Outcomes at One-Year Post Anastomosis from a National Cohort of Infants with Oesophageal Atresia

Background and Aims

We aimed to provide a contemporaneous assessment of outcomes at one-year post oesophageal atresia/tracheoesophageal fistula (OA-TOF) repair, focussing particularly on post-operative complications. It is generally accepted that oesophageal stricture is the most common complication and causes significant morbidity. We also aimed to assess the efficacy of prophylactic anti-reflux medication (PARM) in reducing stricture formation.

Method

A prospective, multi-centre cohort study of all infants live-born with oesophageal atresia in the United Kingdom and Ireland in 2008/9 was performed, recording clinical management and outcomes at one year. The effect of PARM on stricture formation in infants with the type-c anomaly was assessed using logistic regression analysis.

Results

151 infants were live-born with oesophageal atresia in the defined reporting period, 126 of whom had the type-c anomaly. One-year follow-up information was returned for 105 infants (70%); the mortality rate was 8.6% (95% CI 4.7–14.3%). Post-operative complications included anastomotic leak (5.4%), recurrent fistula (3.3%) and oesophageal stricture (39%). Seventy-six (60%) of those with type-c anomaly were alive at one-year with returned follow-up, 57(75%) of whom had received PARM. Of these, 24 (42%) developed a stricture, compared to 4 (21%) of those who had not received PARM (adjusted odds ratio 2.60, 95% CI 0.71–9.46, p = 0.147).

Conclusions

This study provides a benchmark for current outcomes and complication rates following OA-TOF repair, with oesophageal stricture causing significant morbidity. The use of PARM appeared ineffective in preventing strictures. This study creates enough doubt about the efficacy of PARM in preventing stricture formation to warrant further investigation of its use with a randomised controlled trial.     

Exertional gastro-oesophageal reflux: a mechanism for symptoms in patients with angina pectoris and normal coronary angiograms.

During 24 hour oesophageal pH monitoring 52 patients who had angina pectoris and normal coronary angiograms underwent exercise testing, as far as their symptoms allowed, on a treadmill to determine whether gastro-oesophageal reflux occurred during exertion. In 11 patients the 24 hour oesophageal pH score was abnormally high; 10 of these showed exertional gastro-oesophageal reflux, and in nine this was associated with their usual chest pain. A further 13 patients had a normal 24 hour pH score but had exertional reflux coincident with chest pain during exercise testing. The mean lower oesophageal sphincter pressure in both of these groups of patients was appreciably lower than that in 28 patients who had a normal 24 hour pH score and no exertional reflux. These findings suggest that exertional gastro-oesophageal reflux accounts for the symptoms of a large proportion of patients who have angina pectoris and normal coronary angiograms and that oesophageal pH monitoring during exercise testing on a treadmill enables this group of patients to be identified.     

Delays in the diagnosis of oesophagogastric cancer: a consecutive case series.

OBJECTIVES: To examine the time taken to diagnose oesophageal or gastric cancer, identify the source of delay, and assess its clinical importance. DESIGN: Study of all new patients presenting to one surgical unit with carcinoma of the oesophagus or stomach. SETTING: University department of surgery in a large teaching hospital. SUBJECTS: 115 consecutive patients (70 men, mean age 66 years) with carcinoma of the oesophagus (27) or stomach (88). MAIN OUTCOME MEASURES: Interval from the onset of symptoms to histological diagnosis, final pathological stage of the tumour, and whether potentially curative resection was possible. RESULTS: The median delay from first symptoms to histological diagnosis was 17 weeks (range 1 to 168 weeks). 25% (29/115) of patients had a delay of over 28 weeks (median 39 weeks). Total delay was made up of the following components: delay in consulting a doctor (29%), delay in referral (23%), delay in being seen at hospital (16%), and delay in establishing the diagnosis at the hospital (32%). No relation was found between delay in diagnosis and tumour stage in patients with gastric cancer, but for oesophageal cancer those with stage I and II disease were diagnosed within 7 weeks compared with 21 weeks (P < 0.02) for those with stage III and IV disease. CONCLUSIONS: Long delays still occur in the diagnosis of patients with cancer of the stomach or oesophagus. Streamlined referral and investigation pathways are needed if patients with gastric and oesophageal carcinomas are to be diagnosed early in the course of the disease.     

