Adenocarcinomas of the gastro-oesophageal junction : from gene to clinic

Adenocarcinomas of the gastro-oesophageal junction are thought to arise from premalignant Barretr's epithelium. Barrett's epithelium is columnar epithelium that has replaced the normal squamous cell lining of the oesopha",ous. This metaplastic change is driven by duodeno-gastro-oesophageal reflu.'(, which leads to oesophagitis and ultimately, in some patients, to Barrett's epithelium. The development of Barrett's carcinoma involves multiple genetic changes. In PART I, the general introduction of this thesis, CHAPTER 1 reviews our current knowledge on these genetic changes involved in the progression from Barrett's oesophagus to adenocarcinoma. Over the past decades, many researchers focused on the role of cell-cell adhesion in carcinogenesis. The E-cadherin-catenin complex is thought to be the most important regulator of tight cell-cell adhesion in normal tissues, and perturbation of this complex is associated with malignancy. There is evidence that dysfunction of the E-cadherin-catenin complex also plays an important role in the pathogenesis of adenocarcinomas of the gastro-oesophageal junction. In CHAPTER 2, the literature on the role of the E-cadherin-catenin complex in human cancer and the possible clinical implications are discussed. This chapter serves as an introduction to Part IV (chapters 7-10). PART II of the thesis deals ",~th epidemiological and clinical aspects of adenocarcinomas of the gastro-oesophageal junction

Fixed Size of Enlarged Calcified Lymph Nodes in Esophageal Adenocarcinoma despite Complete Remission

Untreated malignant lymph nodes that are calcified are rare. Publications on such calcifications are restricted to case reports. We present a case of calcified lymph nodes in a patient with adenocarcinoma of the gastroesophageal junction that seemed to be nonresponsive to induction chemotherapy, as they did not decrease in size. However, on pathological examination of the resected lymph nodes no vital tumor cells could be detected anymore. Therefore, we hypothesize that a calcified lymph node is unable to shrink, even after adequate remission on induction chemotherapy. This should be taken into account when clinical decision-making depends on the change in size of an enlarged, calcified lymph node as a measure of treatment effect

Patients' Preferences for Surgical Management of Esophageal Cancer: A Discrete Choice Experiment

Background: Obtaining insight into patients' preferences is important to optimize cancer care. We investigated patients' preferences for surgical management of esophageal cancer. Methods: We conducted a discrete choice experiment among adult patients who had undergone esophagectomy for adenocarcinoma or squamous cell cancer of the esophagus. Patients' preferences were quantified with regression analysis using scenarios based on five aspects: risk of in-hospital mortality, risk of persistent symptoms, chance of 5-year survival, risk of surgical and non-surgical complications, and hospital volume of esophageal cancer surgery. Results: The response rate was 68 % (104/142). All aspects proved to influence patients' preferences (p < 0.05). Persisting gastrointestinal symptoms and 5-year survival were the most important attributes, but preferences varied between patients. On average, patients were willing to trade-off 9.5 % (CI 2.4-16.6 %) 5-year survival chance to obtain a surgical treatment with 30 % lower risk of gastrointestinal symptoms, or 8.1 % (CI 4.0-12.2 %) 5-year survival chance for being treated in a high instead of a low-volume hospital. Conclusions: Patients are willing to trade-off some 5-year survival chance to achieve an improvement in early outcomes. Given the preference heterogeneity among participants, the present study underlines the importance of a patient-tailored approach when discussing prognosis and treatment

Rising C-Reactive Protein and Procalcitonin Levels Precede Early Complications After Esophagectomy

BACKGROUND: Elective esophagectomy with gastric tube reconstruction carries a high risk for complications. Early and accurate diagnosis could improve patient management. Increased C-reactive protein (CRP) levels may be associated with any, surgical or infectious, complication and procalcitonin (PCT) specifically with infectious complications. METHODS: We measured CRP and PCT on post-operative days 0, 1, 2, and 3 in 45 consecutive patients. Complications were recorded up to 10 days post-esophagectomy. RESULTS: Twenty-eight patients developed a post-operative complication (5 surgical, 14 infectious, 9 combined surgical/infectious, including anastomotic leakage), presenting on day 3 or later. Elevated days 2 and 3 and a rise in CRP preceded the diagnosis of general or combined surgical/infectious complications (minimum area under the receiver operating characteristics curve (AUROC) 0.75, P = 0.006). Elevated day 3 PCT preceded combined complications (AUROC 0.86, P < 0.001). High day 1 and 3 PCT levels preceded anastomotic leakage (minimum AUROC 0.76, P = 0.005), as did the day 3 CRP levels and their increases (minimum AUROC 0.78, P = 0.002). CONCLUSIONS: This small study suggests that high or increasing CRP levels may precede the clinical diagnosis of general or surgical/infectious complications after esophagectomy. Elevated PCT levels may more specifically and timely precede combined surgical/infectious complications mainly associated with anastomotic leakage

Variation in Classification and Postoperative Management of Complex Appendicitis: A European Survey

Background: Data on common practice in the management of patients with complex appendicitis are scarce, especially for the adult population. Variation in the definition of complex appendicitis, indications for and the type of prolonged antibiotic prophylaxis have not been well studied yet. The aim of this study was to document current practice of the classification and postoperative management of complex appendicitis on an international level. Methods: An online survey was dispersed among practicing surgeons and surgical residents. Survey questions pertained to the definition of a complex appendicitis, indications for antibiotic prophylaxis after appendectomy, the duration, route of administration and antibiotic agents used. Results: A total of 137 survey responses were eligible for analysis. Most respondents were from Northern or Western Europe and were specialized in gastrointestinal surgery. Opinion varied substantially regarding the management of appendicitis, in particular for phlegmonous appendicitis with localized pus, gangrenous appendicitis and iatrogenic rupture of appendicitis. The most common duration of postoperative antibiotics was evenly spread over <3, 3, 5 and 7 days. Whereas most respondents indicated a combined intravenous and oral route of administration was common practice, 28% answered a completely intravenous route of administration was standard practice. Conclusion: Current practice patterns in the classification and postoperative management of complex appendicitis are highly variable