Analysis of clinical factors in endometriosis of the abdominal wall

The mean age of onset was 32.7 ± 4.2 years old (23–51 years old) in the 228 patients with abdominal wall endometriosis. Among them, 226 (99.1%) had a history of caesarean section and 153 (67.7%) underwent a single caesarean section. The surgical scar was a transverse incision of the abdominal wall in 210 patients (92.9%) and a vertical incision of the abdominal wall in 16 (7.1%). Of the remaining two patients, one had previous surgery for leiomyoma and one had primary abdominal wall heterotaxy. Pain in the abdominal wall scar during cyclic menstruation was the first clinical manifestation in 113 patients (77.9%). A palpable abdominal wall mass was the first symptom in 40 patients (17.5%). Heterotopic foci in the original surgical scar were found at caesarean section in 7 patients (3.4%). Pale bloody discharge from the abdominal wall during menstruation was the first symptom in 1 patient. 2 cases were due to the discovery of ectopic foci in the abdominal wall during ovarian surgery (see Table  1 for details). Table 1 General information on the condition of patients with internal heterotaxy of the abdominal wall Features n (%) X ± S (range) Age (years) 32.7 ± 4.2(23–51) BMI(kg/m²) 22.75 ± 3.65(16.9–38.2) CA125 27.28 ± 20.45 LDH 154.74 ± 23.14 ALP 60.79 ± 18.18 FIB 2.82 ± 1.67 PT 11.37 ± 0.62 Number of caesarean sections 1 (case) 153(67.7%) ≥2 (cases) 73(32.3%) Cesarean section incision Transverse incision 210(92.9%) Vertical incision 16(7.1%) Incubation period (years) 3.59 ± 2.04(1–9) Symptoms to surgery (years) 0.96 ± 0.65 Clinical manifestation Cycle pain (cases) 178(78.1%) Abdominal masses (cases) 40(17.5%) Other symptoms (cases) 10(4.4%) Lesion depth Fascia type (cases) 99(43.4%) Rectus abdominis (cases) 108(47.4%) Peritoneal type (cases) 21(9.2%) Number of lesions Single hair type (cases) 188(82.5%) Complex type (cases) 40(17.5%) Imaging Ultrasound (cases) 218(95.6%) MRI (cases) 17(7.5%) Curing Preoperative drug treatment (cases) 8(3.5%) Surgical treatment (cases) 228(100%) Intraoperative mesh (cases) 4(1.8%) Postoperative medication (cases) 0% General information on the condition of patients with internal heterotaxy of the abdominal wall The total number of solitary-type lesions was 188 (82.5%) and the differences in BMI, operation time, intraoperative bleeding, and postoperative hospital stay were statistically significant ( p   0.05) in age, latency time, duration of symptoms, CA125, LDH, ALP, PT, FIB, and maximum lesion diameter. Statistically significant difference in the number of caesarean sections between patients with multiple lesions and those with single lesions ( p  < 0.05).See Table  2 for details. Table 2 Comparison of patient data for solitary versus complicated abdominal wall endometriosis (using Mann-Whitney U test; one-way ANOVA) Lesion type Single-incidence type (188 cases) Complex (40 cases) Statistic P Age (years) 32.81 ± 4.31 32.30 ± 3.79 F = 0.239 0.626 BMI 22.58 (20.8-24.98) 20.99(19.63–22.41) Z=-2.543 0.011 Number of caesarean sections 1.37 ± 0.508 1.11 ± 0.315 Z=-2.184 0.029 Incubation period (years) 3 (2–5) 4(2–5) Z=-0.683 0.495 Persistence of symptoms (years) 1 (0–1) 1(0–2) Z=-1.463 0.143 CA125 20.75 (13.83–31.64) 25.57 (19.34–40.59) Z=-1.704 0.088 LDH 152 (139–168) 147.45(139.85–162.5) Z=-0.683 0.567 ALP 57.7 (50–69) 55.2 (47.95–67.9) Z=-0.349 0.727 PT 11.3 (10.9–11.7) 2.66 (2.31–3.02) Z=-1.218 0.223 FIB 2.52 (2.31–2.96) 2.66 (2.31–3.02) Z=-0.936 0.350 Maximum diameter of lesion (cm) 2.5 (2–3) 2.9 (2.0–4.0) Z=-1.778 0.075 Surgical time (min) 30 (20–45) 52.5 (31.25-75) Z=-3.545 < 0.01 Bleeding volume (ml) 5 (5–10) 10 (5–10) Z=-2.558 0.011 Post-operative hospitalisation (days) 4 (3–4) 4.5 (4–5) Z=-4.109 < 0.01 Comparison of patient data for solitary versus complicated abdominal wall endometriosis (using Mann-Whitney U test; one-way ANOVA) 22.58 (20.8-24.98) 3 (2–5) 1 (0–1) 20.75 (13.83–31.64) 25.57 (19.34–40.59) 152 (139–168) 57.7 (50–69) 55.2 (47.95–67.9) 11.3 (10.9–11.7) 2.66 (2.31–3.02) 2.52 (2.31–2.96) 2.66 (2.31–3.02) 2.5 (2–3) 2.9 (2.0–4.0) 30 (20–45) 52.5 (31.25-75) 5 (5–10) 10 (5–10) 4 (3–4) 4.5 (4–5) Based on depth of infiltration of the lesions, abdominal wall endometriosis was classified into fascial, rectus abdominis, and peritoneal types. There was no statistically significant difference between the three types in terms of age, BMI, number of caesarean sections, duration of symptoms, LDH, ALP, PT, and FIB ( p  > 0.05). The differences in incubation time, maximum diameter of the lesion, CA125 level, operative time, haemorrhage and postoperative hospital stay were statistically significant in patients with the peritoneal type compared with the other two types ( p  < 0.05).See Table  3 for details. Table 3 Comparison of general data of patients with different lesion types (Kruskal-Wallis test; one-way ANOVA) Lesion type Fascial type Rectus abdominis type Peritoneal Statistic P Age (years) 32.41 ± 3.86 32.80 ± 4.82 33.73 ± 2.05 F = 0.454 0.636 BMI 22.21 21.91 21.83 χ2 = 0.362 0.834 Number of caesarean sections 1.39 ± 0.492 1.28 ± 0.455 1.27 ± 0.647 χ2 = 1.911 0.385 Incubation period (years) 3 (2-4.5) 3 (2–5) 4 (4–6) χ2 = 4.757 0.045 Persistence of symptoms (years) 1 (0–1) 0.5 (0–1) 2 (1–2) χ2 = 6.196 0.093 CA125 14.75(11.31–25.86) 25.57(18.85–37.7) 35.96(19.87–62.60) χ2 = 21.209 0.000 LDH 153(142-167.75) 149(138.2–168) 144.15(137.1-168.2) χ2 = 1.647 0.439 ALP 57.85(53.08–70.08) 55 (45.9–68) 55.2(44.73–62.9) χ2 = 1.677 0.432 PT 11.3 (10.9–11.7) 11.4(11.1–11.7) 11.45(10.93–11.55) χ2 = 0.227 0.893 FIB 2.52 (2.27–3.02) 2.29(2.34–2.95) 2.57 (2.3–3.05) χ2 = 0.025 0.987 Maximum diameter of lesion (cm) 2.0 (1.65-3.0) 2.5(2.0-3.125) 3.0 (2.5-4.0) χ2 = 10.395 0.006 Surgical time (min) 30 (17.5–45) 35 (25–50) 55 (30–75) χ2 = 9.522 0.009 Bleeding volume (ml) 5 (5–10) 5 (5–10) 10 (5–10) χ2 = 6.824 0.033 Post-operative hospitalisation (days) 3 (3–3) 4 (4–4) 5 (5–6) χ2 = 56.649 < 0.01 Comparison of general data of patients with different lesion types (Kruskal-Wallis test; one-way ANOVA) Age (years) 3 (2-4.5) 3 (2–5) 4 (4–6) 1 (0–1) 0.5 (0–1) 2 (1–2) 55 (45.9–68) 11.3 (10.9–11.7) 2.52 (2.27–3.02) 2.57 (2.3–3.05) 2.0 (1.65-3.0) 3.0 (2.5-4.0) 30 (17.5–45) 35 (25–50) 55 (30–75) 5 (5–10) 5 (5–10) 10 (5–10) 3 (3–3) 4 (4–4) 5 (5–6) Approximately 173 cases of transverse incision caesarean section were of the solitary type and 37 cases were of the complex type. Among the patients with vertical incision caesarean section, 15 cases were of solitary type and 6 were of complex type. The difference between the two was not statistically significant (see Table  4 for details). Among transverse incision cases, the likelihood of the lesion being on the right side was slightly higher than on the left side (see Table  5 for details). Table 4 Effect of Cesarean section incision orientation on lesion type (Person’s chi-square test) Direction