Photodynamic Eye Research Articles

Understanding healing complications in implant-based breast reconstruction using novel metrics for indocyanine green angiography

IntroductionIndocyanine green (ICG) angiography for the intraoperative evaluation of tissue perfusion is commonly used in implant-based breast reconstruction (IBR). The assessment of ICG images depends on the surgeon’s interpretation and is qualitative or semiqualitative in nature. To quantify ICG metrics, this study aimed to apply a novel assessment of fill-rate dynamics to predict wound-healing complications and provide pragmatic assessment tools in IBR. MethodsThis was a retrospective cohort study of patients who underwent IBR with ICG using the photodynamic eye (PDE-Neo II) qualitative imaging system between April 2021 and September 2023. ICG recordings were reviewed to quantify the relative surface area and fluorescence intensity of visual perfusion deficits using ImageJ. The primary outcome was the incidence of wound-healing complications. t-tests and logistic regression were performed for statistical testing. ResultsA total of 112 patients (201 breasts) were included. The incidence of wound-healing complications was 12.9%. A higher relative surface area of ischemic regions was significantly associated with wound-healing complications (3.3% vs. 0.90%; p = 0.001). The rate of change in the surface area of ischemic regions was significantly associated with wound-healing complications (0.35% per second vs. 1.29% per second; p = 0.003%). On average, the duration of transient ischemic areas was significantly longer in breasts with wound-healing complications (46.0 s vs. 36.0 s, p = 0.01). ConclusionA transient ischemic area of > 5% of the breast and/or failure to resolve transient ischemic areas after 60 s may predict wound-healing complications and inform surgical reconstructive decision-making in IBR.

Clinical Study of Sentinel Lymph Node Detection Using Photodynamic Eye for Abdominal Radical Trachelectomy.

This study aimed to assess the accuracy of predicting pelvic lymph node status using sentinel lymph node (SLN) biopsy with indocyanine green (ICG) and to examine the outcomes of SLN biopsy-guided abdominal radical trachelectomy (ART). Patients with stage IA2–IB2 cervical cancer from January 2009 to January 2021 were included. ICG was injected before ART and SLNs were identified, excised, and assessed intraoperatively using fast-frozen sections. Systemic pelvic lymphadenectomy was subsequently performed. The SLN detection rate, sensitivity, and false-negative rate were determined. Thirty patients desiring fertility preservation were enrolled, of whom 26 successfully completed ART and four underwent radical hysterectomies because of metastatic primary SLNs. Bilateral SLNs were identified in all patients. The sensitivity, false-negative rate, and negative predictive value were 100%, 7.7%, and 92.3%, respectively. Three (12%) patients were lost to follow-up: two relapsed and one died of tumor progression. Of the nine patients who tried to conceive after surgery, four achieved pregnancy and three delivered healthy live infants. In women with early-stage cervical cancer who desired to conserve fertility, SLN mapping with ICG had a very high detection rate, sensitivity, and low false-negative rate. SLN biopsy-guided ART is a feasible and accurate method for assessing pelvic node status.

計画的二期手術にて救命し得た，高浸透圧高血糖症候群を契機に発症した非閉塞性腸管虚血症の1例(Succesful treatment of non–occlusive mesenteric ischemia induced by hyperosmolar hyperglycemic state, requiring planned two–stage surgery: a case report)

要旨症例は67歳の男性で，喉頭癌（cT3N1M0 stage III）に対し喉頭亜全摘術および気管切開術を施行された。術後の経管栄養開始後に血糖上昇傾向となり，その後，高浸透圧高血糖症候群（hyperosmolar hyperglycemic syndrome: HHS）を発症した。さらに浸透圧利尿による脱水にて腸管低灌流を合併したことによると思われる非閉塞性腸管虚血症（non–occlusive mesenteric ischemia: NOMI）が疑われたため，緊急で診断的腹腔鏡検査を施行した。その結果，明らかに壊死した腸管を認めたため開腹手術に移行し，初回手術では壊死腸管の切除のみを行った。集中治療後に二期的に腸管再建術を施行し，その際にインドシアニングリーン蛍光法にて残存腸管に血流障害がないことを確認した。今回我々は，HHSを契機に発症したと考えられるNOMIの1例を経験した。NOMIは非常に致死率の高い予後不良な疾患であるが，計画的な二期手術および集中治療にて救命し得た。自験例について，文献的考察を交えて報告する。

Fluorescence navigation with indocyanine green for identification of intersegmental planes using a photodynamic eye camera.

