Distribution of laminins in the basement membranes of the upper gastrointestinal tract and Barrett's oesophagus.

Barrett's oesophagus predisposes to oesophageal adenocarcinoma. In vitro, laminin, a component of the epithelial basement membrane (BM), is important in regulation of cell differentiation. There is limited information on the distribution of laminin chains in the upper gastrointestinal tract (GIT) and none in Barrett's oesophagus. This study aimed to investigate qualitatively the distribution of laminins in the normal upper GIT mucosa and Barrett's oesophagus in order to understand the role of laminins in metaplasia. Immunoperoxidase staining for laminin chains alpha1, alpha2, alpha3, alpha5, beta1, beta2, beta3, gamma1, and gamma2 was performed on frozen endoscopic squamous and Barrett's oesophageal biopsies and surgical resection specimens from squamous oesophagus (in resection specimens for oesophageal cancer), and in oesophageal and gastric biopsies from control subjects. alpha1 laminin was expressed in the BM of submucosal glands and ducts in squamous oesophagus and Brunner's glands in the duodenum, but not in Barrett's oesophagus or elsewhere in the upper GIT. alpha2 laminin chain was expressed in a granular distribution in the BM of squamous epithelium. In columnar epithelium, including Barrett's oesophagus, alpha2 laminin chain was expressed continuously in the BM of glands and deeper pits, but expression was reduced and granular in the surface epithelial BM. beta2 laminin was continuous in squamous epithelial BM, but in Barrett's and cardia, gastric body, and duodenum, it was expressed faintly in the surface but continuously in the BM of glands and deeper pits. The constituents of laminin-5 were continuously expressed in the BM of squamous epithelium, but in the cardia, gastric body, duodenum, and Barrett's, they were expressed only in the BM of surface epithelium, with a sharp decline in the glandular and deeper pit BM. Site-specific distribution of the alpha2 and beta2 laminin chains may therefore have an important role in Barrett's metaplasia. However, the absence of alpha1 laminin in Barrett's mucosa suggests that this is unlikely to play an important role in columnar metaplasia.

Primary lung carcinoma after heart or lung transplantation: management and outcome.

OBJECTIVE: We sought to examine our management and outcome of lung carcinoma occurring after thoracic organ transplantation. METHODS: We performed a retrospective review of cases of primary lung carcinoma diagnosed between 1990 and 2000 in patients who have previously undergone thoracic transplantation at our institution. RESULTS: Seventeen patients were identified (1 lung and 16 heart transplants). Median time from transplantation to diagnosis of lung carcinoma was 89 months (range, 46-138 months). Predominant presentation was as an incidental finding at chest radiography (13/17). All patients had smoked cigarettes before transplantation, with 5 continuing to smoke after transplantation. Histologic types were squamous (n = 11), adenocarcinoma (n = 3), small cell (n = 2), and undifferentiated (n = 1). Revised International Union Against Cancer (UICC) clinical stage at the time of diagnosis was stage I or II in 11 of 17 patients. Of these, 9 underwent surgical resection; 2 patients unfit for surgical intervention had radiotherapy. Surgical procedures were lobectomy (n = 5), wedge excision (n = 3), and no resection (n = 1). Median survival after diagnosis was 12 months for all patients and 24 months if the tumor was resected. Six patients who had surgical resection subsequently died (survival of 2, 9, 21, 21, 36, and 67 months); 2 remain alive after 12 and 54 months, respectively. CONCLUSIONS: When possible, surgical intervention should be undertaken for early stage lung cancer occurring after thoracic transplantation because medium-term survival is achievable. Sublobar excisions and definitive radiotherapy should be considered if comorbidity prevents optimal surgical treatment.

Non-toxic ubiquitous over-expression of utrophin in the mdx mouse.

