Inne H M Borel Rinkes

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (264)762.71 Total impact

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    ABSTRACT: Preoperative differentiation between malignant and benign pancreatic tumors can be difficult. Consequently, a proportion of patients undergoing pancreatoduodenectomy for suspected malignancy will ultimately have benign disease. The aim of this study was to compare preoperative clinical and diagnostic characteristics of patients with unexpected benign disease after pancreatoduodenectomy with those of patients with confirmed (pre)malignant disease.
    Pancreatology 05/2014; 13(3):S11. · 2.04 Impact Factor
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    ABSTRACT: /st>Transthoracic oesophagectomy requires prolonged one-lung ventilation causing systemic and local inflammatory responses. Application of continuous positive airway pressure (CPAP) to the collapsed lung potentially reduces pulmonary damage, hypoxia, and consequent inflammation. This randomized controlled trial studied the influence of CPAP applied to the collapsed right lung during thoracoscopic oesophagectomy on local and systemic inflammatory response. /st>Broncho-alveolar lavage fluid (BALF) from the right collapsed and left ventilated lung and serum samples were obtained during surgery from 30 patients undergoing thoracolaparoscopic oesophagectomy for cancer who were randomized for one-lung ventilation with or without CPAP applied to the collapsed right lung. Concentrations of cytokines and chemokines, in BALF and serum, were determined with Luminex. /st>Patients from the control (no CPAP) group had significantly increased concentrations of interleukin (IL)-1α, IL-1β, IL-10, tumour necrosis factor-alpha, macrophage inflammatory protein (MIP)-1α, pulmonary and activation-regulated chemokine (PARC), and IL-8 in the collapsed (right) lung when compared with patients from the CPAP group (P<0.05). The ventilated (left) lung of the control group showed increased concentrations of monocyte chemoattractant protein (MCP)-1 and MIP-1α (P<0.05). Serum concentrations of cytokines and chemokines increased during surgery, but did not differ between the control and CPAP groups. /st>A significantly lower local immune response was observed during one-lung ventilation when CPAP was applied to the collapsed lung. The findings suggest a beneficial effect of CPAP on the collapsed lung during oesophagectomy with one-lung ventilation.
    BJA British Journal of Anaesthesia 02/2014; · 4.24 Impact Factor
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    ABSTRACT: Resection of colorectal liver metastases (CRLM) is often hindered by their location close to the major hepatic vessels. So far, radiofrequency ablation for perivascular tumours was thought to be ineffective and unsafe due to either the heat sink effect or vascular thrombosis. The aim of this study was to examine whether RFA using multipolar probes could be a safe and effective option for CRLM adjacent to major hepatic vessels. Patients were treated with multipolar RFA during an open procedure using 3 simultaneously placed electrodes. In 52 consecutive patients with CRLM, 144 tumours were ablated with RFA. In 16 out of 52 (31%) patients, metastases were abutting major hepatic vessels. We examined whether perivascular location was a risk factor for local tumour progression. The relation between perivascular location and time to local tumour progression and recurrence free survival was assessed using cox-regression analysis. All patients were followed for at least 3 years after RFA unless they deceased before this time. Local tumour progression following RFA occurred in 17 out of 144 tumours (12%), of which 4 out of 21 were perivascular tumours. Tumour size was the only risk factor for local tumour progression in this study. Proximity to large vessels was neither a risk factor for local local tumour progression, nor for time to local tumour progression or recurrence free survival. This study indicates that patients with CRLM abutting any of the large hepatic vessels can be safe and effectively treated with RFA when using a multipolar system.
    The surgeon: journal of the Royal Colleges of Surgeons of Edinburgh and Ireland 01/2014; · 1.97 Impact Factor
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    ABSTRACT: To assess the impact of first recurrence location on survival following surgery of colorectal liver metastases. A total of 265 consecutive patients with colorectal liver metastases undergoing liver surgery (2000-2011) were categorized according to first site of tumor recurrence. Time to recurrence (TTR) and overall survival (OS) were determined. Uni- and multivariate analysis were performed to identify factors associated with TTR and OS. Median TTR was 1.16 years following liver resection, and 0.56 years following radiofrequency ablation (RFA). Intrahepatic recurrence following liver resection resulted in a significantly shorter median TTR compared to extrahepatic recurrence. Intrapulmonary recurrence was associated with superior survival compared to other recurrence locations. Such patterns were not observed in the RFA-treated group. Multivariate analysis identified the type of surgical treatment and extra-hepatic first-site recurrence (other than lung) as independent predictors for OS. Pre-operative chemotherapy and simultaneous intrahepatic and extrahepatic recurrence were independent predictors for both TTR and OS. Patients with intrahepatic recurrence following liver resection have a significantly shorter TTR and OS when compared to patients developing extrahepatic recurrence. Pulmonary recurrence following resection is associated with longer survival. Simultaneous intra- and extrahepatic recurrence is an independent prognostic factor for TTR and OS.
