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Pierre Bourgeois,1– 4 Mirela Mariana Roman,5 Justine Schweicher,6 Pauline Lavoisier,6 Philippe Maquet,6 Clarence Karler,7 Mateusz Lizewski,8 Alessandro Fouarge,8 Nicolas Cuylits,8 Véronique del Marmol,1 Olivier Leduc6 1Service of Dermatology, Hospital Erasme, Université Libre de Bruxelles, Brussels, Belgium; 2Services of Nuclear Medicine, HIS-IZZ Hospitals, Université Libre de Bruxelles, Brussels, Belgium; 3Multi-Disciplinary Clinic of Lymphology, Institute Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; 4Service of Vascular Surgery, HIS-IZZ Hospitals, Université Libre de Bruxelles, Brussels, Belgium; 5Department of Mammo-Pelvic Surgery, Institute Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; 6Unité de lympho-phlébologie, Haute Ecole Bruxelles-Brabant, Haute Ecole Robert Schuman, Brussels, Belgium; 7Department of Anesthesia-Algologia, Hospital Moliere, Université Libre de Bruxelles, Brussels, Belgium; 8Service of Plastic, Reconstructive and Aesthetic Surgery, Hospital Erasme, Université Libre de Bruxelles, Brussels, BelgiumCorrespondence: Pierre Bourgeois, Department of Dermatology, University Hospital Erasme, Université Libre de Bruxelles, 808, route de Lennik, Brussels, 1070, Belgium, Tel +32495201906, Email pierre.bourgeois@erasme.ulb.ac.beBackground: The number of people within the European population having at least one tattoo has increased notably and with it the number of tattoo-associated clinical complications. The injected inks are known to be removed by the lymphatic vessels and can be found in the draining lymph nodes.Aim of the Study: To report our observations on the lymphatic drainages seen under tattoos using near infrared fluorescence imaging of these lymphatic vessels after the injection of indocyanine green.Material and Methods: Indocyanine green was injected intradermally at the basis of the 20 tattooed area(s) in 19 subjects (nine women and ten men; mean age = 28.6). Ten subjects had only black tattoos (six upper limbs and four lower limbs), five (two upper limbs and three lower limbs) black and white tattoos and five multi-colored tattooed limbs (four lower limbs and one upper limb).Results: The imaging exams revealed alterations in eight individuals, seven of whom had tattoos on their lower limbs. Furthermore, the imaging results showed that the abnormalities might be related to the tattooed limb, the tattoo extent and colour.Conclusion: Alterations of the cutaneous lymphatic channels are frequently observed under tattooed territories. Their causal factors should be more precisely studied in future works and these lymphatic alterations should be considered in tattooed patients when using similar imaging techniques for therapeutic and surgical assessments.Keywords: tattoo, near infra-red fluorescence lymphatic imaging, indocyanine green, lymphatic, lymph vessel

Background: Axillary web syndrome (AWS) is a frequent complication after surgery for breast cancer, but its lymphatic involvement is not definitively established. Here we report the results of lymphoscintigraphic investigations in patients with AWS. Methods and Findings: We conducted a retrospective, single-center review of lymphoscintigraphic investigations performed in 46 patients with AWS that was either clinically obvious or suspected. Of this group, 23 patients had two investigations with a mean interval of 19 weeks between them (range, 6-98 weeks). Results of the lymphoscintigraphic investigations, which were performed according to a well-standardized protocol, were classified into four patterns: normal; functional lymphatic insufficiency only (no lymphatic vascular morphologic abnormality); lymphovascular blockade without collateralization; and vascular collateralization and/or dermal backflow. Of the 46 patients, on the first lymphoscintigraphic investigation, four (8.6%) had a normal pattern, seven (15.2%) had functional lymphatic insufficiency only, four (8.6%) had lymphovascular blockade without collateralization, and 31 (67.3%) had vascular collateralization and/or dermal backflow. Among patients who underwent two investigations, four of the five who had only functional lymphatic insufficiency at the first investigation had developed vascular collateralization and/or dermal backflow by the second. The three patients who had lymphovascular blockade without collateralization at the first examination had also progressed to collateralization and/or dermal backflow at the second. None of the 15 patients who initially had vascular collateralization and/or dermal backflow showed any reversal at the second examination. Conclusions: Our analysis confirms the lymphatic nature of AWS and shows the lymphoscintigraphic patterns and evolutions of the lymphatic lesions with potential therapeutic implications. The retrospective review of our database is approved by the institutional ethics committee under number 2048.

ICG with other tracers can be injected pre and/or per operatively to identify the axillary Lymph Nodes (LN) draining the breast cancer (the SLN nodes) and/or the ipsilateral arm (the ARM nodes). to evaluate the impact on this temporal variable-variation on the identification of these ARM LN. Material and methods: One hundred and nine women, who were scheduled to undergo, either lumpectomy with selective lymphadenectomy (SLN), or mammary surgery (either lumpectomy, or mastectomy) with complete axillary node dissection (CALND) for a histologically proven mammary tumor, had administered the day before the surgery one subcutaneous injection of ICG in the first interdigital space of the ipsilateral hand (pre-op subgroup (SLN=28 and CALND=15), or the same day as the surgery (per op subgroup (SLN=26 and CALND= 20). The fluorescent characteristics of the SLN and/or axillary LN were then analyzed and compared between the two subgroups.

