A comparison of the left thoracoabdominal and Ivor-Lewis esophagectomy.

The purpose of this study was to assess the oncological outcomes of a large multicenter series of left thoracoabdominal esophagectomies, and compare these to the more widely utilized Ivor-Lewis esophagectomy. With ethics approval and an established study protocol, anonymized data from five centers were merged into a structured database. The study exposure was operative approach (ILE or LTE). The primary outcome measure was time to death. Secondary outcome measures included time to tumor recurrence, positive surgical resection margins, lymph node yield, postoperative death, and hospital length of stay. Cox proportional hazards models provided hazard ratios (HR) with 95% confidence intervals (CI) adjusting for age, pathological tumor stage, tumor grade, lymphovascular invasion, and neoadjuvant treatment. Among 1228 patients (598 ILE; 630 LTE), most (86%) had adenocarcinoma (AC) and were male (81%). Comparing ILE and LTE for AC patients, no difference was seen in terms of time to death (HR 0.904 95%CI 0.749-1.1090) or time to recurrence (HR 0.973 95%CI 0.768-1.232). The risk of a positive resection margin was also similar (OR 1.022 95%CI 0.731-1.429). Median lymph node yield did not differ between approaches (LTE 21; ILE 21; P = 0.426). In-hospital mortality was 2.4%, significantly lower in the LTE group (LTE 1.3%; ILE 3.6%; P = 0.004). Median hospital stay was 11 days in the LTE group and 14 days in the ILE group (P < 0.0001). In conclusion, this is the largest series of left thoracoabdominal esophagectomies to be submitted for publication and the only one to compare two different transthoracic esophagectomy strategies. It demonstrates oncological equivalence between operative approaches but possible short- term advantages to the left thoracoabdominal esophagectomy.

A national audit of colonic interposition for esophageal replacement.

Esophageal replacement by colonic interposition is an uncommon procedure. This study sought to identify the frequency of this operation in England, identify techniques and associated problems, and also assess health-related quality of life (HR QOL) from the two largest centers performing this procedure. Hospital Episode Statistics were used to identify patients and centers undertaking colon interposition between March 2001 and March 2015. An online survey of UK consultants discussed methods and experience. HR QOL was assessed using the Short Form 36(SF-36v2) with additional gastrointestinal questions. Hospital Episode Statistics identified 328 interpositions (22 in pediatric hospitals). The two highest volume units did 42 and 45 operations, respectively. Thirty-four surgeons (79% response rate) replied to the survey. Fifty-two percent preferred to use the left colon with 81% preferring a substernal placement. The HR QOL survey was performed on 24 patients with a median of 3 years after surgery (ranging from 9 months to 10 years) from the two largest centers and a 56% response rate. Five patients had physical QOL scores above population average and 10 had mental scores above population average. All patients had early satiety, 20 described dysphagia, and 18 regularly took antireflux medication. There was an estimated mean loss of 13.1% body weight (10.6 kg) postoperatively and three patients still relied on a feeding tube for nutrition after an average of 3 years. Colon interposition results in an acceptable long-term QOL. Few centers regularly perform this operation, and centralizing to high-volume centers may lead to better outcomes.

Surgical resection strategy and the influence of radicality on outcomes in oesophageal cancer.

BACKGROUND: The optimal surgical approach to tumours of the oesophagus and oesophagogastric junction remains controversial. The principal randomized trial comparing transhiatal (THO) and transthoracic (TTO) oesophagectomy showed no survival difference, but suggested that some subgroups of patients may benefit from the more extended lymphadenectomy typically conducted with TTO. METHODS: This was a cohort study based on two prospectively created databases. Short- and long-term outcomes for patients undergoing THO and TTO were compared. The primary outcome measure was overall survival, with secondary outcomes including time to recurrence and patterns of disease relapse. A Cox proportional hazards model provided hazard ratios (HRs) and 95 per cent confidence intervals (c.i.), with adjustments for age, tumour stage, tumour grade, response to chemotherapy and lymphovascular invasion. RESULTS: Of 664 included patients (263 THO, 401 TTO), the distributions of age, sex and histological subtype were similar between the groups. In-hospital mortality (1·1 versus 3·2 per cent for THO and TTO respectively; P = 0·110) and in-hospital stay (14 versus 17 days respectively; P < 0·001) favoured THO. In the adjusted model, there was no difference in overall survival (HR 1·07, 95 per cent c.i. 0·84 to 1·36) or time to tumour recurrence (HR 0·99, 0·76 to 1·29) between the two operations. Local tumour recurrence patterns were similar (22·8 versus 24·4 per cent for THO and TTO respectively). No subgroup could be identified of patients who had benefited from more radical surgery on the basis of tumour location or stage. CONCLUSION: There was no difference in survival or tumour recurrence for TTO and THO.

