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Purpose The aim of the study is to construct an intraoperative nomogram for the prediction of non-sentinel lymph node (NSLN) metastasis based on the one-step nucleic acid amplification assay in breast cancer patients. Methods A total of 552 patients were enrolled in the training study and 1090 patients were enrolled in the validation study. The nomogram was constructed based on the molecular assay with logistic multivariate regression analysis in the training study and was validated in the validation study. Results A novel nomogram model was constructed with the total tumor load, the clinical primary tumor size, the number of positive and negative sentinel lymph nodes. The area under the receiver operating characteristic curve (AUC) of the model was 0.842. The AUC of the model which was sensitive to discern the patients with the stage of pN1 and ≥pN2 was 0.861. Conclusion The nomogram model will help to guide the axillary management intraoperatively and precisely confirm the target region of radiotherapy postoperatively.

More attention has been paid to the axillary management over the past 50 years, and clinical practice has been changed as results of the random controlled trials. The American College of Surgeons Oncology Group Z0011 and International Breast Cancer Study Group (IBCSG) 23-01 trials provided high-level evidence to support the omission of axillary lymph nodes dissection (ALND) in sentinel lymph node (SLN)-positive patients receiving breast-conserving surgery (BCS) and adjuvant systemic treatment. In patients treated with BCS, whole breast irradiation (WBI) with tangential fields could lead to substantial axillary irradiation and control the residual tumor burden in axilla, whereas (intraoperative) partial breast irradiation has no therapeutic effect on these residual axillary metastases. In the observation group of the IBCSG 23-01 trial, 425 patients received BCS and 80 (18.8%) of them just underwent intra-operative radiotherapy. While the 10-year axillary recurrence rate was acceptable low (1.7%, 8/467) in the no ALND group, it was 4.5% (6/134) in patients without axillary management, which was significantly higher than that of 0.6% (2/333) in patients with axillary management (P=0.0024). Should we accept an axillary recurrence rate as high as 4.5% in patients with only SLNs micrometastases? What is the best way to control the residual tumor burden in the axilla and decrease the recurrence rate if there is no ALND? The evidence showed that both WBI after BCS (Z0011, AATRM [Agencia d'Avaluacio de Tecnologia i Recerca Mediques]) and axillary regional nodal irradiation after mastectomy/BCS OTOASOR (Optimal Treatment Of the Axilla - Surgery Or Radiotherapy), AMAROS (After Mapping of the Axilla: Radiotherapy Or Surgery) could control the regional residual tumor burden when the SLN is positive and an ALND is omitted. In the modern era, systemic therapy could further decrease the risk of local/regional recurrences. After the subanalysis of the POSNOC (POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy), SERC (Sentinelle Envahiet Randomisation du Curage), and Dutch BOOG (BOrstkanker Onderzoek Groep) trials, a prediction model might be established to identify those patients who could beneft from no axillary management as a guide to clinical practice. At present, axillary management should still be required for patients with SLN micrometastases.

A novel method for the determination of trace gatifloxacin was established by resonance fluorescence techniques. It was based on the fact that oxidation of rhodamin 6G by hydrogen peroxide and Cu2+ was inhibited by gatifloxacin in Tris-HCl buffer medium and in presence of cetyl trimethyl ammonium bromide. The enhanced intensity (ΔF) of resonance fluorescence at 540 nm was proportional to the concentration of gatifloxacin in the range of 9.8 × 10−3 − 1.75 µg mL−1. The limit of detection was 2.9 ng mL−1 and the average recovery was 101.8% (n = 6) for gatifloxacin. The present method was applied to the determination of trace gatifloxacin in milk and biological fluids, and the obtained results were in good agreement with those obtained by HPLC.

