Percutaneous Hepatic Perfusion with Melphalan in Patients with Unresectable Ocular Melanoma Metastases Confined to the Liver: A Prospective Phase II Study.

BACKGROUND: Ocular melanoma is the most common primary intraocular malignancy and has a very poor prognosis once liver metastases occur. The aim of this study was to prospectively assess the efficacy and safety of percutaneous hepatic perfusion with melphalan (M-PHP) using the new second-generation (GEN 2) hemofiltration system in patients with ocular melanoma metastases confined to the liver. METHODS: Prospective, single-center, single-arm, phase II study including patients with unresectable ocular melanoma metastases confined to the liver. Treatment consisted of two M-PHP procedures at 6-8 weeks interval. Procedures were performed using the CHEMOSAT (GEN 2) system with 3 mg/kg melphalan. Primary endpoints were overall response rate (ORR) and best overall response (BOR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety. RESULTS: Sixty-four M-PHP procedures were performed in 35 patients between February 2014 and June 2017. The ORR was 72%. BOR was as follows: complete response in 3%, partial response in 69%, stable disease in 13%, and progressive disease in 16%. There was no treatment-related mortality. Fourteen serious adverse events occurred. At a median follow-up of 19.1 months (range 5.6-69.5), median OS was 19.1 months and was significantly longer in responders than in nonresponders (27.5 vs. 11.9 months, p < 0.001). The 1- and 2-year OS was 77% and 43%, respectively. PFS and hPFS were 7.6 and 11.2 months, respectively. CONCLUSIONS: M-PHP using the GEN 2 filter can achieve a high ORR and prolonged survival in patients with liver-only ocular melanoma metastases.

First-in-Human Assessment of cRGD-ZW800-1, a Zwitterionic, Integrin-Targeted, Near-Infrared Fluorescent Peptide in Colon Carcinoma.

PURPOSE: Incomplete oncologic resections and damage to vital structures during colorectal cancer surgery increases morbidity and mortality. Moreover, neoadjuvant chemoradiotherapy has become the standard treatment modality for locally advanced rectal cancer, where subsequent downstaging can make identification of the primary tumor more challenging during surgery. Near-infrared (NIR) fluorescence imaging can aid surgeons by providing real-time visualization of tumors and vital structures during surgery. EXPERIMENTAL DESIGN: We present the first-in-human clinical experience of a novel NIR fluorescent peptide, cRGD-ZW800-1, for the detection of colon cancer. cRGD-ZW800-1 was engineered to have an overall zwitterionic chemical structure and neutral charge to lower nonspecific uptake and thus background fluorescent signal. We performed a phase I study in 11 healthy volunteer as well as a phase II feasibility study in 12 patients undergoing an elective colon resection, assessing 0.005, 0.015, and 0.05 mg/kg cRGD-ZW800-1 for the intraoperative visualization of colon cancer. RESULTS: cRGD-ZW800-1 appears safe, and exhibited rapid elimination into urine after a single low intravenous dose. Minimal invasive intraoperative visualization of colon cancer through full-thickness bowel wall was possible after an intravenous bolus injection of 0.05 mg/kg at least 2 hours prior to surgery. Longer intervals between injection and imaging improved the tumor-to-background ratio. CONCLUSIONS: cRGD-ZW800-1 enabled fluorescence imaging of colon cancer in both open and minimal invasive surgeries. Further development of cRGD-ZW800-1 for widespread use in cancer surgery may be warranted given the ubiquitous overexpression of various integrins on different types of tumors and their vasculature.

Development of a national medical leadership competency framework: the Dutch approach.

BACKGROUND: The concept of medical leadership (ML) can enhance physicians' inclusion in efforts for higher quality healthcare. Despite ML's spiking popularity, only a few countries have built a national taxonomy to facilitate ML competency education and training. In this paper we discuss the development of the Dutch ML competency framework with two objectives: to account for the framework's making and to complement to known approaches of developing such frameworks. METHODS: We designed a research approach and analyzed data from multiple sources based on Grounded Theory. Facilitated by the Royal Dutch Medical Association, a group of 14 volunteer researchers met over a period of 2.5 years to perform: 1) literature review; 2) individual interviews; 3) focus groups; 4) online surveys; 5) international framework comparison; and 6) comprehensive data synthesis. RESULTS: The developmental processes that led to the framework provided a taxonomic depiction of ML in Dutch perspective. It can be seen as a canonical 'knowledge artefact' created by a community of practice and comprises of a contemporary definition of ML and 12 domains, each entailing four distinct ML competencies. CONCLUSIONS: This paper demonstrates how a new language for ML can be created in a healthcare system. The success of our approach to capture insights, expectations and demands relating leadership by Dutch physicians depended on close involvement of the Dutch national medical associations and a nationally active community of practice; voluntary work of diverse researchers and medical practitioners and an appropriate research design that used multiple methods and strategies to circumvent reverberation of established opinions and conventionalisms. IMPLICATIONS: The experiences reported here may provide inspiration and guidance for those anticipating similar work in other countries to develop a tailored approach to create a ML framework.