Fluorescence imaging with indocyanine green is increasingly used during lymphedema patient management. However, to date, no guidelines exist on when it should and should not be used or how it should be performed. Our objective was to have an international panel of experts identify areas of consensus and nonconsensus in current attitudes and practices in fluorescence imaging with indocyanine green use during lymphedema surgery patient management.A 2-round Delphi study was conducted involving 18 experts in the use of fluorescence imaging during lymphatic surgery, all asked to vote on 49 statements on patient preparation and contraindications (n = 7 statements), indocyanine green dosing and administration (n = 10), fluorescence imaging uses and potential advantages (n = 16), and potential disadvantages and training needs (n = 16).Consensus ultimately was reached on 40/49 statements, including consistent consensus regarding the value of fluorescence imaging with indocyanine green in almost all facets of lymphedema patient management, including early detection, assessing disease extent, preoperative work-up, surgical planning, intraoperative guidance, monitoring short- and longer-term outcomes, quality control, and resident training. All experts felt it was very safe, while 94% felt it should be part of routine care and that indocyanine green was superior to colored dyes and ultrasound. Nonetheless, there also was consensus that limited high-quality evidence remains a barrier to its widespread use and that patients should still be provided with specific information and asked to sign specific consent for both fluorescence imaging and indocyanine green.Fluorescence imaging with or without indocyanine green appears to have several roles in lymphedema prevention, diagnosis, assessment, and treatment.

Background: Primary lower limb lymphedemas (LLLEs; not present at birth) are classified as early- and late-onset. In both groups, distal lymphangiopathy distal dermal backflow (DDB) may be observed...

Follicular thyroid cancer (FTC) is a less common form of differentiated thyroid cancer. Liver metastasis of differentiated thyroid cancer frequently occurs in the late onset of the metastatic disease, are often unrescetable and noniodine avid, leading to a poor prognosis. A 69-year-old man with a 14-year history of multi-metastatic follicular thyroid cancer was treated iteratively with 131-Iodine allowing to maintain a stable disease. Upon a recent exponential increase of the thyroglobulin, a peritoneal mass and a voluminous hepatic metastasis were discovered, comorbidities and an insufficient future remnant liver function excluded liver surgical resection. The tumour board proposed a resection of the peritoneal mass followed by selective internal radiation therapy of the liver mass. Due to the already impaired liver function, personalized dosimetry allowed a safe treatment delivering low activity to the nontumoral liver followed by a clinical and imaging response of the liver mass at 3 months. At our knowledge, this is the first case of thyroid liver metastasis treated by selective internal radiation therapy. Keywords: Liver metastasis, Personalized dosimetry, Radioembolization, Thyroid Cancer

Background: Near-infrared fluorescence imaging (NIRFI) of breast cancer (BC) after the intravenous (IV) injection of free indocyanine green (fICG) has been reported to be feasible. However, some questions remained unclarified. Objective: To evaluate the distribution of fICG in BC and the axillary lymph nodes (LNs) of women undergoing surgery with complete axillary LN dissection (CALND) and/or selective lymphadenectomy (SLN) of sentinel LNs (NCT no. 01993576 and NCT no. 02027818). Methods: An intravenous injection of fICG (0.25 mg/kg) was administered to one series of 20 women undergoing treatment with mastectomy, the day before surgery in 5 (group 1) and immediately before surgery in 15 (group 2: tumor localization, 25; and pN+ CALND, 4) as well as to another series of 20 women undergoing treatment with tumorectomy (group 3). A dedicated NIR camera was used for ex vivo fluorescence imaging of the 45 BC lesions and the LNs. Results: In group 1, two of the four BC lesions and one large pN+ LN exhibited fluorescence. In contrast, 24 of the 25 tumors in group 2 and all of the tumors in group 3 were fluorescent. The sentinel LNs were all fluorescent, as well as some of the LNs in all CALND specimens. Metastatic cells were found in the fluorescent LNs of the pN+ cases. Fluorescent BC lesions could be identified ex vivo on the surface of the lumpectomy specimen in 14 of 19 cases. Conclusions: When fICG is injected intravenously just before surgery, BC can be detected using NIRFI with high sensitivity, with metastatic axillary LNs also showing fluorescence. Such a technical approach seems promising in the management of BC and merits further investigation., SCOPUS: ar.j, info:eu-repo/semantics/published

Facial edemas not secondary to surgery and/or radiotherapy for head and neck cancer are relatively uncommon. Our aim is to report a retrospective analysis of the lymphoscintigraphic and SPECT-CT investigations obtained in patients with such facial edema. Retrospective review of exams (planar imagings in all and with SPECT-CT in 5) obtained after the subcutaneous injection of 99mTc HSA Nanosized colloids between the eyebrows in five men and seven women. Four main lymphatic pathways were identified on sequential planar imagings: para-nasal left and right and supra- ocular left and right. For eleven patients, the absence of visualization of lymphatic drainage and/or their delayed appearance correlated well with the localisation of the edematous areas. In two patients with post-traumatic and post- surgical edemas, SPECT-CT showed one deep left sided cervical lymph node (LN) in front of the first cervical vertebra. This lymphoscintigraphic approach represents a simple and valuable way to assess the lymphatic drainage pathways of the face and to establish the diagnosis of facial lymphedema.