of incision Number of examples Floppy Complex type Chi-square value P Transverse incision 210 173(82.4%) 37(17.6%) 1.374 0.241 Vertical incision 16 15 (93.8%) 1 (6.2%) Effect of Cesarean section incision orientation on lesion type (Person’s chi-square test) 15 (93.8%) 1 (6.2%) Table 5 Location of lesions at different incisions Direction of incision Lesion location Counting Transverse incision total 210(100%) left side 92(43.8%) interlocutory 4(1.9%) right side 114(54.3%) Vertical incision (grand) total 16(100%) top 4(25%) interlocutory 4(25%) bottom 8(50%) Location of lesions at different incisions The maximum diameter of the lesion was related to the operation time, bleeding, postoperative hospital stay, latency time, CA125, and the type of lesion (see Table  6 for details). All of them showed a linear relationship (see Fig.  1 ). Table 6 Linear regression relationship between lesion size and general patient information Lesion size Post-operative length of stay Intraoperative bleeding Surgical time CA125 Incubation period Age Type of lesion R² 0.1718 0.1224 0.2571 0.092 0.06455 0.04178 0.0806 P-value 0.00 0.00 0.00 0.003 0.007 0.0292 0.002 Linear regression relationship between lesion size and general patient information Fig. 1 Linear regression of lesion size with CA125, operation time, bleeding, postoperative hospital stay, age, and focus of infection range Linear regression of lesion size with CA125, operation time, bleeding, postoperative hospital stay, age, and focus of infection range The 218 patients underwent preoperative ultrasound examination of the abdominal wall, and 17 of them were also given MRI examination. By comparing the ultrasound, surgical, and MRI data, we found no significant differences between the three in determining the maximum diameter of the lesion and whether the lesions were multiple ( p  > 0.05). There was a statistical difference in determining the depth of the lesion ( p  < 0.05) (see Table  7 for details). Table 7 Comparison of imaging general patient data General information Ultrasound Nuclear magnetic resonance (NMR) Surgeries P Maximum lesion diameter (cm) 2.43 ± 1.11 2.53 ± 1.07 2.4 ± 1.16 0.961 Lesion depth 0.02 Fascial type (cases) 6(23.5%) 1(5.9%) 2(11.8%) Rectus abdominis muscle (cases) 10(70.6%) 10(58.8%) 10(58.8%) Peritoneal type (cases) 1(5.9%) 6(35.3%) 5(29.4%) Number of lesions 0.382 Single-shot 15(88.2%) 12(70.6%) 12(70.6%) Frequent 2(11.8%) 5(29.4%) 5(29.4%) Comparison of imaging general patient data We used ROC curve for combined ultrasound and CA125 for prediction of peritoneal versus non-peritoneal lesions. The cut-off value was 25.27 U/ml, at which point the sensitivity was 88.9%, the specificity 97.6%, and the Yoden index 0.865. Eight patients were treated conservatively with GnRH-a medication prior to surgery, and after 3 courses of treatment, the size of the abdominal wall lesions decreased compared with that before medication, with no significant improvement in symptoms. Symptoms worsened after medication stopped and all of them were admitted to hospital for surgical treatment. All surgical patients received no medication treatment after surgery. During postoperative follow-up (11–131 months), except 49 patients who were lost to follow-up, 6 of the 179 patients (3.4%) had a recurrence. Among them, 4 cases were treated with surgery in other hospitals, 1 case was not treated due to minor symptoms, and 1 case was treated conservatively with medication.

