New treatment for Barrett's oesophagus.

Barrett's esophagus is characterised by the presence of specialised intestinal metaplasia in the lower esophagus. Its importance is related primarily to its link with adenocarcinoma of the lower esophagus, often preceded by dysplastic changes. The incidence of this carcinoma has increased dramatically over the last few decades. Although modern treatments, particularly acid suppression with proton pump inhibitors, have been most useful in controlling the reflux symptoms associated with Barrett's esophagus, they have not reduced the incidence of adenocarcinoma of the esophagus. The same can be said about anti-reflux surgery. Surgical excision of Barrett's esophagus has been advocated when high-grade dysplasia is detected; this carries considerable morbidity and mortality, so alternative treatments are being developed. This update summarises recent information concerning newer treatments aimed at eradicating Barrett's esophagus. These vary from thermal coagulation (using electrocoagulation and heater probes) to lasers, photodynamic therapy and mechanical methods. Of these, photodynamic therapy using a porphyrin precursor (5-amino-laevulinic acid) seems to give the most consistent satisfactory results with a minimum of complications. However, persistence of some metaplastic cells beneath the neo-squamous layer remains a problem. Ongoing effective acid control (by medical or surgical therapy) is also essential to prevent recurrence of Barrett's esophagus. Future research is aimed at perfecting these methods. Ultimately, it may be possible to understand the molecular biology which could help to predict which patients are at greatest risk of developing dysplastic and carcinomatous changes.     

Molecular events associated with Barrett's oesophagus

The development and progression of Barrett's epithelium are accompanied with the acquisition of many molecular changes of the oesophageal mucosa. Gastro-oesophageal reflux and inflammation cause the oxidative stress and free-radical generations, which result in the expression of oxidative-stress-related genes and the induction of DNA damage. The development of Barrett's epithelium follows a metaplasia-dysplasia-adenocarcinoma sequence, characterized by the accumulation of many genetic and epigenetic alterations, which are seen in carcinogenesis. Abnormalities in the expression of tumor suppressor genes, such as p53, p16, APC, and a number of molecules involved in cell proliferation, apoptosis or angiogenesis are observed. These genetic alterations affecting the cancer hallmarks provide a better understanding of the etiology and pathogenesis of the disease.     

Barrett's Oesophagus: A Clinical Study of 52 Patients

This paper reports a series of 52 patients with Barrett's (orcolumnar-lined) oesophagus from one medical unit diagnosed overa six-year period. The commonest associated symptoms were heartburn,regurgitation and dysphagia but 10 patients had no oesophagealsymptoms and two had no symptoms at all. Gastrointestinal bleeding(overt or occult) was observed in almost one-third of patients.At diagnosis, 26 patients had oesophagitis, 23 had oesophagealulceration and 10 had benign oesophageal strictures. An associationbetween oesophageal ulceration and non-steroidal anti-inflammatorydrug ingestion was suggested by the data and patients with oesophagealulceration were significantly older than patients with uncomplicatedBarrett's oesophagus. No patient had adenocarcinoma of the oesophagusat diagnosis and neither carcinoma nor dysplasia were seen duringa mean period of 16.4 months. However, 17 per cent of patientsin the series had malignancies in other sites. Most patientsdid well on medical treatment and only two were referred foranti-reflux surgery (both for non-healing oesophageal ulcers).Barrett's oesophagus was seen in 10 per cent of patients withgastro-oesophageal reflux at endoscopy. Oesophageal ulcerationin patients with Barrett's oesophagus made up 21 per cent ofoesophageal ulcers seen and benign oesophageal stricture inpatients with Barrett's oesophagus constituted 13 per cent ofall benign strictures seen. Barrett's oesophagus is common inour population and despite complications, it can be managedsuccessfully, at least in the short term, by conservative means.     

Eradication of dysplastic Barrett's oesophagus using photodynamic therapy: long-term follow-up

BACKGROUND AND STUDY AIMS: Barrett's oesophagus is a major risk factor for oesophageal adenocarcinoma, a condition which is rapidly increasing in incidence. Photodynamic therapy (PDT) is a developing treatment in which tissue damage is caused by the action of light on a previously administered photosensitizing agent. We present the results of long-term follow-up of its efficacy in patients with dysplastic Barrett's oesophagus. PATIENTS AND METHODS: A total of 40 patients with low-grade dysplasia in Barrett's oesophagus were treated with oral 5-aminolaevulinic acid (ALA) at a dose of 30 mg/kg, followed by laser endoscopy 4 hours later. Patients were treated between December 1995 and December 1998, and all were followed up regularly with endoscopy and biopsies in our surveillance programme. RESULTS: Among the patients, 35 (88%) showed a macroscopic reduction in the area of the columnar epithelium, and in all 40 patients dysplasia was found to be eradicated at 1 month. The effect has been maintained for a median follow-up of 53 months (range 18-68 months), although one patient developed a late carcinoma in an untreated area of Barrett's oesophagus 3 years after the intervention. CONCLUSIONS: Safe and effective ablation of low-grade dysplastic Barrett's oesophagus can be achieved with the use of ALA-induced PDT, and the effects are maintained in the long term.     

