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The aim of this study is to determine the prevalence and incidence of vitamin B12 deficiency after esophagectomy for cancer. It is unknown if patients after esophagectomy with gastric tube reconstruction are at an increased risk for vitamin B12 deficiency. A cross-sectional cohort (group A) and a prospective cohort (group B) of patients who underwent esophagectomy for cancer in two tertiary referral centers in the Netherlands were included. Serum levels of holo-transcobalamin (Holo-TC) and methyl malonic acid (MMA) were determined. Vitamin B12 deficiency was defined as Holo-TC < 21 pmol/L and/or MMA > 0.45µmol/L. Vitamin B12 status was assessed in group A at a single time point between one and three years postoperatively and before and every three months after resection in group B. Ninety-nine patients were analyzed in group A. The median time between surgery and analysis of vitamin B12 deficiency was 19.3 months. In 11 of 99 (11%) patients, vitamin B12 deficiency was detected. In group B, 5 of 88 (5.6%) patients had vitamin B12 deficiency preoperatively, and another 9 (10.2%) patients developed vitamin B12 deficiency after the operation at a median time of 6 months postoperatively. The estimated one-year incidence of vitamin B12 deficiency was 18.2%. None of the patients with vitamin B12 deficiency had a megaloblastic anemia. Vitamin B12 deficiency can be anticipated in 18% of patients after esophagectomy with gastric tube reconstruction for cancer. During follow-up, Holo-TC and MMA levels should be measured to detect vitamin B12 deficiency and commence treatment timely. [ABSTRACT FROM AUTHOR]

Background Oesophageal adenocarcinoma ( OAC) is a highly aggressive malignancy with poor survival, which is highly variable amongst patients with comparable conventional prognosticators. Therefore molecular biomarkers are urgently needed to improve the prediction of survival in these patients. SRY (sex determining region Y)-box 2, also known as SOX2, is a transcription factor involved in embryonal development of the gastrointestinal tract as well as in carcinogenesis. The purpose of this study was to see whether SOX2 expression is associated with survival in patients with OAC. Methods SOX2 was studied by immunohistochemistry in patients who had undergone potentially curative oesophagectomy for adenocarcinoma. Protein expression of SOX2 was evaluated using tissue microarrays from resection specimens, and results were analysed in relation to the clinical data by Cox regression analysis. SOX2 was evaluated in two independent OAC cohorts (Rotterdam cohort and a multicentre UK cohort). Results Loss of SOX2 expression was independently predictive of adverse overall survival in the multivariable analysis, adjusted for known factors influencing survival, in both cohorts (Rotterdam cohort: hazard ratio ( HR) 1·42, 95 per cent c.i. 1·07 to 1·89, P = 0·016; UK cohort: HR 1·54, 1·08 to 2·19, P = 0·017). When combined with clinicopathological staging, loss of SOX2 showed an increased effect in patients with pT1-2 tumours ( P = 0·010) and node-negative OAC ( P = 0·038), with an incrementally adverse effect on overall survival for stage I OAC with SOX2 loss ( HR 3·18, 1·18 to 8·56; P = 0·022). Conclusion SOX2 is an independent prognostic factor for long-term survival in OAC, especially in patients with stage I OAC. [ABSTRACT FROM AUTHOR]

Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers ( UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer. [ABSTRACT FROM AUTHOR]