Endometriosis refers to the location of the glands and mesenchyme of the endometrium outside the uterine lining, accompanied by cyclical pain during menstruation, and is one of the most common gynaecological endocrine disorders affecting approximately 5–10% of women [ 1 ]. Symptoms of endometriosis are varied depending on the location of the lesion. The symptoms are mostly characterised by a close association with the menstrual cycle. The most typical symptoms are secondary dysmenorrhoea, progressively worsening [ 2 ]. The location of the pain is mostly in the lower abdomen, lumbosacral region and central pelvis. Some patients also experience increased menstrual flow and prolonged periods. If the lesion is located in other specific areas such as the lungs, coughing up blood during menstruation may occur [ 3 , 4 ].The most common site of endometriosis is pelvis, with ovaries and vaginal-rectal fossa being the most common sites. It is less common to find endometriosis outside the pelvis, with abdominal wall endometriosis being the most common, with a prevalence of about 0.03–3.5% according to relevant studies [ 5 ]. Abdominal wall endometriosis (AWE) refers to the infiltration of endometrial glands and mesenchyme into the abdominal wall, mostly secondary to a history of gynaecological surgery such as caesarean section, uterine, and ovarian surgery. With the recent increase in caesarean section rate, the incidence of AWE has gradually increased, and the variability of its clinical manifestations, latency time, and other characteristics has gradually increased, making it difficult to distinguish AWE from lipoma, haematoma, granuloma, and other diseases. In addition, there are fewer research reports on the diagnosis and treatment of AWE. In this paper, by collecting and analysing the clinical data of abdominal wall endometriosis in our hospital from 2013 to 2022, we disscuss the aetiology, clinical characteristics, treatment and prognosis of abdominal wall endometriosis, hoping to provide new ideas for the clinical diagnosis and treatment of abdominal wall endometriosis.

Endometriosis usually affects the pelvic organs (e.g. ovaries, uterine ligaments), but in about 1–5 per cent of cases it can occur in rare sites such as the lungs, diaphragm, abdominal wall, brain and even the extremities [ 1 , 2 ]. Clinical manifestations of pleuropulmonary endometriosis are usually cyclical pneumothorax or coughing up blood, which may coincide with the menstrual cycle, while endometriosis of the brain is extremely rare and may cause epilepsy or cyclical headaches [ 4 ]. The pathogenesis of these specialised areas is inconclusive, but most scientists believe that they develop as a result of a combination of theories in which immune dysfunction may play a key role [ 7 ]. The main theories are currently classified as retrograde menstrual flow and corpora cavernosa epithelial chemotaxis, vascular/lymphatic spread, immune regulatory abnormalities, stem cell theories and so on [ 7 , 8 ]. The classic Sampson theory suggests that retrograde menstrual blood flow leads to implantation of endometrial cells, but does not fully explain thoracic or intracranial lesions. The abnormal immune regulation hypothesis is the mechanism thought to be central to the progression of endometriosis. This hypothesis suggests that there is a failure of immune surveillance in the patient, with a decline in the function of natural killer cells (NK cells), which are unable to effectively eliminate ectopic endometrial cells [ 9 ]; also that the inflammatory microenvironment in vivo, with the predominant polarisation of M2-type macrophages to promote angiogenesis and pro-inflammatory factors such as IL-6 and TNF-alpha to maintain the activity of the lesion; and that the production of autoantibodies may lead to immune escape by molecular mimicry of the attacking ectopic tissue [ 10 ]. The mechanism of endometriosis formation in the abdominal wall is not clear, and there are theories of local implantation, epithelial metaplasia, lymphatic, or blood dissemination [ 11 ]. Among them, the local implantation doctrine proposed by Sampson et al. is now widely accepted in clinical practices. This doctrine suggests that when patients with AWE undergo caesarean section or other uterine surgery, the endothelial tissue is implanted into the abdominal wall wounds, causing a local focal inflammatory response with hormonal fluctuations. 99.6% of patients in this study had a history of related surgery, which is consistent with the study by Zhang et al. [ 12 – 14 ] and in line with this type of doctrine. In patients with primary AWE, epithelial hyperplasia, lymphatic or blood dissemination can better explain its formation. The typical triad of AWE: history of previous caesarean section, localised abdominal mass, and cyclical pain [ 15 ]. Recent clinical studies confirmed caesarean section as an independent risk factor for AWE [ 16 ]. In this study, 99.1% of patients had a history of caesarean section, 178 patients (78.1%) had cyclical pain as the first symptom, and 40 patients (17.5%) had abdominal wall mass as the first symptom. Not all patients with AWE had this symptom. One patient in our study was admitted for menstrual fluid discharge from a primary abdominal wall wound, and nine were asymptomatic but confirmed due to other intraoperative findings. The local abdominal