes with previous studies on the expression of the receptor in a Chinese hamster ovary cell line suggests that the property of agonist-specific coupling of the receptor to different second messenger systems may be cell-specific, depending upon the G-protein environment of any particular cell type.     

The Saeed Six-Shooter: a prospective study of a new endoscopic multiple rubber-band ligator for the treatment of varices

BACKGROUND AND STUDY AIMS: Rubber-band ligation is superior to sclerotherapy, and is considered to be the endoscopic treatment of choice for bleeding varices. The single-shot mechanism of the ligation device generally used is inherently inefficient, and makes the procedure tedious. It also requires overtube placement, associated with discomfort and complications. This study describes the Saeed Six-Shooter, a multiple ligation device. PATIENTS AND METHODS: Twenty-seven consecutive patients with variceal bleeding were prospectively studied. After initial endoscopic ligation, subsequent sessions were every 7-10 days. The parameters studied were the ease of use, the ability to control active bleeding and eradicate varices, survival, and complications. RESULTS: Active bleeding was controlled in all seven (100%) patients. Esophageal varices were eradicated in 70% (3.2 +/- 1.2 sessions), and gastric varices in 88% of patients (2 +/- 1.2 sessions). Five patients re-bled, two from esophageal varices, two from gastric varices, and one from treatment-induced ulcer. There were four deaths, none due to exsanguination. A single complication, esophageal stricture, resolved with balloon dilation. Intubation was no more difficult with the endoscope loaded with the Six-Shooter than with the endoscope alone (P > 0.3). Six ligations were performed in 39% of cases within 60 seconds, and in 74% of cases within 90 seconds. For gastric varices, the device was effectively used with the endoscope retroflexed. CONCLUSIONS: The Saeed Six-Shooter is a safe and efficient instrument for the endoscopic ligation of varices, and has overcome the limitations of the single-shot ligator.     

Local staging of esophageal cancer using endoscopic magnetic resonance imaging: prospective comparison with endoscopic ultrasound

Thyroid cancer is associated with abnormal thyroid peroxidase (TPO) expression as shown by abolition of immunodetection by monoclonal antibody 47 (Mab 47). The purpose of this study was to determine the relation of this abnormality with differentiation and proliferative potential of follicular tumors evaluated by analyzing thyroglobulin (TG) expression and proliferative cell nuclear antigen (PCNA) index. TPO, TG, and PCNA immunostaining were performed in a series of 30 thyroid follicular tumors ranging from adenoma to invasive carcinoma. Our findings confirmed that TPO abnormalities and PCNA index were correlated with malignancy, and that PCNA as well as TPO could be used to determine the growth potential of follicular proliferations in fine-needle aspirates. The most discriminant parameter was the ratio between the percentage of Mab-47 and PCNA positive cells. Ratios under 0.6 were correlated with malignancy in 90% of the cases, with only 3 cases of atypical adenomas being misdiagnosed as carcinomas. An inverse correlation was found between TPO and PCNA expression, but TG, which persisted at high levels in several actively growing follicular carcinomas, did not appear directly linked to cellular proliferation. These findings confirm that, unlike a decrease in TG synthesis that merely reflects the progressive loss of differentiation occurring in high-grade proliferations, alteration of TPO is an early marker of thyroid follicular tumors, closely related to acceleration of tumor growth in the first stages of malignant transformation.     

Factors associated with endodontic flare-ups: a prospective study

The purpose of this prospective study was to assess the incidence of flare-ups (a severe problem requiring an unscheduled visit and treatment) among patients who received endodontic treatment by the two authors in their respective practices during a period of one year, and also to examine the correlation with pre-operative and operative variables. The results showed an incidence of 1.58% for flare-ups from 1012 endodontically treated teeth. Statistical analysis using the chi-square test (P<0.05) indicated that flare-ups were found to be positively correlated with multiple appointments, retreatment cases, periradicular pain prior to treatment, presence of radiolucent lesions, and patients taking analgesic or anti-inflammatory drugs. In contrast, there was no correlation between flare-up, and age, sex, different arch/tooth groups and the status of the pulp.     