Fluorescence-guided tumor detection with a novel anti-EpCAM targeted antibody fragment: Preclinical validation.

Tumor-specific fluorescent imaging agents are moving towards the clinic, supporting surgeons with real-time intraoperative feedback about tumor locations. The epithelial cell adhesion molecule (EpCAM) is considered as one of the most promising tumor-specific proteins due its high overexpression on epithelial-derived cancers. This study describes the development and evaluation of EpCAM-F800, a novel fluorescent anti-EpCAM antibody fragment, for intraoperative tumor imaging. Fab production, conjugation to the fluorophore IRDye 800CW, and binding capacities were determined and validated using HPLC, spectrophotometry and cell-based assays. In vivo, dose escalation-, blocking-, pharmacokinetic- and biodistribution studies (using both fluorescence and radioactivity) were performed, next to imaging of clinically relevant orthotopic xenografts for breast and colorectal cancer. EpCAM-F800 targets EpCAM with high specificity in vitro, which was validated using in vivo blocking experiments with a 10x higher dose of unlabeled Fab. The optimal dose range for fluorescence tumor detection in mice was 1-5 nmol (52-260 µg), which corresponds to a human equivalent dose of 0.2-0.8 mg/kg. Biodistribution showed high accumulation of EpCAM-F800 in tumors and metabolizing organs. Breast and colorectal tumors could clearly be visualized within 8 h post-injection and up to 96 h, while the agent already showed homogenous tumor distribution within 4 h. The blood half-life was 4.5 h. This study describes the development and evaluation of a novel EpCAM-targeting agent and the feasibility to visualize breast and colorectal tumors by fluorescence imaging during resections. EpCAM-F800 will be translated for clinical use, considering its abundance in a broad range of tumor types.

[Intraoperative imaging using fluorescence, 5 years later]. / Intraoperatieve beeldvorming met fluorescentie, 5 jaar later.

Fluorescence imaging is a technique that uses near-infrared light combined with a fluorescent contrast agent to visualise specific tissue structures. This technique can be used to visualise vital anatomical structures, sentinel nodes, primary tumours and metastases during surgery or laparoscopic procedures. The development of various tumour-specific contrast agents has led to an increase in indications for the use of fluorescence imaging.

A practical guide for the use of indocyanine green and methylene blue in fluorescence-guided abdominal surgery.

Near-infrared (NIR) fluorescence imaging is gaining clinical acceptance over the last years and has been used for detection of lymph nodes, several tumor types, vital structures and tissue perfusion. This review focuses on NIR fluorescence imaging with indocyanine green and methylene blue for different clinical applications in abdominal surgery with an emphasis on oncology, based on a systematic literature search. Furthermore, practical information on doses, injection times, and intraoperative use are provided.

Detecting tumour-positive resection margins after oral cancer surgery by spraying a fluorescent tracer activated by gamma-glutamyltranspeptidase.

OBJECTIVES: Tumour-positive resection margins are a major problem during oral cancer surgery. gGlu-HMRG is a tracer that becomes fluorescent upon activation by gamma-glutamyltranspeptidase (GGT). This study aims to investigate the combination of gGlu-HMRG and a clinical fluorescence imaging system for the detection of tumour-positive resection margins. MATERIALS AND METHODS: The preclinical Maestro and clinical Artemis imaging systems were compared in vitro and ex vivo with cultured human head and neck cancer cells (OSC19, GGT-positive; and FaDu, GGT negative) and tumour-bearing nude mice. Subsequently, frozen sections of normal and oral cancer tissues were ex vivo sprayed with gGlu-HMRG to determine the sensitivity and specificity. Finally, resection margins of patients with suspected oral cancer were ex vivo sprayed with gGlu-HMRG to detect tumour-positive resection margins. RESULTS: Both systems could be used to detect gGlu-HMRG activation in vitro and ex vivo in GGT positive cancer cells. Sensitivity and specificity of gGlu-HMRG and the Artemis on frozen tissue samples was 80% and 87%, respectively. Seven patients undergoing surgery for suspected oral cancer were included. In three patients fluorescence was observed at the resection margin. Those margins were either tumour-positive or within 1 mm of tumour. The margins of the other patients were clear (≥8 mm). CONCLUSION: This study demonstrates the feasibility to detect tumour-positive resection margins with gGlu-HMRG and a clinical fluorescence imaging system. Applying this technique would enable intraoperative screening of the entire resection margin and allow direct re-resection in case of tumour-positivity.

Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study.

BACKGROUND: Tumour-targeted fluorescence imaging has the potential to advance current practice of oncological surgery by selectively highlighting malignant tissue during surgery. Carcinoembryonic antigen (CEA) is overexpressed in 90% of colorectal cancers and is a promising target for colorectal cancer imaging. We aimed to assess the tolerability of SGM-101, a fluorescent anti-CEA monoclonal antibody, and to investigate the feasibility to detect colorectal cancer with intraoperative fluorescence imaging. METHODS: We did an open-label, pilot study in two medical centres in the Netherlands. In the dose-escalation cohort, we included patients (aged ≥18 years) with primary colorectal cancer with increased serum CEA concentrations (upper limit of normal of ≥3 ng/mL) since diagnosis, who were scheduled for open or laparoscopic tumour resection. In the expansion cohort, we included patients (aged ≥18 years) with recurrent or peritoneal metastases of colorectal cancer, with increasing serum concentrations of CEA since diagnosis, who were scheduled for open surgical resection. We did not mask patients, investigators, or anyone from the health-care team. We assigned patients using a 3 + 3 dose design to 5 mg, 7·5 mg, or 10 mg of SGM-101 in the dose-escalation cohort. In the expansion cohort, patients received a dose that was considered optimal at that moment of the study but not higher than the dose used in the dose-escalation cohort. SGM-101 was administered intravenously for 30 min to patients 2 or 4 days before surgery. Intraoperative imaging was done to identify near-infrared fluorescent lesions, which were resected and assessed for fluorescence. The primary outcome was tolerability and safety of SGM-101, assessed before administration and continued up to 12 h after dosing, on the day of surgery, the first postoperative day, and follow-up visits at the day of discharge and the first outpatient clinic visit. Secondary outcomes were effectiveness of SGM-101 for detection of colorectal cancer, assessed by tumour-to-background ratios (TBR); concordance between fluorescent signal and tumour status of resected tissue; and diagnostic accuracy in both cohorts. This trial is registered with the Nederlands Trial Register, number NTR5673, and ClinicalTrials.gov, number NCT02973672. FINDINGS: Between January, 2016, and February, 2017, 26 patients (nine in the dose-escalation cohort and 17 in the expansion cohort) were included in this study. SGM-101 did not cause any treatment-related adverse events, although three possibly related mild adverse events were reported in three (33%) of nine patients in the dose-escalation cohort and five were reported in three (18%) of 17 patients in the expansion cohort. Five moderate adverse events were reported in three (18%) patients in the expansion cohort, but they were deemed unrelated to SGM-101. No changes in vital signs, electrocardiogram, or laboratory results were found after administration of the maximum dose of 10 mg of SGM-101 in both cohorts. A dose of 10 mg, administered 4 days before surgery, showed the highest TBR (mean TBR 6·10 [SD 0·42] in the dose-escalation cohort). In the expansion cohort, 19 (43%) of 43 lesions were detected using fluorescence imaging and were not clinically suspected before fluorescent detection, which changed the treatment strategy in six (35%) of 17 patients. Sensitivity was 98%, specificity was 62%, and accuracy of fluorescence intensity was 84% in the expansion cohort. INTERPRETATION: This study presents the first clinical use of CEA-targeted detection of colorectal cancer and shows that SGM-101 is safe and can influence clinical decision making during the surgical procedure for patients with colorectal cancer. FUNDING: Surgimab.

Intraoperative Near-Infrared Fluorescence Imaging of Multiple Pancreatic Neuroendocrine Tumors: A Case Report.