Background Survival after oesophagectomy for cancer seems to be improving. This study aimed to identify the most important contributors to this change. Methods Patients who underwent oesophagectomy from 1999 to 2010 were extracted from the Netherlands Cancer Registry. Four time periods were compared: 1999-2001 (period 1), 2002-2004 (period 2), 2005-2007 (period 3) and 2008-2010 (period 4). Hospital type, tumour location, tumour type, tumour differentiation, neoadjuvant therapy, operation type, (y) pT category, involvement of surgical resection margins, number of removed lymph nodes and number of involved lymph nodes were investigated in relation to trends in survival using multivariable analysis. Results A total of 4382 patients were identified. Two-year overall survival rates improved from 49·3 per cent in period 1 to 58·4, 56·2 and 61·0 per cent in periods 2, 3 and 4 respectively ( P < 0·001). Multivariable survival analysis revealed that the improvement in survival between periods 3 and 4 was related to the introduction of neoadjuvant therapy. The improvement in survival between periods 1 and 2 could not be explained completely by the factors studied. The number of examined lymph nodes increased, especially between periods 2 and 3, but this increase was not associated with the improvement in survival. Conclusion The observed increase in long-term survival after surgery for oesophageal cancer between 1999 and 2010 in the Netherlands is difficult to explain fully, although the recent increase seems to be partly attributable to the introduction of neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: Various definitions are used to calculate postoperative mortality. As variation hampers comparability between reports, a study was performed to evaluate the impact of using different definitions for several types of cancer surgery. Methods: Population-based data for the period 1997-2008 were retrieved from the Rotterdam Cancer Registry for resectional surgery of oesophageal, gastric, colonic, rectal, breast, lung, renal and bladder cancer. Postoperative deaths were tabulated as 30-day, in-hospital or 90-day mortality. Postdischarge deaths were defined as those occurring after discharge from hospital but within 30 days. Results: This study included 40 474 patients. Thirty-day mortality rates were highest after gastric (8·8 per cent) and colonic (6·0 per cent) surgery, and lowest after breast (0·2 per cent) and renal (2·0 per cent) procedures. For most tumour types, the difference between 30-day and in-hospital rates was less than 1 per cent. For bladder and oesophageal cancer, however, the in-hospital mortality rate was considerably higher at 5·1 per cent (+1·3 per cent) and 7·3 per cent (+2·8 per cent) respectively. For gastric, colonic and lung cancer, 1·0 per cent of patients died after discharge. For gastric, lung and bladder cancer, more than 3 per cent of patients died between discharge and 90 days. Conclusion: The 30-day definition is recommended as an international standard because it includes the great majority of surgery-related deaths and is not subject to discharge procedures. The 90-day definition, however, captures mortality from multiple causes; although this may be of less interest to surgeons, the data may be valuable when providing information to patients before surgery. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Cachexia and obesity have been suggested to be risk factors for postoperative complications. However, high body mass index (BMI) might result in a higher R0-resection rate because of the presence of more fatty tissue surrounding the tumor. The purpose of this study was to investigate whether BMI is of prognostic value with regard to short-term and long-term outcome in patients who undergo esophagectomy for cancer. Methods: In 556 patients who underwent esophagectomy (1991-2007), clinical and pathological outcome were compared between different BMI classes (underweight, normal weight, overweight, obesity). Results: Overall morbidity, mortality, and reoperation rate did not differ in underweight and obese patients. However, severe complications seemed to occur more often in obese patients ( p = 0.06), and the risk for anastomotic leakage increased with higher BMI (12.5% in underweight patients compared with 27.6% in obese patients, p = 0.04). Histopathological assessment showed comparable pTNM stages, although an advanced pT stage was seen more often in patients with low/normal BMI ( p = 0.02). A linear association between BMI and R0-resection rate was detected ( p = 0.02): 60% in underweight patients compared with 81% in obese patients. However, unlike pT-stage ( p < 0.001), BMI was not an independent predictor for R0 resection ( p = 0.12). There was no significant difference in overall or disease-free 5-year survival between the BMI classes ( p = 0.25 and p = 0.6, respectively). Conclusions: BMI is not of prognostic value with regard to short-term and long-term outcome in patients who undergo esophagectomy for cancer and is not an independent predictor for radical R0 resection. Patients oncologically eligible for esophagectomy should not be denied surgery on the basis of their BMI class. [ABSTRACT FROM AUTHOR]

Purpose: To analyse the treatment results of neo-adjuvant chemoradiation combined with regional hyperthermia in patients with resectable esophageal cancer. Patients and methods: Between August 2003 and December 2004, 28 patients entered a phase II study combining chemoradiation over a 4.5-week period with five sessions of regional hyperthermia. Chemotherapy consisted of carboplatin (AUC = 2) and paclitaxel (50 mg/m2) and radiotherapy of 41.4 Gy in 1.8 Gy daily fractions. Locoregional hyperthermia was applied using the AMC phased array of four 70 MHz antennas, aiming at a stable tumor temperature of 41°C for one hour. Carboplatin was infused during the hyperthermia session. Esophageal resection was planned at 6-8 weeks after the end of radiotherapy. The majority of the patients had a T3 tumor (86%) and were cN+ (64%). Median follow-up for survivors was 37 months (range 31-46). Results: Twenty-five patients (89%) completed the planned neo-adjuvant treatment and acute toxicity was generally mild. Twenty-six patients were operated on. A pathologically CR, PRmic, PR and SD were seen in 19%, 27%, 31% and 23% respectively. All patients had a R0 resection. In-field locoregional control during follow up for the operated patients was 100%. Quality of life was good for patients without disease progression. Survival rates at one, two and three years were 79%, 57% and 54% respectively. Conclusion: Neo-adjuvant chemoradiation combined with regional hyperthermia followed by esophageal resection for patients with esophageal cancer resulted in good locoregional control and overall survival. [ABSTRACT FROM AUTHOR]