    Journal of Gastrointestinal Surgery 01/2014; · 2.36 Impact Factor
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    ABSTRACT: Background Resection of colorectal liver metastases (CRLM) is often hindered by their location close to the major hepatic vessels. So far, radiofrequency ablation for perivascular tumours was thought to be ineffective and unsafe due to either the heat sink effect or vascular thrombosis. The aim of this study was to examine whether RFA using multipolar probes could be a safe and effective option for CRLM adjacent to major hepatic vessels. Methods Patients were treated with multipolar RFA during an open procedure using 3 simultaneously placed electrodes. In 52 consecutive patients with CRLM, 144 tumours were ablated with RFA. In 16 out of 52 (31%) patients, metastases were abutting major hepatic vessels. We examined whether perivascular location was a risk factor for local tumour progression. The relation between perivascular location and time to local tumour progression and recurrence free survival was assessed using cox-regression analysis. Results All patients were followed for at least 3 years after RFA unless they deceased before this time. Local tumour progression following RFA occurred in 17 out of 144 tumours (12%), of which 4 out of 21 were perivascular tumours. Tumour size was the only risk factor for local tumour progression in this study. Proximity to large vessels was neither a risk factor for local local tumour progression, nor for time to local tumour progression or recurrence free survival. Discussion This study indicates that patients with CRLM abutting any of the large hepatic vessels can be safe and effectively treated with RFA when using a multipolar system.
    The Surgeon. 01/2014;
  • Cancer 12/2013; · 5.20 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate whether a change in the routine feeding strategy applied after pancreatoduodenectomy (PD) from nasojejunal tube (NJT) feeding to early oral feeding improved clinical outcomes. An observational cohort study was performed in 102 consecutive patients undergoing PD. In period 1 (n = 51, historical controls), the routine postoperative feeding strategy was NJT feeding. This was changed to a protocol of early oral feeding with on-demand NJT feeding in period 2 (n = 51, consecutive prospective cohort). The primary outcome was time to resumption of adequate oral intake. The baseline characteristics of study subjects in both periods were comparable. In period 1, 98% (n = 50) of patients received NJT feeding, whereas in period 2, 53% (n = 27) of patients did so [for delayed gastric empting (DGE) (n = 20) or preoperative malnutrition (n = 7)]. The time to resumption of adequate oral intake significantly decreased from 12 days in period 1 to 9 days in period 2 (P = 0.015), and the length of hospital stay shortened from 18 days in period 1 to 13 days in period 2 (P = 0.015). Overall, there were no differences in the incidences of complications of Clavien-Dindo Grade III or higher, DGE, pancreatic fistula, postoperative haemorrhage and mortality between the two periods. The introduction of an early oral feeding strategy after PD reduced the time to resumption of adequate oral intake and length of hospital stay without negatively impacting postoperative morbidity.
    HPB 12/2013; · 1.94 Impact Factor
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    ABSTRACT: To assess the contribution of hypoxia and bone marrow-derived cells to aggressive outgrowth of micrometastases after liver surgery. Liver surgery generates a microenvironment that fosters aggressive tumor recurrence. These areas are characterized by chronic hypoxia and influx of bone marrow-derived cells. The contribution of hematopoietic cell types was studied in mice lacking specific components of the immune system and in irradiated mice lacking all bone marrow-derived cells. Tumor cells were derived from colorectal cancer patients and from a metastatic tumor cell line. Hypoxia-induced changes in stem cell and differentiation marker expression, clone-forming potential, and metastatic capacity were assessed. The effect of vascular clamping on cancer stem cell (CSC) characteristics was performed in mice bearing patient-derived liver metastases. Immune cells and bone marrow-derived cells were not required for aggressive outgrowth of micrometastases in livers treated with surgery. Rather, hypoxia was sufficient to promote invasion and accelerate metastatic outgrowth. This was associated with a rapid loss of differentiation markers and increased expression of CSC markers and clone-forming capacity. Likewise, metastases residing in ischemia-reperfusion-injured liver lobes acquired CSC characteristics. Despite their renowned general resistance to chemotherapy, clone-forming CSCs were readily killed by the hypoxia-activated prodrug tirapazamine. Surgery-generated hypoxia in the liver causes rapid dedifferentiation of tumor cells into immature CSCs with high clone- and metastasis-forming capacity. The results help explain the phenomenon of aggressive local tumor recurrence after liver surgery and offer a potential strategy to kill aggressive CSCs by hypoxia-activated prodrugs.