Introduction The classical lymphoscintigraphic investigations of lower-limb lymphatic edema [LLLE] sometimes reveal either no or few lymph nodes [LNs] at the root of the limb[s] and/or in the abdomen. The aim of the present paper is to report the results of performing one additional injection at the root of the edematous limb[s] to force the visualization of the LNs and/or to demonstrate the collateral lymphatic pathways in such patients. Methods and findings We retrospectively reviewed our database and found 99 patients [44 primary LLLE with 47 limbs injected and 55 with LLLE secondary to treatments for cancer with 64 limbs injected] where such an additional injection had been performed. In the 43 LLLE patients where no LNs were seen at the end of the classical exam [15 primary LLLE and 28 secondary LLLE], the extra injection showed lymphatic drainage toward LN[s] in all except 3 and when at least one LN was seen, the injection showed lymphatic drainage in every case toward the same ipsilateral [inguinal and/or iliac] LNs [as shown by the classical injection] and/or toward additional LNs. In 40.7% of patients, we observed one or more additional lymphatic pathways: prepubic superficial lymphatic vessels [LV] crossing the midline anteriorly toward contralateral inguinal LNs in 21 [18.9%], “posterior” LV [toward contralateral inguinal LNs and/or ipsi- or contralateral lumbo-aortic and/or para-renal LNs] in 14 [12.6%], but deep LV toward the ipsilateral common iliac LNs passing between the gluteal muscles in 32 [28.8%]. Conclusion Our work pinpoints one limitation of classical bipedal radionuclide lymphangiography. In patients with primary and secondary LLLE where inguinal and/or iliac LNs cannot be seen on bipedal radionuclide lymphangiography, this additional injection reveals the true lymphonodal status and shows unexpected collateral lymphatic pathways in 40% of cases. Such information is of the utmost importance in LLLE management and its acquisition is consequently recommended in these patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Using human induced pluripotent stem cells (iPSC), recent studies have shown that the events underlying autism spectrum disorders (ASD) can occur during neonatal development. We previously analyzed the iPSC-derived pyramidal cortical neurons of a subset of patients with ASD carrying de novo heterozygous mutations in postsynaptic SHANK3 protein, in culture. We reported altered spinogenesis of those neurons. The transplantation of human iPSC-derived neuronal precursors into mouse brain represents a novel option for in vivo analysis of mutations affecting the human brain. In this study, we transplanted the neuronal precursor cells (NPC) into the cortex of newborn mice to analyze their integration and maturation at early stages of development and studied axonal projections of transplanted human neurons into adult mouse brain. We then co-transplanted NPC from a control individual and from a patient carrying a de novo heterozygous SHANK3 mutation. We observed a reduction in cell soma size of selective neuronal categories and in axonal projections at 30 days post-transplantation. In contrast to previous in vitro studies, we did not observe any alteration in spinogenesis at this early age. The humanized chimeric mouse models offer the means to analyze ASD-associated mutations further and provide the opportunity to visualize phenotypes in vivo.

