Analysis of related factors for postoperative recurrence of abdominal wall endometriosis: a retrospective cohort study

A total of 501 patients with histopathologically diagnosed abdominal wall endometriosis were selected from January 2016 to July 2022, among which 54 AWE patients were excluded less than one year after surgery, and a total of 447 patients were included in the follow-up, among which 49 patients were lost to follow-up. According to the follow-up requirements, a total of 398 cases of abdominal endometriosis were followed up, of which 34 cases had relapsed, with a recurrence rate of 8.54%. The median time to relapse was 16.00 (3.00–65.00) months.Of these, there was no significant difference between the two groups in age of onset, body mass index, incubation period, gravidity, parity, length of menstrual cycle, length of menstruation, dysmenorrhea, hospital day, lesion size, mesh placement, number of lesions ( P  > 0.05). Compared with the non-recurrent group ( n  = 364) and the recurrent group ( n  = 34), the recurrent group had more cesarean sections ( P  = 0.016), longer operation time ( P  = 0.023), more intraoperative blood loss ( P  = 0.017), and more peritoneal lesions ( P  = 0.004). The results are shown in Table  1 . Table 1 Description of the study population Nonrecurrence Recurrence P -value Number of patients 364 34 Age of onset (years, mean ± SD) 30.78 ± 5.21 30.78 ± 4.81 0.769 Body mass index (kg/m 2 , mean ± SD) 23.93 ± 3.64 23.63 ± 3.04 0.698 Incubation period(months, mean ± SD) 38.99 ± 28.87 34.88 ± 30.25 0.202 Gravidity 2.50 ± 1.29 2.59 ± 1.10 0.493 Parity 1.67 ± 0.60 1.76 ± 0.50 0.283 Cesarean Sections 1.44 ± 0.54 1.65 ± 0.49 0.016 Length of menstrual cycle (days) 29.50 ± 4.50 28.29 ± 5.69 0.628 Length of menstruation (days) 5.93 ± 1.90 5.74 ± 1.54 0.937 Dysmenorrhea, n (%) 0.972  NO 258(70.88%) 24(70.59%)  YES 106(29.12%) 10(29.41%)  Operation time(minutes, mean ± SD) 43.31 ± 26.76 56.38 ± 37.14 0.023  Blood loss (ml, mean ± SD) 12.85 ± 18.30 24.62 ± 50.52 0.017  Hospital day (days, mean ± SD) 7.02 ± 2.12 7.76 ± 2.24 0.058  Lesion size(cm, mean ± SD) 2.37 ± 1.11 2.56 ± 1.34 0.485 Mesh Placement, n (%) 0.861  NO 335(92.03%) 31(91.18%)  YES 29(7.97%) 3(8.82%) Number of lesions 0.657  Single 320 (87.91%) 29 (85.29%)  Multiple 44 (12.09%) 5 (14.71%) Layers excised 0.004  Subcutaneous/adipose 40(10.99%) 7(20.59%)  Fascia 284(78.02%) 18(52.94%)  Peritoneum 40 (10.99%) 9(26.47%)  Follow up time 26.64 ± 12.24 22.41 ± 19.47 0.003 Description of the study population The association between the number of cesarean sections as well as other covariates and recurrence is shown according to univariate regression analysis. A significant positive relationship between number of cesarean sections, operation time, and surgical bleeding volume and recurrence in AWE patients ( P  < 0.05). The more cesarean sections, more operation time and more surgical bleeding, the greater the recurrence rate after AWE. However, there, no significant association was found between AWE and age of onset, BMI, incubation period, gravidity, parity, length of menstrual cycle, length of menstruation, lesion size, mesh placement, number of lesions, layers excised and follow up time.The results are shown in Table  2 . Table 2 Univariate analysis for recurrence OR (95%CI) P -value Age of onset (years, mean ± SD) 1.00 (0.93, 1.07) 0.997 Body mass index (kg/m 2 , mean ± SD) 0.98 (0.88, 1.08) 0.646 Incubation period(months, mean ± SD) 0.99 (0.98, 1.01) 0.430 Gravidity 1.05 (0.81, 1.38) 0.698 Parity 1.30 (0.72, 2.34) 0.377 Cesarean Sections 1.97 (1.05, 3.69) 0.034 Length of menstrual cycle (days) 0.93 (0.85, 1.01) 0.098 Length of menstruation (days) 0.94 (0.76, 1.15) 0.548 Operation