Sjoerd M. Lagarde

Extended Transthoracic Resection Compared With Limited Transhiatal Resection for Adenocarcinoma of the Mid/distal Esophagus: Five-year Survival of a Randomized Clinical Trial

Objective:To determine whether extended transthoracic esophagectomy for adenocarcinoma of the mid/distal esophagus improves long-term survival. Background:A randomized trial was performed to compare surgical techniques. Complete 5-year survival data are now available. Methods:A total of 220 patients with adenocarcinoma of the distal esophagus (type I) or gastric cardia involving the distal esophagus (type II) were randomly assigned to limited transhiatal esophagectomy or to extended transthoracic esophagectomy with en bloc lymphadenectomy. Patients with peroperatively irresectable/incurable cancer were excluded from this analysis (n = 15). A total of 95 patients underwent transhiatal esophagectomy and 110 patients underwent transthoracic esophagectomy. Results:After transhiatal and transthoracic resection, 5-year survival was 34% and 36%, respectively (P = 0.71, per protocol analysis). In a subgroup analysis, based on the location of the primary tumor according to the resection specimen, no overall survival benefit for either surgical approach was seen in 115 patients with a type II tumor (P = 0.81). In 90 patients with a type I tumor, a survival benefit of 14% was seen with the transthoracic approach (51% vs. 37%, P = 0.33). There was evidence that the treatment effect differed depending on the number of positive lymph nodes in the resection specimen (test for interaction P = 0.06). In patients (n = 55) without positive nodes locoregional disease-free survival after transhiatal esophagectomy was comparable to that after transthoracic esophagectomy (86% and 89%, respectively). The same was true for patients (n = 46) with more than 8 positive nodes (0% in both groups). Patients (n = 104) with 1 to 8 positive lymph nodes in the resection specimen showed a 5-year locoregional disease-free survival advantage if operated via the transthoracic route (23% vs. 64%, P = 0.02). Conclusion:There is no significant overall survival benefit for either approach. However, compared with limited transhiatal resection extended transthoracic esophagectomy for type I esophageal adenocarcinoma shows an ongoing trend towards better 5-year survival. Moreover, patients with a limited number of positive lymph nodes in the resection specimen seem to benefit from an extended transthoracic esophagectomy.

Prediction of appropriateness of local endoscopic treatment for high-grade dysplasia and early adenocarcinoma by EUS and histopathologic features

BACKGROUND Endoscopic techniques are being developed for the local treatment of early stage esophageal cancer. However, such therapy is not appropriate for patients with lymph node metastasis. The aim of this study was to analyze the histopathologic features of high-grade dysplasia and early stage adenocarcinoma and to relate these to lymph node involvement. METHODS Pathology reports were reviewed for all 367 patients who underwent subtotal esophagectomy for high-grade dysplasia or adenocarcinoma of the esophagus or the gastroesophageal junction between January 1993 and December 2001. Patients with histopathologically confirmed high-grade dysplasia or T1 carcinoma were included (n = 77). Pre-operative EUS results were assessed. All lesions were histopathologically subdivided in 6 different stages (mucosal 1-3 and submucosal 1-3). RESULTS EUS staged 61 patients as N0. EUS correctly predicted the absence of positive lymph nodes in 57 (93%) of these patients. Histopathologically, m1, m2, m3, and sm1 cancers never had lymph node metastases, whereas 3 of 13 sm2 tumors (23%) and 9 of 13 sm3 tumors (69%) had lymph node involvement. Lymphangio invasion was present exclusively in sm2 and sm3 cancers. Factors that predicted the presence of lymph node metastasis were the following: tumor diameter greater than 3 cm, infiltration of malignancy beyond sm1, poor differentiation grade, and lymphangio invasion, although only infiltration beyond sm1 remained significant in the definitive multivariate analysis. CONCLUSIONS EUS and the histopathologic features of high-grade dysplasia and early stage adenocarcinoma of the esophagus or the gastroesophageal junction can predict the presence of lymph node involvement. These data can be used to identify patients for whom local endoscopic treatment may be appropriate.