Introduction: Positive margins after breast-conserving surgery (BCS) for breast cancer (BC) remain a major concern. In this study we investigate the feasibility and accuracy of indocyanine green (ICG) fluorescence imaging (FI) for the in vivo assessment of surgical margins during BCS. Materials and methods: Patients with BC admitted for BCS from October 2015 to April 2016 were proposed to be included in the present study (NCT02027818). ICG (0.25 mg/kg) was intravenously injected at induction anesthesia and ICG-FI of the surgical beds was correlated with final pathology results. Results: Fifty patients consented to participate and thirty-five patients were retained for final analysis, 15 patients having been excluded for, respectively, incomplete video records data for signal to background ratio (SBR) calculation (11) and in situ tumors (4). The final pathological assessment of 35 breast specimens identified 5 (14.7%) positive margins. Intraoperative ICG-FI revealed hyperfluorescent signals in 15 (42.9%) patients and an absence of fluorescent signals in 20 (57.1%). Median SBR in patients with involved margins was 1.8 (SD 0.7) and was 1.25 (SD 0.6) in patients with clear margins (p = 0.05). The accuracy, specificity, positive and negative predictive value of ICG-FI for breast surgical margin assessment were 71%, 60%, 29% and 100%, respectively. Conclusion: ICG-FI of BC surgical beds has a high negative predictive value for surgical margin assessment during BCS. The absence of residual fluorescence in the surgical bed of patients with fluorescent tumors predicts negative margins at final pathology and allows the surgeon to avoid further intraoperative analysis., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND Nodal staging is a major concern in colorectal cancer as it is an important prognostic factor. Several techniques that could potentially improve patient treatment and prognosis have been developed to increase the accuracy of nodal staging. Sentinel lymph node detection has been shown to accurately reflect nodal status in various tumors and has become the standard procedure in nodal staging of breast cancer and melanoma. However, in colorectal cancer, sentinel lymph node detection techniques are still controversial as the sensitivity reported in the literature varies from one study to another. Recently, indocyanine green fluorescence–guided surgery has been reported to be a useful technique for detection of macroscopic and microscopic metastatic deposits in lymph nodes after intravenous administration of indocyanine green dye. However, no studies have focused on the potential role of sentinel lymph node detection after systemic administration of indocyanine green dye, so-called systemic sentinel lymph nodes, or on the correspondence between the identification of the sentinel lymph node by standard local injection techniques and the detection of fluorescent lymph nodes with this new approach. OBJECTIVE The aim of this protocol is to validate the concept of sentinel lymph nodes identified by fluorescence imaging after intravenous injection of indocyanine green dye and to compare the sentinel lymph nodes identified by fluorescence imaging with sentinel lymph nodes detected by the standard blue dye technique. METHODS This study (SeLyNoFI; Sentinel Lymph Nodes Fluorescence Imaging) is a diagnostic, single-arm, open-label feasibility study, including patients with colorectal adenocarcinoma with or without metastatic disease who are admitted for elective colorectal resection of the primary tumor. This study evaluates the feasibility of a new approach for improving the accuracy of nodal staging using fluorescence imaging after intravenous administration of indocyanine green dye. Sensitivity, positive predictive value, and accuracy of the classical blue dye technique and of the investigatory fluorescence imaging technique will be calculated. Translational research will be proposed, if applicable. RESULTS As of June 2020, this study has been registered. Submission for ethical review is planned for September 2020. CONCLUSIONS The potential correlation between the two different approaches to detect sentinel lymph nodes offers new strategies for improving the accuracy of nodal staging in colorectal cancer. This new concept of the systemic sentinel lymph node and a greater understanding of the interactions between systemic sentinel lymph nodes and standard sentinel lymph nodes may provide important information regarding the underlying mechanism of primary tumor lymphatic drainage. The enhanced permeability and retention effect can also play a role in the fluorescence of systemic sentinel lymph nodes, especially if these lymph nodes are inflamed. In this case, we can even imagine that this new technique will highlight more instances of lymph node–positive colorectal cancer. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/17976

Background. The standard treatment of rectovaginal deep infiltrating endometriosis nodules (RVDIEN) consists in their surgical removal. RVDIEN are anatomically neovascularized. Indocyanine green (ICG) reveals vascularized structures when becoming fluorescent after exposure to near-infrared (NIR) light. This study aims to evaluate if fluorescence-guided surgery can improve the laparoscopic resection of RVDIEN, thus avoiding a rectal perforation. Materials and Methods. Patients with a symptomatic RVDIEN, scheduled for a laparoscopic rectal shaving, were enrolled in the study. Technically, the RVDIEN was targeted and removed with the help of the NIR imager device Image 1 Spies (Karl Storz GmBH & Co KG, Tuttlingen, Germany) or Visera Elite II (Olympus Europe SE & Co KG, Hamburg, Germany), after an intraoperative, intravenous injection of ICG (0.25 mg/kg). Results. Six patients underwent a fluorescence-guided laparoscopic shaving procedure for the treatment of a nonobstructive RVDIEN. Fluorescence of the RVDIEN was observed in all the patients. In one patient, once the main lesion was removed, the posterior vaginal fornix still appeared fluorescent and was removed. No intraoperative rectal perforation occurred. The postoperative hospital stay was 2 days. No postoperative rectovaginal fistula occurred within a median follow-up of 16 months (range = 2-23 months). Conclusion. In this preliminary study, fluorescence-guided laparoscopy appeared to help in separating the RVDIEN from the healthy rectal tissue, without rectal perforation. Moreover, this technique was helpful in deciding if the resection needed to be enlarged to the posterior vaginal fornix.

Aberrant, altered, or blocked lymphatic drainage may contribute to the high recurrence rate of breast cancer. Thus, an efficient evaluation of lymphatic drainage from the breasts and/or upper limbs is essential in the management of lymphedema and in ipsilateral primary or contralateral recurrent breast cancer patients. There are very few reports of lymphatic drainage to the paravertebral lymph nodes in patients with a lymphedema after breast cancer surgery with or without reconstruction.We used lymphoscintigraphy to examine lymphatic drainage in a case series.We observed five patients with upper limb and/or mammary lymphedema (after breast cancer surgery with or without reconstruction) who had lymphatic drainage from the upper limb or breast to the posterior intercostal and/or paravertebral lymph nodes. One patient also presented with nodal relapse at the time of our investigation.The cases from this study demonstrate the unusual, and mostly unrecognized, lymphatic drainage pathways toward lymph nodes, which may be at risk for further evolution of breast cancer.

