| BACKGROUNDNipple discharge is the third most common complaint of breast disease and the second most common reason for consultation among patients requiring breast surgery.Nipple discharge can be physiologic or pathologic.Pathologic nipple discharge(PND),defined as spontaneous single-orifice serous or bloody nipple discharge,is a common clinical manifestation of a group of heterogeneous breast diseases which are caused by intraductal lesions such as intraductal papillary tumors,ductal ectasia,cystic hyperplasia,and breast cancer that affect discharge drainage.The lesions spreading along the affected duct are usually small and multiple.And these different types of benign and malignant lesions can coexist in the same breast and show multicentric and multifocal distribution.There is no consensus on the diagnosis of PND in the world at present.To make a definite diagnosis,patients with PND often need a triple evaluation:clinical,imageological,and pathological evaluation.Imageological evaluation,which is an indispensable part of the evaluation of PND,can evaluate the location and character of the lesions simultaneously.It includes ultrasonography,mammography,digital breast tomosynthesis(DBT),galactography,magnetic resonance imaging(MRI),etc.Limited by the resolution,the lesions in the duct are easy to be missed by various imaging methods because that the lesions are often small and multifocal.And the existing imaging methods are limited in distinguishing benign and malignant lesions.As the most advanced diagnostic method of breast imaging,MRI has not been widely used in PND due to the high cost and long scanning time.Besides,the interference of liquid signals in dilated duct make it harder to distinguish the lesions.Computed tomography(CT)is the first-line diagnostic method for other solid tumors.Owing to the limitations of imaging and ionizing radiation,CT has rarely been used in the diagnosis of breast diseases in the past.The advent of spiral CT has enabled lower radiation,faster scans and a wider range of images.It can be used to evaluate small tumors in three dimensions with an increased resolution.Multislice spiral CT has been used to evaluate breast tumors and the range of breast cancers.Due to tumor-associated angiogenesis,contrast agents can be enriched in tumor and show varying degrees of enhancement.Intravenous contrast agent can enhance suspicious features that are not obvious in plain scan,which is helpful for the identification of malignant lesions.Previous studies have reported the use of contrast-enhanced CT in the diagnosis of intraductal components and small invasive foci of breast cancer.Diversified post-processing technology of CT is also an advantage.Mammary ductoscopy has not been widely used yet.It requires special instruments and has high requirements on the operator.As an invasive endoscopic examination,it has problems such as operation failure and duct damage.Virtual endoscopy,as a noninvasive three-dimensional reconstruction technology of CT,can be used to visualize the interior of hollow organs.It allows the observation of an area where the real endoscope can not reach and facilitates quantitative measurement.Virtual endoscopy has been widely used to visualize the bronchi,colon,heart,blood vessels,and throat.But the application of virtual endoscopy in the duct is rarely reported,while most lesions of PND are located in the duct.OBJECTIVEThe preoperative diagnosis of PND in clinical practice has always been challenging.We hope to find a new diagnostic method which is good at both localization and qualitative diagnosis.In our study,galactography was combined with CT technology,contrast-enhanced technology,three-dimensional reconstruction technology,and virtual endoscopy technology to performe intracavity and extracavity imaging of discharging ducts and visualized the lesions in three dimensions.We proposed multimodal imaging of low-dose CT-galactography which including CT-galactography virtual ductoscopy,three-dimensional CT-galactography,and contrast-enhanced three-dimensional CT-galactography as a preoperative imaging evaluation of PND.It was compared with traditional imaging methods such as ultrasonography,mammography,and galactography to evaluate its diagnostic value in PND.We hope to improve the diagnosis of PND to provide guidance for treatment.METHODS1.A total of 41 female patients with spontaneous single-orifice PND who underwentsurgery at the Department of Breast Surgery of Qilu hospital of Shandong University between September 2020 and May 2021 were included in this study,among which 5 patients were accompanied by bilateral PND so that a total of 46 breasts were included.2.Before the operation,all patients had completed examinations such as ultrasonography,mammography,galactography,cytopathology of discharge,CEA of discharge,CA153 of discharge,and prolactin in plasma.All patients agreed to accept multimodal imaging of low-dose CT-galactography and signed ethical informed consent.3.After the completion of galactography,CT plain scan was performed in 46 breasts of 41 patients and multimodal imaging of low-dose CT-galactography which including three-dimensional CT-galactography and CT-galactography virtual ductoscopy was obtained after image post-processing.Contrast-enhanced CT scan was performed in 34 breasts of 30 patients and multimodal imaging of low-dose contrast-enhanced CT-galactography which including contrast-enhanced three-dimensional CT-galactography and CT-galactography virtual ductoscopy was obtained.We developed grading systems for CT-galactography virtual ductoscopy(including negative,polypoid-solitary,polypoid-multiple,combined,and superficial types),three-dimensional CT-galactography,and contrast-enhanced three-dimensional CT-galactography,respectively,and recorded the results of each imaging mode.All patients had a definite histopathologic diagnosis after surgery.4.The clinical and histopathologic characteristics