http://repub.eur.nl/res/aut/21477/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/27281/ 2010-10-01T00:00:00Z Background: The purpose of this study was to investigate the long-term outcome and technical feasibility of sternal resection. Methods: We performed a 25-year retrospective study of 68 patients who underwent a sternectomy for sarcoma, recurrent breast cancer (BC) or radiation-induced necrosis between 1981 and 2006 in two tertiary referral centres (Erasmus Medical Center/Daniel den Hoed Cancer Center and Netherlands Cancer Center/Antoni van Leeuwenhoek Hospital, Netherlands). Patients were treated with curative intent and followed until May 2009. Medical records were reviewed for patient characteristics, indications for surgery, surgical technique, postoperative complications, and survival. Results: Sternal resection was performed in 43 sarcoma patients, 17 recurrent BC and 8 patients with radiation-induced necrosis with additional rib resection in the majority of patients and with clavicle resection in 13% of patients. Additional scapula, lung, breast or axilla resection, or both, was performed in 10%. Two patients died postoperatively (3%). Mild complications occurred in 24%, and severe complications (namely, pulmonary complications and reinterventions) in 16% of patients. Radical resection was achieved in 80% and 53% of sarcoma and recurrent BC patients, respectively. Five-year overall survival was 64% and 40% in sarcoma and recurrent BC patients, respectively, with 5-year disease-free survivals of 52% and 15%, respectively. Conclusions: Sarcomas, recurrent BC, and radiation-induced necrosis can be successfully managed by sternal resection and reconstruction with curative intent. Low mortality and acceptable morbidity rates justify this operation in a palliative setting as well. Disease-free survival is poor among recurrent BC patients. http://repub.eur.nl/res/pub/27285/ 2010-09-01T00:00:00Z Background: This study analyzes the outcome of esophageal resection in patients 70 or more years of age, compared with patients aged less than 70 years and identifies risk factors for worse outcome in the elderly. Methods: Comorbidity, postoperative morbidity, in-hospital mortality and survival rates were compared between 811 patients aged less than 70 years and 250 patients aged 70 years or more who underwent esophagectomy for esophageal cancer in a single high-volume center from 1985 to 2005. Results: Groups were similar regarding surgical approach, resectability, and tumor stage. More patients aged 70 years or more had cardiovascular and respiratory concomitant disease. Among patients aged 70 years or more, the prevalence of adenocarcinoma and Barrett's transformation was higher (67% versus 53% for patients aged less than 70 years, and 22% versus 15%, respectively). There were no differences in surgical complications (20% versus 17%). Nonsurgical complications occurred more in patients aged 70 years or more (35% versus 27%) and operative mortality was higher among elderly patients (8.4 versus 3.8%), as was in-hospital mortality (11.6% versus 5.4%). The disease-specific 5-year survival was lower for patients aged 70 years or more (27% versus 34%). The 1-year survival, reflecting the impact of operative morbidity and mortality, was 58% for patients aged 70 years or more and 68% for the patients aged less than 70 years (p = 0.002). Among patients aged 70 years or more, respiratory comorbidity and thoracoabdominal resection were risk factors for the occurrence of nonsurgical complications and respiratory comorbidity for in-hospital mortality. Conclusions: Older patients have increased operative and in-hospital mortality and decreased 5-year survival after esophageal resection for cancer. Our results indicate that especially thoracoabdominal resection for esophageal carcinoma should be carefully considered for patients older than 70 years who suffer from respiratory disease. http://repub.eur.nl/res/pub/17955/ 2009-10-01T00:00:00Z BACKGROUND: Patients with carcinoma of the distal esophagus and metastatic celiac lymph nodes (M1a) have a poor prognosis and are often denied surgery. In this study, we evaluated our treatment strategy of chemotherapy followed by surgery in patients with M1a disease. METHODS: Thirty-eight patients who received chemotherapy for carcinoma of the distal esophagus with celiac lymph node involvement between 2000 and 2007 were identified from a prospective database. Clinical and histopathological responses to chemotherapy were analyzed and follow-up comprised review of medical charts. RESULTS: Twelve non-responding patients were not eligible for surgery. Twenty-six patients with partial responses or stable disease were operated on. The resectability rate was 96% (25/26) and tumor-free resection margins (R0) were achieved in 68% (17/25). The overall survival of patients with M1a disease was 16 months. Patients who received chemotherapy alone had a median survival of 10 months; patients who underwent additional surgery had a median survival of 26 months (log-rank P < 0.001). CONCLUSION: The overall survival of patients with carcinoma of the distal esophagus and clinical celiac lymph node involvement is poor. Tumor-free resection margins (R0) in M1a patients with clinical response to chemotherapy are likely to be achieved and contributes to prolonged survival. (c) 2009 Wiley-Liss, Inc. http://repub.eur.nl/res/pub/30339/ 2008-12-01T00:00:00Z Background. A surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases (cT1-3 N0-1 M0). A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone. Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients. We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed. The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has, however, to be proven in a randomized phase III trial. Methods/design. The CROSS trial is a multicenter, randomized phase III, clinical trial. The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer, with inclusion of 175 patients per arm. The objectives of the CROSS trial are to compare median survival rates and quality of life (before, during and after treatment), pathological responses, progression free survival, the number of R0 resections, treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma. Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis. Paclitaxel (50 mg/m2) and Carboplatin (Area-Under-Curve = 2) are administered by i.v. infusion on days 1, 8, 15, 22, and 29. External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week. After completion of the protocol, patients will be followed up every 3 months for the first year, every 6 months for the second year, and then at the end of each year until 5 years after treatment. Quality of life questionnaires will be filled out during the first year of follow-up. Discussion. This study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen. Trial registration. ISRCTN80832026. http://repub.eur.nl/res/pub/37552/ 2006-06-16T00:00:00Z Esophageal adenocarcinoma is a highly aggressive disease from which more than 80% of patients die within 5 years after diagnosis. Worldwide almost 400,000 new patients are diagnosed annually. Herewith esophageal cancer ranks eighth on the list of most common cancers, and sixth on the list of cancer mortality causes 1. More than 90% of esophageal cancers are either squamous cell carcinomas or adenocarcinomas 2. Esophageal cancer incidence has been rapidly increasing in Western Europe and the USA 3-5. This could be mainly ascribed to an increase in the rate of esophageal adenocarcinoma, which by now equals or even exceeds the rate of esophageal squamous cell carcinomas. Esophageal cancer incidence in the Netherlands is 10.2/100,000 for men and 3.2/100,000 for women with around 900 newly diagnosed patients annually 6. Adenocarcinomas of the gastric cardia and of the esophagus, commonly located in the distal esophagus, have several similarities. They show a parallel increase in incidence. Moreover, they show similarities in epidemiological and histomorphological features as well as in patterns of comorbidity 7-9. This thesis mainly deals with molecular biological aspects of adenocarcinomas of the distal esophagus and its precursor lesion, Barrett’s esophagus, but also includes work on adenocarcinomas of the gastric cardia. Adenocarcinomas from the distal third of the esophagus plus adenocarcinomas of the gastric cardia are in this thesis altogether mentioned by the description “gastro-esophageal junction (GEJ) adenocarcinomas”.