A nanostructured thin film obtained from a polystyrene-block-poly(4-vinylpyridine) diblock copolymer was used as a template to produce Janus-type nanoparticles. This was achieved by functionalizing the poly(4-vinylpyridine) microdomains with a diene molecule and by cross-linking them with diiodo compounds. A poly(methacrylate) chain end-functionalized by a triazolinedione group was selectively clicked onto the top of the poly(4-vinylpyridine) microdomains. The Janus nanoparticles were then released in solution by the dissolution of the thin film in a good solvent.

Flexible portable electronic devices have attracted increasing attention during the last decade. Energy consumption of such devices is ever increasing and performing power sources, that are moreover flexible, need to be developed to seamlessly integrate into such architectures. While lithium-ion batteries appear to be the best solution to meet the power and energy requirements, their structural and mechanical considerations still need to be addressed. Here, we realize and study the impact on the electrochemical performances of carbon nanotubes (CNTs) based, current collector-free and binder-free, Li-ion battery electrodes. Multi-walled carbon nanotubes acting as a mechanical and electron conductive scaffold enable structural flexibility and good electrochemical performances. Flexible Li-ion cells made with such electrodes show promising performances while being realized through simple manufacturing approaches.

Background/Aim: Nodal staging is used in colorectal cancer (CRC) to determine which patients should receive adjuvant chemotherapy. The aim of this study was to evaluate the role of indocyanine green fluorescence imaging (ICG-FI) in sentinel lymph node (SLN) detection compared to the standard technique. Materials and Methods: Twenty patients with CRC admitted for elective colectomy were included (NCT01995591). Ex vivo SLN detection was performed using patent blue (PB) and free ICG injected around the tumor. Results: Identification rates were 95% (19/20) for both techniques. Sensitivity was 43% for PB and 57% for ICG. Correlation between the techniques was 83%. FI was more sensitive in patients with body mass index (BMI) >25 kg/m2. Serial section analysis did not allow for up-staging of patients. Conclusion: The use of ICG-FI is superior to the blue dye technique in patients with a BMI >25 kg/m2. However, the sensitivity of ICG-FI in SLN detection remains low, with a high rate of false-negative results.

Background and Objectives: The aim of this study was to investigate the potential role of indocyanine green (ICG) fluorescence imaging after intraoperative intravenous (IV) injection for the “ex vivo” detection of metastatic lymph nodes (mLNs) of colorectal cancer origin. Methods: Fresh-fixed LNs in cassettes and/or paraffin-embedded LNs of patients included in a study that evaluated the role of ICG in the detection of peritoneal metastases of colorectal origin (Protocol NCT-01995591) were further explored with a dedicated near-infrared camera system for their fluorescence. An IV injection of ICG was delivered intraoperatively at 0.25 mg/kg. Signal to background ratios (SBRs) were calculated. Results: LNs on operative specimens were evaluated for 12 patients (5 males, 7 females). A total of 182 LNs were analyzed. The mean LN number per patient was 15.2 (median: 15.5; range 3–22). SBRs of mLNs were significantly more fluorescent than benign LNs, 1.41 versus 1.04 arbitrary units (P 20 mm2) (P

Background We examined time trends in axilla management among patients with early breast cancer in European clinical settings. Material and methods EUROCANPlatform partners, including population-based and cancer center-specific registries, provided routinely available clinical cancer registry data for a comparative study of axillary management trends among patients with first non-metastatic breast cancer who were not selected for neoadjuvant therapy during the last decade. We used an additional short questionnaire to compare clinical care patterns in 2014. Results Patients treated in cancer centers were younger than population-based registry populations. Tumor size and lymph node status distributions varied little between settings or over time. In 2003, sentinel lymph node biopsy (SLNB) use varied between 26% and 81% for pT1 tumors, and between 2% and 68% for pT2 tumors. By 2010, SLNB use increased to 79–96% and 49–92% for pT1 and pT2 tumors, respectively. Axillary lymph node dissection (ALND) use for pT1 tumors decreased from between 75% and 27% in 2003 to 47% and 12% in 2010, and from between 90% and 55% to 79% and 19% for pT2 tumors, respectively. In 2014, important differences in axillary management existed for patients with micrometastases only, and for patients fulfilling the ACOSOG Z0011 criteria for omitting ALND. Conclusion This study demonstrates persisting differences in important aspects of axillary management throughout the recent decade. The results highlight the need for international comparative patterns of care studies in oncology, which may help to identify areas where further studies and consensus building may be necessary.

