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Lumpectomy and Sentinel Lymph Node Biopsy Using Lumicell System for Intraoperative Detection of Residual Cancer

Barbara Smith, MD, PhD
Massachusetts General Hospital

Case Overview

Breast cancer remains one of the most commonly diagnosed cancers and a leading cause of cancer mortality among women globally. According to estimates from the World Health Organization, there were 2.3 million new cases of breast cancer and 685,000 associated deaths worldwide in 2020.1 Early detection and effective treatment are crucial for improving outcomes and survival rates.

Surgical resection, often combined with adjuvant radiation therapy and systemic treatments, is a primary treatment modality for early-stage breast cancer. Lumpectomy, also known as breast-conserving surgery or partial mastectomy, involves the removal of the cancerous tumor along with a surrounding margin of normal breast tissue.2 This approach aims to eliminate the cancer while preserving as much of the healthy breast as possible. However, achieving negative surgical margins, defined as the absence of cancer cells at the outer edge of the excised tissue, remains a significant challenge. Positive or close margins increase the risk of local recurrence and often necessitate additional surgical interventions, leading to increased patient morbidity, cosmetic concerns, and healthcare costs.3

The Lumicell system is an innovative intraoperative imaging technology designed to aid surgeons in the real-time detection and removal of residual cancer cells during breast cancer surgery, particularly lumpectomies and sentinel lymph node biopsies. Prior to the operation, the patient is administered an intravenous injection of the LUM015 fluorescent dye that selectively accumulates in cancerous tissues, enabling surgeons to visualize and target residual tumor cells that might otherwise be missed by standard techniques.4,5 By utilizing the Lumicell system's ability to accurately demarcate tumor margins, surgeons can potentially achieve more complete resection during the initial operation, reducing the need for subsequent surgeries and improving overall outcomes.6,7 

In a randomized-controlled study involving 406 patients the specificity and sensitivity of this method were measured to be 85.2% and 49.3%, respectively. Moreover, the method helped remove tumors that remained after standard lumpectomy in 27 out of 357 patients, with 22 of these cases initially deemed negative based on standard margin evaluation. The method also prevented second surgeries in 9 out of 62 patients who had positive margins.9

This case presentation involved a female patient with breast cancer who provided consent for the aforementioned procedures. The aim was to detect residual tumor cells during the initial operation and avoid subsequent surgeries.

This video provides a thorough presentation of lumpectomy and sentinel lymph node biopsy utilizing the Lumicell system to detect any remaining cancer during surgery. The video covers the entire process, from preoperative preparation to the final step of skin closure. 

Before surgery, the patient received an injection of Lume 015 dye and Technetium (99mTc) tilmanocept for sentinel lymph node mapping. Blue dyes should be avoided as they fluoresce in the same wavelengths as the Lume 015 dye.9 Following the procedures of transferring the patient to the operating room, administering anesthesia, and surgical skin preparation, the tumor boundaries were palpated, and the corresponding skin area was marked to guide the incision placement for optimal tumor removal and cosmetic outcome. Simultaneously, the sentinel node signal was marked, indicating the site for the axillary incision and subsequent node dissection.

A breast skin incision was made at the predetermined location. Dissection proceeded using retractors and electrocautery, with care taken to raise relatively thin skin flaps since the tumor felt superficially located. As dissection continued, the tumor could be palpated, guiding the direction of the flap raising to come around its sides about 1–1.5 cm beyond the tumor extent. The tumor was gradually mobilized, with care taken to maintain a circumferential margin of normal breast tissue around the palpable mass. Retractors were strategically placed around the tumor at approximately 90-degree angles to provide exposure while avoiding excessive tension. The tumor specimen was gradually developed into a cylindrical shape through the dissection process. Frequent reassessment by palpation helped ensure the full extent of the tumor was being removed with a circumferential margin of normal tissue. Any tissue appearing suspicious for tumor involvement was included in the resection. Metallic clips were applied perpendicularly at specific margins to maintain orientation. With the tumor fully mobilized based on the palpable and fluorescent boundaries, the cylindrical specimen was removed.

The specimen was then inked according to protocol, with the anterior margin marked in blue ink before any deformation of the fatty tissues could occur. It was imaged using the Lumicell device to assess for fluorescent signals indicating potential positive margins. On initial gross inspection, the resected specimen appeared to contain the entirety of the tumor with a rim of normal adipose tissue at the margins. However, the final pathology assessment would ultimately determine if the margins were clear of any remaining cancer cells. If residual fluorescence is detected in the cavity, additional targeted "shaved" margins are taken from the corresponding area in the lumpectomy cavity under fluorescence guidance. This process continues until all surfaces demonstrate no residual fluorescent signal, confirming negative margins. These shaved margin specimens were marked by orientation and submitted for pathological assessment alongside the main tumor specimen.

Once the tumor specimen was resected, attention turned to achieving complete hemostasis in the surgical cavity. Meticulous inspection was carried out, using retraction adjustment, irrigation, and electrocautery to cauterize any remaining bleeders. Care was taken to ensure no active bleeding remained that could potentially obscure or distort the surgical margins.

