Diagnostic value of multi-slice spiral computed tomography after adiponectin treatment of tracheal malignancies

Purpose: To determine the diagnostic value of multi-slice spiral computed tomography (CT) after adiponectin treatment of tracheal malignancies. Methods: Sixty patients with tracheal malignancies admitted to Emergency General Hospital from February 2017 to February 2021 were assigned to the study group. After physical examination, 60 healthy subjects in the same period served as the control group. All patients were treated with adiponectin. The control group was subjected to serum tumor marker testing before and after treatment, while the study group received multi-slice spiral CT before and after adiponectin treatment. Results: The 60 patients enrolled in the study group comprised 30 cases of squamous carcinoma, 22 cases of adenocarcinoma, and 8 cases of mucosa-associated lymphoma. Multi-slice spiral CT before treatment showed that 35 patients with tracheal malignant tumors had expansive lumen hyperplasia, while 25 patients with bulging tumors had saddle-like hyperplasia with irregular surfaces, uneven margins, and mean thickness of 5.96 ± 0.65 mm in the tracheal and bronchial walls adjacent to the luminal nodule. After treatment, the thickness of the tracheal and bronchial walls adjacent to the luminal nodule decreased to a mean value of 4.65 ± 0.48 mm. Prior to treatment, the mean enhancement value of contrast-enhanced CT was 18.98±1.23 Hu, and mean tumor diameter was 3.68 ± 0.23 cm. However, after treatment, the mean enhancement value increased to 25.98 ± 1.44 Hu, while mean tumor diameter decreased to 2.54 ± 0.20 cm in the study group. Conclusion: Multi-slice spiral CT has promising diagnostic value for patients with tracheal malignancies after adiponectin treatment. Therefore, it can potentially be used in the diagnosis of patients with tracheal malignancies.


INTRODUCTION
Tracheal malignant tumors develop at the junction of the cartilaginous ring and the membrane. The early stage of the disease presents symptoms such as irritating cough, shortness of breath, and dyspnea. At the advanced stage, the tumor cells usually metastasize to the lung tissue and directly invade the esophagus and larynx, resulting in severe risk of death if treatment is delayed [1]. Currently, surgery is the preferred modality for the treatment of tracheal malignancies. Moreover, partial radiotherapy and chemotherapy are given to patients with unresectable advanced tumors or incompletely resected tumors, based on pathological types [2,3]. However, these patients usually exhibit poor tolerance and impaired immune function. Therefore, research has resulted in the additional provision of adiponectin therapy to patients [4]. This is aimed at enhancing the survival time of cytotoxic T cells, regulating the immunity of the patients, and exerting anti-tumor effects. Given that the survival of patients with tracheal malignancies is affected by various factors such as tumor stage, therapeutic drugs, and treatment modalities, close monitoring of the conditions of the patients after systemic treatment is still indispensable. At present, imaging examinations are mostly performed for disease monitoring in clinical practice [5].
Multi-slice spiral CT is a tumor diagnostic modality with wide applications. Its ability to acquire multi-slice images enables the physician to observe the patient's tracheal morphology from multiple perspectives such the deformation, wall thickening, and luminal manifestations of the diseased segment of the trachea [6][7][8]. Based on review of extant literature, multi-slice spiral CT is used mainly for diagnosis of the early stage of tracheal malignancies. However, no studies have been carried out to investigate its diagnostic value for tracheal malignancies after adiponectin treatment.
Therefore, the present study was aimed at evaluating the clinical benefits associated with the application of multi-slice spiral CT after adiponectin treatment.

Study design
This research was designed as a retrospective study, and carried out at Emergency General Hospital from February 2017 to February 2021. The aim was to investigate the clinical diagnostic value of multi-slice spiral CT after adiponectin treatment of tracheal malignancies. The study was set up at a double-blind level, with neither the study subjects nor the investigator being aware of the trial groupings. Moreover, the study designer was responsible for the arrangement and control of the entire trial.

Recruitment of study subjects
The data of patients with tracheal malignancies who were admitted to Emergency General Hospital from February 2017 to February 2021 were retrospectively analyzed.

Inclusion criteria
Patients who satisfied the following criteria were included in the study: (1) patients who were diagnosed with tracheal malignancy via pathological examination [9]; (2) patients who were treated in Emergency General Hospital only, without death, intermediate transfer, or discontinuation of treatment; (3) those with complete clinical data; (4) patients with expected survival period of more than 3 months, and (5) those who were diagnosed with tracheal malignancies for the first time.