Duchenne muscular dystrophy (DMD) is an inherited, severe muscle wasting disease caused by the loss of the cytoskeletal protein, dystrophin. Patients usually die in their late teens or early twenties of cardiac or respiratory failure. We have previously demonstrated that the dystrophin related protein, utrophin is able to compensate for the loss of dystrophin in the mdx mouse, the mouse model of the disease. Expression of a utrophin transgene under the control of an HSA promoter results in localization of utrophin to the sarcolemma and prevents the muscle pathology. Here we show that the over-expression of full-length utrophin in a broad range of tissues is not detrimental in the mdx mouse. These findings have important implications for the feasibility of the up-regulation of utrophin in therapy for DMD since they suggest that tissue specific up-regulation may not be necessary.

Preoperative ECF chemotherapy in gastro-oesophageal adenocarcinoma.

Epirubicin, cisplatin and continuous 5-fluorouracil (5-FU) infusion (ECF) has been reported to result in high clinical response rates in advanced gastro-oesophageal adenocarcinoma and is currently the 'gold standard' chemotherapy regimen for this tumour site. Despite this, its role as preoperative (neoadjuvant) treatment is unproven and therefore remains under investigation. We report our experience using ECF (intravenous epirubicin 50 mg/m2 and cisplatin 60 mg/m2 every 3 weeks, with continuous infusion of 5-FU 200 mg/m2 per day) as preoperative treatment in locally advanced adenocarcinoma of the lower oesophagus, gastro-oesophageal junction and stomach. Of the 23 patients treated (median age 54 years), 19 had potentially resectable disease, four were unresectable and seven had radiological evidence of lymph node involvement. A median of four cycles of ECF was delivered (range 1-6). Ten of 12 patients (83%) with dysphagia reported improvement of symptoms. Clinical disease progression occurred in six patients (26%) during chemotherapy. WHO grade 3 or 4 toxicity occurred in six patients (26%): four haematological, one mucositis, one vomiting. Seventeen patients (74%) proceeded to surgery; 14 (61%) were resected and three were unresectable. There were two (12%) postoperative deaths from respiratory failure. Major pathological response was seen in three patients (13%): one pathological complete response, two microscopic residual disease. Two patients had Stage II (T2N(0-1)) disease and nine were Stage III (T(3-4)N(0-1)). None of the patients with initially unresectable disease was rendered resectable. After a median follow-up interval of 33 months (range 26-53), the overall median survival was 12 months and 2-year survival was 30%. All patients who were initially unresectable or had radiological evidence of lymph node involvement have died. Therefore, despite good symptomatic response rates, ECF chemotherapy given in the preoperative setting did not appear to improve the outcome of patients with unresectable or radiologically lymph node-positive gastro-oesophageal adenocarcinoma. The role of ECF chemotherapy in resectable tumours is unclear and is currently under investigation in the randomized MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) study.

Dystrophin and utrophin influence fiber type composition and post-synaptic membrane structure.

The X-linked muscle wasting disease Duchenne muscular dystrophy is caused by the lack of dystrophin in muscle. Protein structure predictions, patient mutations, in vitro binding studies and transgenic and knockout mice suggest that dystrophin plays a mechanical role in skeletal muscle, linking the subsarcolemmal cytoskeleton with the extracellular matrix through its direct interaction with the dystrophin-associated protein complex (DAPC). Although a signaling role for dystrophin has been postulated, definitive data have been lacking. To identify potential non-mechanical roles of dystrophin, we tested the ability of various truncated dystrophin transgenes to prevent any of the skeletal muscle abnormalities associated with the double knockout mouse deficient for both dystrophin and the dystrophin-related protein utrophin. We show that restoration of the DAPC with Dp71 does not prevent the structural abnormalities of the post-synaptic membrane or the abnormal oxidative properties of utrophin/dystrophin-deficient muscle. In marked contrast, a dystrophin protein lacking the cysteine-rich domain, which is unable to prevent dystrophy in the mdx mouse, is able to ameliorate these abnormalities in utrophin/dystrophin-deficient mice. These experiments provide the first direct evidence that in addition to a mechanical role and relocalization of the DAPC, dystrophin and utrophin are able to alter both structural and biochemical properties of skeletal muscle. In addition, these mice provide unique insights into skeletal muscle fiber type composition.

Primary esophageal repair for Boerhaave's syndrome.

