Columnar metaplasia in the esophageal remnant after esophagectomy: a systematic review.

Barrett's metaplasia is a well-recognized risk factor for esophageal adenocarcinoma. It is believed to develop in response to the injurious effects of gastroesophageal reflux. Following subtotal esophagectomy and reconstruction with a gastric conduit, many patients experience profound reflux into the remnant esophagus. Barrett's-like epithelium has been described in these patients, and they have been identified as a potential human model in which to study the early events in the development of metaplasia. This phenomenon also raises clinical concerns about the long-term fate of the esophageal remnant following surgery and the potential for further malignant change. This systematic review summarizes the literature on the prevalence and timing of Barrett's metaplasia occurring after esophagectomy, reviews the evidence regarding risk factors and malignant progression in such patients, and considers the implications for clinical practice.

Anti-reflux surgery in lung transplant recipients: outcomes and effects on quality of life.

Fundoplication may improve survival after lung transplantation. Little is known about the effects of fundoplication on quality of life in these patients. The aim of this study was to assess the safety of fundoplication in lung transplant recipients and its effects on quality of life. Between June 1, 2008 and December 31, 2010, a prospective study of lung transplant recipients undergoing fundoplication was undertaken. Quality of life was assessed before and after surgery. Body mass index (BMI) and pulmonary function were followed up. 16 patients, mean ± sd age 38 ± 11.9 yrs, underwent laparoscopic Nissen fundoplication. There was no peri-operative mortality or major complications. Mean ± SD hospital stay was 2.6 ± 0.9 days. 15 out of 16 patients were satisfied with the results of surgery post fundoplication. There was a significant improvement in reflux symptom index and DeMeester questionnaires and gastrointestinal quality of life index scores at 6 months. Mean BMI decreased significantly after fundoplication (p = 0.01). Patients operated on for deteriorating lung function had a statistically significant decrease in the rate of lung function decline after fundoplication (p = 0.008). Laparoscopic fundoplication is safe in selected lung transplant recipients. Patient benefit is suggested by improved symptoms and satisfaction. This procedure is acceptable, improves quality of life and may reduce deterioration of lung function.

Prognostic value of maximum standardized uptake values from preoperative positron emission tomography in resectable adenocarcinoma of the esophagus treated by surgery alone.

Preoperative staging for esophageal adenocarcinoma is suboptimal for predicting outcomes when compared with pathological data. The aim of this study was to assess if the quantitative values obtained by preoperative 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) are independent prognostic indicators for survival in patients with resectable adenocarcinoma of the esophagus undergoing surgical treatment without neoadjuvant therapy. Patients were identified from a prospective database, survival analyses were undertaken using log rank and Cox method. The median follow-up was 44 months (range 18-61 months). Between November 2002 and November 2005, 45 consecutive patients underwent FDG-PET followed by surgery. The median age was 72 years (range 38-82 years). On univariate analysis of overall survival and disease-free survival, preoperative FDG-PET maximum standardized uptake value (SUV(max); P= 0.008 and P= 0.015, respectively) and postoperative pathological stage (P= 0.001 and P= 0.001, respectively) as well as postoperative histological grade (P= 0.001 and P= 0.001, respectively) were significantly associated with outcome. Multivariate analysis demonstrated that only the postoperative pathological variables were independent predictors of outcome (Wald 11.81, P= 0.001). Preoperative FDG-PET SUV(max) is associated with outcome after esophageal adenocarcinoma resection but remains less accurate than postoperative variables. A high FDG-PET SUV(max) could be used to identify a high-risk population who would benefit most from neoadjuvant therapies.

Spontaneous rupture of the oesophagus.

BACKGROUND: The aim of this study was to evaluate the diagnosis, management and outcome of patients with spontaneous rupture of the oesophagus in a single centre. METHODS: Between October 1993 and May 2007, 51 consecutive patients with spontaneous oesophageal rupture were evaluated with contrast radiology and flexible endoscopy. Patients with limited contamination who fulfilled specific criteria were managed by a non-operative approach, whereas the remainder underwent thoracotomy. RESULTS: The median time to diagnosis was 24 (range 4-604) h. Initial diagnosis was by contrast swallow in 18 of 24 patients, computed tomography in 15 of 17 and endoscopy in 18 of 18. There were no deaths among 17 patients who were managed non-operatively with targeted drainage, intravenous antimicrobials, nasogastric decompression and enteral nutrition. Of 31 patients who underwent primary thoracotomy and oesophageal repair (over a Ttube in 29), 11 died in hospital. Three patients could not be resuscitated adequately and did not have surgical intervention. CONCLUSION: Spontaneous oesophageal rupture represents a spectrum of disease. Accurate radiological and endoscopic evaluation can identify those suitable for radical non-operative treatment and those who require thoracotomy.