time(minutes, mean ± SD) 1.01 (1.00, 1.02) 0.012 Blood loss (ml, mean ± SD) 1.01 (1.00, 1.02) 0.032 Lesion size(cm, mean ± SD) 1.14 (0.86, 1.50) 0.363 Mesh Placement, n (%)  NO Reference  YES 1.12 (0.32, 3.88) 0.861 Number of lesions  Single Reference  Multiple 1.25 (0.46, 3.41) 0.6574 Layers excised  Subcutaneous/adipose Reference Reference  Fascia 0.36 (0.14, 0.92) 0.033  Peritoneum 1.29 (0.44, 3.79) 0.649  Follow up time 0.97 (0.94, 1.00) 0.073 Univariate analysis for recurrence Using multiple linear regression analysis, a model adjusted for confounding factors was constructed to analyze the independent effect of the number of cesarean sections for abdominal wall endometriosis and the recurrence after AWE. The odds ratios (OR) and 95% confidence intervals are listed in Table  3 . In addition, according to the results of univariate correlation analysis, after adjusting for age of onset, BMI, pregnancy and lesion typing, the number of cesarean sections was an independent risk factor for AWE recurrence under I and II multiple regression models (OR = 2.95,95%CI:1.14–7.62, P  = 0.026). Table 3 Multiple regression analysis of the number of cesarean sections and AWE recurrence Non-adjusted Adjust I Adjust II Number of cesarean sections before disease onset 1.97(1.05, 3.69) 0.034 2.01(1.07,3.78) 0.031 2.95(1.14,7.62) 0.026 Cesarean section  <2 Reference Reference Reference  ≥ 2 2.56(1.23,5.32) 0.012 2.60(1.25,5.43) 0.011 4.27(1.50,12.15)0.007 Model I: adjusting for age of onset and BMI Model II: adjusting for confounding factors such as age of onset, BMI, incubation period, pregnancy, parity, cycle, length of menstrual cycle, length of menstruation, operation time, surgical bleeding, lesion size, mesh placement, and layers excised Multiple regression analysis of the number of cesarean sections and AWE recurrence 1.97(1.05, 3.69) 0.034 2.01(1.07,3.78) 0.031 2.95(1.14,7.62) 0.026 2.56(1.23,5.32) 0.012 2.60(1.25,5.43) 0.011 Model I: adjusting for age of onset and BMI Model II: adjusting for confounding factors such as age of onset, BMI, incubation period, pregnancy, parity, cycle, length of menstrual cycle, length of menstruation, operation time, surgical bleeding, lesion size, mesh placement, and layers excised The Kaplan-Meier method was employed to evaluate differences in the cumulative recurrence rate between the three types of AWE lesions. As illustrated in Fig.  1 , the results exposed that the peritoneal type had the highest cumulative recurrence rate, followed by subcutaneous fat type, fascia, and the difference between the three groups was statistically significant ( P  < 0.05). Fig. 1 AWE lesion infiltration level and no recurrence curve (Kaplan Meier Survival Curve) AWE lesion infiltration level and no recurrence curve (Kaplan Meier Survival Curve)

Source: This retrospective analysis study was approved by the Ethics Committee of the Affiliated Hospital of Jining Medical College (No.:2022-04-C018) and was conducted in accordance with the Declaration of Helsinki.A total of 501 patients with histopathologically-confirmed abdominal wall endometriosis who underwent surgical treatment from January 2016 to July 2022 in the Affiliated Hospital of Jining Medical College were enrolled. Inclusion criteria: (I) patients who underwent surgery for biopsy-confirmed abdominal wall endometriosis; (II) patients with complete clinical history and follow-up data; (III) postoperative follow-up time was more than 12 months. Exclusion criteria: (I) patients with severe cardiovascular, pulmonary, hepatic, or renal diseases, pregnant women, and patients with malignancies; (II) patients with missing medical records, who were lost to follow-up, or did not consent to follow-up