Multiple endocrine neoplasia type 1 syndrome can feature pancreatic neuroendocrine lesions that have the potential to degenerate into malignancies (pancreatic neuroendocrine tumors [PNETs]). Resection is required in selected cases and aims to cure patients and to prevent metastasis. Preoperative imaging is important to assess the number, size, and location of PNETs. However, sensitivity of preoperative imaging modalities to detect small lesions can be rather disappointing. This makes intraoperative reassessment of the pancreas crucial. Methylene blue (MB) accumulates in neuroendocrine lesions after intravenous administration. Methylene blue emits fluorescence of approximately 700 nm and can be visualized using a dedicated near-infrared (NIR) fluorescence imaging system. We present a 58-year-old male patient with multiple endocrine neoplasia type 1 syndrome and 2 lesions suspected as PNETs identified during regular follow-up. Intraoperative administration of MB allowed successful NIR fluorescence imaging of multiple lesions missed by preoperative imaging. After confirmation by intraoperative ultrasound, this new finding led to a major change in treatment: from enucleations to total pancreatectomy. Histopathologic examination confirmed that the fluorescent lesions were indeed neuroendocrine lesions ranging from microadenomas to PNETs. This case demonstrates that intraoperative assessment of neuroendocrine lesions can be improved by intraoperative NIR fluorescence imaging using MB, a safe and relatively easy technique.

The Best Approach for Laparoscopic Fluorescence Cholangiography: Overview of the Literature and Optimization of Dose and Dosing Time.

BACKGROUND: Fluorescence cholangiography using indocyanine green (ICG) can enhance orientation of bile duct anatomy during laparoscopic cholecystectomy. To ensure clear discrimination between bile ducts and liver, the fluorescence ratio between both should be sufficient. This ratio is influenced by the ICG dose and timing of fluorescence imaging. We first systematically identified all strategies for fluorescence cholangiography. Second, we aimed to optimize the dose of ICG and dosing time in a prospective clinical trial. METHODS: PubMed was searched for clinical trials studying fluorescence cholangiography. Furthermore, 28 patients planned to undergo laparoscopic cholecystectomy were divided into 7 groups, receiving different intravenous doses (5 or 10 mg ICG) at different time points (0.5, 2, 4, 6, or 24 hours prior to surgery). RESULTS: The systematic review revealed 27 trials including 1057 patients. The majority of studies used 2.5 mg administered within 1 hour before imaging. Imaging 3 to 24 hours after ICG administration was never studied. The clinical trial demonstrated that the highest bile duct-to-liver ratio was achieved 3 to 7 hours after administration of 5 mg and 5 to 25 hours after administration of 10 mg ICG. Up to 3 hours after administration of 5 mg and up to 5 hours after administration of 10 mg ICG, the liver was equally or more fluorescent than the cystic duct, resulting in a ratio ≤1.0. CONCLUSION: This study shows for the first time that the interval between ICG administration and intraoperative fluorescence cholangiography should be extended. Administering 5 mg ICG at least 3 hours before imaging is easy to implement in everyday clinical practice and results in bile duct-to-liver ratios >1.0.

Real-time near-infrared fluorescence imaging using cRGD-ZW800-1 for intraoperative visualization of multiple cancer types.

Incomplete resections and damage to critical structures increase morbidity and mortality of patients with cancer. Targeted intraoperative fluorescence imaging aids surgeons by providing real-time visualization of tumors and vital structures. This study evaluated the tumor-targeted zwitterionic near-infrared fluorescent peptide cRGD-ZW800-1 as tracer for intraoperative imaging of multiple cancer types. cRGD-ZW800-1 was validated in vitro on glioblastoma (U-87 MG) and colorectal (HT-29) cell lines. Subsequently, the tracer was tested in orthotopic mouse models with HT-29, breast (MCF-7), pancreatic (BxPC-3), and oral (OSC-19) tumors. Dose-ranging studies, including doses of 0.25, 1.0, 10, and 30 nmol, in xenograft tumor models suggest an optimal dose of 10 nmol, corresponding to a human equivalent dose of 63 µg/kg, and an optimal imaging window between 2 and 24 h post-injection. The mean half-life of cRGD-ZW800-1 in blood was 25 min. Biodistribution at 4 h showed the highest fluorescence signals in tumors and kidneys. In vitro and in vivo competition experiments showed significantly lower fluorescence signals when U-87 MG cells (minus 36%, p = 0.02) or HT-29 tumor bearing mice (TBR at 4 h 3.2 ± 0.5 vs 1.8 ± 0.4, p = 0.03) were simultaneously treated with unlabeled cRGD. cRGD-ZW800-1 visualized in vivo all colorectal, breast, pancreatic, and oral tumor xenografts in mice. Screening for off-target interactions, cRGD-ZW800-1 showed only inhibition of COX-2, likely due to binding of cRGD-ZW800-1 to integrin αVß3. Due to its recognition of various integrins, which are expressed on malignant and neoangiogenic cells, it is expected that cRGD-ZW800-1 will provide a sensitive and generic tool to visualize cancer during surgery.

Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real-time near-infrared fluorescence guidance.

BACKGROUND: Tumor recurrence after radical resection of hepatic tumors is not uncommon, suggesting that malignant lesions are missed during surgery. Intraoperative navigation using fluorescence guidance is an innovative technique enabling real-time identification of (sub)capsular liver tumors. The objective of the current study was to compare fluorescence imaging (FI) and conventional imaging modalities for laparoscopic detection of both primary and metastatic tumors in the liver. METHODS: Patients undergoing laparoscopic resection of a malignant hepatic tumor were eligible for inclusion. Patients received standard of care, including preoperative CT and/or MRI. In addition, 10 mg indocyanine green was intravenously administered 1 day prior to surgery. After introduction of the laparoscope, inspection, FI, and laparoscopic ultrasonography (LUS) were performed. Histopathological examination of resected suspect tissue was considered the gold standard. RESULTS: Twenty-two patients suspected of having hepatocellular carcinoma (n = 4), cholangiocarcinoma (n = 2) or liver metastases from colorectal carcinoma (n = 12), uveal melanoma (n = 2), and breast cancer (n = 2) were included. Two patients were excluded because their surgery was unexpectedly postponed several days. Twenty-six malignancies were resected in the remaining 20 patients. Sensitivity for various modalities was 80 % (CT), 84 % (MRI), 62 % (inspection), 86 % (LUS), and 92 % (FI), respectively. Three metastases (12 %) were identified solely by FI. All 26 malignancies could be detected by combining LUS and FI (100 % sensitivity). CONCLUSION: This study demonstrates added value of FI during laparoscopic resections of several hepatic tumors. Although larger series will be needed to confirm long-term patient outcome, the technology already aids the surgeon by providing real-time fluorescence guidance.

Targeted next-generation sequencing of FNA-derived DNA in pancreatic cancer.

To improve the diagnostic value of fine-needle aspiration (FNA)-derived material, we perform targeted next-generation sequencing (NGS) in patients with a suspect lesion of the pancreas. The NGS analysis can lead to a change in the treatment plan or supports inconclusive or uncertain cytology results. We describe the advantages of NGS using one particular patient with a recurrent pancreatic lesion 7 years after resection of a pancreatic ductal adenocarcinoma (PDAC). Our NGS analysis revealed the presence of a presumed second primary cancer in the pancreatic remnant, which led to a change in treatment: resection with curative intend instead of palliation. Additionally, NGS identified an unexpected germline CDKN2A 19-base pair deletion, which predisposed the patient to developing PDAC. Preoperative NGS analysis of FNA-derived DNA can help identify patients at risk for developing PDAC and define future therapeutic options.

Near-infrared fluorescence sentinel lymph node detection in gastric cancer: A pilot study.

AIM: To investigate feasibility and accuracy of near-infrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node (SLN) detection in gastric cancer. METHODS: A prospective, single-institution, phase I feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 mL ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE™ NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated. RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging (mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90% (70%-99%; 95%CI), which decreased by higher pT-stage (100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4 (range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients. CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified.

Intraoperative fluorescence imaging to localize tumors and sentinel lymph nodes in rectal cancer.

Tumor involvement at the resection margin remains the most important predictor for local recurrence in patients with rectal cancer. A careful description of tumor localization is therefore essential. Currently, endoscopic tattooing with ink is customary, but visibility during laparoscopic resections is limited. Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) could be an improvement. In addition to localize tumors, ICG can also be used to identify sentinel lymph nodes (SLNs). The feasibility of this new technique was explored in five patients undergoing laparoscopic low anterior resection for rectal cancer. Intraoperative tumor visualization was possible in four out of five patients. Fluorescence signal could be detected 32 ± 18 minutes after incision, while ink could be detected 42 ± 21 minutes after incision (p = 0.53). No recurrence was diagnosed within three months after surgery. Ex vivo imaging identified a mean of 4.2 ± 2.7 fluorescent lymph nodes, which were appointed SLNs. One out of a total of 83 resected lymph nodes contained a micrometastasis. This node was not fluorescent. This technical note describes the feasibility of endoscopic tattooing of rectal cancer using ICG:nanocolloid and NIR fluorescence imaging during laparoscopic resection. Simultaneous SLN mapping was also feasible, but may be less reliable due to neoadjuvant therapy.