    Annals of surgery 11/2013; · 7.90 Impact Factor
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    ABSTRACT: Rapid advances in evidence-based treatment schedules are a hallmark of modern oncology. In rare neoplastic diseases, however, clinical expertise is hard to build and evidence based on randomized trials almost impossible to collect. Gorham disease is a rare form of lymphatic proliferation accompanied by osteolysis, which usually occurs in young adults. Despite the fact that the clinical course of Gorham disease is often devastating and occasionally fatal, insights into its biological background are sparse and standardized treatment unavailable. Interestingly, recent knowledge on the mechanisms of lymphangiogenesis may help elucidate the pathophysiology of Gorham disease and lead to novel treatment targets. Here, we discuss our current understanding of Gorham disease, discuss established and emerging therapeutic strategies, and attempt to frame a treatment rationale. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 11/2013; · 2.35 Impact Factor
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    ABSTRACT: Background:Little is known about the factors that drive metastasis formation in colorectal cancer (CRC). Here, we set out to identify genes and proteins in patients with colorectal liver metastases that correlate with early disease recurrence. Such factors may predict a propensity for metastasis in earlier stages of CRC.Methods:Gene expression profiling and proteomics were used to identify differentially expressed genes/proteins in resected liver metastases that recurred within 6 months following liver surgery vs those that did not recur for >24 months. Expression of the identified genes/proteins in stage II (n=243) and III (n=176) tumours was analysed by immunohistochemistry on tissue microarrays. Correlation of protein levels with stage-specific outcome was assessed by uni- and multivariable analyses.Results:Both gene expression profiling and proteomics identified Maspin to be differentially expressed in colorectal liver metastases with early (<6 months) and prolonged (>24 months) time to recurrence. Immunohistochemical analysis of Maspin expression on tumour sections revealed that it was an independent predictor of time to recurrence (log-rank P=0.004) and CRC-specific survival (P=0.000) in stage III CRC. High Maspin expression was also correlated with mucinous differentiation. In stage II CRC patients, high Maspin expression did not correlate with survival but was correlated with a right-sided tumour location.Conclusion:High Maspin expression correlates with poor outcome in CRC after spread to the local lymph nodes. Therefore, Maspin may have a stage-specific function possibly related to tumour cell dissemination and/or metastatic outgrowth.British Journal of Cancer advance online publication, 3 September 2013; doi:10.1038/bjc.2013.489 www.bjcancer.com.
    British Journal of Cancer 09/2013; · 5.08 Impact Factor
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    ABSTRACT: Drug-resistant Cancer Stem Cells (CSCs) have been implicated in tumor recurrence following chemotherapy. However, the contribution of CSCs to drug-resistance in colorectal cancer is unclear and CSC-intrinsic drug-resistance mechanisms are ill-defined. Here, we address these issues by proteomic analysis of the secretomes of CSCs and isogenic differentiated tumor cells (DTCs) isolated from three distinct metastasized colon tumors. Mass spectrometry-based proteomics identified 1254 unique proteins in the conditioned media of the paired CSC and DTC cultures. Ingenuity Pathway Analysis revealed that proteins governing 'Cell Death' were most significantly enriched in the CSC secretome. The vast majority of these (37/43) promote cell survival. The CSC secretome is also characterized by a pro-survival Nrf2 antioxidant signature. Interestingly, proteome-maintenance networks are highly enriched in the CSC secretome. CSCs also secrete high levels of drug-metabolizing enzymes, including aldehyde dehydrogenase 1 (ALDH1A1) and bleomycin hydrolase (BLMH). We show that these enzymes cause extracellular detoxification of maphosphamide and bleomycin respectively. We conclude that colorectal CSCs are characterized by extensive survival and anti-oxidant networks, which are likely to contribute to CSC-intrinsic drug-resistance. In addition, CSCs may modulate drug responses in nearby tumor cells by detoxifying chemotherapeutic drugs in the extracellular space. Cancer stem cells are thought to play an important role in mediating drug resistance and tumor recurrence following chemotherapy. Therefore, it is important to identify the factors that are secreted by them. Our results provide novel insights into the pathways that govern the intrinsic resistance of CSCs to chemotherapy and, furthermore, demonstrate that they can also inactivate chemotherapeutic drugs in the extracellular space. A better understanding of the pathways that govern drug resistance in CSCs may help developing effective CSC-targeting drugs.