mass size may increase with the menstrual cycle, and the local skin colour changed to dark red in some patients [ 15 ]. Symptoms were different for lesions in different locations. Based on depth of infiltration of the lesions, abdominal wall endometriosis was classified into fascial, rectus abdominis, and peritoneal types. The first two are more common in the clinic and their clinical manifestations are more obvious. Patients of the peritoneal type often present localised wound discomfort because the lesion was deeper. In addition, this study found that the latency time of this type was also longer than the other two, which is also consistent with the study by Jiang et al. [ 17 ]. In addition to general physical examination, imaging is one of the most important modalities used clinically to diagnose AWE. Recent studies suggest that the diagnostic accuracy of abdominal ultrasound in AWE is 73.2–96.3% [ 18 ]. In this case, a total of 218 patients underwent preoperative abdominal ultrasound examinations, and all were consistent with postoperative pathology. Ultrasound can clearly delineate the border between the lesion and the surrounding tissue, and blood flow visualisation can show striated or punctate blood flow in or around the lesion [ 19 ]. It is widely used for preoperative diagnosis because it is convenient, non-invasive, and inexpensive. However, it is difficult to diagnose the extent and depth of lesion involvement using ultrasound. In this study, we compared the lesion with ultrasound and nuclear magnetic resonance (NMR) and found that NMR achieved better accuracy. In addition, when ultrasound cannot clearly diagnose the type of lesion, MRI proves to be more advantageous [ 20 ]. Apart from preoperative MRI to identify the depth of lesions, this study, like Guo et al. [ 21 ], found that CA125 is statistically significant for peritoneal lesions compared with the non-peritoneal types ( p  < 0.05). Using ROC curve for combined ultrasound examinations, we considered that the cut-off value was 25.27 U/ml, at which the clinical sensitivity and specificity reached the highest levels. The main treatments for AWE are medication, surgery, cryoablation and high-intensity focused ultrasound(HIFU) [ 6 ].Cryoablation and HIFU are two emerging minimally invasive or non-invasive techniques for the clinical management of abdominal wall endometriosis. Cryoablation destroys the ectopic lesion using low temperature (-40℃ to -100℃), resulting in cellular ice crystal formation, membrane rupture and local ischaemic necrosis. It is suitable for patients with superficial lesions and clear localisation, but there are some risks such as nerve damage, skin frostbite and residual recurrence [ 22 ]. HIFU uses ultrasound to focus on the lesion, generating a high temperature of more than 65 ℃ to cause coagulative necrosis of the tissue, and it is suitable for patients with clear boundaries of the lesion, rich blood supply and not too deep location of the lesion, but there are some risks such as skin burns, pain and higher cost. Due to the narrower indications of these two modalities, their clinical use is still subject to certain limitations and long-term follow-up is required [ 23 ]. Pharmacological treatment includes progestins, short-acting contraceptives, and gonadotropin-releasing hormone analogues. Pharmacological treatment is usually less effective because the lesion is encapsulated by connective tissue.However, some researchers have suggested that preoperative medication can control symptoms and reduce the size of the lesion, facilitating surgery [ 24 ]. In this study, 8 patients were treated conservatively with GnRH-a, but the results were less satisfactory. Therefore, conservative treatment with medication is usually reserved in clinical practices for patients with contraindications to surgery. Surgery is the most important way to prevent recurrence of AWE, and whether or not the lesion can be completely removed during surgery largely determines whether AWE will recur. Surgery is usually performed through an incision in the original abdominal wall, and an ultrasonic knife is used to make a complete resection 0.5–1 cm from the edge of the lesion, and the existing scar on the abdominal wall should also be removed. For deeper infiltration of lesions, such as rectus abdominis or peritoneal lesions, placement of a drain after surgery may be considered to aid wound healing. For large, high-tensile lesions that are difficult to suture, we generally use intraoperative patch placement to cover the defect, reduce local tension, and beautify the wound. In this study, four patients with peritoneal lesions > 5 cm in diameter received intraoperative patches and postoperative negative pressure drainage, and the wounds healed well [ 25 ]. The maximum diameter of intraoperative peritoneal lesions was found to be significantly larger than that in the other two types. We believe that this should be due to its deeper location, longer latency time, and richer peritoneal blood supply. In addition, the operation time, intraoperative bleeding, and postoperative hospital stay were statistically significant for this type. Therefore, patients with peritoneal abdominal wall endometriosis should be better prepared for surgery to better remove the lesions during surgery. Regarding whether postoperative medication should be used as a preventive