BackgroundPulmonary segmentectomy is an important surgical option for complete resection in patients with poor lung function. However, correctly recognizing the intersegmental plane for accurate segmentectomy is sometimes difficult. We therefore developed a novel method that allows the detection of intersegmental planes using an indocyanine green (ICG) fluorescence imaging device, photodynamic eye (PDE) camera, PDE-neo.MethodsAs a prospective study, we performed bronchial ICG-guided segmentectomy using PDE-neo. The patients were placed in a lateral position under general anesthesia, and we performed a combined muscle-sparing minithoracotomy with video assistance. The pulmonary artery, pulmonary vein, and segmental bronchi were separated, and ICG mixed with autologous blood was introduced by spraying through the resected segment bronchi to enable visualization of the intersegmental surface with PDE-neo. This study protocol was approved by the Research Ethics Board of Hamamatsu University School of Medicine, Japan. Written informed consent was obtained from all patients.ResultsOverall, 10 lung malignancy patients, including 8 males and 2 females, participated in this study from March 2011 to October 2013. The median age was 69 years (range, 29–76 years). Pathologic diagnoses were 7 adenocarcinomas, 1 adenosquamous carcinoma, 1 carcinoid tumor, and 1 lung metastasis from the parotid gland cancer. The intersegmental planes of 8 cases could be identified by this method using a PDE-neo, whereas those of 2 cases did not show clear demarcations. The reason was that because of severe emphysema, air flowed from the resected segment to the surrounding segments, obliterating the demarcation between the two segmental planes. There were no recurrent cases and only two deaths due to other diseases were observed; and the 5-year cause-specific survival rate was 100%.ConclusionsIntersegmental planes could be more easily identified using ICG fluorescence imaging during segmentectomy. This method is feasible and effective and has a good long-term prognosis.

Indocyanine green angiography for preventing postoperative mastectomy skin flap necrosis in immediate breast reconstruction.

Indocyanine green angiography for preventing postoperative mastectomy skin flap necrosis in immediate breast reconstruction.

Assessment of Lymphovenous Anastomosis Patency: Technical Highlights.

Assessment of Lymphovenous Anastomosis Patency: Technical Highlights.

Abstract P4-02-05: Indocyanine green (ICG) fluorescence mapping for sentinel lymph node (SLN) localization in early breast cancer

Abstract Background:Dual localization methods with blue dye and radioisotope are commonly employed for SLN identification but allergic reactions together with staining of skin and surgical tissues disadvantage blue dye. A previous feasibility study using blue dye, radioisotope and ICG confirmed high sensitivity of ICG fluorescence for SLN detection with three-quarters of nodes both radioactive and fluorescent.1 This follow-on study has evaluated a combination of ICG with radioisotope for SLN identification. Methods: In a prospective observational study, 79 patients with unilateral clinically node negative tumors scheduled to undergo routine SLN biopsy for core-biopsy proven invasive (n= 78) or non-invasive (n = 1) breast cancer were identified at multidisciplinary meetings [43 screen-detected; 36 symptomatic]. All patients received dual localization with radiocolloid (Technetium nanocolloid, 20MBq) and ICG (0.5%) and had pre-operative axillary ultrasound. The number of nodes was recorded numerically and whether radioactive, fluorescent or both. Lymphatic and nodal tissue were visualized with a Photodynamic Eye camera and sensitivity of individual tracers alone and in combination calculated. Institutional approval was granted for use of ICG instead of blue dye. Statistical analysis was performed using Stata (version 15.1) with student t-test for normal distribution and Mann-Whitney test for other variables. The main objective was to assess non-inferiority of fluorescent (ICG) compared with standard radioisotopic localization. This was based on a confidence interval for the difference in percentage detection rate with a non-inferiority margin of 5%. Results: A total of 162 nodes were retrieved from 79 patients with an average nodal count of 2.04 (range 1 - 4) and an overall identification rate of 98.7% (78/79). Amongst these excised nodes, 154 displayed uptake of tracer and were either fluorescent, radioactive or both (8 nodes were removed incidentally or were palpably suspicious and tracer negative). More than 90% (151/154) of nodes were fluorescent and 73.4% (113/154) were radioactive with at least 10% activity of the hottest node. These results yielded an overall concordance rate of 71.4%. Nodal detection rates for ICG alone or combined with radioisotope were 98.1% (151/154) and 73.4% (113/154) respectively whilst procedural detection rates were 97.5% (77/79) for radioisotope and 98.7% (78/79) for ICG. Metastases were present in 13 nodes (all fluorescent and hot) with 13 patients having a single positive node containing macrometastases (n= 5), micrometastases (n = 6) or isolated tumor cells (n = 2). The node positivity rate was 14.1% for macro- or micrometastases and 2.5% for isolated tumor cells. ICG was non-inferior to radioisotope for both procedural and nodal detection rates with the lower confidence interval not crossing within the pre-defined limit. No serious adverse reactions were recorded. Conclusion: ICG fluorescence imaging permits real-time visualization of lymphatics and provides an additional dimension to SLN biopsy that is safe and effective. These results confirm high sensitivity for fluorescence localization with comparable performance to the gold standard using radioisotope. ICG can reliably be employed as a sole tracer that avoids potential drawbacks of standard tracer agents including availability and costs of radioisotope. 1. Wishart GC, Jones LC, Loh S-W, Benson JR. A feasibility study (ICG-10) of indocyanine green (ICG) fluorescence mapping for sentinel lymph node detection in early breast cancer. Eur J Surg Oncol 2012; Jun 13 Citation Format: Dorin Dumitru, Sujit Gnanakumar, Elena Provenzano, John Benson. Indocyanine green (ICG) fluorescence mapping for sentinel lymph node (SLN) localization in early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-05.