Background Indocyanine green (ICG) has not been studied during therapeutic lymph node dissections after intravenous injection. The purpose of this study was to explore the distribution of ICG in lymphatic nodes during neck dissection. Methods Eleven patients requiring neck dissection with or without resection of the primary lesion were included. ICG was intravenously injected at induction time of anesthesia. Imaging was performed before and after surgical resection. Fluorescence was measured in arbitrary units (AUs) in the pathology department. Mixed linear model and generalized estimating equations (GEEs) were used. Results Mean fluorescence of invaded nodes was 22.6 AUs (SD = 24.9) and 3.9 AUs (SD = 8.1) in negative nodes (p = .016). After adjustment for the size of the node, the risk of invasion when fluorescence was observed was 12.2 (95% confidence interval [CI] = 5.3–28.2; p < .0001). Conclusion This study demonstrates the feasibility of ICG to bring a contrast during surgery between healthy and invaded nodes after i.v. injection. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

An efficient evaluation of the lymphatic drainage from the breasts (thoracic wall) and/or the upper limbs is essential in the management of patients with breast cancer (BC) and/or BC-related lymphedema. Lymphoscintigraphy was performed in 2 patients with lymphedema. Lymphatic drainage was observed from the upper limb or breast to the posterior paravertebral and/or pararenal lymph nodes. The cases demonstrate lymphatic drainage pathways toward unusual and mostly unrecognized lymph nodes, which may be at risk for further evolution of BC and may be important for the physical treatment of BC-related lymphedema.

Background: Nodal staging is a major concern in colorectal cancer as it is an important prognostic factor. Several techniques that could potentially improve patient treatment and prognosis have been developed to increase the accuracy of nodal staging. Sentinel lymph node detection has been shown to accurately reflect nodal status in various tumors and has become the standard procedure in nodal staging of breast cancer and melanoma. However, in colorectal cancer, sentinel lymph node detection techniques are still controversial as the sensitivity reported in the literature varies from one study to another. Recently, indocyanine green fluorescence–guided surgery has been reported to be a useful technique for detection of macroscopic and microscopic metastatic deposits in lymph nodes after intravenous administration of indocyanine green dye. However, no studies have focused on the potential role of sentinel lymph node detection after systemic administration of indocyanine green dye, so-called systemic sentinel lymph nodes, or on the correspondence between the identification of the sentinel lymph node by standard local injection techniques and the detection of fluorescent lymph nodes with this new approach. Objective: The aim of this protocol is to validate the concept of sentinel lymph nodes identified by fluorescence imaging after intravenous injection of indocyanine green dye and to compare the sentinel lymph nodes identified by fluorescence imaging with sentinel lymph nodes detected by the standard blue dye technique. Methods: This study (SeLyNoFI; Sentinel Lymph Nodes Fluorescence Imaging) is a diagnostic, single-arm, open-label feasibility study, including patients with colorectal adenocarcinoma with or without metastatic disease who are admitted for elective colorectal resection of the primary tumor. This study evaluates the feasibility of a new approach for improving the accuracy of nodal staging using fluorescence imaging after intravenous administration of indocyanine green dye. Sensitivity, positive predictive value, and accuracy of the classical blue dye technique and of the investigatory fluorescence imaging technique will be calculated. Translational research will be proposed, if applicable. Results: As of June 2020, this study has been registered. Submission for ethical review is planned for September 2020. Conclusions: The potential correlation between the two different approaches to detect sentinel lymph nodes offers new strategies for improving the accuracy of nodal staging in colorectal cancer. This new concept of the systemic sentinel lymph node and a greater understanding of the interactions between systemic sentinel lymph nodes and standard sentinel lymph nodes may provide important information regarding the underlying mechanism of primary tumor lymphatic drainage. The enhanced permeability and retention effect can also play a role in the fluorescence of systemic sentinel lymph nodes, especially if these lymph nodes are inflamed. In this case, we can even imagine that this new technique will highlight more instances of lymph node–positive colorectal cancer., SCOPUS: ar.j, info:eu-repo/semantics/published

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Background and objectives: The aim of this study was to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the ex vivo detection of metastatic lymph nodes (LNs) in advanced stage ovarian cancer (AOC). Methods: Paraffin-embedded LNs from patients included in a previous ICG-FI study (Protocol NCT01834469) were further assessed for fluorescence. Intravenous injection of ICG was delivered intraoperatively. Tumor-to-background ratios (TBRs) were calculated. Results: A total of 675 LNs from 19 patients were analyzed. The mean LN number per patient was 29.3 (median: 24; range 2-77). Seventy-three LNs were malignant (10.8%), 602 were benign (89.2%). The mean TBR of all LNs was 1.5 (SD 0.8). With a cut-off TBR of 1.3, the sensitivity, specificity, positive predictive, and negative predictive values of ICG-FI for retroperitoneal LNs were 80%, 41%, 2.8%, and 99%, respectively. On univariate analysis, only the fluorescence ratio (TBR ≥ 1.3) was correlated with malignancy at pathology (P = 0.03). No predictive factors of pathological LN status were found on multivariate analysis. Conclusions: Ex vivo ICG-FI of retroperitoneal LNs in AOC had good sensitivity but poor specificity. However, its high negative predictive value could make it an appropriate complementary tool to focus pathological analysis on fluorescent LNs., SCOPUS: ar.j, info:eu-repo/semantics/published

