Photodynamic Eye Camera Research Articles

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.

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.

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 P3-01-01: Fluorescence navigation system using indocyanine green (ICG) instead of radioisotope for sentinel lymph node (SLN) biopsy in early breast cancer

Abstract Background: Dual localisation methods with blue dye and radioisotope are commonly employed for SLN identification but potential drawbacks include allergic reactions, staining of cutaneous/surgical breast tissue, radiation exposure and mandatory licencing. A majority of studies have reported near 100% identification rates using the fluorescent tracer ICG in combination with standard tracer agents. A feasibility study (ICG-10) has confirmed high sensitivity of ICG fluorescence mapping for SLN detection in early breast cancer with 95% of nodes both blue and fluorescent. This follow-on study has specifically evaluated a combination of ICG with blue dye for SLN localization. Methods: As an observational cohort study, 50 consecutive patients (49 female; 1 male) with core biopsy proven unilateral invasive (37 cases) or non-invasive (13 cases) breast cancer underwent SLN biopsy with blue dye and ICG. All patients were clinically and sonographically node negative. Axillary surgery (SLN biopsy) followed neoadjuvant chemotherapy in 5 patients (10%). The median patient age was 48 years and for primary surgical patients median tumor size was 19mm. Patients received a dual peri-areolar/intradermal injection of blue dye [2ml 2.5% Patent Blue] and ICG [2mls 0.5%] after induction of anaesthesia. The number of sentinel nodes for each patient was recorded numerically and whether blue, fluorescent or both. Subcutaneous lymphatics were visualised with a photodynamic eye camera and nodal and procedural detection rates calculated for ICG alone and in combination with blue dye. Results: Final analysis was performed on a total of 87 nodes retrieved from 50 patients with an average nodal count of 1.8 per patient (range 1 – 4). Eighty-four nodes were blue and fluorescent and 3 nodes fluorescent only with no harvesting of non-blue, non-fluorescent nodes. At least one transcutaneous lymphatic channel was visible in all cases. Nodal detection rates for ICG alone and combined with blue dye were 100% (87/87) and 96% (84/87) respectively. Metastases (>0.2mm) were present in 18 nodes which were all blue and fluorescent and a total of 10 patients had at least one positive node (node positivity rate = 20%). The procedural detection rate was 96% (48/50) for blue dye and 100% (50/50) for ICG with 2 patients having fluorescent only nodes which were deemed sentinel (4%). No serious adverse reactions were noted. Conclusion: ICG fluorescence navigation system permits real-time visualization of lymphatic tissues and provides an additional dimension to SLN biopsy using methodology which is sensitive, valuable and safe. These results confirm accuracy of ICG fluorescence for SLN identification with nodal sensitivity of 96% for a combination of blue dye and ICG. With further refinements of the technique, use of ICG as a sole tracer may be possible agent without concerns about excessive nodal yield but improved patient convenience and costs. Citation Format: Benson JR, Pitsinis V, Provenzano E, Wishart GC. Fluorescence navigation system using indocyanine green (ICG) instead of radioisotope for sentinel lymph node (SLN) biopsy in early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-01.

Availability of tissue rinse liquid-based cytology for the rapid diagnosis of sentinel lymph node metastasis and improved bilateral detection by photodynamic eye camera.

On sentinel lymph node navigation surgery for early invasive cervical cancers, to gain high sensitivity and specificity, the sentinel nodes should be detected bilaterally and pathological diagnosis should be sensitive to detect micrometastasis. To improve these problems, we tried tissue rinse liquid-based cytology and the photodynamic eye. From 2005 to 2013, 102 patients with Stage Ib1 uterine cervical cancer were subjected to sentinel lymph node navigation surgery with Technetium-99 m colloid and blue dye. For the recent 11 patients with whom bilateral sentinel node detection was not available, the photodynamic eye was selectively examined. The detected sentinel node was cut along the minor axis into 2 mm slices, soaked in 10 ml CytoRich red and then subjected to tissue rinse liquid-based cytology at the time of surgery. With the accumulation of 102 Ib1 patients subjected to sentinel lymph node navigation surgery, the bilateral sentinel node detection rate was 67.7%. The photodynamic eye was examined for the recent 11 patients who did not have bilateral signals. Out of the 11, 10 patients obtained bilateral signals successfully. During the period of examining the photodynamic eye, a total of 34 patients were subjected to sentinel lymph node navigation surgery. Thus, the overall bilateral detection rate increased to 97% in this subset. Two hundred and five lymph nodes were available as sentinel nodes. The sensitivity of tissue rinse liquid-based cytology was 91.7%, and the specificity was 100%. False positivity was 0% and false negativity was 8.3%. Detection failure was observed only with one micrometastasis and one case of isolated tumor cells. Combination of photodynamic eye detection and tissue rinse liquid-based cytology pathology can be a promising method for more rewarding sentinel node detection.