Clinical picture of primary HIV infection presenting as a glandular-fever-like illness.

The clinical symptoms and signs were assessed in 20 consecutive patients developing infection with the human immunodeficiency virus (HIV). All were male homosexuals and all presented with a glandular-fever-like illness. Changes in laboratory values were compared with findings in 40 HIV negative male homosexual controls. In the 10 patients for whom date of exposure to the virus could be established the incubation period was 11-28 days (median 14). One or two days after the sudden onset of fever patients developed sore throat, lymphadenopathy, rash, lethargy, coated tongue, tonsillar hypertrophy, dry cough, headache, myalgia, conjunctivitis, vomiting, night sweats, nausea, diarrhoea, and palatal enanthema. Twelve patients had painful, shallow ulcers in the mouth or on the genitals or anus or as manifested by oesophageal symptoms; these ulcers may have been the site of entry of the virus. During the first week after the onset of symptoms mild leucopenia, thrombocytopenia, and increased numbers of banded neutrophils were detected (p less than 0.0005). The mean duration of acute illness was 12.7 days (range 5-44). All patients remained healthy during a mean follow up period of 2.5 years. Heightened awareness of the typical clinical picture in patients developing primary HIV infection will alert the physician at an early stage and so aid prompt diagnosis and help contain the epidemic spread of AIDS.     

Oesophageal cancer treatment in North East Thames region, 1981: medical audit using Hospital Activity Analysis data.

Figures from the Hospital Activity Analysis in the North East Thames region in 1981 were used to perform a medical audit on oesophageal cancer treatment. Four hundred and forty four patients were admitted with this diagnosis; 80 had been intubated without a thoracotomy or laparotomy, and 73 had had surgery (two thirds radical and one third palliative) with an overall operative mortality of 33%. Fifty five patients had had radiotherapy and 179 patients had no recorded operation or investigation. One hundred and seventy seven different consultants had looked after all these inpatients, most being general surgeons. Only five consultants had looked after 10 or more patients each year. From a calculated estimate of a total 286 patients in the region, 28% had palliative intubation and 25% had surgery; 20% of all the patients had radiotherapy either as a radical or palliative treatment, the remainder having no recorded therapeutic procedure. One hundred and eighty seven patients (66% of the calculated total) died in hospital. Investigation and treatment do not seem to be limited by lack of money, but money is being wasted by admitting patients for terminal care into acute hospital beds. It would be more humane for these patients to die at home or in a hospice if they wished.     

Upper gastrointestinal Kaposi's sarcoma in patients positive for HIV antibody without cutaneous disease

Six patients with antibodies to the human immunodeficiency virus (HIV) and with persistent gastrointestinal symptoms of HIV infection but without cutaneous lesions of Kaposi''s sarcoma underwent endoscopy. Four also underwent barium meal examination. In all six cases small lesions were seen in the stomach at endoscopy, and histological examination of biopsy specimens taken from the lesions confirmed the diagnosis of Kaposi''s sarcoma. The barium meal examinations were reported as normal in three patients and showed oesophageal candidiasis in the fourth.These findings suggest that Kaposi''s sarcoma of the upper gastrointestinal tract is common in patients positive for HIV antibody, even those without cutaneous lesions. Endoscopy, with biopsy of suspicious lesions, is necessary to make the diagnosis and is recommended in all HIV antibody positive patients with persistent upper gastrointestinal symptoms.     

Oesophageal transit of six commonly used tablets and capsules.

