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Background: Neoadjuvant chemoradiotherapy (nCRT) and surgery is a widely used treatment for locally advanced resectable oesophageal cancer, with 20-50 per cent of patients having a pathological complete response (pCR). Disease, however, still recurs in 20-30 per cent of these patients. The aim of this study was to assess the pattern of recurrence in patients with a pCR after nCRT and surgery. Methods: All patients with a pCR after nCRT and surgery included in the phase II and III CROSS (ChemoRadiotherapy for Oesophageal followed by Surgery Study) trials (April 2001 to December 2008) and after the CROSS trials (September 2009 to October 2017) were identified. The site of recurrence was compared with the applied radiation and surgical fields. Outcomes were median time to recurrence, and overall and progression-free survival. Results: A total of 141 patients with a median follow-up of 100 (i.q.r. 64-134) months were included. Some 29 of 141 patients (20,6 per cent) developed recurrence. Of these, four had isolated locoregional recurrence, 15 had distant recurrence only, and ten had both locoregional and distant recurrence. Among the 14 patients with locoregional recurrences, five had recurrence within the radiation field, seven outside the radiation field, and two at the border. Median time to recurrence was 24 (10-62) months. The 5-year overall survival rate was 74 per cent and the recurrence-free survival rate was 70 per cent. Conclusion: Despite good overall survival, recurrence still occurred in 21 per cent of patients. Most recurrences were distant, outside the radiation and surgical fields. [ABSTRACT FROM AUTHOR]

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Background: After neoadjuvant chemoradiotherapy (nCRT) plus surgery for oesophageal cancer, 29 per cent of patients have a pathologically complete response in the resection specimen. Active surveillance after nCRT (instead of standard oesophagectomy) may improve health‐related quality of life (HRQoL), but patients need to undergo frequent diagnostic tests and it is unknown whether survival is worse than that after standard oesophagectomy. Factors that influence patients' preferences, and trade‐offs that patients are willing to make in their choice between surgery and active surveillance were investigated here. Methods: A prospective discrete‐choice experiment was conducted. Patients with oesophageal cancer completed questionnaires 4–6 weeks after nCRT, before surgery. Patients' preferences were quantified using scenarios based on five aspects: 5‐year overall survival, short‐term HRQoL, long‐term HRQoL, the risk that oesophagectomy is still necessary, and the frequency of clinical examinations using endoscopy and PET–CT. Panel latent class analysis was used. Results: Some 100 of 104 patients (96·2 per cent) responded. All aspects, except the frequency of clinical examinations, influenced patients' preferences. Five‐year overall survival, the chance that oesophagectomy is still necessary and long‐term HRQoL were the most important attributes. On average, based on calculation of the indifference point between standard surgery and active surveillance, patients were willing to trade off 16 per cent 5‐year overall survival to reduce the risk that oesophagectomy is necessary from 100 per cent (standard surgery) to 35 per cent (active surveillance). Conclusion: Patients are willing to trade off substantial 5‐year survival to achieve a reduction in the risk that oesophagectomy is necessary. Organ preservation preferred [ABSTRACT FROM AUTHOR]

Esophageal sarcomas are rare and evidence in literature is scarce making their management difficult. The objective is to report surgical and oncological outcomes of esophageal sarcoma in a large multicenter European cohort. This is a retrospective multicenter study including all patients who underwent en-bloc esophagectomy for esophageal sarcoma in seven European tertiary referral centers between 1987 and 2016. The main outcomes and measures are pathological results, early and long-term outcomes. Among 10,936 esophageal resections for cancer, 21 (0.2%) patients with esophageal sarcoma were identified. The majority of tumors was located in the middle (n=7) and distal (n = 9) third of the esophagus. Neoadjuvant chemoradiotherapy was performed in five patients. All the patients underwent en-bloc transthoracic esophagectomy (19 open, 2 minimally invasive). Postoperative mortality occurred in 1 patient (5%). One patient received adjuvant chemotherapy. Definitive pathological results were carcinosarcoma (n = 7), leiomyosarcoma (n = 5), and other types of sarcoma (n = 9). Microscopic R1 resection was present in one patient (5%) and seven patients (33%) had positive lymph nodes. Median follow-up was 16 (3-79) months in 20 of 21 patients (95%). One-, 3 and 5-year overall survival rates were 74%, 43%, and 35%, respectively. One-, 3 and 5-years disease-free survival rates were 58%, 40%, and 33%, respectively. Median overall survival was 6 months in N+ patients vs. 37 months for N0 patients (p = 0.06). At the end of the follow-up period, nine patients had died from cancer recurrences (43%), three patients died from other reasons (14%), one patient was still alive with recurrence (5%) and the seven remaining patients were free of disease (33%). Recurrence was local (n = 3), metastatic (n = 3), or both (n = 4). In conclusion, carcinosarcoma and leiomyosarcoma were the most common esophageal sarcoma histological subtypes. Lymph node involvement was seen in one third of cases. A transthoracic en-bloc esophagectomy with radical lymphadenectomy should be the best surgical option to achieve complete resection. Long-term survival remained poor with a high local and distant recurrence rate. [ABSTRACT FROM AUTHOR]

