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Objective: To compare single-layered hand-sewn cervical end-to-side (ETS) anastomosis with end-to-end (ETE) anastomosis in a prospective randomized fashion., Background: The preferred organ used for reconstruction after esophagectomy for cancer is the stomach. Previous studies attempted to define the optimal site of anastomosis and anastomotic techniques. However, anastomotic stricture formation and leakage still remain an important clinical problem., Methods: From May 2005 to September 2007, 128 patients (64 in each group) were randomized between ETE and ETS anastomosis after esophagectomy for cancer with gastric tube reconstruction. Routine contrast swallow studies and endoscopy were performed. Anastomotic stricture within 1 year, requiring dilatation, was the primary endpoint. Secondary endpoints were anastomotic leak rate and mortality., Results: Ninety-nine men and 29 women underwent esophagectomy and gastric tube reconstruction. Benign stenosis of the anastomosis, for which dilatation was required, occurred more often in the ETE group (40% vs. ETS 18%, P < 0.01) after 1 year of follow-up. The overall (clinical and radiological) anastomotic leak rate was lower in the ETE group (22% vs. ETS 41%, P = 0.04). Patients with an ETE anastomosis suffered less often from pneumonia; 17% versus ETS 44%, P = 0.002 and had subsequently significantly shorter in-hospital stay (15 days vs. 22 days, P = 0.02). In-hospital mortality did not differ between both groups., Conclusion: ETS anastomosis is associated with a lower anastomotic stricture rate, compared to ETE anastomosis. However, prevention of stricture formation was at high costs with increased anastomotic leakage and longer in-hospital stay. This study is registered with the Dutch Trial Registry and carries the ID number OND1317772.

Background: Self-expandable metals stents (SEMSs) have increasingly been used as a temporary device to bridge chemoradiotherapy in patients with malignant esophageal disease or in patients with benign esophageal defects or stenosis., Objective: To evaluate the outcome of removal of SEMSs in a large cohort of patients with benign and malignant esophageal disease., Design: Observational study with standardized treatment and follow-up., Setting: Single university center., Patients: Between 2001 and 2010, 95 consecutive patients referred for endoscopic SEMS extraction were included., Interventions: Endoscopic stent removal., Main Outcome Measurements: Technical and functional outcome and complications., Results: A total of 124 stent extractions were undertaken in 95 patients; both partially covered (68%) and fully covered (32%) SEMSs were removed. Three patients had 2 overlapping SEMSs in place. Successful primary removal was achieved in 89%; the secondary removal rate was 96%. Uncomplicated primary removal rate was significantly higher for fully covered versus partially covered stents (P = .035) and for single versus overlapping stents (P = .033). Patients with a complicated stent removal had the stent in place significantly longer compared with patients with an uncomplicated primary stent removal (126 days vs 28 days; P = .01). Surgical removal was required in 3 patients (2.4%). Six moderate and severe complications (5%) related to the endoscopic extraction occurred., Limitations: Retrospective, nonrandomized study design., Conclusions: Primary endoscopic removal of an SEMS is feasible in the majority of patients with benign and malignant esophageal disease. A longer time that a stent is in place and the use of partially covered SEMSs both impede removal. Moreover, overlapping SEMSs should be avoided for temporary use because stent disintegration and subsequent complications may occur., (Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Aim: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma., Methods: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes., Results: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenal epithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed significant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05)., Conclusion: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium.

Background: Both endoscopic and surgical treatments are recommended for m3- or sm1-adenocarcinomas of the esophagus, depending on patients' lymph nodal status. Lymphatic dissemination is related to tumor infiltration depth, but varying incidences have been reported in m3- and sm1-adenocarcinomas. The study aim was to investigate whether the presence of occult tumor cells in lymph nodes could explain this variation., Methods: Sixty-three node-negative (N0) patients with early esophageal adenocarcinoma (m2/m3/sm1-tumors) were included. Multilevel-sectioning of lymph nodes was performed; sections were stained by means of immunohistochemistry with cytokeratin marker CAM5.2. Two pathologists searched for micrometastases (0.2-2.0  mm) and isolated tumor cells (ITCs, <0.2  mm)., Results: Positive CAM5.2 staining in lymph nodes was not seen in any of the 18 m2-patients. In 2/25 m3-tumors (8.0%) an ITC was found, but no micrometastases. Tumor cells were identified in 4/20 sm1-tumors (20.0%): three micrometastases and one ITC. Median follow-up was 121 months. Two m3-patients (3.2%) died due to disease recurrence, including one patient in whom an ITC was detected., Conclusions: Lymphatic migration of tumor cells was found in node-negative m3- and sm1-adenocarcinomas of the esophagus (8.0% and 20.0%, respectively). However, the clinical relevance of these occult tumor cells should become apparent from large series of endoscopically treated patients., (2010 Wiley-Liss, Inc.)

