G M van Dam

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (41)127.13 Total impact

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    ABSTRACT: During surgery, disease is often detected by visual inspection alone. Inherently, surgical vision is limited however to superficial contrast. In addition, the human eye can recognize anatomical structures, but it is not able to detect molecular-based features. Human vision can be enhanced via the use of targeted and nontargeted fluorescent agents, which can reveal otherwise invisible disease biomarkers. While the introduction of a new therapeutic agent into clinical use needs to undergo time- and cost-demanding processes, careful selection of lead candidates can shift the paradigm in surgical intervention. This chapter describes the development and applications of fluorescence imaging in surgery, including preclinical and clinical examples. We discuss clinical results employing targeted fluorochromes, which exemplify the potential of fluorescence molecular imaging in humans. A strategy to select best targets and facilitate clinical translation is discussed. Finally the broad possibilities and future perspectives of optical guided surgery using multispectral optoacoustic tomography (MOST) are described.
    Intraoperative Imaging and Image-Guided Therapy, Edited by Ferenc A. Jolesz, 01/2014: chapter Intraoperative Optical Imaging: pages 233-245; Springer New York., ISBN: 978-1-4614-7657-3
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    ABSTRACT: During the European Molecular Imaging Meeting (EMIM) 2013, the fluorescence-guided surgery study group held its inaugural session to discuss the clinical implementation of fluorescence-guided surgery. The general aim of this study group is to discuss and identify the steps required to successfully and safely bring intraoperative fluorescence imaging to the clinics. The focus group intends to use synergies between interested groups as a tool to address regulatory and implementation hurdles in Europe and operates within the intraoperative focus group of the World Molecular Imaging Society (WMIS) that promotes the same interests at the WMIS level. The major topics on the critical path of implementation identified within the study group were quality controls and standards for ensuring accurate imaging and the ability to compare results from different studies, regulatory affairs, and strategies to increase awareness among physicians, regulators, insurance companies, and a broader audience. These hurdles, and the possible actions discussed to overcome them, are summarized in this report. Furthermore, a number of recommendations for the future shape of the fluorescence-guided study group are discussed. A main driving conclusion remains that intraoperative imaging has great clinical potential and that many of the solutions required are best addressed with the community working together to optimally promote and accelerate the clinical implementation of fluorescence imaging towards improving surgical procedures.
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 11/2013; · 2.47 Impact Factor
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    Cancer – Cares, Treatments and Preventions., 05/2013: chapter Optical imaging applications in cancer research and treatment.; iConcept Press.., ISBN: ISBN: 978-1477554-99-9
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    ABSTRACT: BACKGROUND: In ovarian cancer, optimal cytoreductive surgery is of the utmost importance for long-term survival. The ability to visualize minuscule tumor deposits is important to ensure complete resection of the tumor. The purpose of our study was to estimate the in vivo sensitivity, specificity and diagnostic accuracy of an intra-operative fluorescence imaging system combined with a α(v)β(3)-integrin targeted near-infrared fluorescent probe. METHOD: Tumor bearing mice were injected intravenously with a fluorescent probe targeting α(v)β(3) integrins. Fluorescent spots and non-fluorescent tissue were identified and resected. Standard histopathology and fluorescence microscopy were used as gold-standard for tumor detection. RESULTS: Fifty-eight samples excised with support of intra-operative image-guided surgery were analyzed. The mean target to background ratio was 2,2 (SD 0,5). The calculated sensitivity of the imaging system was 95%, the specificity was 88% with a diagnostic accuracy of 96,5 %. CONCLUSION: Near-Infrared Image-Guided Surgery in this model has a high diagnostic accuracy and a fair target to background ratio that supports the development towards clinical translation of α(v)β(3)-integrin targeted imaging.