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]

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is standard of care for locally advanced esophageal cancer in many countries. After nCRT up to one third of all patients have a pathologically complete response in the resection specimen, posing an ethical imperative to reconsider the necessity of standard surgery in all operable patients after nCRT. An active surveillance strategy following nCRT, in which patients are subjected to frequent clinical investigations after the completion of neoadjuvant therapy, has been evaluated in other types of cancer with promising results. In esophageal cancer, both patients who are cured by neoadjuvant therapy alone as well as patients with subclinical disseminated disease at the time of completion of neoadjuvant therapy may benefit from such an organ sparing approach. Active surveillance is currently applied in selected patients with esophageal cancer who refuse surgery or are medically unfit for major surgery after completion of nCRT, but this strategy is not (yet) adopted as an alternative to standard surgery or definitive chemoradiation. The available literature is scarce, but suggests that long-term oncological outcomes after active surveillance are noninferior compared to standard surgical resection, providing justification for comparison of both treatments in a phase III trial. This review gives an overview of the current knowledge regarding active surveillance after completion of nCRT in esophageal cancer and outlines future research perspectives. [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]

18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) has been investigated as a tool for monitoring response to neoadjuvant chemo- and chemoradiotherapy (CT and CRT, respectively) and as a predictor for survival in patients with esophageal cancer. In contrast to patients who undergo neoadjuvant CT, it is not known whether patients who are clinically identified as responders after neoadjuvant CRT show better diseasefree survival (DFS) than patients identified as nonresponders. The aim of the study was to determine the predictive value of FDG-uptake measured prior to and early during neoadjuvant CRT. Patients treated with neoadjuvant CRT between 2004 and 2009 within a randomized trial were included. FDG-uptake was measured at baseline and after 14 days of CRT. According to the PERCIST-criteria, patients were allocated to have metabolic response, stable disease, or progression. Patients were followed until recurrence of disease or death. The predictive value of FDGPET was determined with univariable and multivariable analysis in patients who underwent potentially curative surgery. One-hundred and six patients were included in the analysis. Minimal follow-up for surviving patients was 60 months. No significant differences in DFS were found between patients with metabolic response, stable disease, or progression, with 5-year DFS rates of 66%, 53%, and 67%, respectively (P=0.39). Relative change in FDG uptake after 14 days of CRT is not associated with DFS in patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery. These measurements should not be used for prognostication in this specific group of patients. [ABSTRACT FROM AUTHOR]

Background The value of conventional prognostic factors is unclear in the era of multimodal treatment for oesophageal cancer. This study aimed to quantify the impact of neoadjuvant chemoradiotherapy ( nCRT) and surgery on well established prognostic factors, and to develop and validate a prognostic model. Methods Patients treated with nCRT plus surgery were included. Multivariable Cox modelling was used to identify prognostic factors for overall survival. A prediction model for individual survival was developed using stepwise backward selection. The model was internally validated leading to a nomogram for use in clinical practice. Results Some 626 patients who underwent nCRT plus surgery were included. In the multivariable model, only pretreatment cN category and ypN category were independent prognostic factors. The final prognostic model included cN, ypT and ypN categories, and had moderate discrimination (c-index at internal validation 0·63). Conclusion In patients with oesophageal or oesophagogastric cancer treated with nCRT plus surgery, overall survival can best be estimated using a prediction model based on cN, ypT and ypN categories. Predicted survival according to this model showed only moderate correlation with observed survival, emphasizing the need for new prognostic factors to improve survival prediction. [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]