visits. Patients were considered to have relapsed if any of the following conditions were met: (I) patients with abdominal wall endometriosis underwent at least 12 months after AWE surgery; (II) the pathology confirmed AWE after another AWE or imaging confirmed recurrence; (III) the site of recurrence was the site of the previous surgery. Grouping: The patients were divided into 3 types according to the depth of infiltration of the bottom of AWE lesions during operation: (I) Subcutaneous fat type: the bottom of the lesion infiltrated subcutaneous fat but not the anterior sheath of the rectus abdominis; (II) Fascia: the lesion invaded the rectus abdominis sheath or rectus abdominis, but not reached the peritoneum; (III) Peritoneum type: the lesion invaded the peritoneum or reaches the abdominal cavity. According to the number of lesions, the patients were assigned to either the single group or the multiple group (number of lesions ≥ 2). According to the number of cesarean sections, patients were divided into single cesarean section and multiple cesarean sections (number of cesarean sections ≥ 2).According to whether AWE recurred or not, the patients were divided into either the recurrence group or the non-recurrence group. Data collection: Data were collected on the patient’s age of onset, BMI, incubation period, gravidity, parity, cesarean section, length of menstrual cycle, length of menstrual cycle, length of menstruation, dysmenorrhea, operation time, blood loss, hospital day, lesion size, mesh Placement, number of lesions, layers excised, follow up time.Follow-up methods mainly included telephone follow-up and outpatient follow-up. The chief clinical symptoms of the patients and relapse status of the patients were evaluated as part of the follow-up process. Follow-up intervals were greater than 12 months.The incubation period refers to the time from the last open surgery (cesarean section or gynecological surgery) to the onset of symptoms. Surgical steps were as follows: Abdominal wall ultrasound/MRI examination was performed prior to the surgery to assess the number and location of the lesions. An appropriate surgical incision was made based on the findings of the preoperative imaging examination. Then, the abdominal wall lesion, along with 1 cm of adjacent healthy tissue, was excised. If the surgical resection of many tissue and the large abdominal wall defect, the abdominal wall is difficult to match, according to the abdominal wall defect, polypropylene mesh is used to repair the abdominal wall. All surgeries were carried out by surgeons with more than 5 years of experience in AWE foci resection. Empower 4.0 statistical software was used. All statistical analyses were performed using the R statistical package ( https://www.R-project.org R Foundation) and EmpowerStats ( https://www.empowerstats.com Journal X&Y Solutions, Inc., Boston, Massachusetts, USA). Continuous variables are expressed as mean ± standard deviation, categorical variables are expressed as frequency or percentage. Continuous variables were compared using variance test analysis (normal distribution) or Kruskal-Wallis test (non-normal distribution), and categorical variables were compared using chi-square test. Univariate analysis was used to assess whether other variables were associated with AWE recurrence. Multivariate linear regression adjusted for potential confounders was used to further analyze whether other variables were independently associated with AWE recurrence. The cumulative recurrence rate was estimated by Kaplan-Meier method, and the difference between AWE lesion types was evaluated by log-rank or Mantel-Haenszel test. Bilateral P  < 0.05 was considered statistically significant.