Aims: According to the classification established by the Japanese Society for Oesophageal Disease, early oesophageal cancer can be subdivided into six successive layers of the mucosa or submucosa, which influences the treatment strategy and prognosis of the individual patient. However, the reproducibility of this classification in terms of inter- and intraobserver variability is unclear., Methods: Histological slides from 105 surgical resection specimens of patients who had undergone oesophagectomy for early oesophageal adenocarcinoma were reviewed independently by three gastrointestinal pathologists, and were classified according to the Japanese criteria (m1/m2/m3/sm1/sm2/sm3 tumours). Inter- and intraobserver variation was determined by κ-statistics., Results: The interobserver reproducibility was good between pathologist 1 and 2 (κ=0.61, 95% CI 0.55 to 0.67), and moderate between pathologist 1 and 3 (κ=0.51, 95% CI 0.45 to 0.57) and between pathologist 2 and 3 (κ=0.50, 95% CI 0.38 to 0.61). The intraobserver agreement as assessed by the expert pathologist was good (κ=0.76), with a 95% CI that was interpreted as good to very good (0.67 to 0.85). Most agreement was achieved at the lower (m1) and upper site (sm2, sm3) of the spectrum, whereas the m2 tumours reflected the most discrepant stage. The majority of the observed discrepancy included the variation in one substage only., Conclusions: The reproducibility of the Japanese classification is good in terms of inter- and intraobserver variability when grading early oesophageal adenocarcinoma on surgical resection specimens. The present data confirm that dedicated gastrointestinal pathologists with broad experience are preferred when grading the resection specimens of patients with early oesophageal adenocarcinoma.

Background: A nomogram has been developed recently in order to predict the occurrence and severity of postoperative complications after esophagectomy for cancer. In the present study, we externally validated this nomogram in a new cohort of patients who underwent esophagectomy for cancer in a different high-volume center., Methods: An independent dataset of 777 patients who underwent esophagectomy for cancer was used for validation. The discriminatory capability of the nomogram was determined by using the concordance index (C statistic). Calibration was evaluated by comparing the observed with the expected number of patients with complications, as predicted by the original nomogram across patients with different risk profiles. We also examined whether adjusting the value of the original coefficients of the predictors or adding new predictors would improve the fit of the nomogram., Results: Discrimination of the original nomogram was similar in the validation cohort: the C statistic hardly decreased from 0.65 in the original cohort to 0.64 in the validation cohort. Observed and expected number of patients with complications were in close agreement, reflecting a good calibration (p = 0.84). Reestimation of the coefficients in the validation cohort did not lead to any significant changes of the original nomogram values., Conclusions: External validation of a nomogram predicting the occurrence and severity of complications after esophagectomy showed that the model is applicable in other high-volume hospitals. Nevertheless, preoperative prediction of complications in individual patients remains difficult, most likely due to the complexity of mechanisms causing these complications., (2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: This study analyzes the outcome of esophageal resection in patients 70 or more years of age, compared with patients aged less than 70 years and identifies risk factors for worse outcome in the elderly., Methods: Comorbidity, postoperative morbidity, in-hospital mortality and survival rates were compared between 811 patients aged less than 70 years and 250 patients aged 70 years or more who underwent esophagectomy for esophageal cancer in a single high-volume center from 1985 to 2005., Results: Groups were similar regarding surgical approach, resectability, and tumor stage. More patients aged 70 years or more had cardiovascular and respiratory concomitant disease. Among patients aged 70 years or more, the prevalence of adenocarcinoma and Barrett's transformation was higher (67% versus 53% for patients aged less than 70 years, and 22% versus 15%, respectively). There were no differences in surgical complications (20% versus 17%). Nonsurgical complications occurred more in patients aged 70 years or more (35% versus 27%) and operative mortality was higher among elderly patients (8.4 versus 3.8%), as was in-hospital mortality (11.6% versus 5.4%). The disease-specific 5-year survival was lower for patients aged 70 years or more (27% versus 34%). The 1-year survival, reflecting the impact of operative morbidity and mortality, was 58% for patients aged 70 years or more and 68% for the patients aged less than 70 years (p = 0.002). Among patients aged 70 years or more, respiratory comorbidity and thoracoabdominal resection were risk factors for the occurrence of nonsurgical complications and respiratory comorbidity for in-hospital mortality., Conclusions: Older patients have increased operative and in-hospital mortality and decreased 5-year survival after esophageal resection for cancer. Our results indicate that especially thoracoabdominal resection for esophageal carcinoma should be carefully considered for patients older than 70 years who suffer from respiratory disease., (2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Accumulating evidence has suggested that tumours have a hierarchical organization in which only the cancer stem cells (CSCs) have tumour-initiating properties. Several surface antigens have been employed to isolate CSCs from various malignancies, although not from oesophageal adenocarcinoma (EA). We tested whether Barrett's oesophagus (BE) and EA might serve as a model for the CSC concept. In vivo assays were performed by transplantation of serially diluted bulk EA cells into NOD-SCID mice to establish the presence and frequency of tumour-initiating cells. These were found to be present as ca. 1 in 64 000 cells. The transplanted tumours fully recapitulated the primary lesions. Subsequently, a panel of previously established CSC markers was employed for immunohistochemistry. CD24, CD29 and CD44 showed heterogeneous staining in EA. Nuclear beta-catenin accumulation increased during progression from metaplasia to dysplasia and was often observed in the basal compartment with CD24 and CD29 staining. However, the overall staining patterns were not such to clearly point out specific candidate markers. Accordingly, all markers were employed to sort the corresponding subpopulations of cancer cells and transplant them at low multiplicities in NOD-SCID mice. No increased tumour-initiating capacity of sorted EA cells was observed upon transplantation. These results indicate that tumour-initiating cells are present in EA, thus reflecting a hierarchical organization. However, antibodies directed against novel surface antigens are needed to detect subpopulations enriched for CSCs in EA by transplantation assays.