Human epidermal growth factor receptor 2 ( HER2) is overexpressed in a subset of esophageal adenocarcinomas. Frequently, biopsy material is used for evaluation of HER2 status. The aim of the study was to determine if HER2 expression in preoperative endoscopic biopsies is representative for the entire tumor. Preoperative endoscopic biopsies and matched resection specimens were collected from 75 patients who underwent esophagectomy for esophageal adenocarcinoma. Immunohistochemical staining ( IHC) on HER2 and dual-color in situ hybridization ( ISH) were performed. HER2 status was determined by following a clinical algorithm, first determining HER2 overexpression on immunohistochemistry and, when equivocal (2+), determining HER2 amplification on ISH. Seventy-one of 75 (95%) biopsies and 69/75 (92%) resection specimens could be analyzed due to technical failure. HER2 positivity was seen in 18/71 (25%) biopsies and in 15/69 (22%) resection specimens. Overall, HER2 status in the biopsy was concordant with HER2 status in the resection specimen in 94% of cases. Interobserver agreement on IHC scoring for all three observers was 83% in biopsies and 85% in resection specimens. HER2 positivity was detected in 22% of esophageal adenocarcinomas. Although interobserver agreement was moderate, HER2 status of a primary tumor can be reliably determined based on the endoscopically obtained pretreatment biopsy. [ABSTRACT FROM AUTHOR]

Background: Little is known about recurrence patterns in patients with a pathologically complete response (pCR) or an incomplete response after neoadjuvant chemoradiotherapy (CRT) followed by resection for oesophageal cancer. This study was performed to determine the pattern of recurrence in patients with a pCR after neoadjuvant CRT followed by surgery. Methods: All patients who received neoadjuvant CRT followed by oesophagectomy between 1993 and 2009 were identified from a database, and categorized according to pathological tumour response. Recurrences were classified as locoregional or distant. Results: One hundred and eighty-eight patients were included. Median potential follow-up was 71·6 months. A pCR was achieved in 62 (33·0 per cent) of 188 patients. Recurrence developed in 24 (39 per cent) of 62 patients with a pCR and 70 (55·6 per cent) of 126 without a pCR ( P = 0·044). Locoregional recurrence with or without synchronous distant metastases occurred in eight patients (13 per cent) in the pCR group and 31 (24·6 per cent) in the non-pCR group ( P = 0·095). Locoregional recurrences without synchronous distant metastases occurred four (6 per cent) and ten (7·9 per cent) patients respectively ( P = 0·945). The overall 5-year survival rate was significantly higher in the pCR group than in the non-pCR group (52 versus 33·9 per cent respectively; P = 0·019). Conclusion: Of patients with a pCR, 13 per cent still developed a locoregional recurrence. Although pCR is more favourable for survival, it is not synonymous with cure or complete locoregional disease control. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [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]

The article presents a study which evaluates the incidence of intrathoracic manifestations in patients who have diagnosed with cervical anastomotic leakage after transhiatal (THO) and transthoracic oesophagectomy (TTO) surgery. It uses regression analysis to determine possible risks of manifestations, wherein manifestations were compared after cervical anastomotic leak. Results of the study show the influence of intrathoracic manifestations with protracted hospital stay and high mortality rate.

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]

The article presents a study which evaluated the Physiological and Operative Severity Score for the enUmeration of Mortality adjusted for oesophagogastric surgery (O-POSSUM). It analyzed data on patients who underwent oesophagectomy in a center for adenocarcinoma or squamous cell carcinoma of the oesophagus. Results showed that 24 patients died in hospital and the predicted ratio for in-hospital mortality was 0.29. It was concluded that O-POSUUM overpredicted in-hospital mortality threefold.

The article presents a study which assessed the additional value of fluorodeoxyglucose positron emission tomography (FDG-PET) after a state-of-the-art preoperative staging protocol. Suspicious hot spots in 30 patients were revealed by FDG-PET. Hot spots in seven patients appeared to be synchronous neoplasms. It was concluded that FDG-PET improves the selection of patients with oesophageal cancer for potentially curative surgery.