Abdominal wall endometriosis (AWE) is defined as the growth and infiltration of endometrial tissue in the subcutaneous fat layer or muscle of the abdominal wall, often secondary to a history of abdominal surgery in obstetrics and gynecology, especially cesarean Sects. [ 1 , 2 ]. As a result of an increase in the number of cesarean sections during the last decade, the incidence of AWE has considerably increased. The symptoms of AWE are closely related to the menstrual cycle, often manifesting as periodic abdominal pain and a palpable tender mass with swelling, which severely impacts the quality of life of women of childbearing age [ 2 ]. Surgery is the treatment of choice for AWE, aiming for complete resection of the lesion and leaving no residual endometrial tissue in the affected area [ 3 ]. Nonetheless, these surgeries are typically complicated by the diverse manifestations of AWE lesions, such as a mass surrounding the abdominal wall incision or abdominal wall incision with periodic pain and no mass. Presently, most experts recommend excising 1 cm of healthy tissue around the lesion to provide a clean margin and prevent recurrence [ 4 , 5 ]. Although AWE is a benign disease, it has a certain ability of malignant change, invasion and recurrence, and some properties of endometrial cells are similar to tumor cells [ 6 ]. The recurrence rate after resection of abdominal wall lesions is still as high as 0–15%, and postoperative recurrence of abdominal wall endometriosis eventually reduces the quality of life. Meanwhile, repeated surgery not only brings serious psychological burden to patients, but also increases the risk of adhesion and organ damage [ 7 ]. Currently, there are no biomarkers for the diagnosis of AWE, and the correlation between recurrence and clinically relevant factors remains unknown. Furthermore, the optimal postoperative management of women with abdominal wall endometriosis remains controversial. Therefore, it is crucial to identify risk factors for the recurrence of abdominal wall endometriosis. This study retrospectively analyzed the clinical and follow-up data of patients suffering from abdominal wall endometriosis and aimed to explore factors associated with postoperative recurrence of AWE and provide a theoretical basis for its prevention. By identifying the independent factors that affect the recurrence of AWE, individualized preventive measures can be offered to patients at risk of recurrence to minimize recurrence.

Endometriosis refers to the growth and infiltration of functionally growing endometrial tissues (epithelial or stromal) outside the endometrium. Abdominal endometriosis (AWE) is a rare type of endometriosis [ 8 , 9 ]. Studies on AWE are limited and comprise mostly of case reports, focusing on its clinical manifestations, diagnosis, and management [ 8 ]. In recent years, the incidence of AWE has been reported to range from 0.03 to 3.5%, while the incidence of AWE in cesarean section scars was estimated to be between 0.03% and 0.45% and is increasing every year [ 9 ]. The pathogenesis underlying AWE is predominantly considered to be the implantation theory proposed by Sampson, whereby endometrial cells escape through a uterine incision during surgery and become implanted within the abdominal wound [ 8 , 10 ]. In recent years, several scholars have attempted to use endocrine factors (estrogen-progesterone, estrogen receptor, and progesterone receptor), inflammatory immune factors (tumor necrosis factor-alpha, interleukin, and insulin growth factor-1), angiogenic factors (vascular endothelial growth factor, and matrix metalloprotein-9) and genetic factors (miRNA and microRNA) for the treatment of AWE [ 6 , 11 , 12 ]., with variable degrees of success [ 8 ]. Currently, surgical resection of abdominal wall lesions is the preferred method for the treatment of AWE [ 3 , 9 , 13 ]. However, the recurrence rate in AWE patients after surgical treatment can range from 0 to 15% [ 7 , 14 ]. Recurrence of AWE and repeated surgeries exacerbate patient pain and financial burden. This study retrospectively analyzed multiple factors associated with the recurrence of abdominal wall endometriosis. By following up on 398 AWE patients for at least 12 months, the cumulative postoperative recurrence rate was determined to be 8.53%, and the median follow-up time for recurrence was 16.00 (3.00–65.00)months.When studying the clinical characteristics of recurrent and nonrecurrent AWE, there were more recurrent cesarean sections, longer operation time, more surgical bleeding, and more peritoneal lesions compared with the non-recurrent type. Several factors potentially affecting recurrence were analyzed by univariate analysis and multiple regression, and the results showed that the number of cesarean sections was an independent risk factor for postoperative recurrence ( P  = 0.026).At present, many studies have reported that the increase in the number of cesarean sections is a risk factor for AWE, but no study has reported whether the number of cesarean sections before the onset is related to the recurrence of AWE [ 17 , 18 ].In a case-control study conducted by