Exclusion criteria
Patients in the following categories were excluded: (1) those who were unable to communicate due to impairment of hearing, language impairment, unconsciousness, or mental illness; (2) patients who withdrew from treatment, died, changed their treatment plan, or were lost to follow-up; (3) those with incomplete clinical data, and (4) patients with other serious organic diseases such as malignant tumors and abnormal liver and kidney functions.
A total of 60 patients with tracheal malignancies were included in this study, and designated the study group, while 60 healthy individuals were selected and designated the control group during the same period. On the day of admission, the socio-demographic and clinical presentation data of the patients were collected by the study team.
All patients received multi-slice spiral CT and tests for serum tumor markers. The multi-slice spiral CT was repeated in the test group of patients after adiponectin treatment so as to determine its diagnostic value.

Ethical considerations
The study complied with the principles of Declaration of Helsinki [10]. It was approved by the review board of the ethical review committee of Emergency General Hospital (approval no. 201700230).
After recruitment, the patients were informed of the purpose, significance, content, and confidentiality of the study, and each patient voluntarily signed an informed consent form.

Withdrawal criteria
The case record forms of patients who had the following conditions, and were adjudged by the research group to be unsuitable for continuing their participation in the study, were retained, but data analysis was not performed: (1) patients who had serious adverse events; (2) those whose conditions deteriorated during the study; (3) patients who had some serious co-morbidities or complications, and (4) those who were unwilling to continue the clinical trial during the study, and so requested to withdraw from the trial.

Treatments
All patients were treated with adiponectin. The test group received multi-slice spiral CT examinations before and after treatment. The tube voltage of the multi-slice spiral CT scanner (Philips, State Food and Drug Administration No. 3303600, 2008) was set at 120 kV, with tube current of 100 mA, pitch of 1.15, and scan slice thickness and interval slice thickness of 6 mm. The scanning was performed from the patient's thoracic inlet to the suprarenal pole, including the bilateral adrenal glands, using the end-inspiratory hold method.
The contrast agent for the enhancement scan was iohexol (Zhejiang Haichang Pharmaceutical Co. Ltd, State Pharmacopoeia H20093053) given at a dose of 100 mL. Intravenous injection of contrast agent was done in the forearm of the patient using a high-pressure syringe at a flow rate of 3 mL/s, with a 10-s delay.
The reconstruction was performed using Volume Wizard workstation with a slice thickness and reconstruction interval of 1 mm, while multiplanar reconstruction images were obtained with the multi-planar reconstruction (MPR) technique. The standard plane of the trachea was the coronal and sagittal plane through the central long axis of the trachea. After reconstruction, three experienced radiologists performed image analysis to determine the size of the tumor in the patient's tracheal lumen, the smoothness of the tumor margin, and the growth pattern of the tracheal tumor. The thickness of the wall adjacent to the tumor in the tracheal lumen was measured by a physician using Volume Wizard workstation so as to determine the presence of tracheal malignancy in the patients.
The control group was subjected to serum tumor marker testing before and after treatment. Morning fasting elbow venous blood (5 mL Normal ranges of the above indicators were based on the ranges indicated in the assay kit (i.e. CEA: 0 -3 ng/mL, CYFRA 21 -1: 0 -3.3 ng/mL, and NSE: 0 -16.3 ng/mL).

General patient/subject information
General patient/subject information included number of hospitalizations, name, gender, age, body mass, Body Mass Index (BMI), educational level, living habits, monthly income, and underlying diseases.
In the study group, patients' pathological types comprised squamous carcinoma, adenocarcinoma, and mucosa-associated lymphoma. The number of patients in each pathological type was noted.

Multi-slice spiral CT examination
The characteristics of multi-slice spiral CT performance of the tracheal malignancies were determined.

Diagnostic values of multi-slice spiral CT examination and serum tumor marker test before treatment
Receiver operating characteristic (ROC) curve was used to analyze the diagnostic values of multi-slice spiral CT examination and serum tumor marker test before treatment. The criteria for multi-slice spiral CT examination were determined by physicians, and serum tumor markers were considered positive only when all three criteria were met.

Statistical analysis
The data processing software used in this study was SPSS 20.0, while GraphPad Prism 7 (GraphPad Software, San Diego, USA) was used to generating graphs. Counted data were analyzed using Chi-square test, while measured data were analyzed using Student's t-test. Statistical significance was assumed at p < 0.05.

General information on patients/subjects
There were no statistically significant differences in general information between the two groups of subjects (p > 0.05). These data are shown in Table 1.

Outcome of pathological staging
The 60 patients enrolled in this study consisted of 30 cases of squamous carcinoma, 22 cases of adenocarcinoma, and 8 cases of mucosaassociated lymphoma, the percentage compositions of which are shown in Figure 1.

Multi-slice spiral CT results
Multi-slice spiral CT before treatment showed that 35 patients with tracheal malignant tumors exhibited expansive hyperplasia to the lumen, and 25 patients with bulging tumors had saddlelike hyperplasia with irregular surfaces, and uneven margins, and the tracheal and bronchial walls adjacent to the luminal nodule had mean thickness of 5.96 ± 0.65 mm. However, after treatment, the thickness of the tracheal and bronchial walls adjacent to the luminal nodule decreased, with a mean value of 4.65 ± 0.48 mm.
Before treatment, the mean enhancement value of contrast-enhanced CT was 18.98 ± 1.23 Hu, and the mean tumor diameter was 3.68 ± 0.23 cm. In contrast, after treatment, the mean enhancement value was increased to 25.98 ± 1.44 Hu, while the mean tumor diameter was reduced to 2.54 ± 0.20 cm, in the test group.