Introduction: Lymphatic dissemination of a (non-cervical) esophageal tumor to the neck is generally considered as distant metastasis. The aim of this study was to determine the additional value of external ultrasonography (US) to detect lymphatic metastasis to the neck after normal CT scan (CT) with or without normal PET scan (PET). Methods: Between January 2003 and December 2005, 306 patients were analyzed for esophageal cancer in our department. A total of 233 patients underwent both CT and external US of the neck. PET was performed in 109 of these patients as part of a prospective cohort study. Fine needle aspiration (FNA) was only performed if external US reported suspected lymph nodes. FNA was defined as gold standard. Results: In 176 patients (76%), CT did not identify any suspected nodes, but external US disagreed in 36 of them. In 9 of these patients, FNA confirmed metastasis, resulting in an additional value of external US after normal CT scanning of 5% (9/176). In 74 patients (68%), CT and PET did not identify any suspected nodes, but external US disagreed in 11 of them. In 3 of these patients, FNA confirmed metastasis, resulting in an additional value of external US after normal CT and PET of 4% (3/74). Conclusion: Considering its minimal invasiveness and wide availability in combination with the importance of the potential therapeutic consequences, we conclude that external US of the neck should be part of the routine diagnostic work-up in patients with esophageal cancer, even after normal CT and PET scanning. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose. To analyse the relation between patients' body size and temperatures during locoregional hyperthermia for oesophageal cancer. Methods. Patients were treated with neo-adjuvant chemoradiotherapy plus hyperthermia, given with the AMC-4 waveguide system. Temperatures were measured at tumour location in the oesophageal lumen using multisensor thermocouple probes. Systemic temperature rise (ΔTsyst) was monitored rectally. Steady-state tumour temperatures were expressed in terms of T90, T50 and T10, averaged over the five hyperthermia sessions, and correlated with patients' body mass, dorsoventral and lateral diameter and fat layer thickness, measured at tumour level using a CT scan made in treatment position. Fat percentage (Fat%) was estimated using diameters and fat layer thickness. Effective tumour perfusion (Wb) was estimated from the temperature decay during the cool-down period. Results. Temperatures were inversely related to body mass, diameters, fat layer thickness, and fat percentage. The strongest univariate correlations were found with lateral fat layer thickness, lateral diameter, and body mass. An increase in lateral diameter (28→42 cm), or in lateral fat layer thickness (0→40 mm) or in body mass (50→120 kg) all yielded a ∼1.5°C decrease in tumour temperature rise. Multivariate correlation analysis proved that the combination of Fat%, ΔTsyst and Wb was most predictive for the achieved tumour temperatures, accounting for 81 ± 12% of the variance in temperatures. Conclusions. Intra-oesophageal temperatures during locoregional hyperthermia are inversely related to patients' body size parameters, of which fat percentage is the most significant prognostic factor. These findings could be used to define inclusion criteria of new studies on intrathoracic hyperthermia. [ABSTRACT FROM AUTHOR]

Lymphatic dissemination is the most important prognostic factor in patients with esophageal carcinoma. However, the clinical significance of lymph node micrometastases is still debated due to contradictory results. The aim of the present study was to identify the incidence of potentially relevant micrometastatic disease in patients with histologically node-negative esophageal adenocarcinoma and to analyze the sensitivity and specificity of three different immunohistochemical assays. From a consecutive series of 79 patients who underwent a transthoracic resection with extended 2-field lymphadenectomy, all 20 patients with pN0 esophageal adenocarcinoma were included in this study. A total of 578 lymph nodes were examined for the presence of micrometastases by immunohistochemical analysis with the antibodies Ber-EP4, AE1/AE3 and CAM 5.2. Lymph node micrometastases were detected in five of the 20 patients (25%). They were identified in 16 of the 578 lymph nodes examined (2.8%) and most frequently detected with the Ber-EP4 and AE1/AE3 antibody (sensitivity 95% and 79% respectively). In 114 of the 559 negative lymph nodes (20.4%), positive single cells were found that did not demonstrate malignant characteristics. These false-positive cells were more frequently found with the AE1/AE3 staining (specificity of the Ber-Ep4 and AE1/AE3 antibody 94% and 84% respectively). The presence of nodal micrometastases was associated with the development of locoregional recurrences ( P=0.01), distant metastases ( P=0.01), and a reduced overall survival (log rank test, P=0.009). For the detection of clinically relevant micrometastatic disease in patients operated upon for adenocarcinoma of the distal esophagus or gastric cardia, Ber-EP4 is the antibody of first choice because of its high sensitivity and specificity. Immunohistochemically detected micrometastases in histologically negative lymph nodes have potential prognostic significance and are associated with a high incidence of both locoregional and systemic recurrence. Therefore, this technique has the potential to refine the staging system for esophageal cancer and to help identify patients who will not be cured by surgery alone. [ABSTRACT FROM AUTHOR]