A novel method for the determination of semicarbazide-sensitive amine oxidase (SSAO) activity in blood plasma has been developed. The method was based on the change of light scattering (LS) intensity resulting from the derivative product of the interaction of 2,4-dinitrophenylhydrazine (DNPH) with benzaldehyde produced by catalyzing of SSAO to benzylamine. In Britton-Robinson (B-R) buffer solution, the intensity of system's LS at 514.6 nm was significantly enhanced and was directly proportional to the concentration of benzaldehyde. In this method, SSAO enzyme activity is defined as the concentration of benzaldehyde (nmol) formed per mL plasma per hour. The range of determination of SSAO enzyme activity was 6.40 × 10−3 −0.340 nmol mL−1 h−1 with a detection limit of 1.92 × 10−3 nmol mL−1 h−1. The relative standard deviation was 2.8–4.1% and the average recovery was 67.9% (n = 6).

A simple and fast resonance Rayleigh scattering (RRS) method for the determination of arsenic was developed. The method is based on the formation of ion-association complexes {(IG)3·[As2(Mo2O7)12]H5}m of iodine green (IG) and heteropoly acid anion [As2(Mo2O7)12]14− formed as As (V) reacts with molybdate in H2SO4 solution. The ion-association complexes can lead to distinct enhancement of RRS. The enhanced RRS intensity is proportional to the concentration of As (V) in the range of 0.008–0.40 µg ml−1. The optimum conditions, the influence factors for the reaction, and the effects of coexisting substances have been investigated. The method has high sensitivity and good selectivity; the detection limit for As (V) (3 S 0/S) is 1.50 ng ml−1. The method can be applied to the determination of As (V) in hair samples. Furthermore, the mechanism of the reaction and the reasons for RRS enhancement is discussed.

Dear editor Internal mammary lymph node (IMLN) metastasis has a similar prognostic importance as axillary lymph nodal involvement in breast cancer patients.1 Patients with both axillary- and internal mammary-positive nodes have a very poor prognosis.2 Reliable data for internal mammary nodal metastases are reported to be present in 18%–33% (mean 23.4%) of patients who have not been treated with neoadjuvant chemotherapy (NAC) mostly concomitant with axillary metastases, and metastases exclusively situated in the internal mammary chain occur in 2%–11% of patients,3 but limited data are available in the context of NAC. Current imaging techniques, such as positron emission tomography/computed tomography, ultrasound, and magnetic resonance imaging, could usually detect metastases lesions larger than 5 mm.1 Zhang et al reported that of a total of 112 (n=809; 13.8%) patients considered to have IMLN-positive diseases (the median size of the enlarged IMLN was 1.3 cm [range: 0.5–3.0 cm]) on the basis of imaging reports, only ten patients underwent ultrasound-guided fine-needle aspiration to obtain pathologic confirmation and all of the sampled lymph nodes were confirmed to contain malignant cells before receiving chemotherapy. Patients with positive IMLN before NAC received adjuvant radiation to the breast or the chest wall and the regional lymphatics including the IMLN chain with a median dose of 60 Gy if the IMLNs normalized after chemotherapy and 66 Gy if they did not.4 However, some patients with positive IMLN could not be detected by imaging techniques and fine-needle aspiration could not be performed for all suspicious positive IMLNs under ultrasonographic guidance. High-risk did not mean IMLN metastases, and low-risk did not mean IMLN negative.1 Hence, we recommend internal mammary sentinel lymph node biopsy (IM-SLNB) as a minimally invasive technique for the efficient evaluation of the status of internal mammary sentinel lymph node (IM-SLN) to obtain complete nodal staging and guide adjuvant radiotherapy. Sixty female patients who had histologically proven clinical stage T1 through T4, N0 through N3, M0 primary invasive breast cancer treated at the Breast Cancer Center in Shandong Cancer Hospital and Institute between 2012 and 2014 were enrolled in the study. Anthracycline- and taxane-based regimens were done. An amount of 18.5–37 MBq of 99mTc-labeled sulfur colloid in 1.0–1.2 mL volume was injected intraparenchymally at the 6 and 12 o’clock positions 2–3 cm away from the nipple under ultrasonographic guidance 3–18 hours before surgery in all patients. Subsequently, lymphoscintigraphy was performed 0.5–1.0 hours before surgery. IM-SLNB was performed on all patients with IM-SLN detected by preoperative lymphoscintigraphy or intraoperative gamma-probe. The IM-SLNB was performed from the sternal border in a lateral direction for 3–4 cm, and the pectoral major and minor muscle fibers were separated to expose the posterior intercostal space. The external and internal intercostal muscles were divided transversally from the sternal border. In this procedure, particular care must be taken to avoid injury to the inferior parietal pleura and internal mammary vessels. The visualization rate of IM-SLNB was 63.3% (38/60). The median age of the 38 patients was 50 years (range: 32–68 years). The success rate of IM-SLNB was 97.4% (37/38). The median number of IM-SLNs was 2 (total 60, range: 1–4). The site of IM-SLNs concentrated in the second (44.7%, 17/38) and third (55.3%, 21/38) inter-costal space. The median time consuming was 10 minutes (range: 5–30 minutes). The IM-SLN-positive rate was 8.1% (3/37), and all of them combined with positive axillary lymph nodes. Only two patients had intraoperative surgical complications. One had an injury to pleura and another had an injury to the internal mammary artery. They were repaired intraoperatively with no pneumothorax on postoperative chest radiography and postoperative bleeding. It is necessary to perform IM-SLNB after NAC to ascertain the nodal staging and pathological status as there were still 8.1% of patients with IM-SLNs metastases after NAC. The visualization and success rates of IM-SLNB are acceptable. The 2015 National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines5 recommended that internal mammary radiotherapy should be performed on those patients with clinically and pathologically involved IMLN. IM-SLNB could help to make clear the pathological status and provide an accurate indication of radiation to the internal mammary area in case of under-stage and under-/over-treatment.