The effect of economic deprivation on oesophageal and gastric cancer in a UK cancer network.

AIMS: The National Health Service (NHS) Cancer Plan aims to eliminate economic inequalities in healthcare provision and cancer outcomes. This study examined the influence of economic status upon the incidence, access to treatment and survival from oesophageal and gastric cancer in a single UK cancer network. METHODOLOGY: A total of 3619 patients diagnosed with either oesophageal or gastric cancer in a London Cancer Network (population = 1.48 million) were identified from the Thames Cancer Registry (1993-2002). Patients were ranked into economic quintiles using the income domain of the Multiple Index of Deprivation. Statistical analysis was performed using a chi(2) test. Survival analysis was performed using a Cox's proportional hazards model. RESULTS: Between 1993-1995 and 2000-2002, the incidence of oesophageal cancer in the most affluent males rose by 51% compared with a 2% rise in the least affluent males. The incidence of gastric cancer in most affluent males between 1993-1995 and 2000-2002 fell by 32% compared with a 7% fall in the least affluent males. These changes were less marked in females. Economic deprivation had no effect on the proportion of patients undergoing either resectional surgery or chemotherapy; the least affluent oesophageal cancer patients with a higher incidence of squamous cell carcinoma received significantly more radiotherapy. Economic deprivation had no effect upon survival for either oesophageal or gastric cancer. CONCLUSIONS: There has been an increase in oesophageal cancer and a decrease in gastric cancer incidence among more affluent males in the last 10 years. Economic status did not appear to influence access to treatment or survival.

Surgical management of colonic redundancy following esophageal replacement.

Colonic redundancy is the most common late complication following esophageal replacement by colonic interposition. Redundancy in the colonic graft leads to mechanical dysfunction of the neo-conduit, causing disabling symptoms that may develop decades after the original surgery. When symptoms caused by food retention in the colonic loop occur, surgical correction may be necessary to improve quality of life and to prevent complications such as aspiration if lifestyle modifications fail. We describe two cases where remedial surgery was performed for redundancy in interposed colonic grafts. Particularly attention is given to preoperative work-up and surgical technique. The literature is reviewed for the etiology, clinical features and management options of this condition. These cases illustrate a successful surgical technique for correcting this complication.

Anastomotic strictures and delayed gastric emptying after esophagectomy: incidence, risk factors and management.

The aim of this study was to report the incidence, risk factors, and management of gastric conduit dysfunction after esophagectomy in 177 patients over a 3-year period in a single center. Patients with anastomotic strictures or delayed gastric emptying (DGE) were identified from a prospective database. Anastomotic strictures occurred in 48 patients (27%). Eighty-three percent of early anastomotic strictures (<1 year) were benign, and all late strictures (>1 year) were malignant. Dilatation was effective in 98% of benign and 64% of malignant strictures. DGE occurred in 21 patients (12%), and was associated with both anastomotic leak (P = 0.001) and anastomotic stricture (P = 0.001). 4/8 patients with late DGE (>3 months postesophagectomy) were tumor-related. Pyloric dilatation was effective in 92% of early and 63% of late DGE. Pyloric stents were inserted in 3 patients with tumor-related DGE. After esophagectomy, early anastomotic strictures (within 1 year) and early delayed gastric emptying (within 3 months) are usually benign and respond to dilatation. However, patients presenting later with tumor-related obstruction are unlikely to respond to anastomotic or pyloric dilatation and should be stented.

Substernal long segment left colon interposition for oesophageal replacement.