The lymphoscintigraphic investigation (LySc) of the superficial lymphatic system (SLS) remains the gold standard for the diagnosis of lower limb lymphoedema. However, LySc of the deep lymphatic system (DLS) may be useful for diagnosing deep lymphatic system insufficiency in patients with lower limb oedema (LLE) but normal and/or paradoxical LySc of the SLS. The purpose of this study was therefore to evaluate a new LySc of the deep lymphatic system in patients presenting with a normal and/or paradoxical SLS exam showing LLE. In all, 15 patients with unilateral and 17 with bilateral LLE underwent 3-phased deep LySc of the lower limb via the injection of 99 mTc-labelled human serum albumin (HSA) nanocolloids in the Kager’s triangle. The absence of popliteal lymphatic node visualization after phase 2 of DLS LySc to diagnose a deep lymphatic insufficiency has a specificity and a sensitivity of 89% in patients with unilateral LLE and without associated venous symptoms. An insufficiency of the DLS was observed in 67% of cases with unilateral LLE and 59% of patients with bilateral LLE of venous and/or lymphatic origin. In conclusion, the lymphoscintigraphic visualization of the popliteal lymphatic nodes after the injection of 99 mTc-labelled HSA nanocolloids in the Kager’s triangle seems to be an effective way to diagnose DLS insufficiency in patients with LLE but normal findings in the SLS., SCOPUS: ar.j, info:eu-repo/semantics/published

Background and Objectives No intraoperative imaging techniques exist for detecting tumor nodules or tumor scar tissues in patients treated with upfront or interval cytoreductive surgery (CS) after neoadjuvant chemotherapy (NAC). The aims of this study were to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of peritoneal metastases (PM) and evaluate whether it can be used to detect remnant tumor cells in scar tissue. Methods Patients with PM from ovarian cancer admitted for CS were included. ICG, at 0.25 mg per kg of patient weight, was injected intraoperatively after explorative laparotomy before CS. Results A total of 108 peritoneal lesions, including 25 scars, were imaged in 20 patients. Seventy-three were malignant (67.6%) and 35 benign (32.4%). The mean Tumor to Background Ratio (ex vivo) was 1.8 (SD 1.3) in malignant and 1.0 (SD 0.79) in benign nodules (P = 0.007). Of 25 post-NAC scars, the mean Tumor to Background Ratio (TBR) (in vivo) was 2.06 (SD 1.15) in malignant and 1.21 (SD 0.50) in benign nodules (P = 0.26). The positive predictive value of ICG-FI to detect tumor cells in scars was 57.1%. Conclusions ICG-FI is accurate to demonstrate PM in ovarian cancer but unable to discriminate between benign and malignant post-NAC.

Indocyanine green fluorescence-imaging (ICG-FI) has emerged as a potential tool for increasing the accuracy of staging of patients with primary colorectal cancer (CRC) through the detection of sentinel lymph nodes (SLNs). Here, we report the results of a systematic review of the available literature in the clinical setting of ex vivo and in vivo ICG-FI for the detection of SLNs in primary colorectal cancer. PubMed, Scopus, and Cochrane literature databases were searched for original articles on the use of ICG in the setting of clinical studies of CRC. Eighty studies were identified and screened, 23 were assessed for eligibility and 10 were included for review. Both ex vivo and in vivo ICG-FI are reported to be feasible for the detection of SLNs in CRC. The reported sensitivity of both techniques remains low, varying from 0% to 100% for the in vivo technique and 57% for the ex vivo technique. ICG-FI has not yet been shown to perform better than the standard blue dye technique. In addition, large variability among reported studies in terms of techniques used (ICG dose, type of injection), type of pathologic analyses performed (HE, IHC, serial section), and definition of positive LN status for sensitivity calculations made them difficult to compare directly. ICG-FI is a promising technique for the detection of SLNs in the setting of CRC but more work needs to be done to clearly define protocols and indications for its use and to test its efficacy in larger patient populations.

Background Response to neoadjuvant chemotherapy (NACT), particularly pathologic complete response (pCR), is an independent predictor of favorable clinical outcome in breast cancer (BC). The accuracy of residual disease measurement and reporting is of critical importance in treatment planning and prognosis for these patients. Currently, gross pathological evaluation of the residual tumor bed is the greatest determinant for accurate reporting of NACT response. Fluorescence imaging (FI) is a new technology that is being evaluated for use in the detection of tumors in different oncological conditions. Objective The aim of this study was to evaluate whether indocyanine green fluorescence imaging (ICG-FI) is able to detect residual breast tumor tissue after NACT in breast surgical operative specimens. Methods Patients who underwent NACT for BC and were admitted for breast surgery were selected for participation in this study. Free ICG (0.25 mg/kg) was injected intraoperatively. Tumor-to-background fluorescence ratio (TBFR) was calculated on ex vivo samples from the surgical specimen. Results One hundred and seventy-two samples from nine breast surgical specimens were evaluated for their fluorescence intensity. Among them, 52 were malignant (30.2%) and 120 were.Benign (69.8%). The mean TBFR was 3.3 (SD 1.68) in malignant samples and 1.9 (SD 0.97) in benign samples (p = 0.0002). With a TBFR cut-off value of 1.3, the sensitivity, specificity, negative predictive value, false negative rate, and false positive rate of ICG-FI to predict residual tumoral disease in breast surgical samples post-NACT were 94.2%, 31.7%, 92.7%, 5.8%, and 68.3%, respectively. If we restricted our analysis to only patients who achieved pCR, the negative predictive value for ICG-FI was 100%. Conclusions These first observations indicate that ex vivo ICG-FI is sensitive but not sufficiently specific to discriminate between benign breast tissue and malignant residual tissue. Nevertheless, its negative predictive value seems sufficiently accurate to exclude the presence of residual breast tumor tissue on the operative specimen of patients treated by NACT, representing a potential tool to assist pathologists in the assessment of breast surgical specimens., SCOPUS: ar.j, info:eu-repo/semantics/published