Efficacy of Hepatic Segmental Visualization Using Indocyanine Green Photodynamic Eye Imaging.

To clarify the usefulness of identification of hepatic segmentation stained with an indocyanine green-photodynamic eye (ICG-PDE) system, we sequentially investigated the matching of visualization during hepatectomy in 40 patients at two institutions between 2009 and 2017. A low dose of ICG was administered into the portal flow to stain the estimated segments of the liver to be resected during hepatectomy, and segmentation images were observed using a PDE camera. Intraoperative ICG-PDE could be carried out for all patients without side effects. Complete segmental identification of the liver by blue dye stain and ICG-PDE was achieved in 30 (75%) and 35 (88%) patients, respectively, but the prevalence between them was not significantly different (p = 0.302). ICG-PDE segmentation in the estimated area was incomplete in three patients, and complete failure (no staining) was observed in two patients. The border between the posterior section and the caudate was identified in two patients. This preliminary study showed ICG-PDE to be a useful tool for clearly determining liver segmentation to estimate the area for resection.

Reestablishment of Lymphatic Drainage after Vascularized Lymph Node Transfer in a Rat Model.

Vascularized lymph node transfer has recently received attention as a potential surgical treatment for lymphedema. Despite good results in some series, the mechanism and benefits of vascularized lymph node transfer have yet to be fully understood. This study aimed to investigate the reestablishment of drainage into transferred lymph nodes following vascularized lymph node transfer in a rat model. Seven rats underwent vascularized lymph node transfer. The operation performed on each rat consisted of two parts. First, the left groin lymph node basin with superficial epigastric vessels was harvested as a free flap. Second, the flap was reattached in the left groin of the rat by means of end-to-end microvascular anastomoses. Anastomosis patency was assessed immediately postoperatively and at the time of animal sacrifice. The rats were evaluated for reestablishment of lymphatic flow into the transplanted nodes at 1-month intervals for at least 6 months postoperatively. This was accomplished noninvasively by injecting the rats in their flanks with fluorescent indocyanine green, which was detected using a Photodynamic Eye infrared camera. Anastomoses were patent in all seven rats immediately postoperatively. No indocyanine green uptake was seen in the transplanted lymph node basins in the first 2 months postoperatively in any of the rats. In five of seven rats, however, indocyanine green uptake was demonstrated in the transplanted lymph node basin by 6 months (average, 13 weeks). The authors report uptake of indocyanine green in five of seven rats at an average of 13 weeks after lymph node transplantation, consistent with the reestablishment of lymphatic drainage into the transplanted nodes.

