Comment on Devoogdt et al. The Effectiveness of Fluoroscopy-Guided Manual Lymph Drainage as Part of Decongestive Lymphatic Therapy on the Superficial Lymphatic Architecture in Patients with Breast Cancer-Related Lymphoedema: A Randomised Controlled Trial. Cancers 2023, 15, 1545.

This study is a comment on the non-effectiveness of fluoroscopy-guided manual lymph drainage using ICG as part of decongestive lymphatic therapy on the superficial lymphatic architecture in patients with breast cancer-related lymphoedema in a randomized controlled trial, and the demonstration of one toxicity of indocyanine green on the lymphatic system [...].

Effect of radiation therapy on lymph node fluorescence in head and neck squamous cell carcinoma after intravenous injection of indocyanine green: a prospective evaluation.

BACKGROUND: Indocyanine green (ICG)-guided surgery has proven effective in the identification of neoplastic tissues. The effect of radiation therapy (RT) on lymph node fluorescence after intravenous injection of ICG has not been addressed yet. The objective of this study was to evaluate the influence of RT on node fluorescence during neck dissection in head and neck squamous cell carcinoma (HNSCC). RESULTS: Twenty-four patients with planned neck dissection for HNSCC were prospectively enrolled. Eleven were included without previous radiation therapy and 13 after RT. ICG was intravenously administered in the operating room. The resected specimen was analyzed by the pathology department to determine the status of each resected lymph node (invaded or not). The fluorescence of each resected node was measured in arbitrary units (AU) on paraffin blocs. The surface area (mm2) of all metastatic nodes and of the invaded component were measured. The values of these surface areas were correlated to fluorescence values. A total of 707 nodes were harvested, the mean fluorescence of irradiated nodes (n = 253) was 9.2 AU and of non-irradiated nodes (n = 454) was 9.6 AU (p = 0.63). Fifty nodes were invaded, with a mean fluorescence of 22 AU. The mean fluorescence values in the invaded irradiated nodes (n = 20) and the invaded non-irradiated nodes (n = 30) were 19 AU and 28 AU (p = 0.23), respectively. The surface area of metastatic nodes and of the invaded component were correlated to fluorescence values even after previous RT (p = 0.02). CONCLUSION: No differences were observed between the fluorescence of irradiated and non-irradiated lymph nodes, including invaded nodes. ICG-guided surgery can be performed after failed RT. TRIAL REGISTRATION: EudraCT ref. 2013-004498-29, registered 29 November 2013. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004498-29.

Continuous infusion of meropenem-vaborbactam for a KPC-3-producing Klebsiella pneumoniae bloodstream infection in a critically ill patient with augmented renal clearance.

PURPOSE: To demonstrate the feasibility of continuous infusion of meropenem-vaborbactam to optimize the treatment of carbapenem-resistant Enterobacterales. METHODS: Report of a case of a Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infection comfirmed by whole genome sequencing and therapeutic drug monitoring (TDM) of meropenem. RESULTS: A patient with augmented renal clearance (ARC) went into septic shock caused by an ST11 KPC-3-producing K. pneumoniae bloodstream infection that was successfully treated with a continuous infusion of meropenem-vaborbactam at a dosage of 1 g/1 g q4h as a 4-h infusion. TDM confirmed sustained concentrations of meropenem ranging from 8 to 16 mg/L throughout the dosing interval. CONCLUSION: Continuous infusion of meropenem-vaborbactam was feasible. It could be appropriate for optimizing the management of critically ill patients with ARC, as it resulted in antibiotic concentrations above the minimum inhibitory concentration for susceptible carbapenem-resistant Enterobacterales (up to 8 mg/L) throughout the dosing interval.

Lymphoscintigraphy as a Therapeutic Guidance Tool Can Improve Manual Lymphatic Drainage for the Physical Treatment of Patients with Upper Limb Lymphedema: Randomized Clinical Trial.

Background: The purpose of this study was to measure the effects of lymphoscintigraphically guided manual lymphatic drainage (LG-MLD) and to compare it with standardized manual lymphatic drainage (St-MLD). Materials and Methods: Fifty-two patients with lymphedema of the upper limb who underwent lymphoscintigraphy were randomly allocated into two groups. Following the phase of physical activity, the control group underwent two phases of St-MLD as the experimental group underwent a first phase of St-MLD followed by a second phase of LG-MLD. Areas of interest were then selected [in particular, dermal backflow (DBF) and axillary lymph nodes (LN)], radioactive activities were quantified for each of these areas. Results: If a first phase of St-MLD increased the LN activity by 28% on average, the findings indicated that for the second phase of DLM, LG-MLD was 19% more efficient than St-MLD in increasing LN activity. If a period of rest does not influence the lymph charge of DBF areas, physical activity leads to an average activity increase of 17%, whereas LG-MLD and St-MLD lead to an activity decrease of 11%. Conclusions: For patients with lymphedema, the findings indicate that MLD can increase the lymphatic flow toward the lymphatic nodes by 28% on average and can decrease the charge in the areas of DBF by 11% on average. Moreover, lymphoscintigraphy can be an important therapeutic tool because LG-MLD significantly increases lymphatic flow by 19% more than St-MLD. Concerning the areas of DBF, the LG-MLD and St-MLD decrease the charge in these areas with the same intensity.

Indo-cyanine green administration to identify loss of lymph after axillary lymph node dissection.

