Experimental Study And Clinical Application For Sentinel Lymph Node Mapping Of Breast Cancer

Part I Establishment of Rabbit VX2 Breast Cancer Model and Evaluation of the Feasibility on Sentinel Lymph Node MappingObjective:To establish a rabbit VX2 breast cancer model, then to evaluate the feasibility for sentinel lymph node(SLN) mapping. Materials and Methods:30 New Zealand White Rabbits were injected lml VX2 tumor tissue mass suspension in the left and third breast, and then a rabbit VX2 breast cancer model was established; the imaging examinations were arranged when tumor growth was at the second to third weeks. All the experimental rabbits were gave numbers at random, which was classified odd number group and even number group; all live rabbits with bearing tumor underwent MR-LG examinations, but only odd number group bearing tumor rabbits completed CT-LG and 99Tcm labeled isotope exams orderly. On the 3D images which were obtained by reconstruction using the raw CT or MR imagings, the first one or several lymph node(s) in the lymphatic drainage pathway was/were defined as the SLN(s). According to the presentation condition of SLN and affected lymphatic drainage pathway, the imaging effect was classified as good grade (with both SLN and lymphatic drainage pathway presented) and poor grade (either SLN or lymphatic drainage pathway absented). Results:(1)The overall rate of successful establishment of the model is 100%, and the presentation of necrosis and cyst forming, big ulcer of tumor surface were in 53.3%(16/30) and 36.7%(11/30) implanted tumors, respectively. (2) The imaging examinations were performed at the 2-3 weeks after the VX2 tumor being implanted, and 80%(24/30) bearing tumor rabbits completed MR-LG exam when axillary lymph nodes enlargement were found by palpation in 62.5%(15/24) experimental rabbits. (3) In odd number rabbits, the achievement ratio for CT-LG and 99Tcm isotope exams were 73.3%(11/15) and 66.7%(10/15), respectively. (4) The imaging grade in good, and poor were 79.2%(19/24) and 20.8%(5/24) on MR-LG, and 81.8%(9/11) and 18.2%(2/11) on CT-LG, respectively. Conclusion:This VX2 breast cancer rabbit model is easy to establish, which has high rate of living tumor and good tolerance for the operations of experiment. Part?Animal Experimental Study on CT-LG for SLN Mapping of VX2 Rabbit Breast CancerObjective:To study the fesibility of the interstitial magnetic resonance lymphography(MR-LG) using Magnevist contrast agent for sentinel lymph node mapping in rabbit VX2 breast cancer, as well as to find a suitable scanning parametes. Materials and Methods:MR-LG exams were completed on 30 New Zealand White Rabbits before VX2 tumor being implanted and after the tumor growing to the 2th-3th week. Short TI Inversion Recovery (STIR) sequence scanning and T1-weighted 3-dimensional (3D) scanning, including axial and coronal positions were underwent before and after the undiluted gadopentetate dimeglumine being injected, and the signal noise rate(SNR) was cunted by the ratios of signal intensity(SI) and background noise standard deviation (SD). All lymph nodes were recorded on the imagings of STIR scanning and MR-LG, then comparing with the results of SLN biopsy. Results:(1)A11 rabbits had completed the first MR-LG examinations, and 80%(24/30) bearing tumor rabbits completed the second MR-LG examinations; The 3D imaging grade in good, and poor grade were 79.2%(19/24) and 20.8%(5/24), respectively. (2) The SNR of lymph node were higher than that of affected lymph duct and muscle after the contrast agent being injected on all scanning phases(all P value<0.05), but there were no differences between SLN and n-SLN on affected lymph duct and muscle; the axial scanning images were more clear than coronal scanning images(P value<0.05). (3).There were 26 lymph nodes on CT-LG and 28 lymph nodes on STIR scanning in all, but there was no significant difference about the size of the two(t=0.124,P=0.902).