Comparison of the indocyanine green dye method versus the combined method of indigo carmine blue dye with indocyanine green fluorescence imaging for sentinel lymph node biopsy in breast conservative therapy for stage \u2264IIA breast cancer

BackgroundFluorescence imaging (FI) is one of the methods to identify sentinel lymph nodes (SLNs). However, the procedure is technically complicated and requires procedural skills, as SLN biopsy must be conducted in dim light conditions. As an improved version of this method, we introduced a combined method (Combined mixed dye and fluorescence; CMF) consisting of indigo carmine blue dye and FI. The direct visualization of SLNs under shadowless surgical light conditions is facilitated by the addition of the blue dye. We compared the SLN detection rates of CMF with that of the indocyanine green (ICG) dye method (ICG-D).MethodsA total of 202 patients with stage ≤IIA breast cancer who underwent breast conservative therapy with separate incision from January 2004 to February 2017 were reviewed. Details of the two methods are as follows: (1) ICG-D: 10 mg of ICG was used and the green-stained SLNs were resected via a 3-4 cm axillary incision; (2) CMF: A combination of 5 mg of ICG and 4-8 mg of indigo carmine was used. After a 1.5–2 cm incision was made near the point of disappearance of the fluorescence using Photodynamic Eye (PDE), the blue-stained SLNs were resected under shadowless surgical light conditions.ResultsThere were 92 ICG-D and 110 CMF cases. CMF resulted in a significantly higher SLN detection rate than ICG-D (96.4% vs. 83.7%; p = 0.003). This difference was particularly notable in those aged ≥60 years (98.3% vs. 74.3%) and individuals with body mass index (BMI) ≥25 kg/m2 (90.3% vs. 58.3%).ConclusionCMF is an effective method to identify SLNs which is safe and efficient. CMF achieves a high SLN identification rate and most of this procedure is feasible under shadowless surgical light conditions. CMF can reliably perform SLN biopsy even in those aged ≥60 years and individuals with BMI ≥ 25 kg/m2.

PS02.076: VISUALIZATION OF BLOOD SUPPLY ROUTE TO THE RECONSTRUCTED STOMACH BY INDOCYANINE GREEN FLUORESCENCE IMAGING DURING ESOPHAGECTOMY, 2ND REPORT

Abstract Background Recently, indocyanine green (ICG) fluorescence imaging has been used to visualize the blood supply when anastomosis is performed in vascular surgery. We have reported the three blood supply routes to the reconstructed stomach using ICG fluorescence imaging for reconstruction during esophagectomy. Blood flow routes in the 33 patients with esophageal cancer were classified into categories on the basis of ICG imaging findings: the gastric wall route, the greater curvature route, and the omentum and splenic hiatal route. The gastric wall route was found in 13 patients and characterized by large blood vessels in the gastric wall. The greater curvature route was present in 11 patients and characterized by blood vessels in the greater omentum. The omentum and beside splenic hilum route was found in 22 patients. Blood vessels ran in the greater omentum beside the splenic hilum. a photodynamic eye (PDE) showed blood flow from right gastroepiploic artery, omentum vessels, left gastroepiploic artery, splenic hiatal vessels, short gastric artery, and gastric wall vessels to the top of the reconstructed stomach. The ‘splenic hiatal route’ was present in 66.7% of the patients and was formed by large vessels or networks of small vessels. We rechecked the ‘splenic hiatal route’ cases and recognize that the branch parted from the right gastroepiploic artery. We tried preservation of the ‘splenic hiatal route’. Methods Since January 2017, we have preserved the ‘splenic hiatal route’ and performed ICG fluorescence imaging in 5 patients with thoracic esophageal cancer who underwent thoracic esophagectomy. After pulling up the reconstructed stomach, 2.5 mg of ICG was injected as a bolus. ICG fluorescence imaging was performed with a near-infrared camera, and the images were recorded. Results ICG fluorescence was easily detected in all patients 1 min after injection. Vascular networks were well visualized in the gastric wall and omentum. The blood supply route was visualized the ‘splenic hiatal route’ in all patients. Conclusion On ICG fluorescence imaging, the splenic hiatal vessels would be the major blood supply for the anastomosis in most patients. Disclosure All authors have declared no conflicts of interest.