Laparoscopic cholangiography: a prospective study

This paper describes the analysis of injury-related linked hospital morbidity data by admissions and by individual patients in Western Australia (WA) from 1990 to 1994. Over this five-year period, there were an average of 35,385 admissions and 30,524 people admitted each year for injuries in WA. The age-standardised rates for injury-related hospital admissions and persons admitted for injuries increased significantly, by 2.4% and 1.5% per year respectively, over the five-year period. The number of admissions and the number of persons admitted peaked in the 20-24 years age group but the highest rates were among those aged 75 years and above. Injuries accounted for nearly 10% of all hospital bed day costs and cost about $50 per head of population per year. The cost of hospitalisation rose steadily from $85.2 million in 1990 to $113.6 million in 1994, the average cost being nearly $100 million per year. The average cost per injury related hospital episode was $2,748. Generally, the cost per hospital episode was higher for males and increased with age, following a similar pattern to that for the average length of stay.     

Long-term follow-up of a prospective randomized study of endoscopic versus surgical treatment of bile duct calculi in patients with gallbladder in situ

Eighty-three patients with bile duct calculi were entered in a prospective randomized study of endoscopic sphincterotomy (ES) and stone removal (group 1) versus surgery alone (group 2), and were followed for more than 5 years. In group 1 endoscopic stone clearance was successful in 35 of 39 patients. Thirteen patients subsequently had cholecystectomy with (n = 7) or without (n = 6) biliary symptoms and one had a cholecystostomy for acute cholecystitis. Two patients have had mild biliary colic or pancreatitis. Two patients died from gallbladder carcinoma after 9 days and 18 months. In group 2 bile duct stones were cleared surgically in 37 of 41 patients. Late complications occurred in two patients (incisional hernia and recurrent stone). One patient with gallbladder carcinoma was cured and another died after 16 months. Early major and minor complications occurred in three and four respectively of 39 patients in group 1, and in three and six respectively of 41 patients in group 2. There were no deaths. During follow-up the total morbidity rate reached 28 percent (11 of 39) and 5 percent (two of 41) (P = 0.005) and the non-biliary related mortality rate was 31 percent (12 of 39) and 10 percent (four of 41) (P = 0.02) in groups 1 and 2 respectively. Nine patients in group 1 and two in group 2 died from heart disease (P = 0.02). Total hospital stay was 2-42 (median 13) days and 6-36 (median 16) days in groups 1 and 2 respectively (P not significant). Endoscopic and surgical treatment of bile duct calculi in middle-aged and elderly patients with gallbladder in situ are equally effective in the long term. However, the significantly increased mortality rate from heart disease in patients treated endoscopically compared with those treated surgically might speak in favour of operation.     

Adenocarcinoma arising in Barrett's oesophagus: evidence for the participation of p53 dysfunction in the dysplasia/carcinoma sequence

Adenocarcinoma arising in Barrett's oesophagus is often preceded by mucosal dysplasia, but little is currently known about the aetiology or natural history of this dysplasia/carcinoma sequence. To investigate the participation of the tumour suppressor gene p53 in this sequence, an immunohistochemical analysis of p53 protein overexpression, which is known to closely correlate with point mutation of the p53 gene, was conducted in 30 patients with Barrett's adenocarcinoma. Adjacent Barrett's mucosa was dysplastic in 21 (70%) patients. Sixteen (53%) tumours overexpressed p53, 10 of which had adjacent dysplastic Barrett's mucosa. In all 10 patients, this dysplastic mucosa also overexpressed p53, predominantly in areas of high grade compared with low grade dysplasia. In contrast, none of the dysplastic mucosa adjacent to 11 tumours lacking p53 overexpression showed detectable values of p53. These results suggest that p53 dysfunction may participate in the progression from dysplasia to carcinoma in some patients with Barrett's oesophagus.