Diagnostic values of multi-slice spiral CT examination and serum tumor markers
Before treatment, multi-slice spiral CT showed 56 true positive cases and 54 true negative cases, with a diagnostic sensitivity of 93.3 %, and a specificity of 90.0 %.
The results of serum tumor marker testing showed 50 true positive cases and 48 true negative cases, with a diagnostic sensitivity of 83.3 % and specificity of 80.0 %.

DISCUSSION
Primary tracheal malignancy is relatively rare in clinics, with incidence accounting for only 0.5 -1.2 % of all malignancies [11]. Although the percentage mortality of this disease is much lower than those of other lung cancers, early diagnostic errors and delayed treatment reduce the survival of patients. Therefore, it is important to enhance the detection of tracheal malignancies and carry out systematic monitoring of the treatment process in patients. Currently, imaging is the main strategy used for the diagnosis of tracheal malignancies. Chest radiography assesses tumor size and tumor infiltration, and MRI allows assessment of tissue and vascular involvements in patients [12].
However, chest radiography may predispose to underestimation of tracheal wall involvement, while the application of magnetic resonance imaging and positron emission computed tomography is associated with some limitations. Recent investigations have demonstrated that multi-slice spiral CT examination is a better technique for identification of intraluminal and extraluminal lesions [13]. It is also useful for evaluation of the extent and degree of infiltration of lesions into the cartilaginous ring. Moreover, multi-slice spiral CT examination sufficiently shortens the acquisition time for volumetric scans, which facilitates long-distance and widearea thin-section scanning and improves early detection rates [14].
The 60 patients included in this study comprised 30 cases of squamous carcinoma, 22 cases of adenocarcinoma, and 8 cases of mucosaassociated lymphoma. The overall degree of detection with multi-slice spiral CT was 91.7 %, indicating that this diagnostic modality is beneficial for detecting subtle lesions, and for reducing the possibility of missed diagnosis and misdiagnosis. These advantages are crucial for the development of treatments based on accurate diagnosis.
The high percentage of lesion detection with multi-slice spiral CT stems from its capacity to generate multi-angle and multi-level threedimensional images. The MPR technique allows for arbitrary adjustment of window width and window position, which enables the physician to simultaneously observe the inside and outside of the tube lumen, especially the coronal and sagittal positions. In addition, it provides complete and clear images of tracheal malignancies, thereby fully minimizing the disadvantages of two-dimensional images and serum tumor marker tests [15].
The use of multi-slice spiral CT before treatment showed that 35 patients with tracheal malignant tumors had expansive hyperplasia into the lumen, and 25 patients with bulging tumors had saddle-like hyperplasia with irregular surfaces, uneven margins, and the tracheal and bronchial walls adjacent to the luminal nodule, had mean thickness of 5.96 ± 0.65 mm. Before treatment, the mean enhancement value of contrastenhanced CT was 18.98 ± 1.23 Hu, and the mean tumor diameter was 3.68 ± 0.23 cm. These results are consistent with previous reports of the appearance of endotracheal malignancies in the form of nodular tumors with irregular margins and wall thickening in the tracheal lumen. Thus, multislice spiral CT and MPR techniques are effective in detecting tumors in the tracheal lumen. Most tracheal malignant tumors are spherical in shape, while the tracheal wall is circular in cross-section, and the only part of the spherical tumor in contact with the wall is the base of the tumor. Consequently, a mass adjacent to the tracheal wall is likely to be regarded as the base of the tumor from cross-sectional observation, which reduces the accuracy of observation. It has been demonstrated that 3D images of the central trachea are useful complements to crosssectional images, and that multi-slice spiral CT provides a clearer view of tracheal tumors, reduces the possibility of false positives, and effectively screens recurrence after treatment [16,17].
In the present study, after treatment, the thickness of the tracheal and bronchial walls adjacent to the luminal nodule decreased to a mean value of 4.65 ± 0.48 mm; the mean enhancement value was 25.98 ± 1.44 Hu, while the mean tumor diameter was reduced to 2.54 ± 0.20 cm. These data confirm that multi-slice spiral CT has potential for effective monitoring of the progress of patients treated with adiponectin, and it can be used throughout the diagnosis and treatment process, with satisfactory diagnostic efficacy [18].

CONCLUSION
Multi-slice spiral CT has promising diagnostic value for patients with tracheal malignancies after adiponectin treatment. Therefore, further clinical trials are required to validate this finding.