Richard van Hillegersberg

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

Are you Richard van Hillegersberg?

Claim your profile

Publications (276)830.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Efforts to improve the outcome of liver surgery by combining curative resection with chemotherapy have failed to demonstrate definite overall survival benefit. This may partly be due to the fact that these studies often involve strict inclusion criteria. Consequently, patients with a high risk profile as characterized by Fong's Clinical Risk Score ( CRS) are often underrepresented in these studies. Conceptually, this group of patients might benefit the most from chemotherapy. The present study evaluates the impact of neo- adjuvant chemotherapy in high- risk patients with primary resectable colorectal liver metastases, without extrahepatic disease. Our hypothesis is that adding neo- adjuvant chemotherapy to surgery will provide an improvement in overall survival ( OS) in patients with a high- risk profile. Methods/ Design: CHARISMA is a multicenter, randomized, phase III clinical trial. Patients will be randomized to either surgery alone ( standard treatment, arm A) or to 6 cycles of neo- adjuvant oxaliplatin- based chemotherapy, followed by surgery ( arm B). Patients must be = 18 years of age with liver metastases of histologically confirmed primary colorectal carcinoma. Patients with extrahepatic metastases are excluded. Liver metastases must be deemed primarily resectable. Only patients with a CRS of 3- 5 are eligible. The primary study endpoint is OS. Secondary endpoints are progression free survival ( PFS), quality of life, morbidity of resection, treatment response on neo- adjuvant chemotherapy, and whether CEA levels can predict treatment response. Discussion: CHARISMA is a multicenter, randomized, phase III clinical trial that will provide an answer to the question if adding neo- adjuvant chemotherapy to surgery will improve OS in a well- defined high- risk patient group with colorectal liver metastases.
    BMC Cancer 12/2015; 15(1). DOI:10.1186/s12885-015-1199-8 · 3.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: For gastric cancer patients, surgical resection with en-bloc lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has long been the preferred surgical approach worldwide. However, this procedure is associated with considerable morbidity. Several meta-analyses have shown an advantage in short-term outcomes of laparoscopic gastrectomy compared to open procedures, with similar oncologic outcomes. However, it remains unclear whether the results of these Asian studies can be extrapolated to the Western population. In this trial from the Netherlands, patients with resectable gastric cancer will be randomized to laparoscopic or open gastrectomy. The study is a non-blinded, multicenter, prospectively randomized controlled superiority trial. Patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group performance status 0, 1 or 2 are eligible to participate in the study after obtaining informed consent. Patients (n = 210) will be included in one of the ten participating Dutch centers and are randomized to either laparoscopic or open gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary outcome parameters include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life and cost-effectiveness. In this randomized controlled trial laparoscopic and open gastrectomy are compared in patients with resectable gastric cancer. It is expected that laparoscopic gastrectomy will result in a faster recovery of the patient and a shorter hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be associated with a lower postoperative morbidity, less readmissions, higher cost-effectiveness, better postoperative quality of life, but with similar mortality and oncologic outcomes, compared to open gastrectomy. The study started on 1 December 2014. Inclusion and follow-up will take 3 and 5 years respectively. Short-term results will be analyzed and published after discharge of the last randomized patient. NCT02248519.