Prognostic Factors in Adenocarcinoma of the Esophagus or Gastroesophageal Junction

The incidence of adenocarcinoma of the esophagus is rising rapidly in Western Europe and North America. It is an aggressive disease with early lymphatic and hematogenous dissemination. TNM cancer staging systems predict survival on the basis of the anatomic extent of the tumor. However, the adequacy of the current TNM staging system for adenocarcinoma of the esophagus or gastroesophageal junction (GEJ) is questioned repeatedly. Numerous prognostic factors have been described, but are not included in the TNM system. This review describes clinical parameters, aspects of operative technique, response to preoperative chemoradiotherapy therapy, complications and established pathologic determinants found in the resection specimen that have a prognostic impact. Furthermore, their potential application in the clinical setting in patients with adenocarcinoma of the esophagus or GEJ is discussed. Future directions to improve staging systems are given.

Postoperative complications after esophagectomy for adenocarcinoma of the esophagus are related to timing of death due to recurrence.

Background:Esophagectomy is frequently accompanied by substantial complications with secondary disturbance of the immune system. After esophagectomy for adenocarcinoma of the distal esophagus and/or gastroesophageal junction, the majority of patients develops an early recurrence and dies within 2 years. The aim of this study was to determine the relevance of perioperative complications on the timing of death due to recurrence. Methods:A consecutive series of 351 patients who underwent esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction was reviewed. Results:Of the 351 included patients, 191 patients (54%) died due to recurrence of esophageal adenocarcinoma. Of these 191 patients, 77 (40%), 138 (72%), and 186 patients (97%) died before 12, 24, and 60 months, respectively. Multivariate Cox regression analysis demonstrated that T-stage, lymph node ratio >0.20, the presence of extracapsular lymph node involvement, but not complications were significant factors for the prediction of death due to cancer recurrence. However, in the patients who died, multivariate Cox regression analysis demonstrated that not only the presence of extracapsular lymph node involvement but also the occurrence of complications were significantly related with a shorter time interval until death due to recurrence. Conclusion:The relation between perioperative complications and cancer recurrence per se is not causal. However, postoperative complications are independently associated with the early timing of death due to cancer recurrence. A possible explanation for this phenomenon is that immunologic host factors enhance microscopic residual disease to develop more rapidly into clinically manifest recurrence.

Preoperative Prediction of the Occurrence and Severity of Complications After Esophagectomy for Cancer With Use of a Nomogram

BACKGROUND Predicting the severity of complications after esophagectomy may supply important information for both patient and surgeon. The aim of the present study was to develop a nomogram based on preoperative risk factors to predict the severity of complications in patients who undergo esophagectomy for cancer. METHODS A consecutive series of 663 patients who underwent esophagectomy between January 1993 and August 2005 was used to develop a prognostic model. The model was validated in a second group of patients who were operated between August 2005 and November 2006. Ordinal logistic regression analysis was performed to predict the severity of complications. Diverse simple and conventional preoperative risk factors were evaluated. A nomogram was developed to enhance clinical applicability. RESULTS Patients were divided into three complication categories: those who suffered from no complications (n = 197); minor complications (n = 354); and major complications (n = 112). The following predictors remained in the model after multivariate analysis: higher age (p = 0.014); cerebrovascular accident/transient ischemic attack (CVA/TIA) (p = 0.009) or myocardial infarction in the medical history (p = 0.066); lower forced expiratory volume in the first second of expiration (FEV(1)) (p = 0.030); presence of electrocardiogram-changes (p = 0.008); and more extensive surgery (p < 0.001). A nomogram based on these variables was constructed. Overall agreement between the predicted probabilities and the observed frequencies was good in the development and the validation set. CONCLUSIONS The nomogram predicts the severity of complications for individual patients and may help in informing the patient before undergoing esophagectomy for cancer and in choosing the optimal extent of surgery. When externally validated, the nomogram may play a role in risk-adjusted audit of morbidity after esophagectomy.