BACKGROUND: Boerhaave's syndrome is the most sinister cause of esophageal perforation. The mediastinal contamination with microorganisms, gastric acid, and digestive enzymes results in a mediastinitis that is often fatal if untreated. METHODS: We present a series of 21 patients seen in our unit in the 10 years 1987 to 1996. Esophageal repair was performed in 17 (81%) of them. After the resuscitation of the patient in the intensive care unit, our strategy is primary esophageal repair with a single layer of interrupted absorbable sutures combined with mediastinal toilet, mediastinal drainage, and drainage gastrostomy. The majority of patients (12/21) were referred more than 24 hours after perforation. RESULTS: The mean age of the patients was 60+/-17 years. The mean stay in the intensive care unit was 1.6+/-1.8 days and the median hospital stay, 14 days. There were three deaths, an overall mortality rate of 14.3%. CONCLUSIONS: When combined with mediastinal toilet, mediastinal drainage, and drainage gastrostomy, primary esophageal repair for Boerhaave's syndrome gives an acceptable mortality and should not be reserved for patients seen within 24 hours after spontaneous rupture.

Iatrogenic oesophageal perforations: a clinical review.

Thirty patients with iatrogenically induced perforation of the oesophagus were managed in our unit between January 1986 and December 1996. Thirteen (43%) of these injuries were referred after upper gastrointestinal endoscopy performed by physicians. Ten (33%) cases were referred by ENT surgeons and general surgeons referred 7 (23%) cases. Of these patients, 15 (50%) had no abnormality of the oesophagus found before perforation. Only 18 (60%) of patients were referred within 24 h of injury. The mean duration of care required in the intensive care unit was 1.5 days +/- 2.5 days and the mean inpatient hospital stay 26.5 days +/- 22.1 days. The mortality was 10% (three cases). Oesophageal perforation remains a serious life-threatening injury. The early diagnosis of this uncommon condition requires a high index of suspicion as the symptoms are often non-specific. Identification of the site of perforation is necessary as the management of cervical and thoracic perforations differs considerably. Early referral combined with appropriate therapy would appear to result in a better outcome than previously published data. It is therefore suggested that patients with this relatively rare condition should be referred as soon as possible to a centre with expertise in its management.

Thoracoscopic debridement of empyema thoracis.

BACKGROUND: The primary treatment of empyema thoracis remains intercostal tube drainage together with antibiotics. Failure of primary treatment has until recently been an indication for thoracotomy and decortication. Video-assisted thoracoscopic debridement (VATD) has increased the available treatment options but requires validation. METHODS: A retrospective analysis was undertaken of 44 consecutive patients who presented for surgical treatment of empyema thoracis over a 3-year period. RESULTS: Two patients were unsuitable for VATD and were treated with open decortication (OD). Thirty patients were successfully treated by VATD. Two patients were converted to OD at the first operation, and 10 patients required OD as a second procedure. The mean duration of preoperative symptoms before referral was 37.6 +/- 11.8 days (VATD) and 40.1 +/- 11.6 days (OD) (p = not significant). The mean duration of hospitalization before transfer was 13.7 +/- 2.4 days (VATD) and 11.5 +/- 3.4 days (OD) (p = not significant). Intercostal drainage was required for 4.0 +/- 0.3 days (VATD) and 8.5 +/- 2.0 days (OD) (p = 0.004). The postoperative hospital stay was 5.3 +/- 0.4 days (VATD) and 10.3 +/- 2.1 days (OD) (p = 0.001). CONCLUSIONS: Primary surgical therapy with VATD should be considered for all patients with pleural empyema, irrespective of the duration of symptoms. This approach does not preclude OD as a secondary procedure or conversion to OD after initial thoracoscopic assessment. The major advantages of VATD over OD are a shorter duration of postoperative intercostal drainage and reduced postoperative hospitalization.

Disease recurrence after resection for stage I lung cancer.