Purpose This short communication aims at reporting the potential role of ICG fluorescence imaging after an intraoperative IV injection in the detection of lymph nodes (LNs) of a colorectal cancer origin. Patients and methods Two patients who were included in a protocol study evaluating the role of ICG in the detection of peritoneal metastases of colorectal origin (Protocol NCT-01995591) also had fluorescent LNs at exploration with a dedicated near-infrared camera system (Photodynamic Eye, PDE; Hamamatsu Photonics, Hamamatsu, Japan). An IV injection of ICG was delivered intraoperatively at 0.25 mg/kg. All LNs were also explored for their fluorescence, and tumor to background ratio (TBR) was calculated with IC-Calc 2.0 program. Results One patient had two retroperitoneal lymph node metastases and one mesocolic on a pre-operative work-up. The three tumoural lymph nodes at histopathology were hyperfluorescent in comparison to other uninvolved LNs. One patient had no pre-operatively known LN metastases and had one epigastric hyperfluorescent LN discovered at intraoperative exploration. This LN of 6 mm in size was malignant at histopathology. Conclusion This is the first report about tumoural LN of colorectal cancer origin detected by fluorescence imaging with intraoperative IV free-ICG injection. ICG fluorescence imaging by intraoperative IV injection represents an easy method for detecting metastatic LNs in colorectal cancer. This proof of concept should lead to further research in this field.

Purpose: To compare using immuno-PET/CT the distribution of 89Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with 90Y-labelled rituximab in CD20+ B-cell lymphoma. Methods: Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline 89Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m2) of unlabelled rituximab followed by injection of 89Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by 90Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed. Results: With a cold rituximab preload, the calculated whole-body dose of 90Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82–0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion. Conclusion: Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the “prerituximab era”. Clinical Trial Application: CTA 2011-005474-38 Trial Registry: EudraCT, SCOPUS: ar.j, info:eu-repo/semantics/published

We report a novel approach to synthesize well-defined polymeric Janus nanoparticles by combining the self-assembly of block copolymers in thin films and surface modification by polymer grafting.

In this contribution we disclose an original strategy towards dense grafting of electrochemically active nitroxide-bearing polymer brushes on multi-walled carbon nanotubes (MWCNTs). Our strategy involves the surface initiated polymerization of 2,2,6,6-tetramethylpiperidin-4-yl methacrylate (TMPM) through atom transfer radical polymerization from the high-density initiator functionalized surface of MWCNTs and the oxidation of accordingly obtained PTMPM into poly(2,2,6,6-tetramethylpiperidin-1-oxyl-4-yl methacrylate) (PTMA), leading to MWCNT-g-PTMA composites. Extended chemical and morphological analysis confirmed the compact core–shell morphology with a high active material mass loading of 60 wt%. The electrodes made out of these MWCNT-g-PTMA composites display good cycling stability (87% of capacity retention after 200 cycles), good rate capabilities and an excellent specific capacity (85% of the theoretical capacity). The success of this strategy offers new opportunities to overcome the issue of PTMA solubilization through an electrolyte and minimal utilization of conductive carbon species.

Objective Indocyanine green fluorescence-guided surgery (ICG-FGS) has emerged as a potential new imaging modality for improving the detection of hepatic, lymph node (LN), and peritoneal metastases in colorectal cancer (CRC) patients. The aim of this paper is to review the available literature in the clinical setting of ICG-FGS for tumoral detection in various fields of metastatic colorectal disease. Methods PubMed and Medline literature databases were searched for original articles on the use of ICG in the setting of clinical studies on colorectal cancer. The search terms used were “near-infrared fluorescence”, “intraoperative imaging”, “indocyanine green”, “human” and “colorectal cancer”. Results ICG fluorescence imaging (ICG-FI) is clearly supported as an intraoperative technique that allows the detection of additional superficial hepatic metastases of CRC. Data on the role of ICG-FI in the intraoperative detection of peritoneal metastases and LN metastases are scarce but encouraging and ICG-FI could potentially improve the staging and treatment of these patients. Conclusion ICG-FI is a promising imaging technique in the detection of small infraclinic LN, hepatic, and peritoneal metastatic deposits that may allow better staging and more complete surgical resection with a potential prognostic benefit for patients.