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]

After esophagectomy, pleural drainage is performed to ensure complete drainage of the pleural cavities. The aim of this study was to detect predisposing factors for prolonged drainage. Patients who underwent transhiatal or extended transthoracic esophagectomy for adenocarcinoma of the distal esophagus or gastroesophageal junction were included. Patients who underwent esophagectomy produced a median total drainage volume of 2477 mL (range 30–14 908). Seventy-five patients needed chest drainage = 7 days (short drainage) while 57 patients needed chest drainage > 7 days (prolonged drainage). Factors associated with prolonged drainage were a transthoracic approach ( P  < 0.001), a higher volume of blood loss ( P  = 0.027), a higher number of resected lymphnodes ( P  = 0.046) and a radical dissection ( P  = 0.033). Prolonged pleural drainage is associated with a transthoracic approach and is seen more often in patients after a microscopically radical dissection. Prolonged drainage is a sign of adequate dissection on the site of the primary tumor, probably due to the more extensive trauma to the lymphatic vessels in the mediastinum. [ABSTRACT FROM AUTHOR]

The article aims to establish the incidence and prognostic significance of lymph node metastasis in the proximal field of the chest in patients undergoing transthoracic esophagectomy for adenocarcinoma of the cardia with substantial invasion of the esophagus. The results show that patients had more positive nodes and a shorter medial survival compared to those without metastasis. Positive nodes are identified by multivariate analysis in the proximal field as an independent predictor of poor survival. The study suggests that lymph node metastasis in the proximal field of the chest is common and is an indicator of poor prognosis in patients with adenocarcinoma of the cardia.

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]

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]

SummaryBackground: Although vocal cord paralysis is a well known complication of subtotal oesophagectomy, precise data concerning origin, incidence and associated morbidity are lacking. Methods: A retrospective study was performed of 241 patients who underwent transhiatal oesophagectomy for carcinoma of the mid/distal oesophagus between 1994 and 1998. Preoperative and postoperative laryngoscopy results were available for 140 patients. Results: There were 109 men and 31 women, of mean age 63 years. Thirty-one patients (22 per cent) with recurrent laryngeal nerve paralysis were identified, three with bilateral and 28 with unilateral dysfunction. Paralysis occurred ipsilateral to the side of the cervical incision in 22 of 28 patients. It was permanent in six patients. The associated morbidity was substantial: pulmonary complications were more common in patients with vocal cord paralysis (12 of 31 versus 26 (24 per cent) of 109), leading to significantly more reintubations, and a significantly prolonged ventilation time and stay in the intensive care unit. Conclusion: Although mostly transient, vocal cord paralysis is a frequent complication with significant associated morbidity. In an extended transthoracic resection (including a lymphadenectomy in the aortopulmonary window where the left recurrent laryngeal nerve is at risk) the cervical anastomosis should be made on the left side, to minimize the risk of bilateral vocal cord paralysis. [ABSTRACT FROM AUTHOR]

SUMMARY Recently, a mouse model for Barrett's esophagus based on a zinc-deficient diet supplemented with deoxycholic bile acids has been published. The aim of this study was to attempt to reproduce these data and extend them by employing genetically modified mice and intraperitoneal iron supplementation. The study design encompassed six experimental groups (wild type, Apc-mutant and Smad4-mutant mice, with or without iron injections), with all animals fed with the zinc-deficient diet supplemented with deoxycholic bile acids. All treatments were started at 3-5 weeks of age (the majority [78%] at 5 weeks). Animals were scheduled for euthanasia at two distinct time points, namely at 3 and 6 months of age. All mice showed signs of considerable distress already 4 weeks after the start of the modified diets, and had to be euthanized before the first evaluation time point (mean age 9.3 weeks, range 5-15 weeks). No differences were observed between wild type and genetically modified mice, or between animals with or without iron supplementation. On histological examination, we could not detect any lesions (Barrett's esophagus-like or tumors) other than esophagitis. In the currently presented experimental settings, we were not able to reproduce the mouse model according to which Barrett's-like lesions could be detected in animals fed with the zinc-deficient diet supplemented with deoxycholic bile acids. [ABSTRACT FROM AUTHOR]

Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air–fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process. [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 Neoadjuvant chemoradiotherapy (nCRT) induces a pathologically complete response in approximately 30% of patients with oesophageal cancer. To explore the possibility of safe postponement of surgery, accurate clinical response evaluations are needed to exclude residual disease. The present study aims to assess the value of F-18-FDG-PET/CT for the detection of residual tumour (> 10% tumour cells = TRG3–4 vs. no vital cells = TRG1) or metastases after nCRT. Methods FDG-PET/CT at baseline and 12 weeks after nCRT was performed according to the European Association of Nuclear Medicine guidelines 1.0 (2.3MBq/kg F-18-FDG; scanning 60 ± 5min.) and the protocol of the preSANO study. Qualitative analysis included sensitive reading of presence of residual tumour and/or metastases. A lesion was considered FDG-positive, when any uptake in the lesion itself was above the adjacent oesophageal background uptake. Quantitatively, SUV/lean body mass (SUL) measurements at tumour, lymph nodes, oesophagus, liver and bloodpool were recorded and compared with pathology (resection specimen: gold standard). Results Some 129 of 207 patients with FDG-avid tumours at baseline proceeded to FDG-PET/CT at around 12 weeks after nCRT just before surgery. Forty-one of 129 patients had TRG3–4, of whom 6 were missed on FDG-PET/CT (15% false negative) with SULmax 2.07 ± 0.25, SUL-ratio tumour/oesophagus (SULR) 1.35 ± 0.14. Sensitivity for TRG2–3-4 vs. TRG1 was 57/71 (80%). SULmax and SULR of FDG-positives were 3.76 ± 1.33 and 1.82 ± 0.69 respectively, compared to SULmax 2.21 ± 0.42 and SULR 1.31 ± 0.22 in FDG-negatives. Distant metastases were detected in 18 of 190 (10%) patients. Of all patients with postponed surgery, 12 had ≥ 1 additional FDG-PET/CT during follow-up (25–49.7 weeks after nCRT). Eventually, 4 patients underwent surgery. Three of 4 had increased FDG-signal and TRG3–4; 1 patient had decreased FDG-signal and no tumour left (TRG1). Conclusion FDG-PET/CT at around 12 weeks after nCRT misses TRG3–4 tumours in 15% and detects residual TRG2–3-4 in 80%. Furthermore, PET-CT detects distant metastases in 10% of patients after nCRT. These data indicate that serial FDG-PET may become valuable in an active surveillance approach. Disclosure All authors have declared no conflicts of interest. [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 The presence of signet ring cells (SRC) is associated with poorer survival in multiple cancer types. Here we aimed to determine the predictive and prognostic value of SRC in oesophageal and junctional adenocarcinoma (OAC) for patients treated with neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). Methods Patients who underwent nCRT and nCT followed by surgery for OAC between 2000 and 2016 were identified from two institutional prospective databases. Pre-treatment biopsy and surgical resection pathology reports were used to determine the presence of SRC morphology. The association between SRC histology and clinicopathological characteristics including pathological response was assessed. The prognostic impact of SRC on disease-free survival (DFS) and overall survival (OS) was determined. Survival was calculated with Kaplan Meier method and differences tested with log rank test. Results Of the 689 study patients, 129 had SRC (nCRT; n = 65, nCT; n = 64) and 560 patients had no evidence of SRC (nCRT; n = 326, nCT; n = 234). The SRC group had higher pT stage (P = 0.004) and median number of involved nodes (P = 0.004) following nCT compared with the non-SRC group. There were no significant differences between the two groups with respect to age, gender, tumour site, pN, R status or pathological complete response. For the 129 in the SRC group, nCT patients had significantly worse DFS (median [IQR]; 12 months [50–5]) compared with nCRT patients (median [IQR]; 26 months [111–9], P = 0.021). Moreover, nCT had a worse loco-regional recurrence-free survival (P  = 0.004), but not distant recurrence-free survival (P = 0.74), in the SRC group. In contrast, there were no differences in DFS (P = 0.245) or recurrence patterns between nCRT and nCT among the 560 non-SRC patients. However, there was no significant difference in OS according to SRC status following nCT (P = 0.076) or nCRT (P = 0.541). Conclusion For SRC OAC, nCRT is associated with better DFS and loco-regional control compared with nCT. However, the presence of SRC in OAC was not prognostic for OS following nCT or nCRT. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background An optimal model for predicting pathologic response after neoadjuvant chemoradiotherapy (nCRT) in oesophageal cancer has not been defined yet. FDG-PET/CT is frequently used in response assessments. The aim of this side study of the preSANO trial (NL41732.078.13) was to investigate if the FDG-PET parameters SUVmax, total lesion glycolysis (TLG) and metabolic tumour volume (MTV) were predictive for residual tumour in the resected specimen of oesophageal cancer patients treated with nCRT. Methods Patients underwent FDG-PET/CT at baseline according to the European Association of Nuclear Medicine guidelines 1.0 (2.3MBq/kg F-18-FDG; scanning 60 ± 5min.). All parameters were corrected for lean body mass. MTV was defined as the volume within a 41% of SULmax ( = SUV/lean body mass) isocontour threshold at tumour and lymph nodes. TLG was calculated as SULmean x MTV. Logarithmic transformation was performed because of non-normal distribution of TLG and MTV. Baseline PET parameters were compared to tumour regression grade in the resection specimen (TRG3–4 = > 10% residual tumour vs. TRG1 = complete response). Peroperatively irresectable tumours were recoded as TRG4. Analyses were performed using an independent-samples T-test. Results From a total of 207 patients who underwent FDG-PET/CT before nCRT, 197 were included for analysis (5 were non-FDG avid, 5 had incomplete data). Histological type of tumour: adenocarcinoma (AC) n = 154, squamous cell carcinoma (SCC) n = 42, and one adenosquamous carcinoma. Thirty-seven patients (19%) had TRG1 and 41 patients (21%) had TRG3–4. In complete responders (TRG1), SULmax, TLG and MTV (mean ± SD) were 9.6 ± 5.8, 85.3 ± 85.5 and 13.0 ± 9.9, respectively. In patients with TRG3–4, SULmax, TLG and MTV were 9.4 ± 5.4145.8 ± 164.6 and 21.9 ± 16.2, respectively. SULmax was not significantly different between both groups (P  = 0.8), but log(TLG) and log(MTV) (P  = 0.008 and P  = 0.001) were. In adenocarcinomas, log(TLG) did not differ between groups (P  = 0.1). Conclusion Initial FDG tumour mass, expressed as MTV, (rather than SULmax) is the most contributing factor in predicting residual disease after nCRT in both SCC and AC. The effect is stronger in SCC. Therefore, baseline FDG tumour mass should be included in a prediction model, besides other clinical and tumour parameters. 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]