In this review the preoperative risk assessment and prevention of complications in patients undergoing esophagectomy for cancer is discussed. Age, pulmonary and cardiovascular condition, nutritional status, and neoadjuvant chemo(radio)therapy are known predictive factors. None of these factors is a valid exclusion criterion for esophagectomy, but may help in careful patient selection. Both anesthetists and surgeons play an important role in intraoperative risk reduction by means of appropriate fluid management and application of optimal surgical techniques., ((c) 2010 Wiley-Liss, Inc.)

Introduction: Esophageal cancer should preferably be detected and treated at an early stage, but this may be prohibited by late onset of symptoms and delays in referral, diagnostic workup, and treatment. The aim of this study was to investigate the impact of these delays on outcome in patients with esophageal cancer., Methods: For 491 patients undergoing esophagectomy for cancer between 1991 and 2007, patients' short- and long-term outcome were analyzed according to different time intervals between onset of symptoms, diagnosis, and surgical treatment., Results: Length of prehospital delay (from onset of symptoms until endoscopic diagnosis) did not affect patient's short- or long-term outcome. A shorter hospital delay between establishing the diagnosis of esophageal cancer on endoscopy and surgery was associated with lower overall morbidity and in-hospital mortality. Patients of ASA classes I and II experienced a shorter hospital delay than patients of ASA classes III and IV. Length of hospital delay between endoscopic diagnosis and surgery did not affect pathological tumor-node-metastasis stage or R0-resection rate. Longer hospital delay did not result in worse survival: Overall survival after esophagectomy for cancer was not significantly different between patients with hospital delay <5, 5-8, or >8 weeks (24.7%, 21.7%, and 32.3%, respectively; p = 0.12)., Conclusion: A longer hospital delay (between endoscopic diagnosis and surgery) resulted in worse patient's short-term outcome (higher overall morbidity and mortality rates) but not in a worse long-term outcome (overall survival). This may be explained by a more time-consuming diagnostic workup in patients with a poorer physical status and not by tumor progression.

The most important risk factor for the development of Barrett's esophagus is the reflux of both gastric and duodenal contents into the esophagus. The reason why Barrett's metaplasia develops only in a minority of patients suffering from gastroesophageal reflux disease remains unknown.The exact mechanism behind the transition of normal squamous epithelium into specialized columnar epithelium is also unclear. It is likely that stem cells are involved in this metaplastic change, as they are the only permanent residents of the epithelium. Several tumorigenic steps that lead to the underlying genetic instability, which is indispensable in the progression from columnar metaplasia to esophageal adenocarcinoma have been described. This review outlines the process of pathogenesis of Barrett's metaplasia and its progression to esophageal adenocarcinoma.

Background: Most randomized controlled trials (RCTs) that have compared neoadjuvant chemoradiation followed by surgery with surgery alone for locally advanced esophageal cancer have shown no difference in survival between the two treatments. Meta-analyses on neoadjuvant chemoradiation in esophageal cancer, however, are discordant., Methods: For the present study, published meta-analyses on neoadjuvant chemoradiation for esophageal cancer were identified from the PubMed database and critically appraised in order to make a judgment on the applicability of neoadjuvant chemoradiation in clinical practice and decision making., Results: Two of the six meta-analyses examined did not show a significant survival benefit in patients with resectable esophageal cancer. Differences in the studies included and statistical methods applied might account for this. Moreover, there was heterogeneity between the RCTs included in the meta-analyses with regard to the patients included, tumor histology, and radiotherapy and chemotherapy regimes. Also, surgical technique was not uniform. No data on individual patients were available for most meta-analyses. The RCTs included in the meta-analyses were of inadequate sample size. All were started in the nineties, and hence methods for diagnosis, staging, treatment delivery, and outcome measurement reflect clinical practice during that decade., Conclusions: The current data on neoadjuvant chemoradiation for esophageal cancer strongly indicate the need for designing future high-quality trials that will contribute to a better understanding of the role of neoadjuvant treatment for resectable cancer of the esophagus and help to identify patient subgroups that would benefit most.