Oesophageal adenocarcinoma is an aggressive malignancy with propensity for early lymphatic and haematogenous dissemination. Since conventional TNM staging does not provide accurate prognostic information, novel molecular prognostic markers and potential therapeutic targets are subject of intense research. The aim of the present study was to study the prognostic significance of Met, the hepatic growth factor (HGF) receptor and a possible target for therapy in comparison to cyclooxygenase-2 (COX-2). Tumour sections from 145 consecutive patients undergoing intentionally curative surgery for oesophageal adenocarcinoma were immunohistochemically analysed for Met and COX-2 expression. Clinicopathological data were prospectively collected for all patients. Patients with high Met expression had significantly reduced overall and disease-specific 5-year survival rates (P< or =0.001 and P< or =0.001, respectively) and were more likely to develop distant metastases (P=0.002) and local recurrences (P=0.004) compared to patients with low Met expression. High COX-2 expression tended to be correlated with poor long-term survival but this did not reach statistical significance. Expression of Met was recognised as a significant and independent prognostic factor by stage-specific analysis and multivariate analysis (relative risk=2.3; 95% CI=1.3-4.1). These findings support the importance of Met in oesophageal adenocarcinoma and support the concept of Met tyrosine kinase inhibition as (neo-) adjuvant treatment. [ABSTRACT FROM AUTHOR]

Background: The occurrence of synchronous malignancies in patients suffering from esophageal cancer is a frequent phenomenon, but the reported incidence of synchronous renal cell carcinoma (RCC) is very low. The present study investigated the incidence of synchronously detected RCC since the introduction of preoperative CT scans in a tertiary referral center for esophageal cancer patients. Methods: The medical records of 392 consecutive patients included in a prospective database of patients scheduled to undergo surgery for esophageal tumors were scrutinized for the presence of renal neoplasms. The coincidence of esophageal cancer and RCC was then estimated by analyzing only those patients who were operated on for an esophageal malignancy after a CT scan was obtained. Results: 192 patients were operated on for an esophageal malignancy after abdominal CT scanning was performed. RCC was diagnosed in 4 of these patients resulting in an incidence of synchronous esophageal and renal malignancies of 2.1%. Conclusion: Since the introduction of CT scanning the incidence of synchronous RCC in esophageal cancer patients appears to be much higher than previously reported and suggests a genetic and/or environmental association between these malignancies. Simultaneous treatment of both tumors appeared safe at our institute. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Tumour node metastasis (TNM) staging predicts survival on the basis of the pathological extent of a tumour. The aim of this study was to develop a prognostic model with improved survival prediction after oesophagectomy. Methods: Consecutive patients who had potentially curative oesophagectomy for adenocarcinoma of the oesophagus or gastro-oesophageal junction were included. Cox regression analyses were performed to examine the association between risk factors and time to death from oesophageal cancer. The concordance index, calculated after bootstrapping, was used to measure accuracy. A nomogram was designed for use in clinical practice. Results: Oesophageal cancer-specific survival Pates for the 364 included patients who underwent oesophagectomy between 1993 and 2003 were 75.8, 54.9 and 39.2 per cent at 1, 2 and 5 years respectively. A prognostic model using all prognostic variables outperformed TNM staging (concordance index 0.79 versus 0.68 respectively; P < 0.001). A reduced model derived after backward elimination, containing only T stage, lymph node ratio and extracapsular lymph node involvement, also outperformed TNM staging (concordance index 0.77; P < 0.001). Conclusion: A prognostic model developed to predict disease-specific survival after oesophagectomy was superior to TNM staging. More reliable prognostic information might lead to different approaches to patient follow-up. [ABSTRACT FROM AUTHOR]