A feasibility study of sentinel lymph node mapping by cervical injection of a tracer in Japanese women with early stage endometrial cancer

ObjectiveThe aim of this study was to investigate the feasibility of sentinel lymph node mapping characterized by a cervical tracer injection in endometrial cancer. Materials and methodsThis retrospective study was carried out using data for 57 patients with endometrial carcinoma who had undergone intraoperative sentinel lymph node mapping and subsequent surgical staging. Technetium colloid and/or indocyanine green was injected into the uterine cervix and a gamma-detecting probe and/or photodynamic eye camera system was used intraoperatively to locate hot spots. ResultsOf the 57 patients, 52 (91.2%) had FIGO Stage I disease. Successful unilateral or bilateral mapping occurred in 54 patients (94.7%) and 46 (80.7%), respectively. The median number of sentinel lymph nodes detected was two (range, 0–5). Following sentinel lymph node mapping, 41 patients (71.9%) underwent pelvic lymphadenectomy alone and 16 (28.1%) full lymphadenectomy. The median number of lymph nodes resected was 17 (range, 8–110). Sentinel lymph nodes were involved in four patients (7.0%), two with macrometastases and two with low-volume metastases. The sensitivity and negative predictive value for detecting lymph node metastasis were both 100%. ConclusionSentinel lymph node mapping with the use of cervical tracer injection is highly feasible in Japanese women with early stage endometrial cancer.

Effectiveness of indocyanine green fluorescence in endoscopic marking in gastric cancer surgery:a feasibility study for replacing India ink

When injected, indocyanine green (ICG) immediately combines with lipoproteins to fluoresce. Here, we studied whether ICG fluorescence is effective for endoscopic marking in gastric cancer surgery using a photodynamic eye (PDE) camera and fluorescent endoscope. An ICG solution was endoscopically injected into the submucosal layer of the gastric tumor 3 days before surgery. We observed the lesions using both a PDE camera and a fluorescent endoscope during laparotomy and laparoscopy, respectively;we also observed the fluorescent luminance and fluorescent size of the resected lesions. We could intraoperatively detect the size of the resected lesions in eight patients with early gastric cancer and six patients with advanced gastric cancer. We believe that the use of ICG fluorescence in endoscopic marking requires additional information, such as the volume of the ICG solution and the timing of the ICG injection.

Abstract PD2-07: Real-time navigation for sentinel lymph node biopsy in breast cancer patients using projection mapping with indocyanine green fluorescence

Abstract Background) Sentinel lymph node (SLN) biopsy using indocyanine green fluorescence (fICG) method showed equal or better identification rate compared with blue dye or radioisotope (RI) method. In the fICG method, lymphatic vessels which drain into the SLNs can be seen through skin or subcutaneous tissue using near infrared camera (Photodynamic Eye®: PDE), and we can easily find the SLNs. However, whenever we observe the fluorescence images, we have to hold the PDE, turn off the operating light, and look at a monitor because fluorescence images cannot be seen directly. Medical imaging projection system (MIPS) is a new device which detects fluorescent emission from the organ and projects their images on the location of the fluorescence emission (Panasonic Connected Solutions Company, Japan). Projected images can be adjusted following the body movement or deformation of the organ. Therefore, MIPS could provide an option for real-time navigation for the SLN biopsy. The aim of this study was to evaluate the clinical utility of the MIPS. Patients and methods) Patients with clinically node-negative primary breast cancer underwent the fICG SLN biopsy using MIPS. Primary endpoint was identification rate of the fICG method using MIPS. At first, the study was conducted as an interventional study because the MIPS was the unapproved medical device. After approval of the MIPS, this study was conducted as an observational study. The study protocol was approved by the institutional review board at Kyoto University Hospital. All patients provided informed consent to participate in this study. Results) Between March 2016 and May 2017, 39 patients (40 procedures) underwent the fICG method SLN biopsy using MIPS. The median age was 55 years (range 32–74 years), and the median body mass index was 20.4 kg/m2 (range 17.7–27.7 kg/m2). About half had tumor stage T1 (58%) and 8 (20.0%) had DCIS. 8 procedures (20%) were performed after preoperative systemic therapy (PST). As MIPS itself can illuminate the operating field, SLN biopsy using MIPS was successfully performed without operating light in all procedures. At least one SLN was detected using MIPS for all procedures and the identification rate was 100% (95% CI: 91–100%). Median number of SLNs detected by MIPS was 3 (range 1–9) for all procedures, and 3 (range 2–8) for procedures after PST. Two pathologically positive SLNs and one SLN which included isolated tumor cells were detected by MIPS. In 25 procedures, RI was also used. 62 of 97 SLNs detected by MIPS (64%) were also detected by RI. However, no SLNs were detected only by RI. Conclusions) Although we still may not be able to avoid RI method because 25/40 (62.5%) procedures required the combined use of RI method, the fICG methods SLN biopsy using MIPS, which showed comparable identification rate of SLN with the conventional methods, could be useful tool with a view of allowing us to perform a real-time navigation surgery. Acknowledgements) This study was supported by Acceleration Transformative research for Medical innovation, Japan Agency for Medical Research and Development (AMED). Citation Format: Takada M, Takeuchi M, Suzuki E, Sato F, Matsumoto Y, Torii M, Sakita-Kawaguchi N, Nakayama Y, Okuda T, Nishino H, Seo S, Hatano E, Toi M. Real-time navigation for sentinel lymph node biopsy in breast cancer patients using projection mapping with indocyanine green fluorescence [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-07.