The oesophageal transit of six commonly used tablets and capsules containing barium sulphate was evaluated radiologically using fluoroscopy in 121 healthy volunteers. To determine the influence of the subject''s position and the amount of water taken each subject swallowed three preparations while recumbent and standing and with 25 ml or 100 ml of water. Failure of swallowing (defined as oesophageal transit taking more than 90 seconds) occurred in 22% of 726 swallowings, but globus was complained of in only 33% of these. Sixty per cent of the volunteers had difficulty in taking one or more of the preparations. Many preparations adhered to the oesophageal membrane and started to disintegrate in the lower part of oesophagus. It is recommended that subjects should remain standing for at least 90 seconds after taking capsules or tablets and that all preparations should be taken with at least 100 ml of water. Small tablets are swallowed most easily. Liquid forms of medication (suspensions) should be considered for bedridden patients and those who have difficulty in swallowing.     

Cocaine: its use in otolaryngology

A review of 120 patients who had a discharge diagnosis of intermediate coronary syndrome showed 12 patients with documented transient ST elevation during spontaneous rest pain consistent with Prinzmetal''s angina. Coronary arteriography showed severe proximal occlusive coronary atherosclerosis in nine of the patients, and normal or minimal disease in the other three patients. In two of these three, there was documented coronary arterial spasm with reproduction of symptoms during arteriography. Although a shorter history of chest pain, presence of an old myocardial infarction and a positive finding on electrocardiogram treadmill test tended to predict the patients with severe occlusive coronary artery disease, these methods were inadequate to select candidates for arteriography. All patients responded well to nitroglycerine while in the hospital. Five of the nine patients with coronary artery disease had coronary bypass operations, with two excellent, two fair and one poor result. One of the three patients with normal findings on coronary arteriograms died with refractory ventricular arrhythmia six months after study. The other two have had good-to-moderate relief of symptoms on long-acting vasodilators and propranolol. Current concepts of the syndrome of Prinzmetal''s angina and ST elevation are reviewed. It appears that this syndrome has a wide spectrum of clinical presentations and coronary arteriographic anatomies.     

Ambulatory pH monitoring of gastro-oesophageal reflux in "morning dipper" asthmatics.

A causal relation between gastro-oesophageal reflux and nocturnal asthma has been postulated. Forty four adult asthmatics underwent ambulatory monitoring of their oesophageal pH over 24 hours to find out if there was such a relation. Of these 21 showed significant "morning dipping" in which the peak expiratory flow falls during the night. Asthmatics with morning dipping had a history of nocturnal wheeze and a higher incidence of reflux symptoms, but measurement of oesophageal pH showed no significant difference in the amount or pattern of reflux when compared with "non-dippers." Overall, 15 asthmatics had gastro-oesophageal reflux, and these participated in a randomised, double blind crossover trial of ranitidine versus placebo. No significant difference was found in the peak expiratory flow rates or subjective evaluation of well being of the patients.     

Psychiatric morbidity in men one week after first acute myocardial infarction.

One week after a first myocardial infarction 35 out of 100 consecutive men patients aged under 65 were found by standardised clinical interview to have psychiatric morbidity. In 16 the morbidity had been evident before the infarct, and these patients showed a wider range of psychopathology than those whose symptoms had been precipitated by the infarct. The results suggest that psychiatric morbidity in patients with heart disease is not necessarily a result of the disease process. Thus characterising psychiatric morbidity and identifying the patients'' individual needs are important if rehabilitation is to be effective.     

Controlled trial of plasma exchange in treatment of Raynaud's syndrome.

Twenty-seven patients with Raynaud''s syndrome had their digital vessel patency assessed by Doppler ultrasound after different thermal stresses. Digital vessel patency rates differed significantly after stresses at 15 degrees C and 45 degrees C. In a randomised controlled trial placebo and heparin had no effect either on patients'' symptoms or on the patency of their digital vessels. Plasma exchange improved both symptoms and vessel patency rates at 15 degrees C and 21 degrees C. Improvement in seven out of eight of these patients has been maintained for six months. Assessing digital vessel patency by Doppler techniques allow continuous, atraumatic, and safe evaluation of the effects of different methods of treatment on the patency of the digital vessels and has helped to indicate that plasma exchange is a useful adjunct in the management of patients with severe Raynaud''s syndrome.     