    Gynecologic Oncology 12/2012; · 3.93 Impact Factor
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    ABSTRACT: The ability to track microbes in real time in vivo is of enormous value for preclinical investigations in infectious disease or gene therapy research. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumours following systemic administration. Bioluminescent Imaging (BLI) represents a powerful tool for use with bacteria engineered to express reporter genes such as lux. BLI is traditionally used as a 2D modality resulting in images that are limited in their ability to anatomically locate cell populations. Use of 3D diffuse optical tomography can localize the signals but still need to be combined with an anatomical imaging modality like micro-Computed Tomography (μCT) for interpretation.In this study, the non-pathogenic commensal bacteria E. coli K-12 MG1655 and Bifidobacterium breve UCC2003, or Salmonella Typhimurium SL7207 each expressing the luxABCDE operon were intravenously (i.v.) administered to mice bearing subcutaneous (s.c) FLuc-expressing xenograft tumours. Bacterial lux signal was detected specifically in tumours of mice post i.v.-administration and bioluminescence correlated with the numbers of bacteria recovered from tissue. Through whole body imaging for both lux and FLuc, bacteria and tumour cells were co-localised. 3D BLI and μCT image analysis revealed a pattern of multiple clusters of bacteria within tumours. Investigation of spatial resolution of 3D optical imaging was supported by ex vivo histological analyses. In vivo imaging of orally-administered commensal bacteria in the gastrointestinal tract (GIT) was also achieved using 3D BLI. This study demonstrates for the first time the potential to simultaneously image multiple BLI reporter genes three dimensionally in vivo using approaches that provide unique information on spatial locations.
    PLoS ONE 01/2012; 7(1):e30940. · 3.53 Impact Factor
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    ABSTRACT: Intraoperative imaging using fluorescence is an experimental technique by which specific tissue structures can be visualised. A preoperatively administered optical contrast agent with fluorescence properties is detected during the operation using a light-sensitive camera system. Using this technique, vital anatomical structures such as blood vessels, bile ducts and ureters are rendered visible to the surgeon. The technique can also serve as a detection method for sentinel lymph nodes. Furthermore, tumour-specific fluorescent tracers are being developed to delineate tumours from surrounding tissue. The aim of this is to increase the number of radical cancer operations and reduce iatrogenic tissue damage. Currently, clinical studies are being conducted to investigate the value and feasibility of this technique for different surgical specialties.
    Nederlands tijdschrift voor geneeskunde 01/2012; 156(11):A4316.
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    ABSTRACT: Correct assessment of biliary anatomy can be documented by photographs showing the "critical view of safety" (CVS) but also by intraoperative cholangiography (IOC). Photographs of the CVS and IOC images for 63 patients were presented to three expert observers in a random and blinded fashion. The observers answered questions pertaining to whether the biliary anatomy had been conclusively documented. The CVS photographs were judged to be "conclusive" in 27%, "probable" in 35%, and "inconclusive" in 38% of the cases. The IOC images performed better and were judged to be "conclusive" in 57%, "probable" in 25%, and "inconclusive" in 18% of the cases (P < 0.001 compared with the photographs). The observers indicated that they would feel comfortable transecting the cystic duct based on the CVS photographs in 52% of the cases and based on the IOC images in 73% of the cases (P = 0.004). The interobserver agreement was moderate for both methods (kappa values, 0.4-0.5). For patients with a history of cholecystitis, both the CVS photographs and the IOC images were less frequently judged to be sufficient for transection of the cystic duct (P = 0.006 and 0.017, respectively). In this series, IOC was superior to photographs of the CVS for documentation of the biliary anatomy during laparoscopic cholecystectomy. However, both methods were judged to be conclusive only for a limited proportion of patients, especially in the case of cholecystitis. This study highlights that documenting assessment of the biliary anatomy is not as straightforward as it seems and that protocols are necessary, especially if the images may be used for medicolegal purposes. Documentation of the biliary anatomy should be addressed during training courses for laparoscopic surgery.