OBJECTIVE: To asses the incidence of local recurrence and distant metastases after complete resection for stage I lung cancer in order to predict the predominant prognostic factors. METHODS: We retrospectively reviewed 123 patients with stage I lung cancer who underwent curative resection over a 2-year period between January 1987 and December 1988. There were 83 male and 40 female patients with a mean age of 64.8 +/- 12 years (range between 39 and 82 years). Multivariate analysis of prognostic factors for long term survival was undertaken. RESULTS: T1N0 lesions were found in 34 patients and T2N0 in 89. The histological diagnosis was Squamous carcinoma in 75, Adenocarcinoma in 38, large cell carcinoma in 6 and small cell carcinoma in 4 patients. Pneumonectomy was performed in 27 patients (5 T1 and 22 T2) while 96 required lobectomy (29 T1 and 67 T2). At 5 years 50 patients died. This was due to local recurrence in 12, distant metastasis in 24, second primary in 1, unrelated disease in 3, while the cause was unknown in 10 patients. At 5 years, 10 patients were alive with evidence of recurrence. The mean interval for local recurrence was 19.8 months and for distant metastasis was 18 months. The overall 5 year survival was 67% +/- 4 for T1 and 56% +/- 5 for T2 lesions (NS). The rate of recurrence was significantly less for T1 lesions (P = 0.02). Survival was significantly less for patients requiring pneumonectomy rather than lobectomy (P = 0.01) whether for T1 or T2. CONCLUSION: In stage I lung cancer T2 lesions requiring pneumonectomy for complete resection had a worse prognosis and higher incidence of local recurrence.

Homograft as a conduit for superior vena cava syndrome.

This report outlines the management of a 30-year-old man with severe multiresistant mycobacterium tuberculosis of his right lung. Despite medical therapy he had open tuberculosis with positive sputum smears. A right pneumonectomy was undertaken, but due to distorted hilar anatomy, the superior vena cava was resected. Postoperatively, superior vena cava syndrome developed and failure of venous drainage was demonstrated by bilateral arum venography and computed tomographic scanning. The superior vena cava syndrome was successfully relieved using an aortic homograft as a superior vena cava replacement instead of a spiral vein graft or a prosthetic conduit.

"Sneeze of a cancer from the lung": sternumentum carcinomae pulmonariae.

The protean manifestations of the clinical presentation of carcinoma of the lung are well known. In the following case report we describe an unusual presentation of such a carcinoma. We further describe this occurrence in Latin as befits what we believe to be a new presentation.

Factors affecting long term survival following resection for lung cancer.

BACKGROUND: Survival following pulmonary resection for primary lung cancer is considered to be principally dependent on the clinical stage of the disease. A study was undertaken to verify this and to identify other contributing factors. METHODS: The case records of all patients who underwent surgery for lung cancer over a two year period between January 1987 and December 1988 were reviewed retrospectively. RESULTS: One hundred and forty-seven lobectomies and 60 pneumonectomies were performed with 2.8% and 5.3% operative mortality, respectively. Squamous carcinoma was the commonest pathology (60%) followed by adenocarcinoma (30%). The overall five year survival was 45.5% (95% CI 44.1% to 57.9%). There were 123 patients with stage I disease, 40 with stage II, and 37 in stage IIIa with five year survival of 59.4% (95% CI 50.8% to 68%), 30% (95% CI 15.9% to 44.1%), and 16.2% (95% CI 3.5% to 31%), respectively. There were no differences in survival with respect to sex, extent of resection, or cell type. In patients with stage II disease the five year survival of those with T1 lesions (50%, 95% CI 37.3% to 62.9%) was better than those with T2 (28.1%, 95% CI 16.9% to 39.3%). Of eight patients over the age of 70 with stage IIIa disease none survived more than 24 months. CONCLUSIONS: Stage at operation is the most accurate predictor of long term survival in early lung cancer and surgery remains an effective treatment, particularly in stage I and II disease. Further study is needed to assess the prognostic value of subdividing stage II disease into T1 and T2 lesions. Major resection for locally advanced disease in older patients may be relatively ineffective.

Videothoracoscopy in the treatment of early empyema: an initial experience.