    BMC Cancer 12/2015; 15(1):556. DOI:10.1186/s12885-015-1551-z · 3.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Resection of breast cancer liver metastases (BCLM) combined with systemic treatment is increasingly accepted as a therapeutic option; however, the potential benefit of repeat hepatectomy for recurrent BCLM is unknown. All consecutive female patients who underwent liver resection for BCLM at our center between January 1985 and December 2012 were included. Patients who had a single hepatectomy (N = 120) were compared with those who also underwent repeat hepatectomy (N = 19). Patients were selected for repeat hepatectomy based on operability and disease control. Prognostic factors of survival after repeat hepatectomy were determined. Median overall survival since first hepatectomy was 35 months, with a 3- and 5-year survival rate of 50 and 38 %, respectively. Overall survival following repeat hepatectomy was 64 and 46 % at 3 and 5 years, respectively. From the time of first hepatectomy, patients who underwent repeat hepatectomy had a better survival than those who had only one hepatectomy (95 and 84 vs. 50 and 38 % at 3 and 5 years, respectively) (p = 0.002). Median survival was 35 and 100 months, respectively, and median survival since the diagnosis of BCLM was 51 and 112 months in the single and repeat hepatectomy groups, respectively. Since the time of diagnosis, overall 3-, 5-, and 7-year survival rates were 75, 57, and 44 %, respectively, for all 139 patients. Improved overall survival after repeat hepatectomy was related to a time interval between breast cancer diagnosis and first hepatectomy of >2 years, a limited hepatectomy, solitary liver metastasis, positive progesterone receptor status, and chemotherapy following repeat hepatectomy. Patients with single BCLM at first hepatectomy had a 3- and 5-year overall survival rate of 76 and 76 % compared with 51 and 17 % in patients with multiple metastases (p = 0.023). In selected patients with BCLM, repeat hepatectomy for liver recurrence combined with systemic treatment provided survival rates comparable to those after first hepatectomy.
    Annals of Surgical Oncology 08/2015; DOI:10.1245/s10434-015-4785-8 · 3.94 Impact Factor
  • Source
    Peter S N van Rossum · Lucas Goense · Richard van Hillegersberg · Jelle P Ruurda
    European journal of cancer (Oxford, England: 1990) 07/2015; DOI:10.1016/j.ejca.2015.05.029 · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Results from the recent CROSS trial showed that neoadjuvant chemoradiotherapy (nCRT) significantly increased survival as compared to surgery alone in patients with potentially curable esophageal cancer. Furthermore, in the nCRT arm 49% of patients with a squamous cell carcinoma (SCC) and 23% of patients with an adenocarcinoma (AC) had a pathologically complete response in the resection specimen. These results provide a rationale to reconsider and study the timing and necessity of esophagectomy in (all) patients after application of the CROSS regimen. We propose a "surgery as needed" approach after completion of nCRT. In this approach, patients will undergo active surveillance after completion of nCRT. Surgical resection would be offered only to those patients in whom residual disease or a locoregional recurrence is highly suspected or proven. However, before a surgery as needed approach in oesophageal cancer patients (SANO) can be tested in a randomized controlled trial, we aim to determine the accuracy of detecting the presence or absence of residual disease after nCRT (preSANO trial). This study is set up as a prospective, single arm, multicenter, diagnostic trial. Operable patients with potentially curable SCC or AC of the esophagus or esophagogastric junction will be included. Approximately 4-6 weeks after completion of nCRT all included patients will undergo a first clinical response evaluation (CRE-I) including endoscopy with (random) conventional mucosal biopsies of the primary tumor site and of any other suspected lesions in the esophagus and radial endo-ultrasonography (EUS) for measurement of tumor thickness and area. Patients in whom no locoregional or disseminated disease can be proven by cytohistology will be offered a postponed surgical resection 6-8 weeks after CRE-I (ie, approximately 12-14 weeks after completion of nCRT). In the week preceding the postponed surgical resection, a second clinical response evaluation (CRE-II) will be planned that will include a whole body PET-CT, followed again by endoscopy with (random) conventional mucosal biopsies of the primary tumor site and any other suspected lesions in the esophagus, radial EUS for measurement of tumor thickness and area, and linear EUS plus fine needle aspiration of PET-positive lesions and/or suspected lymph nodes. The main study parameter is the correlation between the clinical response assessment during CRE-I and CRE-II and the final pathological response in the resection specimen. The first patient was enrolled on July 23, 2013, and results are expected in January 2016. If this preSANO trial shows that the presence or absence of residual tumor can be predicted reliably 6 or 12 weeks after completion of nCRT, a randomized trial comparing nCRT plus standard surgery versus chemoradiotherapy plus "surgery as needed" will be conducted (SANO trial). Netherlands Trial Register: NTR4834; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4834 (archived by Webcite at http://www.webcitation.org/6Ze7mn67B).