Extracapsular lymph node involvement in node-positive patients with adenocarcinoma of the distal esophagus or gastroesophageal junction

In adenocarcinoma of the esophagus or gastroesophageal junction, little attention has been paid to the biologic significance of extracapsular lymph node involvement (LNI). In the present study, a consecutive series of 251 patients with lymph node dissemination were reviewed. All patients underwent esophagectomy for adenocarcinoma and were prospectively followed. A total of 1562 positive lymph nodes were reexamined. Extracapsular LNI was identified in 456 lymph nodes (29%) in 166 patients (66%). Extracapsular LNI was confined to one lymph node in 63 patients (38%). The occurrence of extracapsular LNI increased significantly with the depth of invasion, presence of positive resectable truncal nodes, number of resected nodes, number of positive nodes, and lymph node ratio. The median potential follow-up period was 58 months (range, 12-143 months). In this period, 178 patients died of recurrent disease. The pattern of recurrence was comparable between patients with and without extracapsular LNI (P = 0.938). The median survival in patients with extracapsular LNI was 15 months (95% confidence interval, 12-18 months) compared with 41 months (95% confidence interval, 19-64 months) in those without extracapsular LNI (P < 0.001). Median survival of patients with 2 or more lymph nodes was 12 months (95% confidence interval, 8-15 monhts). Multivariate analysis demonstrated that T-stage, extracapsular LNI, and lymph node ratio were independent prognostic factors. The presence of extracapsular LNI identifies a subgroup with a significantly worse long-term survival. Together with the T-stage and the lymph node ratio, extracapsular LNI reflects a particularly aggressive biologic behavior and has significant prognostic potential.

Molecular Prognostic Factors in Adenocarcinoma of the Esophagus and Gastroesophageal Junction

ObjectiveThis review describes genetic and molecular changes related to adenocarcinoma of the esophagus and gastroesophageal junction (GEJ) with emphasis on prognostic value and possibilities for targeted therapy in clinical setting.Summary background dataAdenocarcinoma of the esophagus or GEJ is an aggressive disease with early lymphatic and hematogenous dissemination. Molecular pathology has revealed many molecular mechanisms of disease progression, which are related to prognosis. Some of these factors can be seen as prognostic factors per se. Better knowledge of molecular bases may lead to new paradigms, improved prognostication, early diagnosis and individually tailored therapeutic options.MethodsA review of recent English literature (1990–October 2005) concerning esophageal adenocarcinoma was performed. This review focuses on genetic and molecular changes as prognosticators of adenocarcinoma of the esophagus and GEJ.ResultsA bewildering number of biomarkers have been described. Many genes and molecules have prognostic impact (cyclin D1, EGFR, Her-2/Neu, APC, TGF-β, Endoglin, CTGF, P53, Bcl-2, NF-κB, Cox-2, E-cadherin, β-catenin, uPA, MMP-1,3,7,9, TIMP, Th1/Th2 balance, CRP, PTHrP).ConclusionsAdenocarcinomas of the esophagus and GEJ show multiple genetic alterations, which indicate that progression of cancer is a multistep complex process with many different alterations. Presumably, it is not one molecular factor that can predict the biological behavior of this cancer. The combination of diverse genetic alterations may better predict prognosis. In future, gene expression analysis with microarrays may reveal important prognostic information and the discovery of new genes and molecules associated with tumor progression and dissemination will enhance prognostication and offers adjuvant therapeutic options.

Evaluation of O-POSSUM in predicting in-hospital mortality after resection for oesophageal cancer†

The aims of the present study were to validate the Physiological and Operative Severity Score for the enUmeration of Mortality adjusted for oesophagogastric surgery (O‐POSSUM).

Prognostic nomogram for patients undergoing oesophagectomy for adenocarcinoma of the oesophagus or gastro-oesophageal junction

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.

Evidence-Based Surgical Treatment of Esophageal Cancer: Overview of High-Quality Studies

Evidence-based medicine is the conscientious, explicit, and judicious use of best available evidence in making decisions for individual patient care. The present review gives an evidence-based review of esophageal cancer surgery. The literature search was restricted to the highest level of evidence on the surgical treatment of esophageal cancer.