Objective: The sentinel node concept is of great value in the treatment of various malignancies. In this study we investigated whether the application of the sentinel node procedure is feasible in esophageal adenocarcinoma and whether it can tailor surgical treatment of the individual patient., Methods: In 40 patients with an adenocarcinoma of the distal esophagus or gastroesophageal junction, blue dye was injected around the tumor intraoperatively. Sentinel nodes (blue-stained) and nonsentinel nodes were identified and dissected during transhiatal esophagectomy. In sentinel nodes negative for tumor cells on routine hematoxylin-eosin examination, multilevel sectioning and immunohistochemical staining were performed to search for micrometastases., Results: The sentinel node procedure was technically successful in 39 of 40 patients (98%). The median number of sentinel nodes identified was 4. Sentinel nodes were present in more than 1 nodal station in 8 patients (21%). In 6 patients in whom the sentinel node was negative for metastasis, nonsentinel nodes were positive for tumor cells (false-negative rate 6/39 = 15%). Micrometastases and isolated tumor cells were detected in 7 of 19 patients (37%) with sentinel nodes, but this finding did not affect the false-negative rate., Conclusion: Detection of sentinel nodes is technically feasible during esophagectomy for cancer. However, given the relatively high false-negative rate of 15% and the high frequency of sentinel nodes in more than 1 nodal station, the clinical relevance of the sentinel node concept (through application of the blue dye technique) in the current treatment of patients with an adenocarcinoma of the distal esophagus or gastroesophageal junction seems limited.

Introduction: Ablation of Barrett's esophagus using Argon plasma coagulation (APC) is usually followed by the formation of a neosquamous epithelium. Investigating simple columnar or stratified squamous epithelium associated cytokeratin and microRNA (miRNA) expression in neo-squamous epithelium could help determine the identity and stability of the neosquamous epithelium., Methods: Nine patients underwent ablation of Barrett's esophagus with APC. Biopsies were collected from Barrett's esophagus mucosa and proximal normal squamous epithelium before ablation, and from neosquamous and normal squamous epithelium after ablation. Additional esophageal mucosal biopsies from ten nonrefluxing subjects were used as a reference. RNA was extracted and real-time polymerase chain reaction was used to measure the expression of the cytokeratins CK-8 and CK-14 and the microRNAs miR-143 and miR-205., Results: CK-8 and miR-143 expression were significantly higher in Barrett's esophagus mucosa, compared to neosquamous and normal squamous epithelium before and after APC, whereas miRNA-205 and CK-14 expression was significantly lower in Barrett's esophagus mucosa compared to all categories of squamous mucosa. The expression of CK-8, CK-14, miR-205, and miR-143 was similar between neosquamous epithelium compared to normal squamous epithelium in patients with Barrett's esophagus. Only miR-143 expression was significantly higher in neosquamous and normal squamous epithelium before and after APC compared to normal squamous epithelium from control subjects (p < 0.004)., Conclusions: The expression levels of cytokeratins and miRNAs studied in post-ablation neosquamous epithelium and normal squamous epithelium in patients with Barrett's esophagus are similar. In patients with Barrett's esophagus, miR-143 expression is still elevated in both neosquamous mucosa, and the squamous mucosa above the metaplastic segment, suggesting that this mucosa may not be normal; i.e., it is different to that seen in subjects without Barrett's esophagus. miR-143 could promote a Barrett's epithelium gene expression pattern, and this could have a role in development of Barrett's esophagus.

Background: Controversy exists over the Sixth Edition of the International Union Against Cancer (UICC) TNM staging system for esophageal cancer. Inclusion of additional information such as the number of metastatic lymph nodes and extracapsular lymph node invasion may improve the current staging system and lead to optimization of patient treatment., Methods: All patients in Adelaide who underwent resection for esophageal cancer between 1997 and 2007 were identified from a prospective database. Two independent observers then reexamined all pathology slides from the original resection. Univariate and multivariate analysis was performed to identify significant prognostic factors. The goodness of fit and accuracy of additional prognostic factors were assessed, and the staging system was modified according to this information., Results: There were 240 patients (mean age, 62 years) who met the inclusion criteria. The 5-year overall survival rate was 36% (median, 24 months). Only histological grade and a refined pN stage were found to be independent prognostic factors that could then be used to improve current TNM staging. Subdivision of pN stage into three groups (0, 1-2, and >2 positive nodes) showed significant differences in 5-year survival between all three groups: 53% vs 27% vs 6%, respectively (P < .01). The optimal staging model was the same for patients who received neoadjuvant therapy and surgery (n = 116), and those who underwent surgery alone (n = 124)., Conclusion: A staging model that incorporates a refined pN stage and histological grade appears to be more accurate than the current UICC-TNM staging system. This staging model is still applicable in patients who receive neoadjuvant therapy.

Background: This study was designed to determine whether there is a learning curve for laparoscopic cardiomyotomy for the treatment of achalasia., Methods: All patients who underwent a primary laparoscopic cardiomyotomy for achalasia between 1992 and 2006 in our hospitals were identified from a prospective database. The institutional and the individual surgeon's learning experiences were assessed based on operative and clinical outcome parameters. The outcomes of cardiomyotomies performed by consultant surgeons versus supervised trainees also were compared., Results: A total of 186 patients met the inclusion criteria; 144 procedures were undertaken by consultant surgeons and 42 by a surgical trainee. The length of operation decreased after the first ten cases in both the institutional and each individual experience. The rate of conversion to open surgery also was significantly higher in the first 20 cases performed. Intraoperative complications, overall satisfaction with the outcome, reoperation rate, and postoperative dysphagia were not associated with the institutional or the surgeon's operative experience. Although the length of the operation was greater for surgical trainees (93 versus 79 minutes; p < 0.01), no differences in outcome between the operations performed by consultant surgeons and surgical trainees were detected., Conclusion: An institutional (20 cases) and an individual (10 cases) learning curve for laparoscopic cardiomyotomy for achalasia can be defined. The clinical outcome for laparoscopic cardiomyotomy does not differ between supervised surgical trainees and consultant surgeons.