Antibiotic regimens for secondary peritonitis of gastrointestinal origin in adults.

BACKGROUND: Secondary peritonitis is associated with a high mortality rate and if not treated successfully leads to development of abscesses, severe sepsis and multi-organ failure. Source control and adjunctive antibiotics are the mainstay of treatment. However, no conclusive evidence suggest that one antibiotic regimen is better than any other but at the same time have a lower toxicity. OBJECTIVES: To ascertain the efficacy and adverse effects of different antibiotic regimens in treating intra-abdominal infections in adults. Outcomes were divided into primary (clinical success and effectiveness in reducing mortality) and secondary (microbiological success, preventing wound infection, intra-abdominal abscess, clinical sepsis, remote infection, superinfection, adverse reactions, duration of treatment required, effectiveness in reducing hospitalised stay, and time to defervescence). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 4, 2004), MEDLINE (from 1966 to November 2004), EMBASE (from 1980 to November 2004) and Cochrane Colorectal Cancer Group specialised register SR-COLOCA. Bibliographies of identified studies were screened for further relevant trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing different antibiotic regimens in the treatment of secondary peritonitis in adults were selected. Trials reporting gynaecological or traumatic peritonitis were excluded from this review. Ambiguity regarding suitability of trials were discussed among the review team. DATA COLLECTION AND ANALYSIS: Six reviewers independently assessed trial quality and extracted data. Data collection was standardised using data collection form to ensure uniformity among reviewers. Statistical analyses were performed using the random effects model and the results expressed as odds ratio for dichotomous outcomes, or weight mean difference for continuous data with 95% confidence intervals. MAIN RESULTS: Fourty studies with 5094 patients met the inclusion criteria. Sixteen different comparative antibiotic regimens were reported. All antibiotics showed equivocal comparability in terms of clinical success. Mortality did not differ between the regimens. Despite the potential high toxicity profile of regimens using aminoglycosides, this was not demonstrated in this review. The reason for this could be the inherent bias within clinical trials in the form of patient selection and stringency in monitoring drug levels. AUTHORS' CONCLUSIONS: No specific recommendations can be made for the first line treatment of secondary peritonitis in adults with antibiotics, as all regimens showed equivocal efficacy. Other factors such as local guidelines and preferences, ease of administration, costs and availability must therefore be taken into consideration in deciding the antibiotic regimen of choice. Future trials should attempt to stratify patients and perform intention-to-treat analysis to allow better external validity.

A pragmatic randomised controlled trial of the cost-effectiveness of palliative therapies for patients with inoperable oesophageal cancer.

OBJECTIVES: To compare whether treatment with self-expanding metal stents (SEMS) is more cost-effective than treatment with conventional modalities in patients with inoperable oesophageal cancer. Quality of life effects were also considered. DESIGN: A multicentre pragmatic, randomised controlled trial with health economic analysis. SETTING: Seven NHS hospitals selected to represent a cross-section of UK hospitals in terms of facilities and staffing. PARTICIPANTS: All patients attending the centres with oesophageal cancer deemed unsuitable for surgery were assessed for inclusion in the main trial; 217 patients were randomised. A health state utilities substudy was also performed in 71 patients who had previously received curative surgery for oesophageal cancer. INTERVENTIONS: Eligible patients were randomised to one of four treatment groups within two study arms. Assessments were performed at enrolment, 1 week following treatment and thereafter at 6-weekly intervals until death, with prospective data collection on complications and survival. Structured interviews to elicit patient preferences to health states and treatments were performed in a substudy. MAIN OUTCOME MEASURES: Dysphagia grade and quality of life were examined at 6 weeks. Survival, resources consumed from randomisation to death and quality-adjusted life-years were also considered. RESULTS: There was no difference in cost or effectiveness between SEMS and non-SEMS therapies, and 18-mm SEMS had equal effectiveness to, but less associated pain than, 24-mm SEMS. Rigid intubation was associated with a worse quality of swallowing and increased late morbidity. Bipolar electrocoagulation and ethanol tumour necrosis were poor in primary palliation. A survival advantage was found for non-stent therapies, but there was a significant delay to treatment. The length of stay accounts for the majority of the cost to the NHS. Patients were found to have distinct individual treatment preferences. CONCLUSIONS: It was suggested that rigid tubes and 24-mm SEMS should no longer be recommended and bipolar electrocoagulation and ethanol tumour necrosis should not be used for primary palliation. The choice in palliation would between non-stent and 18-mm SEMS treatments, with non-stent therapies being made more available and accessible to reduce delay. A multidisciplinary team approach to palliation is also suggested. A randomised controlled clinical trial of 18-mm SEMS versus non-stent therapies with survival and quality of life end-points would be helpful, as would an audit of palliative patient admissions to determine the reasons and need for inpatient hospital care, with a view to implementing cycle-associated change to reduce inpatient stay. A study of delays in palliative radiotherapy treatment is also suggested, with a view to implementing cycle-associated change to reduce waiting time.