Background: Postoperative complications after open transthoracic esophagectomy could possibly be reduced if the abdominal phase is performed laparoscopically. The aim of this study was to investigate the feasibility of laparoscopic mobilization of the stomach and gastric tube formation in patients undergoing an open transthoracic esophagectomy for cancer. Methods: Thirteen patients underwent an open transthoracic esophagectomy with extended en bloc lymphadenectomy combined with laparoscopic gastric tube formation. Clinicopathological data were derived from a prospective database and patient files. Results: The median operation time was 484 min (range 347–573) and the median intraoperative blood loss was 1,500 ml (range 250–3,700). In 2 patients the laparoscopic procedure was converted to a laparotomy because of technical difficulties. Median postoperative stay in the ICU was 3 days (range 1–8) and median hospital stay was 29 days (range 12–104). One patient died in the hospital. Postoperatively 3 patients suffered from anastomotic leakage, 5 from pneumonia and 3 from vocal cord palsy. Conclusions: The complication rate was high in this series of patients undergoing an open extended transthoracic esophagectomy with laparoscopic mobilization of the stomach and gastric tube formation. Laparoscopic mobilization of the stomach and gastric tube formation are feasible, but need carefully guided testing before this technique can be applied routinely. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Chyle leakage from the chest after extended esophagectomy originating from the abdomen is a rare complication with various clinical presentations and treatments. Methods: Two cases of chylothorax originating from the abdomen are discussed and the literature concerning diagnosis, management and outcome is reviewed. Results and Conclusion: Initially conservative measures should be installed; however, prolonged conservative treatment should be avoided. Reoperation gives an opportunity to identify the leak. If the leakage originates from the abdomen, compartimentalization is the essential step to solve the problem. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In this review we discuss the different strategies to improve surgical outcomes after potentially curative resection for oesophageal adenocarcinoma. For tumours of the distal oesophagus, there is a 17% survival benefit after transthoracic resection with two-field lymph node dissection when compared with transhiatal resection. This survival benefit is absent for tumours of the gastro-oesophageal junction or gastric cardia. These patients should, in the absence of tumour-positive lymph nodes at or proximal to the carina, undergo a transhiatal resection to minimise peri-operative complications. New developments include endoscopic resection or minimally invasive oesophagectomy, but these therapies should still be considered experimental. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Esophageal cancer and cancer of the gastric cardia, in particular adenocarcinomas, have shown a rapid and largely unexplained increase in incidence in many developed countries around the world. These diseases have a poor prognosis and current therapies have a modest impact on survival. This review presents recent advances in the epidemiology, etiology, diagnosis, staging, prevention and treatment of resectable and advanced disease. Although significant progress has been made in these areas of research and patient management over the past years, prognosis for most patients diagnosed with esophageal cancer or cancer of the gastric cardia remains poor. New diagnostic procedures, improved surgical procedures, combined treatment modalities and new treatment modalities are being evaluated and may be expected to contribute to improved patient outcomes and better palliation of symptoms in the future. [ABSTRACT FROM AUTHOR]

Background: Various studies suggest that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. Epidemiological studies have found that long-term use of NSAIDs is associated with a reduced incidence of colorectal, gastric and oesophageal cancers, while experimental and clinical studies have demonstrated that treatment with NSAIDs causes a statistically significant reduction in both the number and the size of polyps in familial adenomatous polyposis (FAP) patients. Methods: In this review, the mechanisms by which NSAIDs exert their chemopreventive and antineoplastic effects are described. Results: Although the precise anticancer actions of NSAIDs are not fully explained, they probably involve inhibition of cyclooxygenase (COX), which is the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of this enzyme (COX-1 and COX-2) have been identified. COX-1 is constitutively expressed and considered to be a housekeeping gene, while COX-2 is not usually detectable in normal tissues, but can be readily induced in processes like inflammation, reproduction and carcinogenesis. The mechanisms by which COX-2 is thought to be involved in the carcinogenesis include resisting apoptosis, increasing cell proliferation, stimulating angiogenesis and modulating the invasive properties of cancer cells. Conclusion: This report reviews the mechanisms by which COX-2 can contribute to carcinogenesis, its role in prognosis, and the possible place of selective COX-2 inhibitors in the prevention and treatment of gastrointestinal malignancies, focusing particularly on oesophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Adenocarcinomas of the gastric cardia and distal oesophagus are at present often considered as one clinical entity because of their comparable increasing incidence, prognosis, and optimal treatment options. However, it is still a mailer of debate whether these malignancies have the same pathogenesis and genotype. Aims: The aim of this study was to analyse expression of cyclooxygenase 2 (COX-2) in cardia carcinomas, and correlate this expression with clinicopathological parameters and survival. The results were compared with the prognostic value of COX-2 found for Barren carcinomas. Methods: Tumour sections of 134 consecutive patients undergoing potentially curative surgery for an adenocarcinoma of the gastric cardia and substantially invading the distal oesophagus were immunohistochemically stained using a COX-2 monoclonal antibody. Specimens were blindly scored based on intensity and extent of COX-2 immunopositivity. Results: COX-2 expression was negative to weak in 59% ("COX-2 low") and moderate to strong in 41% ("COX-2 high") of tumours. This was significantly lower than in Barreil carcinomas (p<0.0001). COX-2 expression was not correlated with any clinicopathological parameter. A correlation between elevated COX-2 expression and reduced survival, as described for Barrett carcinomas, was not identified for cardiac carcinomas. Conclusions: There is a difference in COX-2 expression with respect to intensity and prognostic significance between adenocarcinomas of the gastric cardia and distal oesophagus. This suggests a different pathogenesis and different genetic constitution of these two cancers. Based on these findings, the role of selective COX-2 inhibitors in the treatment of adenocarcinomas of the gastric cardia is less promising than in Barren carcinomas. [ABSTRACT FROM AUTHOR]