Long segments of colon, transposed on a vascular pedicle, have been used for oesophageal substitution for a long time. However the techniques employed for colonic reconstruction remain debated. We describe our substernal long segment replacement technique and emphasise several key aspects which are important in management of these patients. Optimising nutritional status and pulmonary function remain important aspects. Thymectomy allows room for the colonic segment preventing venous congestion. These patients are best managed in specialist units incorporating a multidisciplinary approach with good intensive care and radiological support.

Transhiatal oesophagectomy: techniques, tips and outcomes.

AIM: To demonstrate our technique and valuable tips for transhiatal oesophagectomies. METHOD: 215 patients underwent transhiatal oesophagectomies in our unit between 2000 and 2006. RESULTS: In-hospital mortality was 0.9%. Anastomotic leak in 12 patients (5.6%). Chyle leak was seen in five patients and recurrent nerve neuropraxia in six patients. Iatrogenic splenectomy rate was 6%. The median operative time was 151 minutes (range 93-276 minutes). Overall median length of hospital stay was 15 days (range 8-95 days). The median survival for all patients undergoing transhiatal oesophagectomy for invasive malignancy was 42.9 months and the one-year and five-year survival were 81% and 48% respectively. CONCLUSION: This is a safe and oncologically sound procedure. We feel that the tips can be helpful for anyone performing this procedure.

Boerhaave's syndrome: diagnosis and surgical management.

Spontaneous oesophageal perforation, or Boerhaave's syndrome, represents barogenic oesophageal injury. Patients don't always present with classical features and treatment may be delayed. Various approaches and strategies have been described but, despite advances in surgery and critical care, the condition continues to carry a high morbidity and mortality. Primary repair may be undertaken in patients who present within 24 hours of perforation and remains the gold standard. Increasingly, this strategy is being adopted for patients who present later with similar mortality rates. Diversion with exclusion and resectional procedures may be undertaken when repair is not possible.

Neoadjuvant chemotherapy for locally advanced carcinoma of the lower oesophagus and oesophago-gastric junction.

AIMS: To evaluate a single unit's experience with neoadjuvant chemotherapy for treating locally advanced non-metastatic initially resectable and unresectable oesophago-gastric cancer. METHODS: The medical records of all patients with either locally advanced carcinoma of the lower oesophagus or cardia treated with neoadjuvant chemotherapy between August 1999 and January 2003 were reviewed. RESULTS: Sixty-four patients with initially resectable tumours (T2-3 or N+) and 38 patients with initially unresectable tumours (T4 or M1a) received neoadjuvant chemotherapy (83% combination Epirubicin, Cisplatin and 5-Fluorouracil). Symptomatic grade III/IV toxicity was observed in 33% of patients. Chemotherapy was not completed in 20 patients because of death (5.9%) and inadequate tumour response/toxicity (13.7%). Forty-three patients (67.3%) with initially resectable tumours and 19 patients (50%) with initially unresectable tumours underwent surgery. CONCLUSIONS: Chemotherapy in this study was associated with appreciable toxicity. Patients with initially unresectable locally advanced disease can be downstaged with neoadjuvant chemotherapy.

Symptomatic responses to neoadjuvant chemotherapy for carcinoma of the oesophagus and oesophagogastric junction: are they worth measuring?

AIMS: Neoadjuvant chemotherapy is used to downstage locally advanced oesophagogastric cancer. This study assessed whether changes in dysphagia and weight correlated with radiological and pathological assessment of response and surgical decision-making. MATERIALS AND METHODS: All patients with locally advanced carcinoma of the lower oesophagus or oesophagogastric junction treated with neoadjuvant ECF (epirubicin, cisplatin, and 5-fluorouracil) chemotherapy from January 2000 to January 2003 were included in this study. Patients were considered to be operable depending upon their chemotherapy response. Weight and swallowing were assessed before and after chemotherapy. Statistical analysis was carried out using ANOVA, unpaired t test and Fisher's exact test. RESULTS: Seventy-eight patients (male-female ratio: 6.8: 1; median age: 62.2 years; range: 44.1-78.0 years) underwent a median of three cycles (range: 1-7) of neoadjuvant ECF chemotherapy. Forty patients (51%) gained weight, and swallowing improved in 53 patients (68%). Radiological changes (based on computed tomography) were assessed according to WHO criteria: complete response (5%), partial response (27%), stable disease (46%) and progressive disease (15%). Patients whose swallowing improved gained significantly more weight (P < 0.0001). Swallowing (P = 0.0009) was significantly improved in radiological responders but not weight (P = 0.06); when radiological non-responders were separated into stable and progressive disease, patients with progressive disease were identified as failing to gain weight (P = 0.005). Both swallowing (P < 0.0001) and weight gain (P < 0.0001) were better in patients undergoing surgery. The use of changes of weight (P = 0.42) and swallowing (P = 0.61) failed to separate pathological responders from nonresponders in the subset of patients undergoing surgery. CONCLUSIONS: Weight gain and improved swallowing are good but not absolute indicators of radiological response to chemotherapy and patient selection for surgery. However, changes in these variables are not sufficiently sensitive to identify pathological responders from non-responders.