The laparoscopic approach is now the technique of choice for the repair of large hiatus hernia. It is associated with a low risk of complications. However, controversy exists as to the optimal technique for laparoscopic repair. In this paper, we describe our approach. This entails full dissection of the hernia sac from the mediastinum, hiatal repair with posteriorly placed sutures, and then construction of an appropriate fundoplication. Whether the use of mesh for hiatal repair will reduce the risk of subsequent reintervention and not add any new risks is, however, unclear. For this reason, we believe that the mesh should only be used in appropriately designed clinical trials, and for now, the standard approach to laparoscopic repair of a large hiatus hernia is sutured repair.

Introduction: Changes in the expression of mucin genes in the esophageal mucosa associated with uncomplicated gastro-esophageal reflux disease have not been evaluated even though such changes could be associated with reflux-induced mucosal damage. We therefore sought to identify reflux-induced changes in mucin gene expression using a cell line and biopsies from the esophageal mucosa in patients with and without reflux., Methods: MUC-1, MUC-3, MUC-4, and MUC-5AC gene expressions were investigated in the HET-1A cell line following exposure to acid (pH 4) and/or bile (120 muM of a bile salt milieu), and in esophageal mucosal biopsies from controls, subjects with non-erosive gastro-esophageal reflux, and subjects with reflux associated with ulcerative esophagitis (erosive). The mucosal biopsies were also evaluated for IL-6 mRNA expression (inflammatory marker) and CK-14 mRNA expression (mucosal basal cell layer marker). Gene expression was determined using real-time reverse transcriptase-polymerase chain reaction analysis., Results: In the cell line studies, there were differences in mRNA levels for all of the evaluated mucins following treatment with either acid or the acid and bile combination. In the studies which evaluated tissue specimens, IL-6 and CK-14 mRNA levels increased according to degree of reflux pathology. The expression of MUC-1 and MUC-4 in mucosa from patients with erosive reflux was lower than in subjects without reflux and in patients with non-erosive reflux, whereas the expression of MUC-3 and MUC-5AC was increased (although these differences did not reach significance at p < 0.05). When mRNA expression data for tissue samples from all groups were combined, significant correlations were identified between IL-6 vs. CK-14 and IL-6 vs. MUC-3, MUC-3 vs. CK-14 and MUC-3 vs. MUC-5AC, and for MUC-1 vs. MUC-5AC. The correlation between IL-6 and CK-14 was also significant within the control and non-erosive reflux groups. The correlation between IL-6 and MUC-3 was significant within the control and erosive reflux groups, and the correlation between MUC-1 and MUC-5AC was significant within the erosive reflux group., Conclusions: The results of this study suggest that the profile of mucin expression in the esophageal mucosa is influenced by the pH and composition of the gastro-esophageal reflux. Further work should explore the response of these genes to acid and bile reflux, and their role in the etiology of mucosal damage in gastro-esophageal reflux.

Background: Both gastroesophageal reflux and paraesophageal hernias are more common in the elderly, but often these patients are not referred for surgery because of their age. In this study we determined the outcome for laparoscopic antireflux surgery in patients aged 70 years or older, in whom either symptoms of gastroesophageal reflux or a large paraesophageal hernia was the indication for surgery., Method: From a prospectively maintained clinical database of patients undergoing laparoscopic antireflux surgery, all patients aged 70 years or older were identified and their outcome was determined., Results: Two hundred ten patients were identified. In 129 a large paraesophageal hiatus hernia was the primary indication for surgery, and in 81 patients the indication was reflux. Mean operation time was significantly longer in patients undergoing surgery for a large hiatus hernia (109 vs. 72 min), and conversion to open surgery was required more often (11.6% vs. 4.4%), compared to patients with reflux alone. Follow-up information was available for 95% of patients. Postoperative symptom scores for heartburn and dysphagia improved significantly and patients' satisfaction with surgery was high., Conclusion: Laparoscopic antireflux surgery in patients aged 70 years or older has a satisfactory clinical outcome. Elderly patients should not be refused laparoscopic antireflux surgery only because of their age.

