| Objective:Sinonasal inverted papilloma(SNIP)is one of the most common benign tumors of the nasal cavity and sinuses and is at risk for recurrence and malignant transformation,which is primarily treated by complete surgical removal of the tumor.Thus,early detection and diagnosis is essential for the treatment of patients with SNIP,providing them with early surgical intervention and reasonable surgical techniques,preventing malignant transformation due to delayed treatment,and avoiding tumor recurrence due to inappropriate selection of surgical procedures.SNIP is mainly identified with unilateral chronic rhinosinusitis with/without nasal polyps(CRSw/s NP),which is the most common sinonasal disease.Its clinical manifestations and imaging examinations are similar to SNIP,leading to some difficulties in clinical diagnosis,especially for outpatients.In addition,there is still lacking reliable serum tumor markers for the diagnosis of SNIP in current clinical practice and need to be further explored.This study aimed to investigate the diagnostic significance of CT features and clinical characteristics for SNIP and establish a clinically effective nomogram,in order to provide guidance for future clinical diagnosis.This study also aimed to investigate the diagnostic value of serum squamous cell carcinoma antigen(SCCA)and cytokeratin fragment antigen 21-1(CYFRA 21-1)for SNIP,and to discover new serum tumor markers for the diagnosis of SNIP.Methods:1.The clinical data of 267 patients with SNIP and 273 patients with unilateral CRSw/s NP who visited the Department of Otorhinolaryngology Head and Neck Surgery at the Affiliated Hospital of Qingdao University between November 2016 and December 2021 were retrospectively collected.Patients’ demographic and clinical characteristics(gender,age,nasal symptoms,history of sinus surgery,smoking,and alcohol dependence)and CT features(lobulated/wavy edge,air sign,focal hyperostosis,diffuse hyperostosis,focal osseous erosion,and CT values)were recorded.Two hundred patients with SNIP and 200 patients with CRS were randomly assigned to the training set,and the remaining 67 patients with SNIP and 73 patients with CRS were assigned to the validation set.In the training set,univariate and multivariate logistic regression analyses were employed to identify independent predictive factors for SNIP,and a nomogram was developed.The calibration curves and receiver operating characteristic(ROC)curves of the training and validation sets were generated to evaluate the diagnostic capacity of the nomogram model.2.The clinical data of 82 patients with SNIP,47 patients with sinonasal squamous cell carcinoma(SNSCC),and 72 patients with unilateral CRSw/s NP who visited the Department of Otorhinolaryngology Head and Neck Surgery at the Affiliated Hospital of Qingdao University between October 2018 and November 2022 were retrospectively collected.Patients’ demographic characteristics(gender,age),smoking and alcohol dependence,and preoperative serum tumor markers’ levels of SCCA and CYFRA 21-1were recorded.The differences in preoperative serum tumor markers’ levels among the above three groups were analyzed.Paitents with SNIP were further divided into SNIP with malignant transformation and SNIP without malignant transformation groups,and the differences in preoperative serum tumor markers’ levels between the SNIP with/withour malignant transformation groups,and between the SNIP with malignant transformation group and the SNSCC group were analyzed.Logistic regression analysis was employed to further screen the serum tumor markers that could be used to diagnose SNIP,and ROC curves were applied to determine the diagnostic cut-off values and evaluate their diagnostic ability.Results:1.In the training set,univariate and multivariate logistic regression analyses showed that age(OR=1.066,95% CI: 1.036-1.097,P<0.001),facial pain/headache(OR=0.391,95%CI: 0.176-0.871,P=0.022),history of sinus surgery(OR=5.741,95% CI: 2.208-14.928,P<0.001),lobulated/wavy edge(OR=14.430,95% CI: 6.042-34.460,P<0.001),air sign(OR=9.841,95% CI: 4.341-22.310,P<0.001),focal hyperostosis(OR=21.453,95% CI:8.170-56.329,P<0.001),focal osseous erosion(OR=3.936,95% CI: 1.434-10.802,P=0.008),and CT values(OR=1.050,95% CI: 1.014-1.087,P=0.006)were significantly associated with SNIP.These eight variables were identified as independent predictors of SNIP,and a nomogram model was established baesd on them.The calibration curves showed that the nomogram model had great fitting degrees both in the in the training and validation sets.In the training and the validation sets,the area under the curve(AUC)of the nomogram model was 0.960(95% CI: 0.942-0.978)and 0.951(95% CI: 0.929-0.971),respectively.2.Serum SCCA and CYFRA 21-1 levels in patients with SNIP were higher than in patients with CRS,and logistic regression analysis showed that serum SCCA and CYFRA21-1 were risk factors for SNIP(SCCA OR=4.351,95% CI: 2.094-9.042,P<0.001;CYFRA 21-1 OR=2.841,95% CI: 1.548-5.214,P=0.001),the ROC curve showed an AUC of 0.889(95% CI: 0.827-0.952,P<0.001)with a predicted cut-off value of 1.59ng/m L for SCCA and an AUC of 0.745(95% CI: 0.650-0.840,P<0.001)with a predicted cut-off value of 2.06 ng/m L for CRFRA 21-1.Serum SCCA levels were higher in patients with SNIP than in patients with SNSCC,and logistic regression analysis showed that serum SCCA was a risk factor for SNIP(OR=1.244,95% CI: 1.044-1.481,P=0.014),the ROC curve showed an AUC value of 0.789(95% CI: 0.692-0.886,P<0.001)and a predicted cut-off value of 1.85 ng/m L for SCCA.Serum CYFRA 21-1 levels were significantly higher in SNIP patients with malignant transformation than in SNIP patients without malignant transformation,logistic regression analysis showed that CYFRA 21-1 was a risk factor for SNIP with malignant transformation(OR=2.623,95% CI: 1.487-4.627,P=0.001),and the ROC curve showed an AUC value of 0.845(95% CI: 0.716-0.974,P<0.001)with a predicted cut-off value of 4.56 ng/m L for CYFRA 21-1.Serum SCCA and CYFRA 21-1 levels were higher in SNIP patients with malignant transformation than in SNSCC patients,logistic regression analysis showed that CYFRA 21-1 was a risk factor for SNIP with malignant transformation(OR=1.466,95% CI: 1.058-2.030,P=0.021),and the ROC curve showed an AUC value of 0.801(95% CI: 0.656-0.945,P=0.002)with a predicted cut-off value of 3.55 ng/m L for CYFRA 21-1.Conclusion:1.Patients with SNIP differed significantly from patients with CRS in age,facial pain/headache,history of sinus surgery,lobulated/wavy edge,air sign,focal hyperostosis,focal osseous erosion,and CT values,which could be independent predictive factors of SNIP.A nomogram prediction model consisting of these eight predictive factors was established and validated,confirming that it had strong predictive power.Therefore,the nomogram model based CT findings and clinical characteristics had excellent diagnostic value and great clinical application prospect for SNIP.2.Serum SCCA could be used to distinguish SNIP from CRS with a cut-off value of1.59 ng/m L and from SNSCC with a cut-off value of 1.85 ng/m L.CYFRA 21-1 could be used to distinguish SNIP from CRS with a cut-off value of 2.06 ng/m L.CYFRA 21-1 could be used to distinguish SNIP with/without malignant transformation with a cut-off value of4.56 ng/m L.CYFRA 21-1 could be used to distinguish SNIP with malignant transformation from SNSCC with a cut-off value of 3.55 ng/m L.These findings revealed that serum SCCA could be a serum tumor marker for the diagnosis of SNIP,and CYFRA 21-1 could a serum tumor marker for SNIP with malignant transformation,providing new potential tools for the diagnosis of SNIP. |
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