A steady increase in the incidence of adenocarcinoma of the oesophagus and oesophagogastric junction has been observed in Western countries. Patients with distinctive-type Barrett oesophagus are predisposed to developing adenocarcinoma of the oesophagus. Distinctive-type Barrett oesophagus is defined by the presence of intestinal-like goblet cells anywhere in the oesophagus. Adenocarcinomas of the oesophagogastric junction may be associated with short segments of intestinal-type columnar epithelium in the distal oesophagus. Prognosis after surgical resection for cancer of the oesophagus or oesophagogastric junction is strongly affected by the extent of the disease at the time of diagnosis. The identification of Barrett oesophagus as a premalignant condition, the recognition of a stepwise neoplastic progression, along with the poor survival rates of advanced oesophageal adenocarcinoma have initiated the practice of endoscopic biopsy surveillance for patients with Barrett oesophagus. There is supporting evidence that endoscopic biopsy surveillance of Barrett oesophagus permits detection of malignancy at an early stage with favourable results after oesophageal resection. Endoscopic treatment modalities should at this time not be generally adopted in the management of patients with early invasive adenocarcinoma of the oesophagus or oesophagogastric junction. [ABSTRACT FROM AUTHOR]

Summary Background The extent of lymph node dissection can affect tumour node metastasis staging. The resulting ‘stage migration’ might hamper stage-by-stage comparison between different forms of oesophageal resection. The aim of this study was to assess the diagnostic impact of extended en bloc lymphadenectomy in staging (adeno)carcinoma of the mid/distal oesophagus or gastric cardia. Methods This was a prospective study of 74 patients (67 men and seven women; median age 63 (range 40–78) years) who underwent extended oesophagectomy between 1994 and 2000. Results A median of 31 (range 15–78) lymph nodes was resected (and identified), with a median of 5 (range 0–31) positive nodes. Twenty-seven patients (36 per cent) had tumour-positive nodes in extended fields: 15 patients (20 per cent) in the abdomen and 15 patients (20 per cent) in the mediastinum. Subcarinal nodes were most affected (19 per cent). Extended resection led to tumour upstaging in 17 patients (23 per cent); two patients had isolated positive subcarinal nodes and 15 other tumours became M1a owing to positive nodes near the coeliac axis, hepatic artery or splenic artery. Tumour positivity in paratracheal or aortopulmonary nodes occurred in 8 per cent of patients, without influencing staging. Conclusion Extended en bloc lymphadenectomy altered staging in 17 of 74 patients (23 per cent) with adenocarcinoma of the oesophagus or cardia, mainly into M1a owing to positive coeliac nodes (20 per cent). Presented in abstract form to United European Gastroenterology Week, Brussels and the British Association of Surgical Oncology, London, November 2000. [ABSTRACT FROM AUTHOR]

Summary Background Transhiatal resection for oesophageal cancer is a major operation with potentially severe physical, emotional and social consequences. The aim of this study was to assess various aspects of quality of life in long-term survivors following oesophageal resection for cancer. Methods Between January 1993 and May 1996, 100 consecutive patients with cancer of the oesophagus or oesophagogastric junction underwent a potentially curative transhiatal oesophagectomy. Patients with a minimum follow-up of 2 years and with no tumour recurrence (n = 35) were mailed questionnaires which consisted of: (a) the Short Form-36 Health Survey to assess general quality of life, (b) an adapted Rotterdam Symptom Checklist to assess disease-specific quality of life, and (c) additional questions about other effects of the operation. Results All patients returned the questionnaire. General quality of life was comparable with reference values for the same age group. However, more than half of the patients still experienced at least some early satiety, fatigue, dysphagia, heartburn and/or psychological irritability. Nine of 13 patients who worked in paid employment before operation continued to do so. Conclusion Patients who survive 2 years or more after transhiatal oesophageal resection for cancer can lead satisfactory lives. Although some residual symptoms may persist, their general quality of life is similar to that of healthy individuals of the same age. [ABSTRACT FROM AUTHOR]