Introduction: It is claimed that a substantial number of patients who undergo antireflux surgery use antireflux medication postoperatively. This study was aimed to determine the prevalence and underlying reasons for antireflux medication usage in patients after surgery., Materials and Methods: A questionnaire on the usage of antireflux medication was sent to 1,008 patients identified from a prospective database of patients who had undergone a laparoscopic antireflux procedure., Results: A total of 844 patients (84%) returned the questionnaire. Mean follow-up was 5.9 years after surgery. A single or combination of medications was being taken by 312 patients (37%): 82% proton pump inhibitors, 9% H2-blockers and 34% antacids. Fifty-two patients (17%) had never stopped taking medication, whereas 260 patients (83%) restarted medication at a mean of 2.5 years after surgery. Return of the same (31%) or different (49%) symptoms were the commonest reasons for taking medication, whereas 20% were asymptomatic or had other reasons for medication use. Postoperative 24-hour pH studies were abnormal in 16/61 patients (26%) on medication and in 5/78 patients (6%) not taking medication., Conclusions: Antireflux medication is frequently taken by many patients for various symptoms after antireflux surgery. Symptomatic patients should be properly investigated before antireflux medications are prescribed.

Background: The opinions of general surgical trainees about their current training program and their future career plans are important because such information can inform any redesign of surgical training programs as well as future surgical manpower planning., Methods: A structured questionnaire was sent to 392 general surgical trainees in the Netherlands in 2005., Results: A total of 239 (61%) questionnaires were returned by 66 (28%) women and 173 (72%) men, mean age 31.3 years. On average, trainees worked in the hospital 55 hours per week (range: 22-80 h). The mean number of operative cases performed per year was 195 (range 35-450), and this had been stable since the year 2000. The quality of the supervision by staff surgeons was rated satisfactory. The vast majority of the trainees are also satisfied with the current single year of differentiation/specialized training into one of the subspecialties, although most trainees (83%) would like to enroll in a fellowship before taking a job as a consultant. There was also a desire to take maternity/paternity leave during training. Both male and female trainees expressed the wish to work an average of 52 hours per week as a consultant, and they want these hours to occur in 4.1 days of work per week., Conclusions: Dutch general surgery trainees are satisfied with their training. They expressed a strong wish for specialization during and after their training. All trainees favored reduced working hours and days of work per week as fully qualified surgeons in the future.

Background: Postoperative dysphagia in patients after Nissen fundoplication might be related to the technique used for the closure of the esophageal hiatus., Methods: A total of 102 patients with gastroesophageal reflux were randomized to undergo laparoscopic Nissen fundoplication with either anterior (47 patients) or posterior (55 patients) repair of the diaphragmatic hiatus., Results: Clinical data at 5 years after surgery were available for 96% of patients enrolled in the trial. There was no significant difference between the 2 techniques for symptoms of dysphagia at the 5-year follow-up evaluation, although more patients who underwent posterior hiatal repair underwent further surgery for dysphagia-related symptoms (8 vs 2). Better control of heartburn was achieved in patients in the anterior hiatal repair group. Patients from both groups were equally satisfied with the overall outcome after surgery., Conclusions: At the 5-year follow-up evaluation, there was no significant difference in dysphagia between anterior closure and posterior hiatal repair.

Objective: To determine the efficacy of endoscopic argon plasma coagulation (APC) for ablation of Barrett esophagus., Summary Background Data: APC has been used to ablate Barrett esophagus. However, the long-term outcome of this treatment is unknown. This study reports 5-year results from a randomized trial of APC versus surveillance for Barrett esophagus in patients who had undergone a fundoplication for the treatment of gastroesophageal reflux., Methods: Fifty-eight patients with Barrett esophagus were randomized to undergo either ablation using APC or ongoing surveillance. At a mean 68 months after treatment, 40 patients underwent endoscopy follow-up. The efficacy of treatment, durability of the neosquamous re-epithelialization, and safety of the procedure were determined., Results: Initially, at least 95% ablation of the metaplastic mucosa was achieved in all treated patients. At the 5-year follow-up, 14 of 20 APC patients continued to have at least 95% of their previous Barrett esophagus replaced by neosquamous mucosa, and 8 of these had complete microscopic regression of the Barrett esophagus. Five of the 20 surveillance patients had more than 95% regression of their Barrett esophagus, and 4 of these had complete microscopic regression (1 after subsequent APC treatment). The length of Barrett esophagus shortened significantly in both study groups, although the extent of regression was greater after APC treatment (mean 5.9-0.8 cm vs. 4.6-2.2 cm). Two patients who had undergone APC treatment developed a late esophageal stricture, which required endoscopic dilation, and 2 patients in the surveillance group developed high-grade dysplasia during follow-up., Conclusions: Regression of Barrett esophagus after fundoplication is more likely, and greater in extent, in patients who undergo ablation with APC. In most patients treated with APC the neosquamous mucosa remains stable at up to 5-year follow-up. The development of high-grade dysplasia only occurred in patients who were not treated with APC.

Background: Although laparoscopic cardiomyotomy is considered to be the treatment of choice for achalasia, there is no consensus about how persistent or recurrent dysphagia after myotomy should be treated. In the current study we evaluated our experience with reoperation following previous cardiomyotomy., Methods: Between 1992 and 2006, 19 patients underwent re-myotomy: 7 for persistent dysphagia, 12 for recurrent dysphagia. Different operative approaches were used, depending on surgeon's preference and the technique used for the first operation., Results: The mean interval between the cardiomyotomies was 81 months. In 12 patients, the alternative body cavity to that used for the first operation was used for access in the revision operation. This was associated with a shorter operation time. Mean follow-up after the revision operation was 3.6 years. Mean satisfaction score was 7 (out of 10), and 89% of patients had an improvement in symptoms., Conclusion: Reoperation for persistent or recurrent achalasia achieves a satisfactory outcome in most patients. Using the alternative body cavity to that used in the original procedure facilitates minimal access techniques, and gives easier access to the operative field.