    Surgical Endoscopy 07/2011; 26(1):79-85. · 3.43 Impact Factor
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    ABSTRACT: This study aimed to identify safety measures practiced by Dutch surgeons during laparoscopic cholecystectomy. An electronic questionnaire was sent to all members of the Dutch Society of Surgery with a registered e-mail address. The response rate was 40.4% and 453 responses were analyzed. The distribution of the respondents with regard to type of hospital was similar to that in the general population of Dutch surgeons. The critical view of safety (CVS) technique is used by 97.6% of the surgeons. It is documented by 92.6%, mostly in the operation report (80.0%), but often augmented by photography (42.7%) or video (30.2%). If the CVS is not obtained, 50.9% of surgeons convert to the open approach, 39.1% continue laparoscopically, and 10.0% perform additional imaging studies. Of Dutch surgeons, 53.2% never perform intraoperative cholangiography (IOC), 41.3% perform it incidentally, and only 2.6% perform it routinely. A total of 105 bile duct injuries (BDIs) were reported in 14,387 cholecystectomies (0.73%). The self-reported major BDI rate (involving the common bile duct) was 0.13%, but these figures need to be confirmed in other studies. The CVS approach in laparoscopic cholecystectomy is embraced by virtually all Dutch surgeons. The course of action when CVS is not obtained varies. IOC seems to be an endangered skill as over half the Dutch surgeons never perform it and the rest perform it only incidentally.
    World Journal of Surgery 03/2011; 35(6):1235-41; discussion 1242-3. · 2.23 Impact Factor
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    ABSTRACT: Breast-conserving surgery (BCS) results in tumour-positive surgical margins in up to 40% of the patients. Therefore, new imaging techniques are needed that support the surgeon with real-time feedback on tumour location and margin status. In this study, the potential of near-infrared fluorescence (NIRF) imaging in BCS for pre- and intraoperative tumour localization, margin status assessment and detection of residual disease was assessed in tissue-simulating breast phantoms. Breast-shaped phantoms were produced with optical properties that closely match those of normal breast tissue. Fluorescent tumour-like inclusions containing indocyanine green (ICG) were positioned at predefined locations in the phantoms to allow for simulation of (i) preoperative tumour localization, (ii) real-time NIRF-guided tumour resection, and (iii) intraoperative margin assessment. Optical imaging was performed using a custom-made clinical prototype NIRF intraoperative camera. Tumour-like inclusions in breast phantoms could be detected up to a depth of 21 mm using a NIRF intraoperative camera system. Real-time NIRF-guided resection of tumour-like inclusions proved feasible. Moreover, intraoperative NIRF imaging reliably detected residual disease in case of inadequate resection. We evaluated the potential of NIRF imaging applications for BCS. The clinical setting was simulated by exploiting tissue-like breast phantoms with fluorescent tumour-like agarose inclusions. From this evaluation, we conclude that intraoperative NIRF imaging is feasible and may improve BCS by providing the surgeon with imaging information on tumour location, margin status, and presence of residual disease in real-time. Clinical studies are needed to further validate these results.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 01/2011; 37(1):32-9. · 2.56 Impact Factor
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    ABSTRACT: Disadvantages of the combined sentinel lymph node (SLN) procedure with radiocolloid and blue dye in vulvar cancer are the preoperative injections of radioactive tracer in the vulva, posing a painful burden on the patient. Intraoperative transcutaneous imaging of a peritumorally injected fluorescent tracer may lead to a one-step procedure, while maintaining high sensitivity. Aim of this pilot study was to investigate the applicability of intraoperative fluorescence imaging for SLN detection and transcutaneous lymphatic mapping in vulvar cancer. Ten patients with early stage squamous cell carcinoma of the vulva underwent the standard SLN procedure. Additionally, a mixture of 1 mL patent blue and 1 mL indocyanin green (ICG; 0.5 mg/mL) was injected immediately prior to surgery, with the patient under anesthesia. Color and fluorescence images and videos of lymph flow were acquired using a custom-made intraoperative fluorescence camera system. The distance between skin and femoral artery was determined on preoperative CT-scan as a measure for subcutaneous adipose tissue. In 10 patients, SLNs were detected in 16 groins (4 unilateral; 6 midline tumors). Transcutaneous lymphatic mapping was possible in five patients (5 of 16 groins), and was limited to lean patients, with a maximal distance between femoral artery and skin of 24 mm, as determined on CT. In total, 29 SLNs were detected by radiocolloid, of which 26 were also detected by fluorescence and 21 were blue. These first clinical results indicate that intraoperative transcutaneous lymphatic mapping using fluorescence is technically feasible in a subgroup of lean vulvar cancer patients.