Oesophageal acid exposure: higher in Barrett's oesophagus than in reflux oesophagitis

Oesophageal acid exposure at different pH intervals between 0 and 8 in patients with Barrett's oesophagus (n = 24) was compared with that in patients with reflux oesophagitis (n = 19) by using 24-h pH monitoring. Prior to the monitoring, the position and pressure of the lower oesophageal sphincter was measured by manometry. Columnar epithelium with intestinal metaplasia and goblet cells was verified histologically in all Barrett patients and grade I—III oesophagitis in patients with reflux oesophagitis. Acid exposure (percentage of total time at pH < 4) in the Barrett group was significantly greater than in the oesophagitis group: 21.5 ± 20.0% SD vs 11.1 ± 11.7% SD (P < 0.01). The number of reflux episodes lasting longer than 5 min (representing oesophageal body clearance function) was also significantly greater in the Barrett group (8.3 ± 5.9 SD) than in the oesophagitis group (4.5 ± 4.7 SD) (P < 0.01). In the Barrett group the acid exposure time was greater at all pH intervals 0-1, 1-2, 2-3 and 3-4, (P < 0.01) but in the oesophagitis group the exposure time was greater at pH interval 5-6 (P < 0.01). There was no significant difference in exposure at pH values above 7. The mean lower oesophageal sphincter pressure was equal in both groups (11.0 vs 11.9 mmHg). In conclusion, oesophageal acid exposure was significantly greater in Barrett's oesophagus than in reflux oesophagitis, and this was associated with decreased oesophageal clearance function. In addition, the results indicated the need for special attention and perhaps higher dosages of drugs to suppress acid production in patients with Barrett's oesophagus.     

Oesophageal acid exposure: higher in Barrett's oesophagus than in reflux oesophagitis

Oesophageal acid exposure at different pH intervals between 0 and 8 in patients with Barrett's oesophagus (n = 24) was compared with that in patients with reflux oesophagitis (n = 19) by using 24-h pH monitoring. Prior to the monitoring, the position and pressure of the lower oesophageal sphincter was measured by manometry. Columnar epithelium with intestinal metaplasia and goblet cells was verified histologically in all Barrett patients and grade I-III oesophagitis in patients with reflux oesophagitis. Acid exposure (percentage of total time at pH < 4) in the Barrett group was significantly greater than in the oesophagitis group: 21.5+/-20.0% SD vs 11.1+/-11.7% SD (P < 0.01). The number of reflux episodes lasting longer than 5 min (representing oesophageal body clearance function) was also significantly greater in the Barrett group (8.3+/-5.9 SD) than in the oesophagitis group (4.5+/-4.7 SD) (P < 0.01). In the Barrett group the acid exposure time was greater at all pH intervals 0-1, 1-2, 2-3 and 3-4, (P < 0.01) but in the oesophagitis group the exposure time was greater at pH interval 5-6 (P < 0.01). There was no significant difference in exposure at pH values above 7. The mean lower oesophageal sphincter pressure was equal in both groups (11.0 vs 11.9 mmHg). In conclusion, oesophageal acid exposure was significantly greater in Barrett's oesophagus than in reflux oesophagitis, and this was associated with decreased oesophageal clearance function. In addition, the results indicated the need for special attention and perhaps higher dosages of drugs to suppress acid production in patients with Barrett's oesophagus.     

Abnormal expression of growth regulatory factors in Barrett's oesophagus.