The use of indocyanine green to detect sentinel nodes in breast cancer: A prospective study

BackgroundAlthough Indocyanine green (ICG) is used to find sentinel nodes (SN) in patients with breast cancer (BC), its role in clinical practice is still debated, and needs a definitive validation to be included in the standard approach to finding sentinel nodes in breast cancer. Materials and methodsTo validate the ICG methods of detecting the SN in BC we have recently concluded a prospective validation trial. Patients with clinically node-negative, invasive early BC scheduled for breast surgery and SN biopsy were included in the trial. All the patients underwent SN detection using both the standard-of-care procedure using radioisotope technetium (99mTc) and the ICG, using the Photodynamic Eye camera. A comparison of the detection rate and the diagnostic accuracy of the two methods was performed to detect the equivalency of the two approaches. ResultsAt the end of the enrolment, 301 patients were considered eligible and included in the trial, and 589 nodes were removed. Five hundred and eighty-three nodes (99%) were identified with ICG (median 2 nodes per patient) and 452 (76.7%) were identified with 99mTc (median 2 nodes per patient). A concordance index of 98.75% (CI, 95% = 97.1%–99.5%) was detected. The dosage given ranged from 0.3 to 1.4 ml. ICG was used in all patients eligible for SN biopsy without any significant acute side effects. ConclusionsThe index of concordance between 99mTc and ICG seems to be extremely high, suggesting that ICG could be validated as an alternative method to 99mTc in the detection of SN in BC.

Abstract P1-01-01: Fluorescence mapping with indocyanine green for sentinel lymph node detection in early breast cancer – results of the ICG-10 study

Abstract Background: Dual localization methods with blue dye and radioisotope are commonly employed for SLN identification but potential drawbacks include allergic reactions, radiation exposure and mandatory licencing. Identification rates exceeding 95% have been reported using the fluorescent tracer indocyanine green (ICG) as a navigation system. A feasibility study was undertaken to confirm the sensitivity and safety of ICG as a tracer agent for sentinel lymph node (SLN) identification in early breast cancer. Methods: In an open, non-randomised study, 100 clinically node negative patients (95 unilateral; 5 bilateral) scheduled to undergo routine SLN biopsy for core-biopsy proven invasive breast cancer were identified at the multidisciplinary team meeting [53 screen-detected; 51 symptomatic]. All patients received triple localization with blue dye (2.5% Patent Blue), radiocolloid and ICG (0.5%). The number of sentinel nodes for each patient were recorded numerically and whether blue, radioactive or fluorescent. Subcutaneous lymphatics were visualized with a Photodynamic Eye camera and sensitivity of individual tracers alone and in combination calculated. Approval was granted by the Local Research Ethics Committee and the Medicines and Healthcare Products Regulatory Agency for use of ICG as a third tracer agent. Results: Final analysis was performed on 104 procedures in 99 patients (1 exclusion - benign adenomyoepithelioma on definitive pathology). A total of 242 nodes were removed of which 201 were defined as sentinel (blue and/or radioactive) with an average nodal retrieval of 2.33 per procedure. Amongst these, 25 contained either macrometastases (n = 16) or micrometastases (n = 9), yielding procedural and node specific positivity rates of 17.3% (18/104) and 12.4% (25/201) respectively. 100% of these ‘true’ SLNs were fluorescent (201/201), 95.0% (191/201) were both fluorescent and blue, 77.6% (156/201) were fluorescent and radioactive whilst 73.1% (147/201) were blue, radioactive and fluorescent. The procedural detection rates were 99% (103/104) for blue dye, 91.3% (95/104) for radioisotope and 100% for fluorescence. All 25 positive nodes were identified with all three tracers and all 18 node positive patients had tumour deposits in the first SLN excised. The majority of ‘non-sentinel’ nodes were fluorescent (36/41) and no serious adverse reactions occurred. Conclusion: ICG fluorescence imaging permits real-time visualization of lymphatics and provides an additional dimension to SLN biopsy which is safe and effective. These results confirm high sensitivity for fluorescence in SLN identification and the combined nodal sensitivity for ICG and blue dye (95.0%) was higher than for blue dye and radioisotope (73.1%). With further refinements in the technique may it may be possible to eventually rely on ICG as a sole tracer agent. Moreover, a marginally higher nodal yield with fluorescent mapping may allow more confident omission of completion axillary dissection in selected SLN positive patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-01.