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.

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.

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.

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.

Fluorescence of Deep Infiltrating Endometriosis During Laparoscopic Surgery: A Preliminary Report on 6 Cases.

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.

ICG fluorescence imaging as a new tool for optimization of pathological evaluation in breast cancer tumors after neoadjuvant chemotherapy.

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.

Use of lymphoscintigraphy to differentiate primary versus secondary lower extremity lymphedema after surgical lymphadenectomy: a retrospective analysis.

BACKGROUND: When managing patients with cancer, lymphedema of the lower limbs (LLL) is commonly reported as secondary to the surgical excision and/or irradiation of lymph nodes (LNs). In the framework of lymphoscintigraphic imaging performed to evaluate secondary LLL, some lympho-nodal presentations have been observed that could not be explained by the applied treatments, suggesting that these LLL might be primary. Therefore, all our lymphoscintigraphic examinations that were performed in patients for LLL after surgery for gynecological or urological cancer were retrospectively analyzed in order to evaluate the frequency in which these LLL might not be secondary (either completely or partially) but primary in origin. METHODS: Lymphoscintigraphies performed in 33 patients who underwent LN dissection (limited to the intra-abdominal LN) with or without radiotherapy for histologically confirmed ovarian cancer (n = 6), uterine cancer (n = 14 with cervical cancer and n = 7 with endometrial cancer), or prostate cancer (n = 6) were compared to lymphoscintigraphies obtained in primary LLL. RESULTS: In 12 (33% of the) patients (3 men plus 9 women, 4 with cervical cancer and 5 with endometrial cancer), scintigraphy of the lower limbs revealed lympho-nodal presentation that did not match with the expected consequences of the surgical and/or radiological treatments and were either suggestive or typical of primary lymphedema. CONCLUSIONS: This retrospective analysis of a limited but well-defined series of patients suggests that the appearance of LLL might not be related to cancer treatment(s) but that these LLL may represent the development of a primary lymphatic disease latent prior to the therapeutic interventions.

ICG-fluorescence imaging for detection of peritoneal metastases and residual tumoral scars in locally advanced ovarian cancer: A pilot study.

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.

Lymphatic Drainages to the Paravertebral and Pararenal Lymph Nodes in Breast Cancer Patients.

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.

Lymphatic Drainage to the Paravertebral Lymph Nodes in Breast Cancer Patients.

INTRODUCTION: 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. METHODS: We used lymphoscintigraphy to examine lymphatic drainage in a case series. RESULTS: 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. CONCLUSIONS: 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.