1. In order to assess potential abnormalities in the control of mucosal proliferation, 30 patients with Barrett's oesophagus were studied in order to evaluate the presence and distribution of epidermal growth factor, transforming growth factor-alpha and epidermal growth factor receptor to determine the Ki-67 labelling index in the affected oesophageal mucosa. Serial sections were analysed immunohistochemically. Ten of the patients had adenocarcinoma in the Barrett's mucosa and the other 20 had differing histological types of Barrett's mucosa (10, intestinal-type; 10, fundic- or cardiac-type). 2. The expression of transforming growth factor-alpha, epidermal growth factor and epidermal growth factor receptor was increased and the Ki-67 labelling index was higher in Barrett's mucosa compared with normal gastric mucosa. The 'intestinal-type' of Barrett's mucosa had the greatest expression of transforming growth factor-alpha, epidermal growth factor receptor and the highest Ki-67 labelling index compared with the other types of Barrett's metaplasia. Five cases of 'intestinal-type' Barrett's metaplasia had especially high Ki-67 labelling indices and these patients over-expressed both transforming growth factor-alpha and epidermal growth factor receptor. The patients with adenocarcinomas in the Barrett's mucosa also over-expressed transforming growth factor-alpha and epidermal growth factor receptor, but not epidermal growth factor, compared with normal gastric mucosa. 3. In conclusion, both normal gastric mucosa and Barrett's mucosa have potential autocrine growth regulatory mechanisms, but Barrett's mucosa has increased expression of both of the measured ligands and of the epidermal growth factor receptor.     

酒精所致精神障碍52例临床分析

对2054例住院病人进行回顾性临床分析中,发现有52例诊断为酒精所致精神障碍,发生率为2.53%,均为男性,平均年龄44.2±9.0岁,发生率呈逐年增加趋势。嗜酒的原因与遗传、职业、文化水平、民族风俗有关,黎族患者占27例(51.92%)。临床以幻觉、被害妄想、妒嫉妄想、行为障碍为多见。治疗:使用奋乃静23例(44.23%)的频率较高,显效率88.46%。长期大量酗酒,可致躯体损害,复发达11例(21.15%)。早期限制及戒酒可减少躯体的损害。     

Familial amyloidosis: a study of 52 North American-born patients examined during a 30-year period.

Between 1961 and 1990, 52 patients with biopsy-proven familial amyloidosis born in North America were examined at the Mayo Clinic. At the time of diagnosis of familial amyloidosis, 83% of these patients had peripheral neuropathy, 33% had autonomic neuropathy, and 27% had cardiomyopathy. Renal disease was noted in fewer than 10%, and liver involvement was rare. The median age at diagnosis was 64 years. The sensitivity of various diagnostic biopsies was similar to that for primary amyloidosis: deposits of amyloid were found in 77 and 78% of the subcutaneous fat aspirates or rectal biopsy specimens, respectively, and in 41% of specimens of bone marrow. The median duration of survival of 5.8 years for patients with inherited amyloidosis was superior to that for patients with primary amyloidosis. When patients were stratified by organ involvement, the survival of patients with familial amyloidosis remained superior. The presence of cardiomyopathy and an interactive variable of age and the presence of autonomic neuropathy were powerful predictors of survival. Of the 52 patients, 22 died, 12 (55%) of cardiac failure or cardiac arrhythmia. Nine patients (41%) died of inanition in conjunction with progressive peripheral or autonomic neuropathy. Transthyretin was identified by immunohistochemical studies in 31 of the 34 tissue specimens tested. A transthyretin mutation was identified in 24 of the 31. A transthyretin mutation was found in five additional patients for whom tissue was unavailable for immunostaining.     

Low frequency electrical bioimpedance for the detection of inflammation and dysplasia in Barrett's oesophagus

Biological tissues undergoing inflammation and dysplasia seem to exhibit changes in the intercellular space that can be sensed using low frequency electrical impedance methods. Basically, low frequency electric current flows through this space and its widening as well as the disruption of the tight junction decrease the resistance, facilitating current flow. The electrical changes accompanying structural changes from columnar tissue to adenocarcinoma in Barrett's metaplastic mucosa and gastric tissue are illustrated using resected tissue from 32 patients. Two hundred and fifty-eight biopsies were analysed, correlating their electrical resistivity (R) at 9.6 kHz and their histopathological interpretation. Compared to non-inflamed non-dysplastic columnar tissue (R = 4.9 ohms m), the results suggest a small but statistically significant decrease of electrical impedance in columnar tissue showing inflammation (R = 4.2 ohms m, p = 0.016) and a larger decrease when dysplasia is present (R = 3.4 ohms m, p = 0.040). If this method is validated further, this technique could be used to obtain guided biopsies from patients undergoing surveillance programmes for Barrett's oesophagus. We aim to refine this technique using a new system with lower frequencies and, possibly, in vitro (cultured cells) and in vivo (rats) models of Barrett's oesophagus.     