Background: Near infrared fluorescence imaging with Indocyanine Green (ICG) is now used for the imaging of lymph nodes and lymphatic vessels. In this work, we investigated the impact of its pre-operative and peri-operative administration on our ability to detect axillary lymphatic loss after breast cancer surgery. Methods: One subcutaneous injection of ICG was administered in the ipsilateral hand of 109 women who were scheduled to have either a mastectomy with total axillary lymph node dissection (CALND) or a lumpectomy with selective lymphadenectomy (SLN) the day before (n = 53) or the same day of surgery (n = 56). The lymph leakages were assessed by means of the application of a compress in the operated armpit and by the presence or absence of fluorescence on it, as well as in the post-operative axillary drains. Results: The compress was fluorescent in 28% of SLN patients and 71% of CALND patients. The liquids in the axillary drains were also fluorescent in 71% of patients with CALND. No statistical significance was observed between the ICG injection groups. The association between compressive fluorescent and the presence of fluorescence in the axillary drains is significant in the pre-operative subgroup and in the whole group. Conclusion: Our research demonstrates that lymphatic leaks aid in the development of seromas and calls into question the effectiveness of the ligatures and/or cauterizations used during surgery. A prospective, multicentric, randomized trial should be conducted to verify the efficacy of this approach.

Lymphatic Alterations Under Tattoos: Preliminary Reports of One Observational Study.

Background: 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.

Use of fluorescence imaging during lymphatic surgery: A Delphi survey of experts worldwide.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: Fluorescence imaging with or without indocyanine green appears to have several roles in lymphedema prevention, diagnosis, assessment, and treatment.

The Impact of Temporal Variation in ICG Administration on Axillary Node Identification During Reverse Mapping Procedures.

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. Results: Basic characteristics were not significantly different between the pre and per op subgroups. The percentage of patients found with fluorescent SLN (28%), the percentage of patients with fluorescent LN in CALND (74.5%), or the percentage of LN fluorescent in CALND (38.5%) did not differ significantly too. Conclusion: Injection of ICG in the first interdigital space of the hand of operated side performed one day before the surgery or the same day as the surgery has no significant influence in our study on detection of the arm nodes. The timing of ICG injection is an independent variable with no effect on the results; this allows the injection to be performed either the day before the surgery or the day of the surgery.

Lymphoscintigraphic Investigations for Axillary Web Syndromes.

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 Results: 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.

Value of one additional injection at the root of the limb in the lymphoscintigraphic evaluation and management of primary and secondary lower-limb lymphedemas.

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 lympho-nodal 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.

Edemas of the face and lymphoscintigraphic examination.

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.

Near-Infrared Fluorescence Imaging of Breast Cancer and Axillary Lymph Nodes After Intravenous Injection of Free Indocyanine Green.

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.

Lymphoscintigraphic Bilateral Disease in Patients with Clinically Unilateral Primary Lower Limb Lymphedemas.

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 and, in clinically unilateral edema, abnormalities may be present at the level of contralateral limb. The aim of this study is to report the frequency of heterolateral lesions in these patients based on lymphoscintigraphic investigations (LySc). Methods and Results: Retrospective review (CE2048) among our database of patients who were referred for LySc of clinically unilateral LLLE and for whose LySc showed DDB. Fifty-six patients could be classified as early-onset ("praecox": group 1: 8 men and 48 women: median age at investigation = 32.5 years: edema was right sided in 26 and left sided in 30) and 47 (8 men and 39 women: edema was right sided in 25 and left sided in 22) as late-onset ("tarda": group 2). DDB at the level of the opposite nonedematous limb was found in 38.8% of the whole series but more frequently (p < 0.001) in group 2 (70%) than in group 1 (15%). In group 1, bilateral disease were seen as frequently (in 4 cases) among the (33) patients <35 years old than in other patients (4 out of 23). Conclusions: These differences between these two clinical groups could support the following hypothesis: we are facing, either two different lymphatic diseases, or, a single disease but affecting two populations of different susceptibility.

Absence of residual fluorescence in the surgical bed at near-infrared fluorescence imaging predicts negative margins at final pathology in patients treated with breast-conserving surgery for breast cancer.

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.

Systemic Sentinel Lymph Node Detection Using Fluorescence Imaging After Indocyanine Green Intravenous Injection in Colorectal Cancer: Protocol for a Feasibility Study.

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 IDENTIFIER (IRRID): PRR1-10.2196/17976.

Personalized selective internal radiation therapy in liver metastasis of thyroid cancer with impaired liver function: A case report.

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.

Filter Optimization for Real-Time Digital Processing of Radio Frequency Signals: Application to Oscillator Metrology.

Software-defined radio (SDR) provides stability, flexibility, and reconfigurability to radio frequency signal processing. Applied to oscillator characterization in the context of ultrastable clocks, stringent filtering requirements are defined by spurious signal or noise rejection needs. Since real-time radio frequency processing must be performed in a field-programmable array to meet timing constraints, we investigate optimization strategies to design filters meeting rejection characteristics while limiting the hardware resources required and keeping timing constraints within the targeted measurement bandwidths. The presented technique is applicable to scheduling any sequence of processing blocks characterized by a throughput, resource occupation and performance tabulated as a function of configuration characteristics, as is the case for filters with their coefficients and resolution yielding rejection and the number of multipliers.

Scintigraphic Investigations of the Deep and Superficial Lymphatic Systems in the Evaluation of Lower Limb Oedema.

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.

Ex vivo indocyanine green fluorescence imaging for the detection of lymph node involvement in advanced-stage ovarian cancer.

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.