After the lumpectomy cavity was addressed, the sentinel lymph node biopsy was undertaken. An incision was made in the axillary area, and dissection was carried down through the subcutaneous fat using electrocautery and blunt dissection with retractors. The Lumicell probe was used to locate and guide the resection of the sentinel lymph node. Once the sentinel node was mobilized into view, metallic clips were applied in a sling-like configuration by the assistant to outline and secure the node. Meticulous dissection was then performed around the clips by the surgeon to remove the sentinel node. Per protocol, the extracted sentinel node was scanned using the Lumicell imaging system to detect any areas of residual fluorescent signal that could indicate metastatic tumor cells. A small focus was detected at one end of the node.

With the sentinel node removed and imaged, the area was palpated to ensure no additional abnormal nodes were present that could represent a falsely negative scenario. After achieving hemostasis, a long-acting local anesthetic (0.25% plain bupivacaine) was infiltrated liberally throughout the surgical sites to provide postoperative analgesia. The intercostal spaces along the chest wall were first injected by the surgeon, with any vessels being avoided. Then, shorter needles were used to infiltrate the subcutaneous tissue circumferentially around the skin incisions and any remaining space beneath the axillary skin flaps.

Once the areas were thoroughly anesthetized, closing sutures were placed at the axillary and breast incision sites. For the breast incision, strategic clip placement marks the lumpectomy cavity for subsequent radiation planning. The breast incision was meticulously closed in layers using 3-0 sutures. The subcuticular 4-0 suture line provided an inverted, seamless final skin closure. Finally, sterile liquid adhesive dressings are applied over both incision lines.

Ensuring proper technique is critical when utilizing the Lumicell fluorescence imaging probe intraoperatively. The entire surgical cavity was methodically scanned, maintaining direct tissue contact with the smooth glass probe face at all times to avoid any air gaps. Narrow thyroid retractors were employed to hold the cavity walls taut and eliminate any folding that could obstruct visualization. Since the system detects faint fluorescent signals, ambient light contamination had to be carefully controlled. Room lighting was dimmed, spotlights were extinguished, and the area around the probe was shielded with a towel to create a light-tight environment optimal for sensitive fluorescence detection.

This video highlights the importance of the Lumicell intraoperative imaging system and the key techniques required for its effective use during breast cancer surgery. The ability to detect and remove all residual cancer through fluorescence-guided visualization has the potential to improve outcomes by preventing the need for additional surgeries down the line. By utilizing this novel fluorescence imaging technology, the surgeon can maximize confidence in achieving negative margins and removing all detectable disease prior to concluding the surgery. This has implications for reducing re-operation rates, facilitating optimal radiation targeting, and potentially downstaging certain node-positive cases.8 While further clinical validation is still needed, this pioneering approach represents a promising step towards improving surgical outcomes and overall quality of care for breast cancer patients.

This video is particularly valuable for surgeons, surgical oncologists, and other healthcare professionals involved in the management and treatment of breast cancer. It provides a detailed, step-by-step demonstration of how to effectively incorporate the Lumicell system into the surgical workflow, highlighting the critical techniques and considerations for optimal utilization. Additionally, it serves as an educational resource for trainees and students in the field, offering insights into the latest technological advancements and their potential impact on breast cancer surgery.

Disclosures

Funding for this article was partially provided by Lumicell.

Statement of Consent

The patient referred to in this video article has given their informed consent to be filmed and is aware that information and images will be published online.

Citations

  1. Arnold M, Morgan E, Rumgay H, et al. Current and future burden of breast cancer: global statistics for 2020 and 2040. Breast. 2022;66. doi:10.1016/j.breast.2022.08.010.
  2. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. NEJM. 2002;347(16). doi:10.1056/nejmoa022152.
  3. Moran MS, Schnitt SJ, Giuliano AE, et al. Society of surgical oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages i and II invasive breast cancer. Int J Radiat Oncol Biol Phys. 2014;88(3). doi:10.1016/j.ijrobp.2013.11.012.
  4. Smith BL, Gadd MA, Lanahan CR, et al. Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system. Breast Cancer Res Treat. 2018;171(2). doi:10.1007/s10549-018-4845-4.
  5. Azari F, Kennedy G, Bernstein E, et al. Intraoperative molecular imaging clinical trials: a review of 2020 conference proceedings. J Biomed Opt. 2021;26(05). doi:10.1117/1.jbo.26.5.050901.
  6. Armani A, Borst J, Douglas S, Goldharber N, Taj R, Blair SL. Intraoperative margin trials in breast cancer. Curr Breast Cancer Rep. 2022;14(3). doi:10.1007/s12609-022-00450-6.
  7. Suurs F V., Qiu SQ, Yim JJ, et al. Fluorescent image-guided surgery in breast cancer by intravenous application of a quenched fluorescence activity-based probe for cysteine cathepsins in a syngeneic mouse model. EJNMMI Res. 2020;10(1). doi:10.1186/s13550-020-00688-0.
  8. Lanahan C, Gadd M, Specht M, et al. Abstract P2-12-05: real-time, intraoperative detection of residual breast cancer in lumpectomy cavity margins using the LUM imaging system: results of a feasibility study. Cancer Res. 2018;78(4_Supplement). doi:10.1158/1538-7445.sabcs17-p2-12-05.
  9. Smith BL, Hunt KK, Carr D, et al. Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery. NEJM Evid. 2023;2(7):EVIDoa2200333. doi:10.1056/EVIDoa2200333.