    Gynecologic Oncology 11/2010; 120(2):291-5. · 3.93 Impact Factor
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    ABSTRACT: The outcome of cytoreductive surgery in patients with peritoneal carcinomatosis is influenced by incomplete resection as a result of inadequate detection of a tumor, i.e. residual disease. The future perspective of complete resection, made possible by application of intraoperative near-infrared fluorescence imaging (NIRF), led to the development and validation of a bioluminescent colorectal peritoneal carcinomatosis xenograft rat model to act as the gold standard for the evaluation of new optical imaging modalities. Twenty nude rats were inoculated intraperitoneally with 2 × 10(6) luciferase-labeled human colorectal tumor cells (HT-29-luc-D6). The peritoneal carcinomatosis index (PCI) was estimated using visual observation (PCI-VO) and VO combined with bioluminescence imaging (PCI-BLI). Subsequently, the BL images were presented, and residual tumor tissue was localized by PCI-BLI scoring and compared with the PCI-VO. BLI revealed additional tumor tissue, confirmed by HE staining, compared to VO alone in 7 out of 8 rats (p < 0.02). The developed model turned out to be suitable. The use of BLI for tumor detection was more sensitive compared to VO alone. In this model, BLI significantly detected residual disease, and therefore, BLI can be denominated as the gold standard for the evaluation of optical imaging modalities like NIRF.
    European Surgical Research 10/2010; 45(3-4):308-13. · 0.75 Impact Factor
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    ABSTRACT: Target volume definition in modern radiotherapy is based on planning computed tomography (CT). So far, 18-fluorodeoxyglucose positron emission tomography (FDG-PET) has not been included in planning modality in volume definition of esophageal cancer. This study evaluates fusion of FDG-PET and CT in patients with esophageal cancer in terms of geographic misses and inter-observer variability in volume definition. In 28 esophageal cancer patients, gross, clinical and planning tumor volumes (GTV; CTV; PTV) were defined on planning CT by three radiation oncologists. After software-based emission tomography and computed tomography (PET/CT) fusion, tumor delineations were redefined by the same radiation-oncologists. Concordance indexes (CCI's) for CT and PET/CT based GTV, CTV and PTV were calculated for each pair of observers. Incorporation of PET/CT modified tumor delineation in 17/28 subjects (61%) in cranial and/or caudal direction. Mean concordance indexes for CT-based CTV and PTV were 72 (55-86)% and 77 (61-88)%, respectively, vs. 72 (47-99)% and 76 (54-87)% for PET/CT-based CTV and PTV. Paired analyses showed no significant difference in CCI between CT and PET/CT. Combining FDG-PET and CT may improve target volume definition with less geographic misses, but without significant effects on inter-observer variability in esophageal cancer.