    Journal of proteomics 07/2013; · 5.07 Impact Factor
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    ABSTRACT: BACKGROUND: In patients with colorectal liver metastases (CLM) there is limited knowledge about the occurrence of radiological heterogeneity in response to chemotherapy. METHODS: A retrospective analysis was performed in the CAIRO and CAIRO II studies on the incidence of intermetastatic heterogeneity in patients with CLM and its association with survival. Mixed response (MR) was defined as >30% difference in individual lesion response, with all lesions showing a similar behaviour; true mixed response (TMR) as two lesions showing progression versus response; homogeneous response (HR) as similar behaviour of all lesions. Patients were classified according to the Response Evaluation Criteria in Solid Tumours (RECIST) categories (partial response (PR), stable disease (SD), progressive disease (PD), complete response (CR)) and then subdivided into MR and TMR in order to compare survival. RESULTS: In the CAIRO and CAIRO II studies, 140 and 150 patients with liver-only disease were identified. 73/290 (25.2%) patients showed MR, and 25/290 (8.6%) patients TMR, and 192/290 (66.2%) patients HR. Overall survival (OS) at 1-4 years was significantly higher for the homogeneous partial responders category compared to other response categories. Median OS was 22.0 months for the entire population. In the partial response category, patients with MR showed significant poorer survival compared to patients with HR (median OS 23.7 versus 36.0 months, respectively, p=0.019). Multivariate analysis identified four independent predictors for OS: serum lactate dehydrogenase (LDH) level (p=0.002), number of first-line chemotherapy cycles (p=0.001), resection of primary tumour (p=0.001) and response category (p=0.012). CONCLUSION: Radiological heterogeneity is present in approximately 35% of patients with CLM. Partial responders according to the RECIST criteria, show a significant poorer survival if classified as heterogeneous partial responder compared to homogeneous partial responders.
    European journal of cancer (Oxford, England: 1990) 05/2013; · 4.12 Impact Factor
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    ABSTRACT: BACKGROUND: A systematic preoperative evaluation to determine the individual resection strategy in patients with colorectal liver metastases (CRLM) was assessed as to its clinical value. PATIENTS AND METHODS: From 2009 to 2011, 75 patients with CRLM who were scheduled for surgery were prospectively included and received an additional preoperative systematic evaluation in the presence of a hepatobiliary radiologist and the hepatobiliary surgeon scheduled to perform the surgery. The following items were assessed in a standardized manner: lesion detection and characterization, presence of extrahepatic disease, vascular anatomy, and resection strategy. Intraoperative findings and histopathological results were prospectively recorded. RESULTS: Five out of 75 patients were not considered to be eligible for surgery due to additional findings, such as additional metastases or extrahepatic disease. Sensitivity and specificity for detection of individual CRLM were 80.9 % (95 % CI 75.7-86.1 %) and 69.1 % (95% CI 59.1-79.1 %), respectively. Radical resections were performed in 87.1 %. There was one futile laparotomy (1.4 %). CONCLUSION: In patients with colorectal liver metastases, standardized preoperative work-up, with subsequent planning of an individualized resection in a jointed meeting of a hepatobiliary radiologist and the surgeon who will perform the operation, leads to a high level of radical resections and a low number of futile laparotomies.
    Journal of Gastrointestinal Surgery 04/2013; · 2.36 Impact Factor
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    ABSTRACT: High-resolution intravital microscopy through imaging windows has become an indispensable technique for the long-term visualization of dynamic processes in living animals. Easily accessible sites such as the skin, the breast and the skull can be imaged using various different imaging windows; however, long-term imaging studies on cellular processes in abdominal organs are more challenging. These processes include colonization of the liver by metastatic tumor cells and the development of an immune response in the spleen. We have recently developed an abdominal imaging window (AIW) that allows long-term imaging of the liver, the pancreas, the intestine, the kidney and the spleen. Here we describe the detailed protocol for the optimal surgical implantation of the AIW, which takes ∼1 h, and subsequent multiphoton imaging, which takes up to 1 month.
