3.1 Clinical general data. There were 24 cervical cancer patients among these excluded cases(Figure 1). In sixteen of the 24 cases, the enlarged lymph nodes that can be showed in CT imaging cannot be visualized by conventional ultrasound. In five of the 24 cases in whom size of nodes were small(<10mm), the US-FNAC operations were abandoned. There were no safe access path for puncture to help avoid injury to major vessels in three patients. Of the 92 cases, the age ranged from 25 to 80 years old (means:51.5±10.8y). The average size of nodes ranged from 11mm to 28mm (average:17.1±4.0mm). In the 92 cases, they ranged in the body mass index（BMI）from 14.6 to 32.0 (means:22.0±3.4). In 79 cases (85.9%) , the multiple nodes were present, and a solitary node was present in thirteen cases(14.1%). 20G and 21G fine needles were used to perform the US-FNAC procedure in 60 cases. The biopsies was performed with 22G and 23G needle using suction in 32 cases.
The anatomical grouping of PLANs are divided into left and right distribution by abdominal aorta. The inferior mesenteric artery is taken as the boundary level line and divided into upper and lower region (Figure 2). There were 55 cases in the left para-aortic region(levelⅠ: 27 cases and level Ⅱ: 28 cases). There were 37 cases in the right para-aortic region(level Ⅲ: 29 cases and level Ⅳ: 8 cases)(Table 1).
3.2 Cytological findings and Final diagnosis. The results of cytological diagnosis by the biopsies were as follows: malignant(n=62;67.4%), suspicious(n=11;12.0%), undetermined(n=5;5.4%),benign(n=10;10.9%), and unsatisfactory(n=4;4.3%). The unsatisfactory materials were provided in 4 cases (4.3%), but 5 cases belonged to undetermined group. In 2 undetermined cases and one inadequate case, a repeat US-FNAC was performed, which provided sufficient sample for the diagnosis of squamous cell carcinoma. The remaining 3 undetermined cases and 2 inadequate cases were confirmed as malignant by clinical follow-up and imaging for final diagnosis. However, the final benign diagnosis was established in one inadequate cases due to obvious shrinkage by four months follow-up. Therefore，among 9 sample, there were 8 malignant(false-negative) and 1 benign cases(true-negative) in final diagnosis(Table 2).
Ten cases were reported as benign diagnosis(Figure 4a). Three cases of FNAC benign results were performed by subsequent surgical resections for therapeutic and diagnostic purposes and the definitive malignant diagnosis was rendered. The final diagnosis of the remaining 7 benign FNAC results were considered as benign diagnosis by clinical follow-up and imaging. There was no a false-positive result in the study. Therefore，final diagnosis in 10 benign sample consisted of 3 malignant(false-negative) and 7 benign cases(true-negative).
Eighty eight (95.7%) biopsy materials were regarded as satisfactory sample by the more than 10 experienced cytopathologist. Of these 73 FNAC malignant specimens, 62 were considered as an unambiguous malignant diagnosis, including 5 cases of adenocarcinoma(Figure 4b), 39 cases of squamous cell carcinoma(Figure 4c), and 18 cases undifferentiated metastatic carcinoma(Figure 4d), while 11 were reported as a probable metastatic carcinoma diagnosis. According to the definition(iv,v),the 73 cases were all regarded as malignant cases in final diagnosis(true-positive).
3.3 Accuracy of US-FNAC. Due to different definitions of false negative and true negative that previous researchers have adopt for assessing diagnostic accuracy(16), we used the following analysis methods to present our data in this study. When we excluded the four inadequate cases in our analyses and regarded undetermined specimens as negative cytologic results. The values of the true positive, false positive, false negative and true negative were 73, 0, 8 and 7 respectively. The sensitivity, specificity, PPV, NPV and accuracy of FNAC in distinguishing benign from malignant were 90.1%(95%CI:0.809-0.953), 100%(95%CI:0.561-1), 100%(95%CI:0.938-1), 46.7%(95%CI:0.223-0.726) and 90.9%(95%CI:0.848-0.970) respectively. If the five cases with undetermined cytologic diagnosis were excluded, the values of the true positive, false positive, false negative and true negative were 73, 0, 3 and 7 respectively. The sensitivity,specificity,PPV,NPV and accuracy of FNAC in distinguishing benign from malignant were 96.1%(95%CI:0.881-0.990),100%(95%CI:0.561-1),100%(95%CI:0.938-1),70.0%(95%CI:0.354-0.919) and 96.4%(95%CI:0.923-1) respectively. There were no significant difference between the two methods (Table 3).
3.4 Factors influencing diagnostic accuracy. Table 4 summarized and compared the correct diagnosis group(n=81) and incorrect diagnosis group (false negative cases, n=11) concerning variables affecting diagnostic accuracy. Experience refers to the years of engaging in interventional ultrasound. Univariate analysis revealed that the diagnostic yield of US-FNAC was significantly related to experience(≤5y vs. >5y) (p=0.008), but not with age, body mass index(≤24 vs. >24 ), nodal size(≤15mm vs. >15mm), nodal number(multiple vs. solitary), lesion location(left paraaortic vs. Right paraaortic), needle size(≤21G vs. ≥22G), cell block(yes vs. no), nature (malignant vs. benign) and period (2010-2015 vs. 2016-2018) (p> 0.05). Furthmore, on the multivariate logistic regression analysis, it was showed that more experienced operators yielded correct diagnosis more easily(p=0.031,OR=0.077,95%CI:0.354-0.919) (Table 4).
3.5 Complications. All patients tolerated the US-FNAC procedure well. Major complications were not occurred during the US-FNAC procedures, such as bleeding, perforation and infection. Nine patients presented slight abdominal discomfort which was relieved after one hour of clinical observation. No further clinical treatment was required.
3.6 Impact of US-FNAC on clinical decision making. Radiotherapy, chemotherapy, and surgery (laparoscopy or laparotomy) should be used in the patients with PALN metastases from cervical cancer. After US-FNAC, 73 patients of cytological malignant patients, of which 59 patients were treated with PLAN radiotherapy and systemic chemotherapy and 9 patients only received chemotherapy. The size of PLANs were significantly reduced after treatment. Surgery was performed in 5 patients. Of the 10 patients with benign cytological diagnosis, 3 patients who was highly suggestive of malignancy by PET/CT imaging, underwent surgical biopsy and were diagnosed as metastatic squamous cell carcinoma. The remaining 7 patients required only observation. After 12-24 months of follow-up, 3 patients experienced reduction in size of PLANs ,while was stable in 4 patients. Of the 4 patients with unsatisfactory samples and 5 undetermined cases, 5 patients were treated with PLAN radiotherapy and systemic chemotherapy on the basis of PET/CT imaging and 3 patients received the same therapy according to secondary US-FNAC result, and there was significantly reduction in the size of PLANs. One patient who was not suggestive of malignancy by PET/CT imaging, was selected for clinical follow-up and then PLAN was shortened after 4 months. Therefore,through US-FNAC technique, the therapeutic methods of 74 patients (80.4%) were subjected to affect.