Respiratory disorders in Manitoba cattle farmers.

A group of 76 cattle farmers from southern Manitoba answered the National Heart, Lung, and Blood Institute questionnaire on respiratory symptoms and supplementary questions on farming and farming-related syndromes. Lung function was tested, serum was examined for precipitating antibodies, and skin testing with common allergens was performed. Analysis of the men''s answers revealed a high prevalence of chronic respiratory symptoms among the farmers in all categories of smoking history, and the presence of these symptoms was significantly associated with a history of symptoms related to handling mouldy hay or grain; 51% of the men had chronic symptoms and 55% had symptoms related to crop handling. In seven farmers (9%) the symptoms related to crop handling suggested an attack of farmer''s lung. One other farmer, with a history of illness after handling mouldy hay, had a reduced total lung capacity, and in 18 the ratio of the forced expiratory volume in the first second to the forced vital capacity was lower than predicted. Precipitating antibodies against Thermoactinomyces were absent in all farmers, but two farmers had antibodies against Aspergillus ruber. Immediate hypersensitivity was found in 16 (21%) of the farmers; sensitivity to Dermatophagoides farinae was commonest.     

Non-steroidal anti-inflammatory drugs and benign oesophageal stricture.

Drug histories were obtained from 76 patients at the time of initial Eder-Puestow dilatation for benign oesophageal stricture. Six patients had consumed drugs known to cause oesophageal ulceration (emepronium bromide and potassium preparations). Of the remaining 70 patients, 22 had regularly taken a non-steroidal anti-inflammatory drug before the onset of dysphagia compared with 10 patients in a control group matched for age and sex; this difference was significant (p less than 0.02). Non-steroidal anti-inflammatory drugs may have a causative role in the formation of oesophageal stricture in patients with gastro-oesophageal reflux, in whom they should be prescribed with caution.     

Is fecundity in plaice (Pleuronectes platessa L.) down‐regulated in response to reduced food intake during autumn?

The effect of controlling food intake during the autumn, which is the time of late vitellogenesis, on fecundity, atresia and follicle and ovary growth was examined for plaice Pleuronectes platessa . Eighteen fish were kept in individual pens and either fed on a high or low ration diet. Fish which increased in whole body condition exhibited an increase in carcass condition which means that when food intake is sufficient to maintain whole body condition some resources are used as storage. Follicle growth rate was positively correlated with change in Fulton's condition and total atresia was negatively correlated with change in Fulton's condition. Thus, the rate of vitellogenesis was dependent on the availability of an exogenous food source. Fecundity at the end of the experiment was positively correlated with mass and total length. Food intake had no effect on relative fecundity; however, fish which had a lower food intake lost mass and had a greater intensity of atresia, lowering their absolute fecundity. One fish in a very low condition at the start of the experiment skipped spawning and one fish exhibited a decrease in average follicle diameter during the experiment which is hypothesized to be a prelude to mass atresia.     

Diabetes and Oesophageal Dysfunction

Cineradiographic and manometric studies of oesophageal function were carried out in four different groups of patients (those suspected of having oesophageal disease, with and without symptoms; and in two groups of diabetes, with and without diabetic neuropathy). All groups were found to have abnormal oesophageal function, and this was not commoner in those with diabetic neuropathy.     

Psychiatric morbidity in patients with alcoholic liver disease.

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients'' likelihood of complying with such advice.     