(4)The achievement ratio of SLN Biopsy was 95.5%(21/22), and all 17 bearing tumor rabbits with good grade imaging underwent the SLN Biopsy, then got 18 SLN and 14 n-SLN. However, the number and size of the SLN, which were got from SLN Biopsy, MR-LG and STIR, were no differences. Conclusion:The Magnevist contrast enhanced MR-LG is useful for the SLN mapping of VX2 rabbit breast cancer, and the axial scanning image is better than that of coronal scanning. Part?Animal Experimental Study on CT-LG for SLN Mapping of VX2 Rabbit Breast CancerObjective:To study the fesibility of the interstitial computed tomography lymphography(CT-LG) using Iopamidol contrast agent for sentinel lymph node mapping in rabbit VX2 breast cancer, as well as to find a suitable scanning parametes. Materials and Methods:Eleven living odd number bearing tumor rabbits were underwent CT-LG examination after 24 hours later of MR-LG exams, and scanning were achieved at instantly,5min and 10min after the contrast agent being injected and massaged. The imaging effect was classed two grades according to the display of SLN and affected lymph duct, and grade good was defined as lymph duct and SLN displaying, while grade poorwith no lymph duct or SLN displaying. All lymph nodes on CT-LG were recorded, then comparing with the result of SLN Biopsy. Results:(1) Eleven odd number bearing tumor rabbits completed CT-LG, and the percentage of CT-LG images were 81.8%(9/11) and 18.2%(2/11), respectively. (2)On the nine good grade CT-LG,20 lymph nodes were seen clearly when scanning instantely after the contrast agent injected and massaged, but only 90% and 65% of these 20 lymph nodes displayed when scannings were set at 5min and 10min after the injection and massage; and the average CT unit of lymph nodes were higher than that of affected lymph duct and muscle, falling-off sharply with the delay of time (P=0.002and 0.017). (3)There were 20 lymph nodes in all on CT-LG images(10 SLN and n-SLN,respectively); and oval shape and bigger size than n-SLN were found frequently, which had no differences between SLN and n-SLN. (4)Ten bearing tumor rabbits with CT-LG examinations had underwent SLN Biopsy successfully, then 13 SLN and 9 n-SLN were achieved; the lymph nodes on CT-LG were smaller than that of SLN Biopsy(P=0.021). Conclusion:CT-LG is useful for the SLN mapping of VX2 rabbits breast cancer, and the instant scanning after injection and massage of Iopamidol is enough for the SLN and its affected lymph duct displaying. Part IV Experimental Study on Lymphography in Evaluating the Sentinel Lymph Nodes of Rabbit'Breast Cancer and InflammationObjective:To establish rabbit breast cancer and inflammation model, then to evaluate the feasibility for sentinel lymph node(SLN) mapping using the method of lymphography. Materials and Methods:30 VX2 rabbit breast cancer and 10 inflammate rabbit models were established by tumor tissue mass suspension and the yolk colloid injection; and all tumor group rabbits were gave numbers at random, then odd number and even number group were divided. All live experimental rabbits underwent MR-LG examinations (STIR sequence scanning were underdone before the injection of contrast agent subcutaneously), and odd number bearing tumor and all inflammate rabbits also had CT-LG examinations. On the 3D images which were obtained by reconstruction using the raw CT or MR imagings, the first one or several lymph node(s) in the lymphatic drainage pathway was/were defined as the SLN(s), and the others were n-SLN, then comparing with the first lymph node from the direction of the tumor to the axillary space, as well as to the results of SLN Biopsy. Results:(1) On CT-LG images, the long and short diameter of SLN and n-SLN in bearing tumor rabbits were bigger than that of inflammate group rabbits, and there were no differences(P value were 0.154,0.283,0.346 and 0.629, respectively); irregular filling defect on the margin was more frequent in metastatic SLN (100%,2/2) than that of in inflammate SLN(10.5%,2/19). (2)On MR-LG images, the long and short diameter of SLN, as well as the shape