Seventeen consecutive patients were referred for management of empyema between April 1991 and March 1992. Fourteen patients defined as having an 'early' empyema were initially treated by videothoracoscopy. The other three patients, defined as having a 'late' empyema proceeded directly to thoracotomy. Videothoracoscopy was successful in 10 out of the 14 patients. The mean postoperative stay was 7.8 days. At a mean follow-up at 16.7 months, these patients were rendered apyrexial with full lung expansion and no residual pleural collection. The postoperative results were at least equivalent to other conventional forms of treatment without an undue level of complications. In this series, thoracoscopy was found to be successful when symptoms had been present up to 31 days before presentation at the first hospital, and the mean length of treatment before referral to Harefield was 47 days. It is now our policy to videothoracoscope all patients with empyema thoracis, regardless of the length of referral. It may circumvent the need for a thoracotomy, it does not add any increased risk of complications, and does not appreciably increase the length of hospital stay should thoracotomy ultimately be required.

Thoracoscopic bullectomy and tetracycline pleurodesis for the treatment of spontaneous pneumothorax.

Initial experience of thoracoscopic bullectomy and tetracycline pleurodesis for the treatment of spontaneous pneumothorax is reported. Thirty-three out of 49 patients admitted with spontaneous pneumothorax were suitable for treatment with this minimally invasive method. This series demonstrates that this surgical management offers early discharge and return to normal activities with excellent medium-term results, despite the three early failures. It is felt that with increased experience in thoracoscopy and improved selection of patients, thoracoscopic bullectomy and pleurodesis will become the treatment of choice for primary spontaneous pneumothorax.

Surgical management of spontaneous pneumothorax.

Despite the promising potential of video-assisted thoracoscopic pleurectomy in the treatment of pneumothoraces, conventional surgical intervention by a thoracotomy and pleurodesis with ligation/stapling of bullae remains the main form of treatment in many hospitals. It is with this in mind that we present our experience of 250 patients who have undergone surgical pleurodesis for treatment of a persistent or recurrent spontaneous pneumothorax. Of these patients, 74 had undergone parietal pleurectomy (PP), 93 pleural abrasion (PA), 60 transaxillary apical pleurectomy (TAP), and 23 had undergone apical pleurectomy via a posterolateral or submammary thoracotomy (APT). In general, there were few complications and we could show no discernible difference in the rate of complications between the groups. Despite there being no significant difference in the median period of postoperative intercostal tube drainage, there was a significant difference between the groups in the number of patients with a postoperative hospital stay equal to or greater than seven days and a postoperative serosanguinous volume loss greater than 500 ml. Those patients that had undergone parietal pleurectomy tended to remain in hospital for a longer period (> or = 7 days) and to have a heavier serosanguinous volume loss (> 500 ml). There have been no recurrent cases in the PP and APT groups. Their respective median follow up periods are 62 (range 15-83) and 32 (range 15-54) months. The median follow up period in the PA group was 42 (range 13-69) months, one recurrence occurred after 7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary repair of iatrogenic thoracic esophageal perforation and Boerhaave's syndrome.

Ten patients seen at our unit over a 24-month period with either iatrogenic (n = 5) or spontaneous thoracic esophageal perforations (n = 5) were retrospectively reviewed. Five patients were seen within 24 hours of onset of symptoms, and 5 were seen after 24 hours or later. There was no significant difference in the presentation or subsequent clinical course in patients seen less or more than 24 hours after the onset of symptoms. Nine patients underwent primary repair together with drainage of the mediastinum, and in 1 of these a Heller's myotomy was also performed for achalasia. One patient had a two-stage esophagogastrectomy for a benign esophageal stricture. One patient (10%) with a spontaneous perforation died 48 hours after operation and was found at postmortem examination to have an in situ carcinoma at the site of the perforation. Four patients (40%) had nonfatal complications. Fistulas developed in 3 patients (30%); in 1 of these patients a second thoracotomy and a further rib resection was required for drainage of a mediastinal abscess. An esophago-cutaneous fistula and a persistent mediastinal abscess developed in 1 patient (10%) and necessitated two further thoracotomies for effective drainage. The mean hospital stay was 38.4 +/- 25.4 days (range, 16 to 76 days). The findings of this study suggest that primary repair combined with a drainage procedure is the treatment of choice for patients with a perforated intrathoracic esophagus, including those seen more than 24 hours after the onset of symptoms.