Neoadjuvant chemotherapy for oesophageal cancer: the need for accurate response prediction and evaluation.

Primary surgical resection for locally advanced oesophageal cancer is associated with systemic failure and poor survival due to presence of micrometastatic disease at the time of diagnosis. Neoadjuvant chemotherapy prior to surgical resection aims to downstage these locally advanced tumours. A review of reported randomised controlled trials has shown only one sufficiently powered trial with a survival advantage for cisplatin-based chemotherapy. Published meta-analyses of neoadjuvant chemotherapy trials have shown little or no overall survival benefit. A subgroup of patients with biologically favourable tumours who respond to this treatment have been consistently shown to have a survival advantage. These patients need to be differentiated from non-responders preferably at an early stage of this potentially toxic treatment. Current clinical, endoscopic and radiological methods of response evaluation are all unreliable. Response evaluation with 18FDG-PET has been shown to accurately assess the pathological response and also to predict the risk of local recurrence and overall survival. The development of integrated PET/CT imaging may enhance the accuracy of this response evaluation. In the future, molecular markers of response prediction prior to initiation of treatment may allow the development of individualised treatment strategies. New emerging chemotherapeutic agents may prove to be more effective in eradicating micrometastatic disease.

Increasing splanchnic blood flow in the critically III.

STUDY OBJECTIVE: To assess the effect of low dose dopexamine and dopamine on splanchnic blood flow as measured by gastric intramucosal pH, hepatic metabolism of lidocaine (lignocaine) to monoethylglycinexy-lidide (MEGX), and plasma disappearance rate of indocyanine green (ICG). DESIGN: Single-blind randomization of patients with a gastric intramucosal acidosis to receive dopexamine (ten patients), dopamine (ten patients), or saline solution (five control patients) for 2 h. SETTING: All 25 patients were in the ICU of Guys' Hospital. PATIENTS: All patients met the criteria for the diagnosis of the systemic inflammatory response syndrome, were mechanically ventilated, and had pulmonary artery catheters placed. All had a low gastric intramucosal pH and had a median first 24-h acute physiology and chronic health evaluation (II) score of 22 (range, 7 to 40). MEASUREMENTS AND INTERVENTIONS: Baseline measurements of gastric intramucosal pH, MEGX formation from lidocaine, ICG plasma disappearance rate, heart rate, mean arterial pressure, pulmonary artery occlusion pressure, cardiac index, oxygen delivery index, oxygen uptake index, systemic vascular resistance, and arterial pH were taken. Dopexamine (1 mg.kg-1.min-1), dopamine (2.5 mg.kg-1.min-1), or 0.9% saline solution was then infused for 2 h, after which a repeated set of the measurements was taken. RESULTS: Dopexamine at a low dose had no effect on any of the systemic measurements. The median intramucosal pH rose from 7.23 to 7.35 (p < 0.005), the median ICG plasma disappearance rate from 7.6 to 11.3%.min-1 (p < 0.02), and the median MEGX concentration from 4 to 10.2 ng.mL-1 (p < 0.005). Dopamine had no effect on any of the measured variables. There were no changes in the control group. CONCLUSIONS: Low-dose dopexamine increases splanchnic blood flow as measured by gastric intramucosal pH, MEGX formation from lidocaine, and ICG clearance. The lack of any change in the systemic measurements suggests that these effects are the result of a selective vasodilatation of the splanchnic vessels. At the dose used in this study, dopamine had no effect on splanchnic blood flow. Dopexamine may be useful in the management of splanchnic ischemia in the critically ill.