Abstract P3-01-15: Sentinel lymph node biopsy by indocyanine green fluorescence detection in breast cancer cT1-4N0M0 patients. Frequency of false-negative results is low

Abstract Breast cancer cT1-4N0M0 patients are usually need in a sentinel lymph node biopsy (SLNB). SLNB by indocyanine green (ICG) fluorescence detection is a modern technique possessing high level of lymph node detection rate, but frequency of false-negative results was not evaluated adequately. Objective was to determine main diagnostic characteristics of the ICG fluorescence-guided SLNB in BC cT1-4N0M0 patients: node detection rate and frequency of false-negative results. Methods: 99 patients with 100 cases of breast cancer cT1-4N0M0 (T1 – 43, T2 – 55, T3 – 1, T4 – 1) were operated, axillary part of operation consisted from the ICG fluorescence-guided SLNB and axillary lymphadenectomy of levels I–II or I–II–III. 12 patients had neoadjuvant chemotherapy and 8 – neoadjuvant hormonotherapy. Photodynamic Eye C9830 (Hamamatsu Photonics K.K) was using for emit near infrared radiation and fluorescent image registration. 2 ml 0.25% solution of ICG were injected inra- and sub- cutaneous periareolary or in a tumor projection, 2-5 minutes later it can be see fluorescent way to axillary. The procedure starting from injection of the ICG to the identification of a signal lymph node takes 15–30 minutes. Results. Transcutaneous fluorescent lymphatic duct was visible in all 100 procedures, but not lymphatic node. Last can be found usually in a wound after Fascia superficialis and Fascia axillaris dissection. A signal lymph node was detected in 98 cases (98 %). Mean amount of sentinel lymphatic nodes = 1.9±0.1 (1-7 nodes). Mean amount of lymphatic nodes took with axillary dissection = 10.5±0.5 (5-26 nodes). In 28 (28.6%) cases of 98 were found to have metastases in signal lymph nodes. Other than signal lymph nodes had metastatic lesion only in 35.7% in signal lymph nodes N+ cases. False negative result occurred in 3 (3.1%) cases of 98, including 2 with metastases in signal lymph node finding by plan histological investigation, but not at froze section. No cases of allergic reactions or other adverse effects were diagnosed with standard subcutaneous use of indocyanine. Conclusion. Fluorescence technique of the detection of signal lymph nodes has its own methodological issues: in most cases a signal lymph node is not visualized through the skin, it should be visualized in surgical wound using the course of lymphatic duct as guidance. Application of ICG fluorescence-guided SLNB in cN0 breast cancer patients allows high signal lymph node detection rate and low false negative rate, - 3%. Acknowledgments. The authors thank Professor Gordon C. Wishart for the Sentinel Lymph Node Detection by ICG Fluorescence Technique teaching. Citation Format: Portnoy SM, Kuznetsov AV, Shakirova NM, Kozlov NA, Maslyaev AV, Karpov AV, Kampova-Polevaya EB, Mistakopulo MG, Egorov YS, Anurova OA, Shendrikova TA, Gornostaeva AS. Sentinel lymph node biopsy by indocyanine green fluorescence detection in breast cancer cT1-4N0M0 patients. Frequency of false-negative results is low [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-15.

A Real-Time Near-Infrared Fluorescence Imaging Method for the Detection of Oral Cancers in Mice Using an Indocyanine Green-Labeled Podoplanin Antibody.