Use of endotracheal silicone stents for relief of tracheobronchial obstruction.

In this article we describe our initial experience with bifurcated and longitudinal silicone stents that can be inserted entirely endoscopically. A total of 10 patients were stented; half had upper airways obstruction resulting from malignant disease and half had anastomotic obstruction after single-lung (3 patients), double-lung (1 patient), or heart-lung transplantation (1 patient). All patients derived immediate relief of life-threatening stridor. Stents were in place for between 5 days and 2 1/2 years (mean, 232.9 days). In the patients with malignant disease, the stents have provided effective relief from stridor for the remainder of their lives. In the transplant recipients, the medium-term results are encouraging, with the stents providing effective relief from stridor, although the longitudinal stents have been associated with distal migration, requiring that the stents be replaced on up to five occasions. The stents have not been associated with infection in the nonimmunosuppressed patients, and during the relatively short follow-up period there has been no tissue reaction to the material.

Elective pneumonectomy: factors associated with morbidity and operative mortality.

We have retrospectively reviewed hospital records of 197 consecutive patients undergoing pneumonectomy for neoplastic disease between 1985 and 1990 to identify predictors of outcome. Seventeen of the 197 patients died during their hospital stay (8.6%; 95% confidence intervals, 6.7% to 11.2%). The most significant predictors of in-hospital mortality were presence of coexisting medical conditions (p less than 0.001), respiratory function tests showing an obstructive picture with a forced expiratory volume in 1 second/forced vital capacity ratio of less than 0.55 (p less than 0.001), 24-hour fluid replacement of more than 3 L (p less than 0.05), postoperative pulmonary edema (p less than 0.001), respiratory tract infection with positive sputum culture (p less than 0.01), postoperative renal failure (p less than 0.001), and cardiac arrhythmias (p less than 0.001). There were 232 postoperative management, problems occurring in 197 patients. The most significant predictors of postoperative morbidity were continued cigarette smoking up to the time of operation (p less than 0.05), perioperative blood loss or more than 2 L (p less than 0.05), and infusion of more than 3 L of fluid in the first 24 hours (p less than 0.05). Although retrospective analyses must be interpreted with caution, this study has identified preoperative and perioperative factors associated with in-hospital morbidity and mortality after pneumonectomy.

Early and late outcome after diagnostic thoracoscopy and talc pleurodesis.

Although thoracoscopy is now recognized to be of both diagnostic and therapeutic value, the risks of this procedure have not been fully addressed. We retrospectively reviewed our experience with 100 patients who underwent 110 thoracoscopies during the period January 1989 to February 1991. Sixty-five men and 35 women (ratio of 1.9:1) underwent thoracoscopy using general anesthesia and intubation with a double-lumen endotracheal tube. The mean age was 64.2 +/- 11.6 years (range, 13 to 85 years). The diagnosis was established in 48 (85.7%) of the 56 patients with undiagnosed pleural effusions. Forty-four patients were referred for therapeutic thoracoscopic talc pleurodesis. Pleurodesis was successful in 42 patients (95.5%). Four patients (4%) had five postoperative complications (two bronchopleural fistulas, two chest infections, and one arrhythmia). Five patients (5%) died after thoracoscopy; mean age was 67.8 +/- 8.1 years (range, 55 to 77 years). The causes of death were cardiac arrest in 2, respiratory failure in 1, and malignant cachexia in 2. The findings of this study confirm that thoracoscopy can achieve high rates of diagnostic and therapeutic success but is not without attendant mortality in a high-risk patient population.

Cardiac torsion after lobectomy with partial pericardectomy.

Cardiac herniation and torsion after intrapericardial pneumonectomy without closure of the pericardium is widely recognized. However, such a complication occurring after lobectomy has been rarely discussed in the literature. We describe a case of cardiac torsion of late onset that developed in a woman who had undergone left upper lobectomy as part of a resection for a malignant thymoma.