    Diseases of the Esophagus 08/2010; 23(6):493-501. · 1.64 Impact Factor
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    ABSTRACT: This study compares lymphatic mapping in early gastric cancer with ICG and infrared ray electronic endoscopy (IREE) to ICG alone. It examines the optimal method for intra-operative detection of metastases and shows long term follow up results. 212 patients underwent the SN procedure with IREE and peritumoural ICG injection. Evaluated parameters were detection of sentinel nodes with IREE versus ICG alone, intra-operative detection rate of lymph node (LN) metastasis with node picking versus lymphatic basin dissection (LBD) and lymphatic drainage patterns. 34 patients had LN metastases. The SN identification rate and sensitivity for IREE versus ICG alone were 99.5 versus 85.8% and 97.0 versus 48.4% respectively. Intra-operative accuracy for detecting LN metastasis was 50% with node picking versus 92.3% with LBD. LN metastases were always in the SN basin. Lymphatic invasion and T-stage were risk factors for nodal metastases. Two patients showed recurrent disease. Both had a tumour with signet cell differentiation. One patient had a T3 tumour, the other patient had a tumour with a diameter of 85 mm. The SN procedure with IREE can detect the SN and is better than ICG alone. LBD of the SN basin is required for accurate intra-operative diagnosis of metastases. LBD dissection based on IREE is a safe method of nodal dissection in patients with T1 or limited T2 tumours.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 06/2010; 36(6):552-8. · 2.56 Impact Factor
  • L Hermus, G M van Dam, C J Zeebregts
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 04/2010; · 2.92 Impact Factor
  • L Hermus, G M van Dam, C J Zeebregts
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    ABSTRACT: Treatment of carotid artery stenosis by endarterectomy or stenting can significantly reduce stroke risk. In clinical practice, indication for surgery or stenting is primarily based on the degree of stenosis, but there is growing awareness that pathophysiological features within a vulnerable plaque play a key role in predicting stroke risk. Important molecular processes associated with plaque vulnerability are inflammation, lipid accumulation, proteolysis, apoptosis, angiogenesis and thrombosis. The rapidly emerging field of molecular and functional imaging strategies allows identification of pathophysiological processes in carotid artery stenosis. We aimed to review the literature regarding the current most promising advanced imaging techniques in carotid artery disease. Various advanced imaging methods are available, such as high-resolution magnetic resonance imaging (HR-MRI), single photon emission computed tomography (SPECT), positron emission tomography (PET) and near-infrared fluorescence (NIRF). Radionuclide and fluorescent tracers that identify inflammation, apoptosis and proteolysis, such as FDG, MMP probes and Annexin A5, are promising. A combination of activity of molecular processes and detailed anatomic information can be obtained, providing a powerful tool in the identification of the vulnerable plaque. With these developments, we are entering a new era of imaging techniques in the selection of patients for carotid surgery.
    European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 02/2010; 39(2):125-33. · 2.92 Impact Factor
  • K T Buddingh, G M van Dam, L M A Crane
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    ABSTRACT: Loosely based on an old folk tale
    BMJ (online) 01/2010; 341:c6641. · 17.22 Impact Factor
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    ABSTRACT: In esophageal cancer, circumferential resection margins (CRMs) are considered to be of relevant prognostic value, but a reliable definition of tumor-free CRM is still unclear. The aim of this study was to appraise the clinical prognostic value of microscopic CRM involvement and to determine the optimal limit of CRM. To define the optimal tumor-free CRM we included 98 consecutive patients who underwent extended esophagectomy with microscopic tumor-free resection margins (R0) between 1997 and 2006. CRMs were measured in tenths of millimeters with inked lateral margins. Outcome of patients with CRM involvement was compared with a statistically comparable control group of 21 patients with microscopic positive resection margins (R1). A cutoff point of CRM at < or = 1.0 mm and > 1.0 mm appeared to be an adequate marker for survival and prognosis (both P < 0.001). The outcome in patients with CRMs < or = 1.0 and > 0 mm was equal to that in patients with CRM of 0 mm (P = 0.43). CRM involvement was an independent prognostic factor for both recurrent disease (P = 0.001) and survival (P < 0.001). Survival of patients with positive CRMs (< or = 1 mm) did not significantly differ from patients with an R1 resection (P = 0.12). Involvement of the circumferential resection margins is an independent prognostic factor for recurrent disease and survival in esophageal cancer. The optimal limit for a positive CRM is < or = 1 mm and for a free CRM is >1.0 mm. Patients with unfavorable CRM should be approached as patients with R1 resection with corresponding outcome.