Podoplanin is distinctively overexpressed in oral squamous cell carcinoma than oral benign neoplasms and plays a crucial role in the pathogenesis and metastasis of oral squamous cell carcinoma but its diagnostic application is quite limited. Here, we report a new near-infrared fluorescence imaging method using an indocyanine green (ICG)–labeled anti-podoplanin antibody and a desktop/a handheld ICG detection device for the visualization of oral squamous cell carcinoma–xenografted tumors in nude mice. Both near-infrared imaging methods using a desktop (in vivo imaging system: IVIS) and a handheld device (photodynamic eye: PDE) successfully detected oral squamous cell carcinoma tumors in nude mice in a podoplanin expression–dependent manner with comparable sensitivity. Of these 2 devices, only near-infrared imaging methods using a handheld device visualized oral squamous cell carcinoma xenografts in mice in real time. Furthermore, near-infrared imaging methods using the handheld device (PDE) could detect smaller podoplanin-positive oral squamous cell carcinoma tumors than a non-near-infrared, autofluorescence-based imaging method. Based on these results, a near-infrared imaging method using an ICG-labeled anti-podoplanin antibody and a handheld detection device (PDE) allows the sensitive, semiquantitative, and real-time imaging of oral squamous cell carcinoma tumors and therefore represents a useful tool for the detection and subsequent monitoring of malignant oral neoplasms in both preclinical and some clinical settings.

Does BMI affect the detection of sentinel lymph nodes with indocyanine green in early breast cancer patients?

Sentinel node biopsy (SNB) has proved to be a useful and safe method for axillary staging in the surgical management of early breast cancer. Sentinel node (SN) detection rates with blue dye (patent blue) and radioisotopes (99m-Tc), either alone or particularly in combination, are high (95% to 100%). Even better detection rates were reported with fluorescent dyes like indocyanine green (ICG). This study was designed to show whether sentinel node detection and mapping of lymphatics with ICG might depend on the body mass index (BMI). Between February 2014 and April 2015, SNB with blue dye, 99m-Tc, and ICG navigation was conducted for 100 consecutive procedures in patients scheduled for surgery of early breast cancer. ICG injection, lymphatic mapping with the Photodynamic Eye (PDE; Hamamatsu Photonics, Hamamatsu, Japan), and identification of the sentinel nodes with blue dye and ICG were followed by a final search for more lymph nodes with a gamma probe. Data were collected prospectively. In all patients, up to six sentinel nodes (mean 2.49) were detected. No statistical correlation was found between the BMI and the identification of lymphatics or the detection of lymph nodes with ICG. Lymphatics were successfully identified preoperatively in no more than 79 cases. In 6 patients, a gamma probe was needed for detection. Adverse events or allergic reactions were absent throughout. SN detection and lymphatic mapping with ICG were not related to the BMI. Pending answers to as yet unsolved questions, the combined use of blue dye and 99m-Tc imaging should, however, be continued.

Engineered polymeric microspheres obtained by multi-step method as potential systems for transarterial embolization and intraoperative imaging of HCC: Preliminary evaluation

The aim of this study was the development of novel fluorescent microspheres as embolic agent for transarterial embolization (TAE) of advanced stages of hepatocellular carcinoma (HCC). TAE is a minimally invasive procedure that induces tumour regression blocking the blood flow by injection of microparticles. The microspheres currently used in clinical application cannot be visualized in vivo. Surgeon could exploit the intraoperative detection of embolic agents during resection of the malignant mass. Biocompatible indocyanine green (ICG)-loaded microspheres (CAB-CS-ICG) were prepared using a multi-step method. Chitosan (CS)-ICG particles were prepared via spray-dryer and then loaded into cellulose acetate butyrate (CAB) microspheres, fabricated by emulsion solvent extraction method. Technological parameters such as yield, size, encapsulation efficiency and morphology were studied. CAB-CS-ICG microspheres showed spherical shape and smooth surface, as well as good injectability through a 21 G×1½ needle. ICG release from CAB-CS-ICG was very low due to the strong interaction between CS and ICG. This result was also confirmed by in vitro fluorescence imaging studies, conducted using Photodynamic Eye (PDE) for the detection of particles incubated in human plasma. CAB-CS-ICG were capable to maintain the fluorescence selectivity for 4weeks. Our data suggested the potential usefulness of CAB-CS-ICG in TAE application as embolic agents and following imaging of tumour during surgical procedure.

Adipose-Derived Stem Cells and Vascularized Lymph Node Transfers Successfully Treat Mouse Hindlimb Secondary Lymphedema by Early Reconnection of the Lymphatic System and Lymphangiogenesis.