Bin-Bin Cong,1,2,* Xiao-Shan Cao,1,2,* Peng-Fei Qiu,1 Yan-Bing Liu,1 Tong Zhao,1 Peng Chen,1 Chun-Jian Wang,1 Zhao-Peng Zhang,1 Xiao Sun,1 Yong-Sheng Wang1 1Breast Cancer Center, Shandong Cancer Hospital and Institute, 2School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China*These authors contributed equally tothis study Abstract: According to the hypothesis of internal mammary sentinel lymph node (IM-SLN) lymphatic drainage pattern, a modified radiotracer injection technique (periareolar intraparenchyma, high volume, and ultrasonographic guidance) was established. To verify the accuracy of the hypothesis and validate the modified radiotracer injection technique and to observe whether the lymphatic drainage of the whole breast parenchyma could reach to the same IM-SLN, different tracers were injected into different locations of the breast. The validation study results showed that the correlation and the agreement of the radiotracer and the fluorescence tracer are significant (case-base, rs=0.808, P

Xiang Bi,1,* Yongsheng Wang,2 Minmin Li,1,* Peng Chen,2 Zhengbo Zhou,2 Yanbing Liu,2 Tong Zhao,2 Zhaopeng Zhang,2 Chunjian Wang,2 Xiao Sun,2 Pengfei Qiu2 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Shandong Cancer Hospital, 2Breast Cancer Center, Shandong Cancer Hospital, Jinan, People’s Republic of China *These authors contributed equally tothis study Background: The main purpose of the study reported here was to validate the clinical value of the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram that predicts non-sentinel lymph node (SLN) metastasis in SLN-positive patients with breast cancer. Methods: Data on 1,576 patients who received sentinel lymph node biopsy (SLNB) at the Shandong Cancer Hospital from December 2001 to March 2014 were collected in this study, and data on 509 patients with positive SLN were analyzed to evaluate the risk factors for non-SLN metastasis. The MSKCC nomogram was used to estimate the probability of non-SLN metastasis and was compared with actual probability after grouping into deciles. A receiver-operating characteristic (ROC) curve was drawn and predictive accuracy was assessed by calculating the area under the ROC curve. Results: Tumor size, histological grade, lymphovascular invasion, multifocality, number of positive SLNs, and number of negative SLNs were correlated with non-SLN metastasis (P