Prognostic significance of peri-operative blood transfusion following radical resection for oesophageal carcinoma.

INTRODUCTION: Peri-operative allogeneic blood transfusion may exert an immunomodulatory effect and has been associated with early recurrence and decreased survival following resection for several gastro-intestinal malignancies. The aim of this study was to evaluate the prognostic influence of transfusion requirements following radical oesophagectomy for cancer. METHODS: A consecutive series of 235 patients undergoing subtotal oesophagectomy with two-field lymphadenectomy in a single centre from April 1990 to June 1999 were studied. RESULTS: The median age was 64 years (30-79) with a male to female ratio of 3:1. The predominant histological subtype was adenocarcinoma (n = 154) compared to squamous carcinoma (n = 81). To avoid the influence of surgical complications data were excluded from the 5.5% of patients suffering in-hospital mortality. In the remaining patients, median blood loss was 900 ml (200-5500) with 46% (103/222) requiring transfusion (median 3 units, range 2-21). Median survival of non-transfused patients was 36 months compared to only 19 months for those receiving transfusion (log-rank = 4.44; 1 df, P = 0.0352). Non-transfused patients had significantly higher 2 and 5-year survival rates of 62% and 41% respectively in contrast to only 40% and 25% in those receiving blood transfusion. Even after stratification of results according to disease stage or the presence of major complications, survival was significantly worse in those receiving transfusion. Multivariate analysis demonstrated that in addition to nodal status, > 4 units transfusion was an independent prognostic indicator. CONCLUSION: Post-operative transfusion is associated with a significantly worse prognosis following radical oesophagectomy. Meticulous haemostasis and avoidance of unnecessary transfusion may prove oncologically beneficial.

Pattern of recurrence following subtotal oesophagectomy with two field lymphadenectomy

Aims: Despite increasingly radical surgery for oesophageal cancer many patients continue to represent with recurrent disease. This study aimed to evaluate the pattern of failure following attempted curative oesophagectomy with mediastinal and upper abdominal lymphadenectomy. METHODS: Some 212 consecutive patients undergoing R0 resection for malignancy between 1 April 1990 and 1 April 1999 were followed up for evidence of recurrence. Clinical evaluation was supported by ultrasonography, computed tomography, isotope scan, endoscopy and laparotomy with biopsy assessment if appropriate. Patients were excluded if recurrence was diagnosed on clinical grounds alone. Statistical analysis was performed using chi2 and log rank tests. RESULTS: Some 142 patients with adenocarcinoma and 70 with squamous carcinoma (SCC) were followed up for a median of 14 (range 1-108) months. Sex and age distribution were similar for both histological subtypes (men : women 3 : 1; median age 64 (30-79) years). Twenty patients died from non-cancer related causes, including 11 (5 per cent) from postoperative complications. Some 89 patients (42 per cent) developed proven recurrent disease of which seven are alive and 82 dead. The median time to recurrence was 11 (2-40) months with a median time to death thereafter of 3 (1-21) months. The pattern of recurrence was locoregional in 23 per cent (oesophageal bed 15 per cent, upper abdominal 3 per cent, upper mediastinal 3 per cent, cervical 2 per cent) and haematogenous in 18 per cent (comprising liver 8 per cent, bone 4 per cent, cerebral 3 per cent, lung 2 per cent, skin 1 per cent) with peritoneal dissemination in 1 per cent. While there was no difference in the overall pattern of dissemination for each histological subtype, the incidence of cervical and upper mediastinal recurrence was significantly higher for adenocarcinoma compared with SCC (chi2 = 5. 9, 1 d.f., P < 0.02). The timing of recurrence was similar for both histological subtypes: 60 per cent of all recurrence occurred within 12 months of surgery, with distant and locoregional recurrence occurring at a median of 10 (2-40) and 11 (2-32) months respectively. CONCLUSIONS: The low incidence of upper mediastinal and cervical recurrence suggests that more extensive lymphadenectomy is unlikely to impact upon survival. Improved staging modalities are required to identify the significant number of patients who develop early recurrence in the first year following surgery in order to offer them multimodality therapies of non-surgical palliation.