    06/2015; 4(2):e79. DOI:10.2196/resprot.4320
  • R J Verhage · A C Croese · R van Hillegersberg
    BJA British Journal of Anaesthesia 06/2015; 114(6):1009-10. DOI:10.1093/bja/aev130 · 4.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Open transthoracic esophagectomy is the worldwide gold standard in the treatment of resectable esophageal cancer. Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RAMIE) for esophageal cancer may be associated with reduced blood loss, shorter intensive care unit (ICU) stay, and less cardiopulmonary morbidity; however, long-term oncologic results have not been reported to date. Between June 2007 and September 2011, a total of 108 patients with potentially resectable esophageal cancer underwent RAMIE at the University Medical Centre Utrecht, with curative intent. All data were recorded prospectively. Median duration of the surgical procedure was 381 min (range 264-636). Pulmonary complications were most common and were observed in 36 patients (33 %). Median ICU stay was 1 day, and median overall postoperative hospital stay was 16 days. In-hospital mortality was 5 %. The majority of patients (78 %) presented with T3 and T4 disease, and 68 % of patients had nodal-positive disease (cN1-3). In 65 % of patients, neoadjuvant treatment (chemotherapy 57 %, chemoradiotherapy 7 %, radiotherapy 1 %) was administered, and in 103 (95 %) patients, a radical resection (R0) was achieved. The median number of lymph nodes was 26, median follow-up was 58 months, 5-year overall survival was 42 %, median disease-free survival was 21 months, and median overall survival was 29 months. Tumor recurrence occurred in 51 patients and was locoregional only in 6 (6 %) patients, systemic only in 31 (30 %) patients, and combined in 14 (14 %) patients. RAMIE was shown to be oncologically effective, with a high percentage of R0 radical resections and adequate lymphadenectomy. RAMIE provided good local control with a low percentage of local recurrence at long-term follow up.
    Annals of Surgical Oncology 05/2015; DOI:10.1245/s10434-015-4544-x · 3.94 Impact Factor
  • Source
    R D L Akkerman · L Haverkamp · P S N van Rossum · R van Hillegersberg · J P Ruurda
    [Show abstract] [Hide abstract]
    ABSTRACT: Gaining insight in long-term health-related quality of life more than 1year after oesophagectomy will assist clinical decision-making and inform patients about the long-term consequences of surgery. In this cross-sectional study, all consecutive patients who underwent oesophageal resection with gastric interposition for cancer at a tertiary referral centre between January 2007 and July 2012 were included. European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 and QLQ-OES18 were sent to all patients alive without recurrence more than 1year after surgery. The questionnaires were completed by 92 of 100 patients. Median duration of follow-up after surgery at completing the questionnaire was 36months (range: 12-75). Global quality of life scores were similar to a general population reference group (76±19 versus 78±17; p=0.26). However, patients scored significantly worse compared to the general population reference group on physical-, role-, cognitive- and social functioning (p<0.001). Neoadjuvant therapy and minimally invasive oesophagectomy were associated with significantly better health-related quality of life (HRQL) and symptom scores (p<0.05). Global HRQL more than 1year after oesophagectomy with gastric tube reconstruction is comparable to the general Dutch background population, while specific functional and symptom scores are significantly worse. Neoadjuvant therapy and minimally invasive surgery are associated with quality of life benefits in long-term survivors. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 05/2015; 366. DOI:10.1016/j.ejca.2015.05.006 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To explore the value of diffusion-weighted magnetic resonance imaging (DW-MRI) for the prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer. In 20 patients receiving nCRT for esophageal cancer DW-MRI scanning was performed before nCRT, after 8-13 fractions, and before surgery. The median tumor apparent diffusion coefficient (ADC) was determined at these three time points. The predictive potential of initial tumor ADC, and change in ADC (ΔADC) during and after treatment for pathologic complete response (pathCR) and good response were assessed. Good response was defined as pathCR or near-pathCR (tumor regression grade [TRG] 1 or 2). A pathCR after nCRT was found in 4 of 20 patients (20%), and 8 patients (40%) showed a good response to nCRT. The ΔADCduring was significantly higher in pathCR vs. non-pathCR patients (34.6%±10.7% [mean±SD] vs. 14.0%±13.1%, p=0.016), as well as in good vs. poor responders (30.5%±8.3% vs. 9.5%±12.5%, p=0.002). The ΔADCduring was predictive of residual cancer at a threshold of 29% (sensitivity of 100%, specificity of 75%, PPV of 94%, and NPV of 100%), and for poor pathologic response at a threshold of 21% (sensitivity of 82%, specificity of 100%, PPV of 100%, and NPV of 80%). In this exploratory study, the treatment-induced change in ADC during the first 2-3weeks of nCRT for esophageal cancer seemed highly predictive of histopathologic response. Larger series are warranted to verify these results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 05/2015; 115(2). DOI:10.1016/j.radonc.2015.04.027 · 4.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of Medical Genetics 05/2015; 52(6). DOI:10.1136/jmedgenet-2015-103094 · 5.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to assess the diagnostic performance of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and integrated (18)F-FDG PET-computed tomography (CT) for diagnosing recurrent esophageal cancer after initial treatment with curative intent. The PubMed, Embase and Cochrane library were systematically searched for all relevant literature using the keywords '(18)FDG PET' and 'esophageal cancer', and synonyms. Studies examining the diagnostic value of (18)F-FDG PET or integrated (18)F-FDG PET/CT, in either routine clinical follow-up or in symptomatic patients suspected of recurrent esophageal cancer were deemed eligible for inclusion. The primary outcome was the presence of recurrent esophageal cancer as determined by histopathological biopsy or clinical follow-up. Risk of bias and applicability concerns were assessed using the QUADAS-2 tool. Sensitivities and specificities of individual studies were meta-analyzed using bivariate random-effects models. Eight eligible studies were included for meta-analysis, comprising a total of 486 patients with esophageal cancer that underwent (18)F-FDG or PET/CT after previous treatment with curative intent. The quality of the included studies assessed by the QUADAS-2 tool was considered reasonable; there were few concerns with regard to the risk of bias and applicability. Integrated (18)F-FDG PET/CT and standalone (18)F-FDG PET were used in 4 and 3 studies, respectively. One other study analyzed both modalities separately. In 4 studies (18)F-FDG PET/CT was performed as part of routine follow-up, whereas in 4 other studies the diagnostic test was performed on indication during clinical follow-up. Pooled estimates of sensitivity and specificity for (18)F-FDG PET or PET/CT in diagnosing recurrent esophageal cancer were 96% (95% confidence interval [CI]: 93%-97%) and 78% (95% CI: 66%-86%), respectively. Subgroup analysis revealed no statistically significant difference in diagnostic accuracy according to type of PET-scanner (standalone PET versus integrated PET-CT) or indication of scanning (routine follow-up versus on indication). (18)F-FDG PET and PET/CT is a reliable imaging modality with a very high sensitivity and moderate specificity for detecting recurrent esophageal cancer after treatment with curative intent. The use of (18)F-FDG PET or PET/CT particularly allows for a minimal false negative rate. However, histopathological confirmation of (18)F-FDG or PET/CT suspected lesions remains required, since a considerable false positive rate is noticed. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 05/2015; DOI:10.2967/jnumed.115.155580 · 5.56 Impact Factor