Liver function and splanchnic ischemia in critically ill patients.

STUDY OBJECTIVE: To investigate the concept that splanchnic ischemia leads to hepatic dysfunction in the critically ill. DESIGN: Prospective study and analysis of patient data. SETTING: A general ICU in an inner-city London teaching hospital. PATIENTS: Twenty-seven consecutive critically ill patients with evidence of inadequate tissue perfusion requiring pulmonary artery catheterization and mechanical ventilation. MEASUREMENTS: In all patients, we measured the hepatic metabolism of lidocaine (lignocaine) to monoethylglycinexylidide (MEGX) and the clearance of indocyanine green (both dynamic, flow-dependent tests of hepatic function) over the first 3 days following admission to the ICU. These were compared with results of standard liver function tests and related to tonometric assessment of gastric intramucosal pH (pHim) and outcome. RESULTS: There were no significant differences in bilirubin, aspartate aminotransferase, alkaline phosphatase, and prothrombin levels, or in indocyanine green clearance between survivors and nonsurvivors. On day 3, the median MEGX level was higher in survivors than in nonsurvivors (16 vs 2.4 ng/mL, p < 0.001), and the median MEGX level in nonsurvivors fell over the 3 days (20.6 to 2.4 ng/mL, p < 0.002). MEGX levels were significantly correlated with pHim (Spearman rank correlation coefficient [Rs] = 0.69, p < 0.001) as were the changes in the two measurements over the 3 days (Rs = 0.46, p < 0.02). The MEGX formation test and gastric pHim were the most discriminatory with regard to death and survival. CONCLUSIONS: Our findings suggest that critically ill patients develop significant hepatic dysfunction that is associated with a poor outcome. This is likely to be due to a mismatch between hepatic metabolic demand and blood flow, and the MEGX formation test appears to be an extremely effective means of assessing liver function and flow in this group of patients.

Juxtaglomerular cell tumor in pregnancy.

BACKGROUND: Although rare, two thirds of juxtaglomerular cell tumors of the kidney occur in young women in their reproductive years. CASE: A primigravid woman with a 6-year history of chronic hypertension was evaluated for the sudden onset of uncontrolled hypertension, proteinuria, and hypokalemia at 16 weeks' gestation. An abdominal sonogram revealed a left flank mass, and magnetic resonance imaging confirmed that the mass was of renal origin. The worsening hypertension was not controlled with labetolol, methyldopa, nifedipine, or hydralazine, and required a nitroglycerine drip. The patient had left nephrectomy and subsequently miscarried at 19 weeks' gestation. Her blood pressure gradually decreased and normalized within 6 months. A pathologic examination of the renal mass confirmed that it was a juxtaglomerular cell tumor. CONCLUSION: This tumor should be considered in the differential diagnosis as a cause of severe hypertension in pregnancy.

Intraoperative assessment of colonic perfusion using scanning laser Doppler flowmetry during colonic resection.

BACKGROUND: Ischemia occurring on mobilization and mesenteric division is thought to be a major factor in the etiology of anastomotic dehiscence after colorectal resection. This study assessed the ability of the new technique of scanning laser Doppler flowmetry to measure changes in human colonic perfusion during mobilization at and adjacent to the anastomotic site. STUDY DESIGN: Colonic perfusion was measured in 10 patients undergoing large-bowel resection by making laser Doppler scans of the proximal bowel before mobilization, after mobilization and mesenteric division, and after resection of the specimen. Mean perfusion was calculated within 1-cm2 regions of interest, each of which contained 1,750 individual measurements of perfusion. These regions represented the anastomosis site and adjacent areas 1 cm and 2 cm proximal and distal to this. The results were expressed as mean perfusion units (PUs). RESULTS: After mobilization, there were significant decreases in perfusion in all the subjects between each time point and in all areas of the colon scanned. Median perfusion at the anastomosis site was 491 PUs before mobilization, and this fell to 212 PUs after mobilization, representing a decrease of 57%; the median within-person decrease was also 57% (p < 0.01). There was a gradient of reduced perfusion between the area 2 cm proximal to the mesenteric division (median within-person fall 25%; p < 0.05) and the area 2 cm distal to the mesenteric division (median within-person fall 84%; p < 0.01). After resection of the specimen, perfusion increased slightly at the anastomosis site to a median of 240 PUs (median within-person fall 41%; p < 0.01), but 2 cm proximal to this, median perfusion remained depressed at 330 PUs. CONCLUSIONS: This new technique can be used intraoperatively and appears to overcome the limitations of single-point laser Doppler flowmetry. In this small preliminary study, it measured large decreases in colonic perfusion during mobilization, and it may have widespread clinical applications.