Management of spontaneous rupture of the oesophagus

AIMS: Spontaneous rupture of the oesophagus (SRO) is a rare and often fatal event. The aim of this study was to evaluate the presentation, management and outcome of SRO in a single unit. METHODS: Data were collected on all patients presenting with SRO over a 5-year period with respect to presenting features, diagnostic investigations and subsequent management. Statistical analysis was by Student's t test, chi2 and Fisher's exact tests. RESULTS: Fourteen patients were identified, 12 men and two women with a median age of 64 (range 18-78) years; eight were tertiary referrals. Thirteen of 14 patients presented with chest or upper abdominal pain following vomiting or retching and 13 had an abnormal initial chest radiograph; only one presented with Mackler's triad of pain, vomiting and surgical emphysema. The median delay to diagnosis was 21 (range 1-84) h; this delay did not significantly affect outcome (P = 0.16). An endoscopic assessment and contrast swallow were performed in all patients. Nine of ten patients with a demonstrable leak and full-thickness tear were managed surgically and the four patients with no leak were managed conservatively (P = 0.005); surgical management consisted of thoracotomy, lavage, repair of the perforation and a feeding jejunostomy. Seven patients had a repair over a T tube and two had a primary repair. All conservatively managed patients had contained, controlled or intramural perforations and two also required a feeding jejunostomy. Patients requiring surgery had a longer hospital stay (mean(s.d.) 57.9(34.8) versus 22.2(30.7) days; P = 0.081) and a significantly longer intensive care unit stay (P = 0.044). The overall mortality rate from SRO was 14 per cent (two patients); no deaths occurred in the conservatively managed group. CONCLUSIONS: SRO continues to be diagnosed late despite a classical history and/or abnormal chest radiograph. Endoscopic assessment of perforations is safe and in combination with a contrast swallow can confidently predict patients with contained or controlled rupture in whom non-operative management is successful.

Cytokeratin expression in breast cancer: phenotypic changes associated with disease progression.

Transition from a normal to a cancerous state is marked by alterations in the cytoskeletal structure of those cells involved. We have examined such changes to determine if these transitions are markers of disease progression. Cytokeratin (CK) protein and messenger RNA (mRNA) expression were examined in malignant and benign breast tissues. Flow cytometric results demonstrated a significant correlation between cytokeratin protein expression detected by 5D3 antibody, specific for cytokeratins 8, 18, and 19 and axillary node metastasis (P = 0.01). A threshold of positivity of 338,000 molecules/cell was determined and reflected the wide range in cytokeratin levels expressed by normal or benign tissues. Examination of cytokeratins 8, 18, and 19 revealed a consistent pattern of expression with respect to tumor grade. Only cytokeratin 19 showed significant correlation with increasing tumor size (P = 0.006). mRNA expression for cytokeratin 8 was significantly higher in node-positive compared with node-negative disease (P = 0.02). Cytokeratin 18 mRNA levels were significantly lower in both node-negative (P = 0.03) and node-positive (P = 0.02) patients when compared with benign samples. Increased levels of cytokeratin 18 mRNA showed an inverse relationship with protein expression (P = 0.05). The results indicate that cytokeratin expression in breast cancer may be associated with tumor progression. Furthermore, the alteration in the expression of individual cytokeratins deserves further investigation to determine the consequences of these changes with respect to cellular function.