Pseudoporphyria: a clinical and biochemical study of 20 patients

OBJECTIVE: To describe the clinical and laboratory findings in patients with pseudoporphyria. PATIENTS AND METHODS: This retrospective review identified 261 patients with either porphyrin metabolism abnormalities or pseudoporphyria who were seen at the Mayo Clinic in Rochester, Minn, between 1992 and 1996. All patients with documented porphyria cutanea tarda (PCT), noncutaneous porphyrias, or variegate porphyria were excluded. RESULTS: Twenty patients had active cutaneous lesions resembling PCT with no diagnostic laboratory abnormalities. The major presenting clinical features were blistering in 19 patients (95%), scarring in 14 (70%), photosensitivity in 13 (65%), skin fragility in 13 (65%), and milia in 8 (40%). Histologically, of 17 patients tested, 12 (71%) had classic findings of subepidermal separation with festooning of dermal papillae. None of the 11 patients tested had hepatitis B or C. In all 20 patients, porphyrin profiles were nondiagnostic. Of 16 patients for whom follow-up was available, 11 reported persistent symptoms for a mean of 2.5 years after evaluation. Five patients were free of symptoms 1 week to 6 months after discontinuation of the presumed offending agent. CONCLUSION: Pseudoporphyria mimics the cutaneous symptoms of PCT in the setting of normal or near-normal porphyrin levels in the serum, urine, or stool. Despite efforts to discontinue an offending medication, symptoms may persist indefinitely.     

A comparison of three types of biopsy forceps in the endoscopic surveillance of Barrett's oesophagus

BACKGROUND AND STUDY AIMS: Periodic endoscopic biopsy surveillance is recommended for selected patients with Barrett's oesophagus. A new angled swing-jaw forceps has become available which is said to facilitate tangential oesophageal biopsy sampling. We examined the size and quality of oesophageal biopsies obtained with the forceps of angled design in comparison with the large cup disposable forceps and the conventional reusable upper gastrointestinal forceps. PATIENTS AND METHODS: In this prospective comparative study, three biopsies were taken at each of three levels, using a different design of forceps at each level, in each of 48 patients undergoing endoscopic surveillance. The order in which the forceps were used was randomized. A pathologist assessed the size and quality of each set of biopsies obtained. RESULTS: The mean biopsy diameter was significantly greater at 3.00 mm with the angled forceps (P < 0.01), in comparison with 2.52 mm with the elliptical forceps and 2.07 mm with the conventional forceps. Fewer biopsies obtained with the angled forceps were graded as inadequate (8.3 %) compared with those obtained using the disposable large cup and conventional forceps (25 % and 22.9 %, respectively). CONCLUSIONS: The design of forceps used influences the size and quality of tissue obtained during endoscopic surveillance of Barrett's oesophagus. The angled swing-jaw forceps are recommended as the most suitable for this purpose.     

Barrett食道和Barrett食道腺癌的临床病理学研究

本文报告Ｂａｒｒｅｔｔ食道４２例，其中８例具有腺癌结构。内镜观察：食道粘膜上皮粗糙、糜烂、颗粒状增生、斑块状隆起、溃疡、粘膜充血或苍白。组织学观察：Ｂａｒｒｅｔｔ食道上皮有三种不同形态，其中胃底型上皮８例，交界型上皮１４例，特殊型上皮２０例，８例具有腺癌结构，特殊型上皮与腺癌结构间可见过渡形态。粘液组化染色观察：２０例特殊型上皮，ＨＩＤ（＋）１８例，８例具有腺癌结构的病例，ＡＢ、ＨＩＤ均呈不同程度的阳性。ＡｇＮＯＲ染色观察，Ｂａｒｒｅｔｔ食道三种上皮与食道腺癌平均每核含ＡｇＮＯＲ颗粒数相比均有非常显著的统计学差异（Ｐ＜０．０１）；观察结果提示：Ｂａｒｒｅｔｔ食道与食道腺癌关系密切，特殊上皮型Ｂａｒｒｅｔｔ食道可能是食道腺癌的癌前病变。     

食管癌患者的心理社会因素相关性研究

目的探讨心理社会相关因素对食管癌患者的影响。方法对49例食管癌患者(研究组)和49名患者邻居(对照组)采用艾森克个性问卷、社会支持量表、生活事件量表进行评定分析。结果研究组艾森克个性问卷E维度得分明显低于对照组,N维度得分及L维度得分明显高于对照组(P<0.01);社会支持量表的客观支持、支持利用度及社会支持总分研究组低于对照组(P<0.01);生活事件量表的总生活事件、负性生活事件得分研究组明显高于对照组(P<0.05)。结论食管癌患者与心理社会因素高度相关,在进行药物治疗的同时应注重心理社会干预。