Objective: To evaluate prognostic factors and tumor staging in patients after esophagectomy for cancer., Summary Background Data: Several reports have questioned the appropriateness of the sixth edition of the International Union Against Cancer (UICC) TNM guidelines for staging esophageal cancer. Additional pathologic characteristics, besides the 3 basic facets of anatomic spread (tumor, node, metastases), might also have prognostic value., Methods: All patients who underwent resection of the esophagus for carcinoma between January 1995 and March 2003 were extracted from a prospective database. Univariate and multivariate analysis was performed to identify prognostic factors for survival. The goodness of fit and accuracy of 3 staging models (UICC-TNM, Korst classification, Rice classification) predicting survival were assessed., Results: A total of 292 patients (mean age, 63 years) underwent esophagectomy. The 5-year overall survival rate was 29% (median, 21 months). pT-, pN-, pm-stage, and radicality of the resection were independent prognostic factors. Subdivision of T1 tumors into mucosal and submucosal showed significant differences in 5-year survival between both groups: 90% versus 47%, respectively (P = 0.01). Subdivision of pN-stage into 3 groups based on the number of positive nodes (0, 1-2, and >3 nodes positive) or the lymph node ratio (0, 0.01-0.2, and >0.2) also refined staging (P = 0.001 and P < 0.001, respectively). The current subclassification of M1 (M1a and M1b) is not warranted (P = 0.41). The staging model of Rice was more accurate than the UICC-TNM classification in predicting survival., Conclusion: This study supports the view that the current (6th edition) UICC-TNM staging model for esophageal cancer needs to be revised.

In a recent evaluation by comparative genomic hybridization, we demonstrated chromosome 14q31-32.1 to be frequently deleted in adenocarcinomas of the gastroesophageal junction. This suggests the presence of a tumor suppressor gene in the deleted region. In the present study, we have performed a detailed loss of heterozygosity analysis in 34 gastroesophageal junction adenocarcinomas and 1 tumor-corresponding dysplastic Barrett's epithelium sample with 37 polymorphic microsatellite markers. Thirty-five markers are in the 14q24.3-32.33 region with a mean distance of 800 kilo base pairs. Of 34 tumor samples, 14 (41%) showed loss of 14q markers. We identified a minimal region of allelic loss of 7105440 base pairs between markers D14S1000 and D14S256 at cytogenetic location 14q31.1-32.11. Within this region, markers D14S1035, D14S55, D14S1037, D14S1022, D14S1052, D14S974, D14S73, D14S1033, D14S67, D14S68, and D14S1058 showed loss in all informative tumors with 14q loss. The region between markers D14S1000 and D14S256 contains 7 known genes. The identification of this minimal deletion and the data base information on the genes present in this region facilitate the search for the candidate tumor suppressor gene(s).

Background: Barrett's esophagus is an acquired metaplastic change that occurs in the distal esophagus secondary to chronic gastroesophageal reflux. This premalignant condition forms the most important risk factor for developing esophageal adenocarcinoma, which is an extremely aggressive tumor with a 5-year survival rate of less than 25%. Carcinomas that arise in the setting of Barrett's esophagus are thought to develop as part of the metaplasia-dysplasia-carcinoma sequence., Objective: To review the current knowledge on the genomic alterations involved in the development of Barrett's esophagus and its progression to dysplasia and/or cancer., Results: Several changes in gene structure, gene expression, and protein structure are associated with the progression of Barrett's esophagus to adenocarcinoma. Accumulation of these changes seems to be essential, rather than the exact sequence of these changes. Multiple molecular pathways are involved and interact with each other. Alterations in tumor suppressor genes, amongst which p53 and p16, are early events in the metaplasia-dysplasia-adenocarcinoma sequence, followed by loss of cell cycle checkpoints. Ongoing genomic instability leads to cumulative genetic errors and thereby the generation of multiple clones of transformed cells., Conclusions: Within the multistep process of esophageal adenocarcinogenesis, to date no single molecular marker came forward able to predict who will and who will not develop cancer in the setting of Barrett's esophagus. Instead, panels of markers need to be developed in the future allowing to indicate disease progression. Identification of crucial molecular pathways involved in esophageal adenocarcinogenesis would ultimately improve therapy and facilitate development of new treatment strategies., ((c) 2005 Wiley-Liss, Inc.)