The Gastric Band That Is Not to Be : Efficacy, Safety and Performance of the Easyband™: a Multicenter Experience.

BACKGROUND: Access port problems after laparoscopic adjustable gastric banding can be significant complications. The Easyband™ is an innovative type of gastric band, whose internal diameter can be adjusted by a telemetrically activated motor. The aim of this study was to evaluate safety, efficacy and performance of the Easyband™. METHODS: A total of 110 morbidly obese patients were prospectively enrolled. The Easyband™ was implanted laparoscopically by experienced bariatric surgeons in six different hospital locations. Patient characteristics, surgery details, postoperative weight loss, and complications were recorded. Follow-up lasted 2 years. RESULTS: Follow-up was completed by 78.2 % of the patients. Surgeons rated 71 % of each aspect of Easyband™ implantation as "easy" or "very easy". Adjustments were successful in 91 % of the attempts. One or more adverse events occurred in 79.1 % of the patients. Thirty-six serious adverse events were reported, of which 50 % was device-related. One or more functional tests failed in 20.9 % of the devices, 8.2 % passed after a repeated test. A reintervention was necessary in 15.5 % of the patients. Mean weight loss after 2 years was 24.2 ± 14.0 kg, mean excess weight loss was 46.1 ± 24 %. CONCLUSION: Excess weight loss with the Easyband™ was comparable with other gastric banding devices. Adjustment of the device was simple, non-invasive and more acceptable to patients than with a standard access port. However, a high incidence of device-related problems requiring surgical explantation occurred. The Easyband™ represents a major advance in gastric band design, but significant technical problems need to be resolved before further implants can be recommended.

Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging.

The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible to create near-infrared (NIR) fluorophores with different tissue specificities driven by their inherent chemical structures. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head and neck surgery: the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake into these glands after a single intravenous (IV) injection of 0.06 mg kg(-1) in a pig. By using a dual-channel NIR imaging system, we observed-in real time and with high sensitivity-the unambiguous distinction of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays a foundation for performing head and neck surgery with increased precision and efficiency along with potentially lower morbidity, and it provides a general strategy for developing targeted NIR fluorophores.

Current and future intraoperative imaging strategies to increase radical resection rates in pancreatic cancer surgery.

Prognosis of patients with pancreatic cancer is poor. Even the small minority that undergoes resection with curative intent has low 5-year survival rates. This may partly be explained by the high number of irradical resections, which results in local recurrence and impaired overall survival. Currently, ultrasonography is used during surgery for resectability assessment and frozen-section analysis is used for assessment of resection margins in order to decrease the number of irradical resections. The introduction of minimal invasive techniques in pancreatic surgery has deprived surgeons from direct tactile information. To improve intraoperative assessment of pancreatic tumor extension, enhanced or novel intraoperative imaging technologies accurately visualizing and delineating cancer cells are necessary. Emerging modalities are intraoperative near-infrared fluorescence imaging and freehand nuclear imaging using tumor-specific targeted contrast agents. In this review, we performed a meta-analysis of the literature on laparoscopic ultrasonography and we summarized and discussed current and future intraoperative imaging modalities and their potential for improved tumor demarcation during pancreatic surgery.

Real-time near-infrared fluorescence guided surgery in gynecologic oncology: a review of the current state of the art.

Near-infrared (NIR) fluorescence imaging has emerged as a promising complimentary technique for intraoperative visualization of tumor tissue, lymph nodes and vital structures. In this review, the current applications and future opportunities of NIR fluorescence imaging in gynecologic oncology are summarized. Several studies indicate that intraoperative sentinel lymph node identification in vulvar cancer using NIR fluorescence imaging outperforms blue dye staining and provides real-time intraoperative imaging of sentinel lymph nodes. NIR fluorescence imaging can penetrate through several millimeters of tissue, revealing structures just below the tissue surface. Hereby, iatrogenic damage to vital structures, such as the ureter or nerves may be avoided by identification using NIR fluorescence imaging. Tumor-targeted probes are currently being developed and have the potential to improve surgical outcomes of cytoreductive and staging procedures, in particular in ovarian cancer. Research in the near future will be necessary to determine whether this technology has additional value in order to facilitate the surgical procedure, reduce morbidity and improve disease-free and overall survival.