DNA damage levels are raised in Barrett's oesophageal mucosa relative to the squamous epithelium of the oesophagus

Barrett's oesophagus (BE) is a pre-malignant metaplastic tissue predisposing to oesophageal adenocarcinoma (EC), and gastro-oesophageal reflux is a risk factor for both conditions. Reflux of acid and bile can cause mucosal injury and initiate chronic inflammation. These processes can induce DNA damage, possibly via an oxidative stress mechanism, thus increasing the likelihood of progression from Barrett's metaplasia to dysplasia and finally carcinoma. The comet assay was optimized for the detection of DNA damage (strand breaks and alkali-labile sites) in oesophageal biopsies, including incorporation of the DNA repair enzyme Fapy-DNA glycosylase (Fpg). Fpg allows the detection of 8-hydroxy-2-deoxyguanosine (8-OHdG) sites, a known pro-mutagenic DNA lesion. BE patients were recruited from BE surveillance clinics and oesophageal biopsies collected at endoscopy. Comet analysis revealed significantly increased (p<0.001) DNA damage in Barrett's epithelium compared with matched squamous epithelium, with median % tail DNA values of 25.1% (first to third quartile 21.7–29.6%) and 18.6% (first to third quartile 16.9–21.4%), respectively. The median % tail DNA was up to 70% higher in the matched BE tissue compared with squamous epithelium from the same patient. Fpg sensitive sites were demonstrated in both tissue types at similar levels. The raised level of DNA damage in the premalignant BE may contribute to the accumulation of genetic alterations occurring during progression to EC. Understanding these underlying mechanisms provides a basis for cancer prevention strategies in BE patients.     

Final results from 10 year cohort of patients undergoing surveillance for Barrett's oesophagus: observational study

ObjectivesTo review the benefit of an endoscopic surveillance programme for patients with Barrett''s oesophagus.DesignObservational study.SettingUniversity teaching hospital.Participants409 patients in whom Barrett''s oesophagus was identified during 1984-94; 143 were entered into the annual surveillance programme.ResultsThe average period of surveillance was 4.4 years; 55 patients were reassessed in 1994 but only eight remained in the programme in 1999, withdrawal being due to death (not from carcinoma of the oesophagus), illness, or frailty. Five of the patients who entered surveillance developed carcinoma of the oesophagus. Only one cancer was identified as a result of a surveillance endoscopy, the others being detected during endoscopy to investigate altered symptoms. Of the 266 patients who were not suitable for surveillance, one died from oesophageal cancer and 103 from other causes. Surveillance has resulted in 745 endoscopies and about 3000 biopsy specimens.ConclusionThe current surveillance strategy has limited value, and it may be appropriate to restrict surveillance to patients with additional risk factors such as stricture, ulcer, or long segment (>80 mm) Barrett''s oesophagus.     

Prenatal echographic diagnosis of laryngeal atresia as part of a multiple congenital anomalies (MCA) syndrome

Prenatal echographic diagnosis of laryngeal atresia as part of a multiple congenital anomalies (MCA) syndrome: In this report we present the prenatal second trimester echographic diagnosis of laryngeal atresia in a male fetus with multiple associated congenital anomalies: oesophageal atresia, crossed fused ectopy of the right kidney, mild cutaneous syndactyly of fingers III-V and toes II-III, distinct facial appearance and single umbilical artery. Bilateral voluminous echogenic lungs were the major echographic diagnostic sign. The associated multiple congenital anomalies were not diagnostic for a distinct, recognizable multiple malformation syndrome.     

Combination Chemotherapy in Generalized Hodgkin's Disease

Fifty-two patients with generalized Hodgkin''s disease were treated with a combination of mustine hydrochloride, vinblastine, procarbazine, and prednisolone. Complete remissions were obtained initially in six out of seven patients (86%) who had previously received no treatment, in 15 out of 19 (79%) who had had only radiotherapy in the past, and in 9 out of 26 (35%) who had previously been given chemotherapy with or without radiotherapy. Of these 30 patients in whom a complete remission was obtained 22 have been free of any symptoms or signs of disease for periods ranging from 4 to 22 months. The response to treatment was rapid, and toxicity was not a major problem, except in those who had previously been treated with cytotoxic drugs used continuously and not in courses. A comparative trial of radiotherapy and combination therapy in the treatment of Stage III Hodgkin''s disease is strongly recommended.