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website ( ). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length. [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.

Background: After potentially curative resection of oesophageal cancer and prevertebral gastric tube reconstruction, approximately one-quarter of patients develop secondary dysphagia due to locoregional recurrence. In half of them dysphagia can be prevented by using an extra-anatomical reconstruction route. The present randomized study was conducted to compare the technical and functional results after prevertebral and retrosternal gastric tube reconstruction. Methods: Sixty patients underwent resection of a carcinoma of the oesophagus or gastro-oesophageal junction with curative intent. Subsequently, these patients were randomly allocated to either prevertebral (n=30) or retrosternal (n=30) gastric tube reconstruction. Early and late complications and functional results were carefully monitored. Results: Creation of the retrosternal tunnel was not accompanied by any perioperative complications. Postoperative recovery, anastomotic leakage and benign stricture formation were not significantly different between the two groups. Functional results, as measured by scintigraphic gastric emptying, quantitative and qualitative oral food intake, and changes in body-weight were similar in the two groups. Conclusion: After subtotal oesophagectomy retrosternal gastric tube reconstruction can be performed easily and safely, and gives functional results similar to those obtained with prevertebral reconstruction. In patients at high risk for developing secondary malignant dysphagia the extra-anatomical route is the reconstruction of first choice. [ABSTRACT FROM AUTHOR]

Background: Intrathoracic herniation of abdominal viscera is a potentially life-threatening condition, especially when diagnosis is delayed. The aim of this study was to estimate its incidence following oesophageal resection and to define contributing factors that might influence its occurrence. Methods: All radiographic studies of the chest that were made during follow-up in a series of 218 patients who underwent oesophagectomy between 1993 and 1997 were reviewed. Results: Herniation of bowel alongside the oesophageal substitute was detected in nine patients (4 per cent). Four hernias occurred within the first week after operation and five were detected at late follow-up. Surgical treatment was indicated in six patients. Analysis of predisposing factors revealed that extended incision and partial resection of the diaphragm were associated with an increased risk of postoperative hernia formation (four of 29 following extended enlargement versus five of 189 after routine opening of the oesophageal hiatus; P = 0·02). Conclusion: Diaphragmatic herniation was found in 4 per cent of patients after oesophagectomy. After extended iatrogenic disruption of the normal hiatal anatomy, narrowing of the diaphragmatic opening may be indicated to avoid postoperative herniation of bowel into the chest. Awareness of its possible occurrence may help prevent the development of intestinal obstruction and strangulation. [ABSTRACT FROM AUTHOR]