    Nature Protocols 02/2013; 8(3):583-94. · 7.96 Impact Factor
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    ABSTRACT: High-resolution intravital microscopy through imaging windows has become an indispensable technique for the long-term visualization of dynamic processes in living animals. Easily accessible sites such as the skin, the breast and the skull can be imaged using various different imaging windows; however, long-term imaging studies on cellular processes in abdominal organs are more challenging. These processes include colonization of the liver by metastatic tumor cells and the development of an immune response in the spleen. We have recently developed an abdominal imaging window (AIW) that allows long-term imaging of the liver, the pancreas, the intestine, the kidney and the spleen. Here we describe the detailed protocol for the optimal surgical implantation of the AIW, which takes ∼1 h, and subsequent multiphoton imaging, which takes up to 1 month.
    Nature Protocol 02/2013; 8(3):583-94. · 8.36 Impact Factor
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    ABSTRACT: BACKGROUND: Current European guidelines recommend routine enteral feeding after pancreato-duodenectomy (PD), whereas American guidelines do not. The aim of this study was to determine the optimal feeding route after PD. METHODS: A systematic search was performed in PubMed, Embase and the Cochrane Library. Included were studies on feeding routes after PD that reported length of hospital stay (primary outcome). RESULTS: Of 442 articles screened, 15 studies with 3474 patients were included. Data on five feeding routes were extracted: oral diet (2210 patients), enteral nutrition via either a nasojejunal tube (NJT, 165), gastrojejunostomy tube (GJT, 52) or jejunostomy tube (JT, 623), and total parenteral nutrition (TPN, 424). Mean(s.d.) length of hospital stay was shortest in the oral diet and GJT groups (15(14) and 15(11) days respectively), followed by 19(12) days in the JT, 20(15) days in the TPN and 25(11) days in the NJT group. Normal oral intake was established most quickly in the oral diet group (mean 6(5) days), followed by 8(9) days in the NJT group. The incidence of delayed gastric emptying varied from 6 per cent (3 of 52 patients) in the GJT group to 23·2 per cent (43 of 185) in the JT group, but definitions varied widely. The overall morbidity rate ranged from 43·8 per cent (81 of 185) in the JT group to 75 per cent (24 of 32) in the GJT group. The overall mortality rate ranged from 1·8 per cent (3 of 165) in the NJT group to 5·4 per cent (23 of 424) in the TPN group. CONCLUSION: There is no evidence to support routine enteral or parenteral feeding after PD. An oral diet may be considered as the preferred routine feeding strategy after PD. Copyright © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
    British Journal of Surgery 01/2013; · 4.84 Impact Factor
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    ABSTRACT: BACKGROUND: To potentially improve outcomes in pancreatic resection, robot-assisted pancreatic surgery has been introduced. This technique has possible advantages over laparoscopic surgery, such as its affordance of three-dimensional vision and increased freedom of movement of instruments. A systematic review was performed to assess the safety and feasibility of robot-assisted pancreatic surgery. METHODS: The literature published up to 30 September 2011 was systematically reviewed, with no restrictions on publication date. Studies reporting on over five patients were included. Animal studies, studies not reporting morbidity and mortality, review articles and conference abstracts were excluded. Data were extracted and weighted means were calculated. RESULTS: A total of 499 studies were screened, after which eight cohort studies reporting on a total of 251 patients undergoing robot-assisted pancreatic surgery were retained for analysis. Weighted mean operation time was 404 ± 102 min (510 ± 107 min for pancreatoduodenectomy only). The rate of conversion was 11.0% (16.4% for pancreatoduodenectomy only). Overall morbidity was 30.7% (n = 77), most frequently involving pancreatic fistulae (n = 46). Mortality was 1.6%. Negative surgical margins were obtained in 92.9% of patients. The rate of spleen preservation in distal pancreatectomy was 87.1%. CONCLUSIONS: Robot-assisted pancreatic surgery seems to be safe and feasible in selected patients and, in left-sided resections, may increase the rate of spleen preservation. Randomized studies should compare the respective outcomes of robot-assisted, laparoscopic and open pancreatic surgery.
