Study On The Lymphatic Drainage Pattern Of Internal Mammary Area In Breast Cancer

Objective: Internal mammary lymph node?IMLN? metastasis has a similar prognostic importance as axillary lymph node?ALN? involvement in breast cancer patients. Axillary sentinel lymph node biopsy?ASLNB? is now regarded as the standard of care for patients without clinical and imaging evidence of ALN metastases. The accuracy of the hypothesis of axillary sentinel lymph node?ASLN?, the lymphatic drainage pattern of axilla, and the accuracy of ASLNB had been proved with subsequent axillary lymph node dissection?ALND?. With the development of sentinel lymph node biopsy, internal mammary sentinel lymph node biopsy?IM-SLNB? might be a minimally invasive technique for effective evaluation of the status of IMLN and help to guide individualized diagnosis and treatment. However, internal mammary sentinel lymph node?IM-SLN? was identified only in a small proportion of patients with the tradition radiotracer injection technique, which has been the restriction for IM-SLNB to date, and the accuracy of IM-SLNB is still controversial. A modified injection technique has been established in our breast cancer center, which could significantly improve the visualization rate of the IM-SLN. The modified injection technique broke through the bottle-neck of the low IM-SLN visualization rate with traditional radiotracer injection technique, which helps to the extensive development of IM-SLNB. As the extended radical mastectomy?ERM? has been abandoned for failing to increase the survival of cancer patients, we cannot validate the accuracy of the IM-SLN and the modified injection technique by this way. ^99mTc-dextran 40 can quickly display the lymph vessel and drain into the secondary lymph node from the sentinel lymph node. It has been evaluated in the pilot study of mice model. Then in clinical trial, ^99mTc-dextran 40 was injected intraparenchymally of breast guided by modified injection technique and observed the lymph drainage pattern of breast by lymphoscintigraphy to reflect the real lymphatic drainage of the breast from the aspects of the anatomy and physiology. Furthermore, we can validate that the IM-SLN detected by the modified injection technique is the true sentinel lymph node in the internal mammary.Methods: 1. In the test group, 24 mice were divided into four groups, with six mice in each, and used to validate the ability of making the lymph nodes imaging. ^99mTc-Dextran 40 was injected subcutaneously into the hind footpad of mice of the experimental groups?group A: 25 ?Ci; group B: 50 ?Ci; group C: 250 ?Ci?. ^99mTc-sulfur colloid?boiling time 5 min, 50 ?Ci? was injected subcutaneously into the hind footpad of mice in the control group?group D?. The injection point, background, sentinel lymph node?popliteal lymph node?, secondary lymph node?iliac lymph node?, tertiary lymph node?renal lymph node?, and contralateral hind foot sentinel lymph node were detected by ? detector on surface. Each group was separated into two subgroups. Subgroup one was observed for 2 h continuously after injection and subgroup two was observed for 12 hours before being anatomized. The mice were sacrificed via cervical dislocation and subjected to popliteal dissection, following by blue dyed draining lymph vessel to the blue dyed lymph nodes. The blue dye was administered in the both hind footpads at the same way 30 min prior to dissection. The injection point, background, blue stained popliteal lymph node, iliac lymph node, renal lymph node, contralateral popliteal sentinel lymph node, heart, liver, spleen, lung, and kidney collected and detected the radionuclide counts by a handheld ? detector.2. Based on the modified injection technique and SPECT/CT image fusion technology, thirty primary breast cancer patients were planned to enroll into this study to observe the real lymphatic drainage of the breast. The radiotracer(1.0¹.2ml, 37 MBq ^99mTc-labeled sulfur colloid) was injected into intraparenchyma of the affected side at the 6 and 12 o'clock positions 0.5¹.0 cm from the areola guided by ultrasound 16¹8h before surgery. The ^99mTc-Dextran 40?1.0¹.2 ml, 74MBq? was injected into intraparenchyma on the contralateral breast with the same way. Dynamic SPECT?Philips Bright View XCT? scintigrphatic images were obtained 60 min after injection. Subsequently, SPECT/CT was performed to identify the IMLNs and their intercostal. The first “hot spot” caught on lymphoscintigraphic images was considered to be a sentinel lymph node. IM-SLNB was performed for patients with the radioactive IM-SLNs in the affected side. By observing the lymph drainage of the breast at different time, we can analyze the accuracy of the sentinel lymph node of internal mammary area.The study was conducted within a single institute?Breast Cancer Center, Shandong Cancer Hospital and Institute?. All patients gave informed consent to participate in the study which had approval from the Shandong Cancer Hospital and Institute Research Ethics Board?No.: SDTHEC20130324?.Results: 1. Sentinel lymph node and secondary lymph node could be detected radionuclide counts by ? detector 5 min after injected ^99mTc-Dextran 40 in the experimental groups. The stained popliteal lymph node, iliac lymph node, and renal lymph node could be detected radionuclide counts after dissection in subgroup one. The counts of iliac lymph node and renal lymph node were equal to or greater than 10% of the popliteal lymph node. The counts of contralateral popliteal lymph node were equal to the background. All the lymph nodes in subgroup two could be detected radionuclide counts after 12 h. ^99mTc-Dextran 40 could drain into the lymph system quickly. The radionuclide counts increased with the increasing of radiation dose injection. The radionuclide counts of kidney and liver detected in all experimental groups was higher than spleen and lung, and the counts was increasing as time went on, which indicating that the radiotracer was primary collected in kidney and liver. The radionuclide counts were only detected in the sentinel lymph node in the control group.2. From Sep. 2015 to Feb. 2016, a total of 30 patients enrolled into this study. Lymph vessel drained to internal mammary area could be detected by SPECT 5³0min later after the ^99mTc-Dextran 40 injected intraparenchymally in the sound breast. SPECT/CT helps to locate the intercostal of IMLN. IMLNs imaged in 22 of the 30 patients. The first IMLN caught on lymphoscintigraphy was located in the first to fourth intercostal, and the proportion of them was 13.6%?3/22?, 27.3%?6/22?, 54.5%?12/22?, and 4.5%?1/22? respectively. Most of them concentrated on the second and third intercostal space. The lymph drainage of other IMLNs was drained from the first IMLN detected by SPECT/CT. The lymph drained step by step. In the affected side, IM-SLN was detected by both the SPECT/CT and ? detector. The visualization rate of IM-SLN was 63.3%?19/30?. All of them received IM-SLNB. The success rate of IM-SLNB was 94.7%?18/19?. The median number of IM-SLNs was 2?total 35, range 1⁴?. The site of IM-SLNs concentrated in the second?44.4%, 8/18? and third?55.6%,10/18? intercostal space. The median time-consuming of IM-SLNB was 10 min. The IM-SLN positive rate was 5.6%?1/18?, combining with ALNs metastases.Conclusions: 1. ^99mTc-Dextran 40 could drain into the lymph vessel and locate at sentinel lymph node, secondary lymph node, and tertiary lymph node of mice quickly, and does not affect the contralateral sentinel lymph node imaging.2. The lymph from different region of the breast could drain into the same IMLN, and then outward to other IMLN step by step, which means that the concept of IM-SLN is accurate.3. It also proved that the accuracy of the hypothesis of IM-SLN lymphatic drainage pattern, a fact that IM-SLN receives not only the lymphatic drainage from the primary tumor area but the entire breast parenchyma, and supported the IM-SLNB guided by “modified injection technology” from the aspects of anatomy and physiology.