Anti-Yo-associated paraneoplastic cerebellar degeneration is a cancer-related syndrome affecting the nervous system. This syndrome occurs almost exclusively in middle-aged women with gynecological cancers and it is rarerly found in patients with other types of cancer or in males. In this report we describe a male patient adenocarcinoma of the gastroesophageal junction and PCD with anti-Yo antibodies. To our knowledge, this is only the third report of PCD with positive anti-Yo antibodies in an esophageal tumor and the first report in a tumor of the gastroesophageal junction. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In this report, a case is presented of an adenocarcinoma in a Barrett's esophagus metastatic to the choroid. A 54-year-old woman presented with a rapidly progressive decrease of vision in the right eye 8 months after intentionally curative esophagectomy for an adenocarcinoma. Fundoscopy, ultrasonography, and magnetic resonance imaging findings were suggestive of a metastasis. The patient received palliative external beam irradiation to the right eye for visual restoration, but she died before any beneficial effect was achieved. [ABSTRACT FROM AUTHOR]

Background After curatively intended neoadjuvant chemoradiotherapy (nCRT) according to CROSS plus surgery for esophageal cancer, 29% of patients have a pathologic complete response. Active surveillance after nCRT, in which patients undergo frequent clinical examinations and where esophagectomy is only offered to those with a locoregional regrowth without distant metastases, has been proposed as novel treatment option. This study provides a systematic review and meta-analysis of the literature regarding the accuracy of endoscopic biopsies, endoscopic ultrasound (EUS) and 18F-FDG PET(-CT) for detecting residual disease after nCRT for esophageal cancer. Methods A systematic literature search in Embase, Medline, Cochrane and Web of Science was performed. Two reviewers independently collected studies on the diagnostic accuracy of endoscopic biopsies, EUS and 18F-FDG PET(-CT) for detecting residual disease after nCRT at the primary tumor site or in regional lymph nodes for potentially curable esophageal adenocarcinoma (AC) or squamous cell carcinoma (SCC). Histopathological examination of the resection specimen was the reference standard. Study quality was appraised with the QUADAS-2 tool. Sensitivity and specificity values were calculated and pooled using meta-analyses. Subgroup analyses were performed to investigate possible sources of heterogeneity. Results 60 studies were included for qualitative analysis and 40 for quantitative analysis. For detecting residual disease at the primary tumor site, 11 studies evaluated endoscopic biopsies, 11 described EUS qualitatively, 14 evaluated PET qualitatively, 12 evaluated PET quantitatively, 6 of them using SUVmax and 6 of them using DSUVmax. Summary sensitivity values were 0.36 (95%CI 0.27–0.45), 0.97 (95%CI 0.94–0.98), 0.74 (95%CI 0.66–0.81), 0.68 (95%CI 0.61–0.74) and 0.68 (95%CI 0.54–0.79), respectively. Summary specificity values were 0.93 (95%CI 0.85–0.97), 0.09 (95%CI 0.04–0.19), 0.52 (95%CI 0.40–0.63), 0.70 (95%CI 0.61–0.78), 0.70 (95%CI 0.60–0.78) and respectively. For detecting residual malignant lymph nodes, 11 studies evaluated EUS with a summary sensitivity of 0.68 (95%CI 0.54–0.80) and a summary specificity of 0.58 (95%CI 0.45–0.70). Subgroup analyses demonstrated that sensitivity of endoscopic biopsy, PET DSUVmax and EUS for nodal was higher in SCC than in AC. Conclusion Current literature suggests insufficient accuracy of endoscopic biopsies, EUS and 18F-FDG PET(-CT) as individual modalities for detecting residual disease after nCRT for potentially curable esophageal cancer. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background An active surveillance approach has been proposed for patients with a clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (SANO trial). To justify renouncing surgical resection, patients with residual disease after nCRT should be accurately identified. However, substantial residual disease (TRG3–4) cannot be detected in 10% of patients with current diagnostic tests (preSANO trial). Circulating cell free tumor DNA (ctDNA) potentially improves detection of residual malignancy after nCRT and could be used for disease monitoring. The objective of this study was to investigate the feasibility of using ctDNA as biomarker for disease status after nCRT in esophageal cancer. Methods Twelve typical patients from the preSANO trial with variable pathological responses to nCRT were included. Blood was drawn and processed pretreatment. The feasibility of detecting TP53 mutations in baseline tumor biopsies was investigated using a next generation sequencing (NGS) panel. Subsequently, baseline blood samples of patients in whom specific TP53 mutations could be identified in baseline tumor biopsies or the surgical resection specimen were analyzed for ctDNA using cell free DNA NGS kits with single molecule barcoding (Oncomine Thermo Fisher). Results Baseline biopsy samples were available in 8 out of 12 patients. In 7 of these 8 patients (88%) specific TP53 mutations could be identified in their baseline biopsies. In 11 out of 12 patients (92%) specific TP53 mutations could be identified in baseline biopsies or the resection specimen. Eight of these 11 mutations were potentially detectable by the Oncomine panel. The panel detected TP53 mutational ctDNA in 4 of these 8 samples (50%). Conclusion Specific and clonal TP53 mutations can be identified in pretreatment biopsy samples and in surgical resection specimens of patients with esophageal cancer. These mutations can be matched to ctDNA identified in blood samples. Hence, ctDNA analyses in blood samples can potentially be used for disease monitoring during active surveillance and for disease monitoring in follow-up after surgical resection. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