Background and Objectives: P120-catenin (p120ctn) is a member of the E-cadherin-catenin cell-cell adhesion complex. Impairment of one or more of the components of this complex is associated with tumorigenesis. The role of p120ctn in malignancy is not clear yet. We studied the in vivo expression and cellular localization of p120ctn in adenocarcinomas of the gastroesophageal junction., Methods: Immunohistochemical staining for p120ctn was performed on 96 tumor samples, 20 cases of Barretts metaplasia and 13 lymph node metastases. The relationship with pathological characteristics and patient survival was also assessed., Results: Loss of normal surface p120ctn expression was found in 4/20 (20%) Barretts metaplasia, in 65/96 (68%) tumors, and 11/13 (85%) lymph node metastases. Nuclear immunoreactivity for p120ctn was seen in five tumors. Loss of normal expression of p120ctn was associated with a higher tumor grade (P < 0.0001) but not with pTNM-stage. Reduced expression of p120ctn was correlated with poor survival (P = 0.0002). Cox regression analysis showed that p120ctn is an independent prognostic marker., Conclusions: Abnormal p120ctn expression is frequently seen in adenocarcinomas of the gastroesophageal junction, and may be a useful as a prognostic marker in these tumors., ((c) 2005 Wiley-Liss, Inc.)

We estimated the prevalence and prognostic significance of neuroendocrine (NE) cells in a series of 208 resection specimens containing gastroesophageal junction (GEJ) adenocarcinomas, with 56 specimens containing Barrett's mucosa. Immunohistochemically, chromogranin A (CGA) was positive in 49% (102/208) of GEJ adenocarcinomas and in 68% (38/56) of Barrett's mucosas. CGA in GEJ tumors correlated with pTNM stage. CGA in Barrett correlated with pTNM stage and tumor grade of the adjacent carcinoma. Patients with CGA in Barrett had better survival than patients without CGA in Barrett, with 5-year survival percentages of 56% and 9%, respectively. In multi-variate analysis, CGA in Barrett was an independent prognostic factor for survival after surgery. Therefore CGA in Barrett adjacent to GEJ adenocarcinoma might be helpful in the assessment of patient outcome.

Background: Controversy exists about the best surgical treatment for esophageal carcinoma., Methods: We randomly assigned 220 patients with adenocarcinoma of the mid-to-distal esophagus or adenocarcinoma of the gastric cardia involving the distal esophagus either to transhiatal esophagectomy or to transthoracic esophagectomy with extended en bloc lymphadenectomy. Principal end points were overall survival and disease-free survival. Early morbidity and mortality, the number of quality-adjusted life-years gained, and cost effectiveness were also determined., Results: A total of 106 patients were assigned to undergo transhiatal esophagectomy, and 114 to undergo transthoracic esophagectomy. Demographic characteristics and characteristics of the tumor were similar in the two groups. Perioperative morbidity was higher after transthoracic esophagectomy, but there was no significant difference in in-hospital mortality (P=0.45). After a median follow-up of 4.7 years, 142 patients had died--74 (70 percent) after transhiatal resection and 68 (60 percent) after transthoracic resection (P=0.12). Although the difference in survival was not statistically significant, there was a trend toward a survival benefit with the extended approach at five years: disease-free survival was 27 percent in the transhiatal-esophagectomy group, as compared with 39 percent in the transthoracic-esophagectomy group (95 percent confidence interval for the difference, -1 to 24 percent [the negative value indicates better survival with transhiatal resection]), whereas overall survival was 29 percent as compared with 39 percent (95 percent confidence interval for the difference, -3 to 23 percent)., Conclusions: Transhiatal esophagectomy was associated with lower morbidity than transthoracic esophagectomy with extended en bloc lymphadenectomy. Although median overall, disease-free, and quality-adjusted survival did not differ statistically between the groups, there was a trend toward improved long-term survival at five years with the extended transthoracic approach., (Copyright 2002 Massachusetts Medical Society)

Background: Worldwide population-based studies suggest that the incidence of oesophageal and gastric cardia adenocarcinomas has increased since the 1970s., Objective and Methods: We studied time trends in mortality and incidence rates of oesophageal and gastric carcinomas according to subsite and histology in the south-east Netherlands since 1978., Results: The age-adjusted mortality and incidence rates for oesophageal cancer doubled in males over the entire 19-year study period from 2.7 to 5.6 and from 2.4 to 4.8 per 100,000 person years, respectively. In females, a similar trend for the mortality and incidence rates was seen, but at a lower level. The age-adjusted mortality and incidence rates for gastric cancer decreased with time from 20.7 to 12.8 and from 21.6 to 15.9 per 100,000 person years in males, respectively. In females, age-adjusted mortality and incidence rates for gastric cancer also decreased. Analysis of incidence rates by subsite and subtype showed an increase in adenocarcinomas of the oesophagus and gastric cardia, largely restricted to males. In females, the rise in incidence of squamous cell carcinoma of the oesophagus appeared to be more marked than the rise in adenocarcinomas, whereas the incidence of gastric cardia carcinomas has remained stable over the last 10 years. Neither the decrease in the number of unspecified tumours with time, nor the increase in the use of diagnostic endoscopy and imaging techniques, is likely to explain completely the observed increases., Conclusion: The increase in incidence of adenocarcinomas at the gastro-oesophageal junction in the south-eastern Netherlands seems, at least in part, to represent a true underlying increase that is restricted largely to males.