    HPB 01/2013; 15(1):1-10. · 1.94 Impact Factor
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    ABSTRACT: The robot-assisted transaxillary (hemi)thyroidectomy (RATT) is a new surgical technique using the da Vinci S surgery robot. This technique has recently been successfully introduced in the Netherlands. In a RATT a subcutaneous tunnel from the axilla is created to gain access to the thyroid gland. The operation is then carried out with the robot much like an open procedure. Using a RATT, a total thyroidectomy can be performed. However, surgeons at the beginning of the learning curve are advised to start with hemithyroidectomies only. The indication area consists of nodules up to three centimeters and most probably being benign. The major advantage of this technique is the prevention of a potentially disfiguring scar. The most important disadvantage of this technique is its high cost compared with the conventional procedure. In order to successfully introduce the RATT procedure, thorough preparation by both surgeons and operating room personnel is required. A proctoring program is also necessary.
    Nederlands tijdschrift voor geneeskunde 01/2013; 157(28):A5841.
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    ABSTRACT: Cell dynamics in subcutaneous and breast tumors can be studied through conventional imaging windows with intravital microscopy. By contrast, visualization of the formation of metastasis has been hampered by the lack of long-term imaging windows for metastasis-prone organs, such as the liver. We developed an abdominal imaging window (AIW) to visualize distinct biological processes in the spleen, kidney, small intestine, pancreas, and liver. The AIW can be used to visualize processes for up to 1 month, as we demonstrate with islet cell transplantation. Furthermore, we have used the AIW to image the single steps of metastasis formation in the liver over the course of 14 days. We observed that single extravasated tumor cells proliferated to form "pre-micrometastases," in which cells lacked contact with neighboring tumor cells and were active and motile within the confined region of the growing clone. The clones then condensed into micrometastases where cell migration was strongly diminished but proliferation continued. Moreover, the metastatic load was reduced by suppressing tumor cell migration in the pre-micrometastases. We suggest that tumor cell migration within pre-micrometastases is a contributing step that can be targeted therapeutically during liver metastasis formation.
    Science translational medicine 10/2012; 4(158):158ra145. · 10.76 Impact Factor
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    ABSTRACT: Background: Disease-related malnutrition is highly prevalent in hospital patients and varies from 25-40%. Early nutritional screening of patients at admission helps to improve recognition of malnourished patients to allow early interventions and enhance clinical outcomes. Method: A total of 104 preoperative surgical patients with oesophageal (34), stomach (17) or pancreatic cancer (53) were recruited in our study. The risk of malnutrition was examined using the quick-and-easy Malnutrition Universal Screening Tool (MUST). Anthropometric data and information on percent weight change over the past six months, unintentional weight loss, dietician referrals, and history of nutritional intervention were collected. Results: A total of 75% of our participants were at high malnutrition risk with a mean (±SD) percentage weight loss of 5.18 (±6.23)%, despite a mean BMI of 26.09 (±5.73) kgm-2. Participants with a significantly higher percent weight loss, unintentional weight loss, dietician referral and nutritional intervention had a higher risk of malnutrition (p.
    The Netherlands Journal of Medicine 10/2012; 70(8):365-9. · 2.38 Impact Factor

Publication Stats

3k Citations
762.71 Total Impact Points

Institutions

  • 2000–2014
    • University Medical Center Utrecht
      • Department of Surgery
      Utrecht, Utrecht, Netherlands
  • 2013
    • Hubrecht Institute
      Utrecht, Utrecht, Netherlands
  • 2012
    • University of Malaya
      • Department of Surgery
      Kuala Lumpur, Kuala Lumpur, Malaysia
  • 2008–2011
    • National and Kapodistrian University of Athens
      • Division of Surgery V
      Athens, Attiki, Greece
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 2002–2011
    • Diakonessen Hospital Utrecht
      Utrecht, Utrecht, Netherlands
  • 1995–2006
    • Leiden University Medical Centre
      • • Department of Molecular Cell Biology
      • • Department of Surgery
      Leyden, South Holland, Netherlands
  • 1997–1999
    • Erasmus MC
      • • Department of Oncological Surgery
      • • Department of Radiology
      Rotterdam, South Holland, Netherlands
    • Netherlands Cancer Institute
      • Division of Surgical Oncology
      Amsterdam, North Holland, Netherlands
  • 1992–1994
    • Massachusetts General Hospital
      • Department of Surgery
      Boston, MA, United States
    • Harvard Medical School
      • Department of Surgery
      Boston, Massachusetts, United States
  • 1991
    • Erasmus Universiteit Rotterdam
      • Department of Surgery
      Rotterdam, South Holland, Netherlands
  • 1990
    • Het Oogziekenhuis Rotterdam
      Rotterdam, South Holland, Netherlands