Secondary lymphedema is often observed in postmalignancy treatment of the breast and the gynecologic organs, but effective therapies have not been established in chronic cases even with advanced physiologic operations. Currently, reconstructive surgery with novel approaches has been attempted. The hindlimbs of 10-week-old male C57BL/6J mice, after 30-Gy x-irradiation, surgical lymph node dissection, and 5-mm gap creation, were divided into four groups, with vascularized lymph node transfer abdominal flap and 1.0 × 10 adipose-derived stem cells. Lymphatic flow assessment, a water-displacement plethysmometer paw volumetry test, tissue quantification of lymphatic vessels, and functional analysis of lymphatic vessels and nodes were performed. Photodynamic Eye images, using indocyanine green fluorescence, demonstrated immediate staining in subiliac lymph nodes, and linear pattern imaging of the proximal region was observed with the combined treatment of adipose-derived stem cells and vascularized lymph node transfer. Both percentage improvement and percentage deterioration with the combined treatment of adipose-derived stem cells and vascularized lymph node transfer were significantly better than with other treatments (p < 0.05). The numbers of lymphatic vessels with LYVE-1 immunoreactivity significantly increased in mice treated with adipose-derived stem cells (p < 0.05), and B16 melanoma cells were metastasized in groups treated with vascularized lymph node transfers by day 28. Adipose-derived stem cells increase the number of lymphatic vessels and vascularized lymph node transfers induce the lymphatic flow drainage to the circulatory system. Combined adipose-derived stem cell and vascularized lymph node transfer treatment in secondary lymphedema may effectively decrease edema volume and restore lymphatic function by lymphangiogenesis and the lymphatic-to-venous circulation route.

Abstract P2-01-39: Axillary reverse mapping using fluorescence imaging in the surgical treatment for breast cancer patients

Abstract Background: Axillary lymph node dissection (ALND) is the standard surgical treatment for breast cancer patients who have axillary nodal metastasis but do not meet the criteria of Z0011 trial. Arm lymphedema is one of the most common and serious complications of ALND. Based on the hypothesis that the lymphatic system of the upper extremity may be separate from that of the breast, the axillary reverse mapping (ARM) technique has been developed to identify the axillary lymph nodes and lymphatics that receive the lymph from the upper limb, and to preserve them during ALND in order to prevent arm lymphedema. However, it is difficult to keep the arm lymphatic system intact because of the lack of full understanding of anatomical variations of the ARM nodes and lymphatics in the axilla, the inconsistency of different ARM techniques in identifying the axillary ARM nodes, and the potentially high rate of ARM nodal metastases in breast cancer patients. The aims of this study was to know (1) the identification rate of ARM with fluorescence imaging (2) the distribution of these ARM nodes and (3) whether it's safe to spare the ARM nodes in breast cancer patients during SLNB or ALND. Method: Forty female patients of primary invasive breast cancer between 28 to 69 years old were included in the prospective study. Patients who had bilateral breast cancer, the history of axillary surgery, or the history of neoadjuvant chemotherapy were excluded. Methylene blue dye was used in the SLNB procedure. The ARM procedure was carried out to all the patients with a subcutaneous injection of the fluorescent dye indocyanine green into the medial bicipital sulcus in the upper arm about 15 minutes before SLNB or ALND. During surgery, photodynamic eye was used to detect the fluorescent nodes in the axilla. The fluorescent ARM nodes in the surgical region were removed and sent for pathological examination of node metastasis. Results: ARM was successful in 8 out of the 35 patients who underwent SLNB + ARM, in 3 out of the 5 patients who underwent ALND + ARM and in 25 out of the 35 patients who underwent ALND following SLNB + ARM. The ARM identification rate was 22.9%(8/35) in SLNB, and was 93.3%(28/30) in ALND. Totally, 119 fluorescent ARM nodes were detected, and 57.1 % (68/119) of them were located under the axillary vein, above the 2nd intercostobrachial nerve, and in the lateral of thoracic dorsal neurovascular bundle. Six out of 35 patients were found to have ARM-SLN crossover during SLNB+ARM procedure. Two out of 24 patients were found to have the ARM nodal metastases, with the pathological node stage being pN2, pN3 respectively. Conclusion: ARM with fluorescence imaging using indocyanine green was sensitive for identification of ARM nodes in ALND with a high success rate; ARM nodes had a certain distribution pattern in the axilla; ARM should not be performed to the patients with multiple nodal metastases in the axilla. Citation Format: Liu J, Li J, Zhou J, Cui H, Xiang J, Jia P, Xiang A, Chen H. Axillary reverse mapping using fluorescence imaging in the surgical treatment for breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-39.