  • M J D Prins · J P Ruurda · M P Lolkema · R Sitarz · F J W Kate Ten · R van Hillegersberg
    [Show abstract] [Hide abstract]
    ABSTRACT: E-cadherin, β-catenin, epidermal growth factor receptor (EGFR), neuronal cadherin (N-cadherin) and Cyclin D1 are involved in epithelial to mesenchymal transition (EMT). However, the prognostic significance of EMT markers in oesophageal adenocarcinoma (OAC) is unknown. Aim of this study was to evaluate the prognostic value of, and the association between different EMT markers in OAC. Tumour cores of 154 patients with OAC were included in a tissue microarray. Scoring criteria was based on immunohistochemical staining intensity. EMT-associated markers were expressed in OAC: reduced membranous E-cadherin and β-catenin were seen in 11.4% and 51.7%, nuclear β-catenin in 19.1% and EGFR and Cyclin D1 overexpression in 56.5% and 27.4% of tumours. Mesenchymal marker N-cadherin was not expressed in OAC. A positive correlation was seen between membranous β-catenin and E-cadherin expression (R=0.209, p=0.001) and between EGFR and Cyclin D1 (R=0.257, p=0.002). In univariate analysis, EGFR overexpression and membranous β-catenin staining were significantly associated with a poor survival (HR 2.145; 95% CI 1.429 to 3.218, p<0.001 and HR 1.665; 95% CI 1.114 to 2.488; p=0.013). However, Cyclin D1 (HR 1.092; 95% CI 0.702 to 1.698; p=0.697), nuclear β-catenin (HR 1.322; 95% CI 0.799 to 2.189; p=0.277) and E-cadherin (HR 1.012; 95% CI 0.554 to 1.851; p=0.968) were not associated with survival. In multivariate analysis, EGFR overexpression was an independent prognostic factor for poor survival (HR 1.678; 95% CI 1.055 to 2.668; p=0.029) together with T stage (HR 2.759; 95% CI 1.356 to 5.576; p=0.005). This study supports the presence of EMT in OAC. Moreover, EGFR overexpression was independently associated with a poor survival. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of clinical pathology 04/2015; DOI:10.1136/jclinpath-2015-202962 · 2.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. © 2015 International Society for Diseases of the Esophagus.
    Diseases of the Esophagus 03/2015; DOI:10.1111/dote.12347 · 2.06 Impact Factor
  • Hylke Brenkman · Richard van Hillegersberg · Sylvia van der Horst · Jelle Ruurda
    Surgery 03/2015; DOI:10.1016/j.surg.2015.01.019 · 3.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Locally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2-3 months. Several innovative local ablative therapies have been explored as new treatment options. This systematic review aims to provide an overview of the clinical outcomes of these ablative therapies. A systematic search in PubMed, Embase and the Cochrane Library was performed to identify clinical studies, published before 1 June 2014, involving ablative therapies in LAPC. Outcomes of interest were safety, survival, quality of life and pain. After screening 1037 articles, 38 clinical studies involving 1164 patients with LAPC, treated with ablative therapies, were included. These studies concerned radiofrequency ablation (RFA) (7 studies), irreversible electroporation (IRE) (4), stereotactic body radiation therapy (SBRT) (16), high-intensity focused ultrasound (HIFU) (5), iodine-125 (2), iodine-125-cryosurgery (2), photodynamic therapy (1) and microwave ablation (1). All strategies appeared to be feasible and safe. Outcomes for postoperative, procedure-related morbidity and mortality were reported only for RFA (4-22 and 0-11 per cent respectively), IRE (9-15 and 0-4 per cent) and SBRT (0-25 and 0 per cent). Median survival of up to 25·6, 20·2, 24·0 and 12·6 months was reported for RFA, IRE, SBRT and HIFU respectively. Pain relief was demonstrated for RFA, IRE, SBRT and HIFU. Quality-of-life outcomes were reported only for SBRT, and showed promising results. Ablative therapies in patients with LAPC appear to be feasible and safe. © 2014 BJS Society Ltd Published by John Wiley & Sons Ltd.