were no significant different between the tumor and inflammate group rabbits(P value were 0.311,0.914 and 0.677, respectively); Comparing with the SLN biopsy pathology, the long diameter of metastatic SLN was bigger than that of inflammate SLN, and ring-liking enhancement was more frequent found in inflammate SLN(2/10 vs 13/18), which were significant differences between metastatic and inflammate SLN(P=0.04 and 0.016). (3)There was no difference in the long and short diameter of SLN on MR-LG and of the first lymph node of STIR between the tumor bearing and inflammate rabbits. (4)Comparing with the results of SLN Biopsy, both the long and short diameter of SLN in bearing tumor and inflammate rabbits were smaller than that of SLN achieved by SLN Biopsy, but the difference was bigger in MR-LG than that of CT-LG(P value were 0.011 and 0.004,respectively) in tumor bearing group rabbits. Conclusion:Metastatic and inflammate SLN has some characteristics on CT-LG and MR-LG images; and SLN in CT-LG images is more true reflection SLN in SLN Biospy than that of MR-LG.Part V The Clinical Application Study on CT-LG for Sentinel Lymph Node Mapping of Breast CancerObjective:To determine the accuracy of computed tomographic (CT) localization and the feasibility of Sentinel Lymph Node (SLN) mapping with CT lymphography (CT-LG), and then directing of sentinel lymph node biopsy(SLNB) in early-stage breast cancer patients. Materials and Methods:Thirty-four patients with confirmed breast cancer underwent 40-row CT scanning, and the first one or several lymph node(s) in the lymphatic drainage pathway was/were defined as the SLN(s). To accurately localize the SLN,19 patients (55.9%) underwent the percutaneous lymph node puncture procedure.Then comparing with SLNB, if the number was equal, the evaluation was coherence, more or less were respective high and low evaluation. The quality of imaging were classed?and?by lymph duct appearance or not on the image which were reconstructed by volume. Obesity was defined when the value of body mass index (BMI) was more 25. The morphologic features of all the SLNs on CT scans were analyzed and compared with the SLN biopsy pathologic diagnosis. Results:(1)The accuracy of CT localization for SLN was 89.5%, and the accuracy increased to 100% when the CT scan technique was combined with the blue dye method. (2)All 34 patients showed SLN, and 88.2%(n=30) cases mapping class were grade?,11.8%(n=4) were grade?. The obese patients were difficult to acquire high quality mapping, and the difference was significant (P<0.05). (3)Eighty-five SLN and sixty-three lymph duct in all of 34 patients were identified on CT-LG mapping. Comparing with the results of SLNB,47.1%(n=16) patients CT-LG mapping were equal evaluation,20.6%(n=7) and 32.3%(n=11) patients had high and low evaluation, respectively. The BMI was the main reasons, which had significant differences(P< 0.05). (4) Twenty-three patients with 78 SLNs were negative, and eleven patients with 19 SLNs were positive confirmed by pathology, but on CT-LG mapping,67 negative and 18 positive SLNs were acquired. The 22.4%(15/67)negative SLN and 66.7%(12/18) positive SLN were round shape, the difference was significant(P< 0.05). The 9.0%(6/67) negative SLNs and 27.8(5/18) positive SLNs demonstrated filling defect on the center, but irregular filling defect on the margin were found only in 33.3%(6/18) of positive SLNs. However,4 SLNs (3 patients) combined with multi-small lymph nodes on CT-LG mapping were also confirmed tumor cell invasive by pathology. Conclusion:CT-LG is useful for accurate localization for SLN, and the accuracy increased to 100% when the CT scan technique was combined with the blue dye method; CT-LG can sufficiently visualize breast lymphatic drainage and may have potential utility for breast SLN mapping, but can be influenced by the obese patients. On CT-LG mapping, SLN that showed round shape, filling defect on the margin, and combined with multi-small lymph nodes around, were likely to metastatic SLN.