After publication of the long-term results of the CROSS-trial neoadjuvant chemoradiotherapy (nCRT) followed by radical surgical resection is considered standard of potentially curative care in most Western countries. By adding nCRT the 5-year overall survival has improved from 34% after surgery alone to 47% after combined therapy [1, 2]. Surprisingly, about one-third of patients have a pathologically complete response (pCR) in the resection specimen after pretreatment with the CROSS regimen. This high pCR rate imposes an ethical imperative to identify these patients in order to avoid potentially unnecessary surgery. Before embarking on a strategy of 'active surveillance' in patients with a clinically complete response (cCR), an optimal set of diagnostic modalities must be defined, which enables the accurate identification of patients with substantial residual disease after nCRT. For this purpose the Dutch diagnostic preSANO trial has recently been completed [3]. In 220 patients clinical response assessments were prospectively performed 6-12 weeks after the end of nCRT. By combining repeated PET-CT, endoscopy with multiple bite-on-bite biopsies and endosonography with fine needle aspiration of suspected lymph nodes a false-negativity rate of 10% was accomplished. Moreover, intercurrent distant metastases were detected in another 10%. A stepped-wedge cluster randomized trial has now been initiated in 12 Dutch centers, aiming to include prospectively 300 patients with cCR after chemoradiotherapy [4]. In this SANO-trial the novel strategy of active surveillance will be randomly compared to standard therapy (i.e. immediate surgical resection). Primary endpoint will be 5-year overall survival. Secondary endpoints include quality of life, complications after (delayed) surgery, distant dissemination rate, and costs. [ABSTRACT FROM AUTHOR]

The optimal surgical technique for the potentially curative treatment of patients with esophageal cancer is still under debate. The transhiatal esophagectomy ( THE) with limited lymphadenectomy mainly focuses on a decrease of postoperative morbidity and mortality by preventing a formal thoracotomy. The transthoracic esophagectomy ( TTE) with extended two-field lymphadenectomy attempts to improve the radicality of the resection and thus to increase locoregional tumor control, but is associated with increased postoperative morbidity. The recent introduction of different minimally invasive techniques probably decreases postoperative morbidity following TTE, with reduction of especially pulmonary complications, but high-quality evidence is still limited. It is widely agreed that extended lymphadenectomy as performed during TTE provides the benefit of more accurate staging, but its effect on improvement of survival is still debated. The literature on this topic is contradictory and the choice of surgical approach is primarily driven by personal opinions and institutional preferences. Moreover, the available evidence is mainly based on patients who underwent surgery alone without neoadjuvant therapy. Results of recent studies suggest that neoadjuvant chemoradiotherapy abolishes any possibly positive effect of extended lymphadenectomy as performed during TTE on survival, but this effect should be confirmed in future research. This review gives an overview and reflects the authors' personal view on the role of TTE and THE in the treatment of potentially curative treatment of patients with locally advanced esophageal cancer in the era of minimally invasive esophagectomy and neoadjuvant treatment and outlines future research perspectives. [ABSTRACT FROM AUTHOR]

Discusses recent advances in endoscopy for the diagnosis of adenocarcinoma arising on a background of Barrett's change. Increased potential of Barrett's esophagus for malignant degeneration, especially when the columnar epithelium demonstrates specialized intestinal metaplasia; Use of endoscopic mucosal resection (EMR) for safe removal of relatively large focal lesions in Barrett's esophagus; Importance of EMR as a therapeutic option in selected patients with early Barrett's cancer.