    British Journal of Surgery 02/2015; 102(3). DOI:10.1002/bjs.9716 · 5.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Perioperative epirubicin, cisplatin, and capecitabine (ECC) chemotherapy was evaluated in patients who underwent esophageal resection for adenocarcinoma of the esophagus or gastroesophageal junction (GEJ). Methods A cohort of 93 consecutive patients was analyzed. The median follow-up period was 60 months. Source data verification of adverse events was performed by two independent observers. Results All three planned preoperative chemotherapy cycles were administered to 65 patients (69.9 %). Only 27 % of the patients completed both pre- and postoperative chemotherapy. The reasons for not receiving postoperative adjuvant chemotherapy could be separated in two main problems: toxicity of the preoperative chemotherapy and postoperative problems involving difficulty in recovery and postoperative complications. Finally, 25 patients (27 %), completed three preoperative and three postoperative cycles. Grades 3 and 4 nonhematologic adverse events of preoperative chemotherapy mainly consisted of thromboembolic events (16.2 %) and cardiac complications (7.5 %). A history of cardiac and vascular disease was independently associated with discontinuation of preoperative chemotherapy and the occurrence of grade 3 or higher adverse events. Surgery was performed for 94 % of all the patients who started with ECC chemotherapy. A radical resection (R0) was achieved in 93 % of the patients. A complete pathologic response was observed in 8 % of the patients. During a median follow-up period of 60 months, the median disease-free survival time was 28 months, and the median overall survival time was 36 months. The 3-year overall survival rate was 50 %, and the 5-year overall survival rate was 42 %. Conclusion For patients with adenocarcinoma of the esophagus or GEJ, six cycles of ECC-based perioperative chemotherapy is associated with a relatively high number of adverse events. Although this toxicity did not affect the esophageal resectability rate, this regimen should be used with caution in this patient population.
    Annals of Surgical Oncology 01/2015; 22(5). DOI:10.1245/s10434-014-4120-9 · 3.94 Impact Factor
  • Source
    Leonie Haverkamp · Jelle P. Ruurda · Richard van Hillegersberg
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose. Sealing esophageal anastomoses with a sealant patch (TachoSil) containing human fibrinogen and thrombin may improve mechanical strength. The aim was to evaluate the technical feasibility of the application of a sealant patch in upper gastrointestinal surgery. Methods. In total 15 patients, 18-80 years old, undergoing thoracolaparoscopic esophagectomy with esophagogastrostomy or laparoscopic total gastrectomy with esophagojejunostomy was included. Different techniques of anastomotic TachoSil patch application were tested and recorded on video. Results. TachoSil was successfully applied to the esophagogastrostomy () and to the esophagojejunostomy (). A median of 2 (1-6) attempts was necessary to reach successful application. The median duration was 7 (3-26) minutes before successful application was accomplished. The best technique in esophagectomy was the application of TachoSil with the use of 2 cellophane sheets. For total gastrectomy, the patch was folded into a harmonica shape and wrapped around the esophagojejunostomy. Although not significant, the number of attempts and time to success showed a decreasing trend along with the increased experience. Conclusion. Application of TachoSil as a sealant of esophageal anastomoses was technically feasible. Future studies may investigate the value of TachoSil application on the prevention of anastomotic leakage.
    Gastroenterology Research and Practice 01/2015; 2015:1-6. DOI:10.1155/2015/534080 · 1.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Occasionally incurable cancer is encountered after completion of the thoracic (first) phase of a three-phase esophagectomy. The outcome of aborting the operation at this stage, leaving the mobilized thoracic esophagus in situ, is unknown. A multicenter retrospective analysis was performed of patients in whom a completely mobilized thoracic esophagus was left in situ when incurable disease was discovered intraoperatively. The occurrence of esophageal necrosis or perforation, mortality, and all other adverse events were recorded and graded by severity. Some 18 patients were included. The median admission time was 9 days. All patients had resumed oral intake at discharge, except for 1 patient who was fed through a nasojejunal tube. After the operation, the median overall survival was 2.9 months. Postoperatively, 7 patients (39%) experienced major surgical adverse events, and 11 patients (61%) had no or only minor adverse events. Major adverse events were associated with the patient's death in 6 patients (33%), within 5 to 34 days postoperatively. Esophageal perforation or ischemia developed in 4 patients (22%) and 1 patient (6%), respectively. No predictive factors could be identified. Leaving a completely mobilized thoracic esophagus in situ when incurable cancer was discovered intraoperatively was a successful strategy in more than half of the patients. However, one third experienced major adverse events leading to mortality. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of Thoracic Surgery 12/2014; 99(2). DOI:10.1016/j.athoracsur.2014.08.041 · 3.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: During thoracoscopic oesophageal surgery, we observed not previously described fascia-like structures. Description of similar structures in rectal cancer surgery was of paramount importance in improving the quality of resection. Therefore, we aimed to describe a new comprehensive concept of the surgical anatomy of the thoracic oesophagus with definition of the meso-oesophagus. We retrospectively evaluated 35 consecutive unedited videos of thoracoscopic oesophageal resections for cancer, to determine the surgical anatomy of the oesophageal fascia's vessels and lymphatic drainage. The resulting concept was validated in a prospective study, including 20 patients at three different centres. Additional confirmation was sought by a histologic study of a cadaver's thorax. A thin layer of connective tissue around the infracarinal oesophagus, involving the lymph nodes at the level of the carina, was observed during thoracoscopic esophagectomy in 32 of the 35 patients included in the retrospective study and in 19 of the 20 patients included in the prospective study. A thick fascia-like structure from the upper thoracic aperture to the lower thoracic aperture was visualized in all patients. This fascia is encountered between the descending aorta and left aspect of the infracarinal oesophagus. Above the carina it expands on both sides of the oesophagus to lateral mediastinal structures. This fascia contains oesophageal vessels, lymph vessels and nodes and nerves. The histologic study confirmed these findings. Here we described the concept of the "meso-oesophagus". Applying the description of the meso-oesophagus will create a better understanding of the oesophageal anatomy, leading to more adequate and reproducible surgery.
    Surgical Endoscopy 12/2014; DOI:10.1007/s00464-014-3972-1 · 3.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: This study was designed to define a statistically sound and clinically meaningful cutoff point for annual hospital volume for esophagectomy. Higher hospital volumes are associated with improved outcomes after esophagectomy. However, reported optimal volumes in literature vary, and minimal volume standards in different countries show considerable variation. So far, there has been no research on the noncategorical, nonlinear, volume-outcome relationship in esophagectomy. METHODS: Data were derived from the Netherlands Cancer Registry. Restricted cubic splines were used to investigate the nonlinear effects of annual hospital volume on 6 month and 2 year mortality rates. Outcomes were adjusted for year of diagnosis, case-mix, and (neo)adjuvant treatment. RESULTS: Between 1989 and 2009, 10,025 patients underwent esophagectomy for cancer in the Netherlands. Annual hospital volumes varied between 1 and 83 year, increasing over time. Increasing annual hospital volume showed a continuous, nonlinear decrease in hazard ratio (HR) for mortality along the curve. Increasing hospital volume from 20 year (baseline, HR = 1.00) to 40 and 60 year was associated with decreasing 6 month mortality, with a HR of 0.73 (95 % confidence interval (0.65-0.83) and 0.67 (0.58-0.77) respectively. Beyond 60 year, no further decrease was detected. Higher hospital volume also was associated with decreasing 2 year mortality until 50 esophagectomies year with a HR of 0.86 (0.79-0.93). CONCLUSIONS: Centralization of esophagectomy to a minimum of 20 resections/year has been effectively introduced in the Netherlands. Increasing annual hospital volume was associated with a nonlinear decrease in mortality up to 40-60 esophagectomies/year, after which a plateau was reached. This finding may guide quality improvement efforts worldwide.
    Annals of Surgical Oncology 12/2014; 21(13). DOI:10.1245/s10434-014-3873-5 · 3.94 Impact Factor

Publication Stats

3k Citations
830.26 Total Impact Points

Institutions

  • 2007–2015
    • University Medical Center Utrecht
      • • Department of Surgery
      • • Department of Gastroenterology and Hepatology
      • • Department of Pathology
      Utrecht, Utrecht, Netherlands
  • 2006–2015
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 2010
    • Orbis Medisch Centrum
      Sittard, Limburg, Netherlands
  • 2002–2003
    • Erasmus MC
      • Department of Surgery
      Rotterdam, South Holland, Netherlands
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1991–2001
    • Erasmus Universiteit Rotterdam
      • Department of Surgery
      Rotterdam, South Holland, Netherlands