measure, studies have shown that such medication won’t reduce the recurrence rate [ 26 , 27 ]. In this paper, 228 patients were not treated with postoperative prophylaxis and the recurrence rate after surgery was only 3.4%. There was no significant difference in AWE recurrence rate from that of postoperative medication. High-intensity focused ultrasound is a new clinical tool currently used to treat AWE. This treatment option has now been shown to be superior to traditional surgical methods in terms of operation time and bleeding. However, it can cause some damage to the surrounding tissues and has narrower indications, and the current clinical trial is relatively small, which requires further research [ 28 ]. To prevent AWE, the clinic should first control the rate of caesarean section and the indication for surgery. Isolation measures should be employed during surgery, such as placing sterile gauze or incision protectors over the wound, repeated irrigation of the pelvis and wound after suturing the uterus to avoid local endothelial implantation, and avoiding using the same suture when suturing the uterine incision and other tissues [ 29 , 30 ]. AWE is most common in fascial and rectus abdominis types and occurs on both sides of the wound. It may be related to the limitations of the operation, resulting in the ease of implantation of endothelial tissue compared to other sites. Therefore, repeated irrigation prior to closure of the abdomen to release only the fascial layer is important. It has been suggested that by comparing cesarean transverse incision with straight incision, the latency time of straight incision is longer than that of transverse incision. It was suggested that straight incision in cesarean section is better than transverse incision for prevention of AWE [ 10 ]. This study compared the latency time between the two, 3.6 ± 2.02 years for straight incision and 3.5 ± 2.33 years for transverse incision, and found the difference to be statistically insignificant ( p  > 0.05). It was therefore concluded that the two approaches won’t increase the likelihood of AWE, and a larger amount of data is still needed for further research. In conclusion, with the increasing caesarean section rate in recent years, the incidence of AWE has gradually stepped up, so we are taking good intraoperative non-neoplasma measures. For patients with a clinical history of uterine surgery, abdominal wall mass, and cyclical pains, AWE should be highly suspected. In addition to ultrasound, CA125, and other auxiliary examinations, surgical treatment should be adopted earlier to avoid further increase of the lesion. The study sample in this paper is relatively small and the conclusions need to be confirmed by a larger amount of data.

The data of a total of 228 patients with abdominal wall endometriosis who attended Changzhou Second People’s Hospital affiliated with Nanjing Medical University from January 2013 to December 2022 were collected. All of them underwent resection for abdominal wall lesions in our hospital after excluding contraindications to surgery, and postoperative pathology suggested abdominal wall endometriosis. The extent of surgical resection is located at the margin of the lesion about 0.5–1 cm. Complete clinical and follow-up data are available. All subjects signed an informed consent form before the examination. The retrospective study was approved by the Ethics Evaluation Committee of Changzhou Second People’s Hospital affiliated with Nanjing Medical University. This study was conducted in accordance with the principles of the Declaration of Helsinki. Inclusion criteria: 1. age between 18 years and pre-menopausal;2. pathological histological examination suggestive of endometriosis of the abdominal wall;3. complete clinical history of diagnosis and treatment and follow-up information. Exclusion criteria: (1) History of severe hepatic or renal dysfunction and autoimmune disease; (2) Pregnancy or lactation; (3) History of fibroids, adenomyosis, ovarian endometriosis or other malignant diseases. The patients’ age, number of pregnancies and births, number of caesarean sections, latency time, clinical symptoms, surgical history, BMI, CA125, lactate dehydrogenase, alkaline phosphatase, imaging, operation time, bleeding, and hospital stay were recorded. We divided the patients into three groups according to the depth of infiltration of lesion: fascial (infiltration into subcutaneous fat or superficial fascia), rectus abdominis (infiltration into the anterior sheath or muscle), and peritoneal (infiltration into the peritoneum) [ 6 ]. Based on whether the lesion was solitary or not, we classified patients into solitary and complex types. SPSS 26.0 statistical software was used, and measures conforming to normal distribution were described by‾X ± S. T-test was used for two groups of data, while ANOVA test was used for multiple groups of data. Measures not conforming to normal distribution were described as the median (P25-P75). The Mann-Whitney U test was used for two groups of data and the Kruskal-Wallis test for multiple groups of data. The relationships between two variables were analysed using linear regression correlation analysis, the Person chi-square test for unordered categorical variables, and ROC curves in the predictive model. Difference with p  < 0.05 was considered statistically significant.