    Annals of Surgical Oncology 11/2009; 17(3):812-20. · 4.12 Impact Factor
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    ABSTRACT: To study the influence of morphology of surgical meshes on the course of bacterial infection under the influence of the host immune system in an in vivo chronic bacterial infection model. The use of prosthetic meshes has increased dramatically the last decades in abdominal wall reconstructive surgery. Whereas infection is becoming a more frequent complication, attention is increasingly drawn to the influence of the surgeon's mesh choice on the course of this complication. Samples of 6 often applied surgical meshes were contaminated with a bioluminescent strain of Staphylococcus aureus and implanted subcutaneously in an immunocompetent BALB/c mouse. The intensity and the spreading of bioluminescence (ie, p/s/cm/sr) were analyzed non-invasively in vivo during a 10-day follow-up period. Over the course of infection, multifilament polypropylene and hydrophobic materials showed a significantly higher persistence of bacteria as well as spreading of infection compared to all other meshes. In contrast, infection resolved in almost all animals with a low-weight polyester mesh. The results of this study are in accordance with circumstantial evidence from limited clinical reports on infection involving surgical meshes and suggest that multifilament and hydrophobic meshes significantly increase bacterial persistence or spreading in the infected area in contrast to monofilament polypropylene and lightweight meshes. Therefore, the surgeon should consider this outcome when choosing a mesh graft for limiting infection in abdominal wall repair.
    Annals of surgery 10/2009; 251(1):133-7. · 7.90 Impact Factor
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    ABSTRACT: Many apparent healthy persons die from cardiovascular disease, despite major advances in prevention and treatment of cardiovascular disease. Traditional cardiovascular risk factors are able to predict cardiovascular events in the long run, but fail to assess current disease activity or nearby cardiovascular events. There is a clear relation between the occurrence of cardiovascular events and the presence of so-called vulnerable plaques. These vulnerable plaques are characterized by active inflammation, a thin cap and a large lipid pool. Spectroscopy is an optical imaging technique which depicts the interaction between light and tissues, and thereby shows the biochemical composition of tissues. In recent years, impressive advances have been made in spectroscopy technology and intravascular spectroscopy is able to assess the composition of plaques of interest and thereby to identify and actually quantify plaque vulnerability. This review summarizes the current evidence for spectroscopy as a measure of plaque vulnerability and discusses the potential role of intravascular spectroscopic imaging techniques.
    The international journal of cardiovascular imaging 09/2009; 26(1):111-9. · 2.15 Impact Factor
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    ABSTRACT: Inadequate surgical margins represent a high risk for adverse clinical outcome in breast-conserving therapy (BCT) for early-stage breast cancer. The majority of studies report positive resection margins in 20% to 40% of the patients who underwent BCT. This may result in an increased local recurrence (LR) rate or additional surgery and, consequently, adverse affects on cosmesis, psychological distress, and health costs. In the literature, various risk factors are reported to be associated with positive margin status after lumpectomy, which may allow the surgeon to distinguish those patients with a higher a priori risk for re-excision. However, most risk factors are related to tumor biology and patient characteristics, which cannot be modified as such. Therefore, efforts to reduce the number of positive margins should focus on optimizing the surgical procedure itself, because the surgeon lacks real-time intraoperative information on the presence of positive resection margins during breast-conserving surgery. This review presents the status of pre- and intraoperative modalities currently used in BCT. Furthermore, innovative intraoperative approaches, such as positron emission tomography, radioguided occult lesion localization, and near-infrared fluorescence optical imaging, are addressed, which have to prove their potential value in improving surgical outcome and reducing the need for re-excision in BCT.
    Annals of Surgical Oncology 08/2009; 16(10):2717-30. · 4.12 Impact Factor

Publication Stats

534 Citations
127.13 Total Impact Points

Institutions

  • 2012
    • Leiden University Medical Centre
      Leyden, South Holland, Netherlands
  • 2007–2011
    • Universitair Medisch Centrum Groningen
      • Department of Surgery
      Groningen, Groningen, Netherlands
  • 1996–2011
    • University of Groningen
      • • Department of Surgery
      • • Faculty of Medical Sciences
      Groningen, Province of Groningen, Netherlands
  • 1994
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States