of all patients were statistically analyzed.According to the postoperative histopathologic diagnosis which were regarded as the gold standard for diagnosis,the qualitative and localization diagnostic effects of multimodal imaging of low-dose CT-galactography and traditional imaging methods were evaluated.RESULTS1.PND with palpable mass had a higher malignant tendency(p=0.023).2.There were many different pathologic types of lesions causing PND.34.78%(16/46)of them were heterogeneous.80.65%(25/31)of high-risk and malignant lesions were multifocal or multicentral.Breast cancer with PND were in a variety of pathologic types.Lesions of breast cancer with PND tended to be multifocal,multicentral(p=0.000),and heterogeneous(p=0.000).62.50%(10/16)of the breast cancer were Luminal A type.And lymph node metastasis was rarely seen(2/16,12.50%).Some of the pathological results of the frozen section of PND were uncertain and inaccurate.3.Patients with PND could receive multi-mode imaging such as CT-galactography virtual ductoscopy,three-dimensional CT-galactography,and contrast-enhanced three-dimensional CT-galactography.4.The localization diagnostic performance of mammography did not show consistency with that of histopathologic examination(p=0.000,Kappa=0.096<0.4).The sensitivity of ultrasonography,galactography,multimodal imaging of low-dose CT-galactography,multimodal imaging of low-dose contrast-enhanced CT-galactography were 43.33%,53.33%,63.33%,and 97.30%.The sensitivity of multimodal imaging of low-dose contrast-enhanced CT-galactography was higher than that of multimodal imaging of low-dose CT-galactography,which showed consistency with galactography and was higher than that of ultrasonography.The specificity of ultrasonography,galactography.multimodal imaging of low-dose CT-galactography,multimodal imaging of low-dose contrast-enhanced CT-galactography were 85.29%.84.71%.81.18%,and 85.71%,which showed consistency with each other.Both of multimodal imaging of low-dose contrast-enhanced CT-galactography and multimodal imaging of low-dose CT-galactography were better than various traditional imaging methods in localization diagnosis.And multimodal imaging of low-dose contrast-enhanced CT-galactography was more sensitive.5.To identify the high-risk or malignant lesions,the cut-off value of CT-galactography virtual ductoscopy was the polypoid-solitary type,and that of both three-dimensional CT-galactography and contrast-enhanced three-dimensional CT-galactography was level 3.In the qualitative diagnosis of a whole breast,the sensitivity of ultrasonography,mammography,galactography,combination of traditional imaging methods,CT-galactography virtual ductoscopy.three-dimensional CT-galactography.contrast-enhanced three-dimensional CT-galactography,multimodal imaging of low-dose CT-galactography,and multimodal imaging of low-dose contrast-enhanced CT-galactography were 64.52%,32.26%,35.48%,74.19%,87.10%,96.77%,95.65%,93.55%,and 95.65%.The specificity of them were 66.67%,93.33%,93.33%,66.67%,73.33%,80.00%,81.82%,93.33%.and 90.91%.Area under receiver operating characteristic(AUC)of them were 0.672,0.628,0.588,0.731,0.876,0.941,0.947,0.981 and 0.974.The ability of every imaging mode of low-dose CT-galactography was better than that of every traditional imaging method.There was no statistical difference in the diagnostic performance between multimodal imaging of low-dose CT-galactography and multimodal imaging of low-dose contrast-enhanced CT-galactography,both of which were superior to the combination of the traditional imaging methods.In the qualitative diagnosis of a single lesion,galactography did not show consistency with that of histopathologic examination(p=0.146).The sensitivity of ultrasonography,mammography,combination of traditional imaging methods,three-dimensional CT-galactography,and contrast-enhanced three-dimensional CT-galactography were 35.90%,11.54%,51,28%,70.51%,and 87.72%.The specificity of them were 76.19%,100.00%,76.19%,76.19%.and 85.71%.AUC of them were 0.512,0.558,0.637,0.720,and 0.897.The ability of contrast-enhanced three-dimensional CT-galactography was better than that of three-dimensional CT-galactography,which had no significant difference from the combination of traditional imaging methods,but was better than ultrasonography or mammography.6.The average effective dose of multimodal imaging of low-dose CT-galactography was 1.66±0.78 mSv,while the average effective dose of multimodal imaging of low-dose contrast-enhanced CT-galactography was 2.68±0.84 mSv.One patient was excluded due to failure in galactography.60.87%(28/46)patients experienced mild pain which was easily tolerated.All patients tolerated well without serious complications.CONCLUSIONThe preoperative diagnosis of PND has always been challenging for the reason that there were many different pathologic types of lesions causing PND.PND with palpable mass had a higher malignant tendency.Multimodal imaging of low-dose CT-galactography showed better diagnostic performance than traditional imaging methods such as ultrasonography,mammography,and galactography.It was expected to be a one-stop preoperative imaging evaluation to assist the clinical diagnosis of PND.SIGNIFICANCE1.With galactography combined with CT technology,contrast-enhanced technology,three-dimensional reconstruction technology,and virtual endoscopy technology,the application of multimodal imaging of low-dose CT-galactography was proposed in preoperative image evaluation of PND for the first time.2.The diagnostic performance of multimodal imaging of low-dose CT-galactography were compared with the traditional imaging methods to confirm the former was better.3.Grading systems for CT-galactography virtual ductoscopy,three-dimensional CT-galactography,and contrast-enhanced three-dimensional CT-galactography were developed,respectively,to aid decision-making and communication between clinicians in clinical practice. |