Intraoperative scanning laser Doppler flowmetry in the assessment of gastric tube perfusion during esophageal resection.

BACKGROUND: Ischemia from tissue hypoperfusion in the gastric tube after esophagectomy is believed to contribute significantly to postoperative complications associated with anastomotic failure. This study assessed the ability of the new technique of laser Doppler flowmetry to measure differential levels of blood flow in human gastric tubes during esophagectomy. STUDY DESIGN: Gastric perfusion was measured in 16 patients undergoing esophagectomy by making laser Doppler scans of the stomach before mobilization and after formation of the gastric tube. Mean perfusion was calculated within the whole anterior surface of the stomach or tube and within 1 cm2 regions of interest, each of which contained 1,750 individual measurements of perfusion. These regions represented the cephalic end of the gastric tube, 10 adjacent 1 cm2 regions distally along the tube, and the proposed anastomosis site. Results were expressed as mean perfusion units, and tissue blood flow from each scan in each region was compared. RESULTS: There were significant decreases in gastric perfusion measured with the scanning laser Doppler in all patients after formation of the gastric tube. Mean perfusion of the stomach fell 41% (p<0.0005) after mobilization. In all patients there was a gradient of perfusion from the proximal end of the tube where flow was poor, to more distal areas where it was higher. At the proximal end of the tube perfusion fell by a mean of 72%, 5 cm distally the mean fall was 44%, and 10 cm from the proximal end of the tube the mean fall was 28%. At the anastomosis site mean perfusion fell 55%. CONCLUSIONS: This new technique can be used intraoperatively and appears to overcome the limitations of single point laser Doppler flowmetry. It has measured large differences in perfusion at different sites within the gastric tubes and could therefore have widespread clinical applications.

The effect of minor gastric surgery on gastric emptying in the rat.

A new minimally invasive technique has recently been described which enables gastric emptying to be assessed on repeated occasions without the need for animal sacrifice. This technique has been applied to study the effect of a laparotomy or gastrotomy on gastric emptying in the rat. Groups of 10 animals underwent either a laparotomy or a gastrotomy, or were unoperated controls. Solid and liquid gastric emptying studies were performed preoperatively, and for two postoperative months. Emptying was unchanged in unoperated controls. Laparotomy animals showed delayed emptying of both solids and liquids, returning to normal by two months. Gastrotomy animals showed a similar delay in solid emptying, but liquid emptying was within the normal range postoperatively. It is concluded that minor abdominal surgery causes marked alteration in gastric emptying. The comparable emptying delay for patients is unknown, but this should be considered when patients are recovering from operation, and when interpreting postoperative gastric emptying studies.

A review of experimental adenocarcinoma in the intact and post-operative rat glandular stomach with particular reference to mucin histochemistry.

The majority of experimental studies on the development of gastric adenocarcinoma have been performed in the rat. There is evidence for two pathways of carcinogenesis in the intact stomach following carcinogen administration. The first has a sequence of hyperplasia, dysplasia, carcinoma with a benign proliferating phase associated with damage and repair mechanisms. The second sequence progresses through increasing grades of dysplasia in an undisturbed mucosa leading to carcinoma formation. Early experiments concerning the effects of gastric surgery on carcinogen induced adenocarcinoma may have simply altered the effectiveness of the carcinogen. Recently it has been shown that surgery alone can induce adenocarcinomas and the number of tumours is related to the degree of duodenogastric reflux. The component of that reflux which seems to be responsible is pancreaticoduodenal secretions and not bile. Intestinal metaplasia is not an important intermediate stage in carcinogenesis in the rat.