Khan et al., of 2539 women undergoing surgery for endometriosis from Mayo Clinic, 1.34% developed AWE, mostly attributed to cesarean Sect. (59%) [ 15 ]. The results in this study showed that the number of cesarean sections was an independent risk factor for AWE recurrence. The more cesarean sections before the onset, the higher the incidence of recurrence. Considering that this may have some relationship to the multiple exposure of the abdominal wall surgical incision to the endometrial environment. Zhang et al. [ 3 ] explained that during cesarean section, endometrial tissue was directly inoculated into the cesarean section incision. Under appropriate nutrient supply and hormone stimulation, these endometrial cells survive and proliferate, and eventually cause the occurrence of cesarean section scar endometriosis (Cesarean scar endometriosis, CSE). It can be deduced that the mechanism underlying AWE mainly involves the local environment of the implantation site, and repeated cesarean sections create a local environment for endometrial cells and stromal growth, including estrogen exposure and chronic inflammation [ 16 , 17 ]. Neamtu, R. reported that endometrial cells are exposed during cesarean section and can survive in the treated abdominal wound. The amniotic fluid may overflow and enter the abdominal wound, and its components can facilitate the separation of viable cells so that the cells can easily penetrate the amniotic fluid into the pelvic floor and be transported to the skin, subcutaneous tissue, or muscles adjacent to the surgical incision [ 18 , 19 ]. On the other hand, the blood vessels cut during cesarean section and various activating factors in the blood may also be involved in the recurrence of AWE.Canis M et al. [ 20 ]reported that activated platelets in the blood are involved in the initial steps of tissue repair and are regarded as the cause of disease development; they may upregulate ERβ receptor expression in endometriosis stromal cells and COX-2 synthesis in monocytes, endothelial cells, and stromal cells. The activated platelets further release von Willebrand factor (vWF), adenosine diphosphate (ADP), serotonin, PAF, TXA2, and chemokine ligand 4 (CXCL4), leading to further platelet aggregation and perpetuating coagulation activation, which eventually induces fibrosis in endometriotic lesions through TGF-β1 release and activation of TGF-β1/Smad3 signaling [ 21 ]. Regarding the correlation between recurrence and the depth of lesion invasion, the cumulative recurrence rate was estimated using Kaplan-Meier analysis and found that the recurrence rate in the infiltration level of the excised lesion: peritoneal type > subcutaneous fat type > fascia type, indicating that the level of lesion infiltration was related to recurrence. Similarly, univariate analysis validated that the level of lesion invasion was correlated with the postoperative recurrence rate. Contrastingly, multiple regression analysis of the depth of invasion after adjusting for confounding factors did not find a correlation with the recurrence of AWE. Our findings are inconsistent with those of Zhao et al. [ 14 ], who retrospectively reviewed 64 AWE patients and noted that the recurrence of abdominal wall endometriosis was correlated with the size and depth of the lesion. The larger and deeper the lesion, the higher the risk of recurrence [ 14 ]. We speculate that the causes for the discrepancies in the results are as follows: this study included a larger sample size, and before adjusting for confounding factors, all factors that had a high impact on the results were included and adjusted by covariate screening before the analysis was carried out. In addition, univariate analysis and multiple regression analysis were statistically performed.On the other hand, we do not rule out the possibility of preoperative or intraoperative missed diagnosis in deep lesions with a high risk of recurrence.The manifestations of lesions in patients with AWE are diverse, such as only palpable abdominal mass or mild pain without abdominal mass or some are still in the latent period.During the operation, the operator may focus on the lesions with obvious mass and ignore other potential lesions. After surgical stimulation (intraoperative bleeding, postoperative vascular reconstruction, etc.), the potential lesions will gradually appear and appear “recurrence”.This needs further research to confirm. Since several studies have demonstrated inadequate treatment of AWE with pharmaceuticals like GnRH-a and progesterone, none of the study’s participants had a history of endometriosis or medication use. Moreover, no medications were utilized to prevent endometriosis recurrence following the initial AWE surgery. Due to extensive lesions and peritoneal infiltration, only two patients had abdominal exploration at the time of abdominal wall endometriosis surgery, and none of them showed intraoperative results indicating the existence of pelvic endometriosis. The sample size of this paper is larger than the previous studies. Compared with domestic and foreign studies, the sample size of AWE varies from 35 to 372 cases. In addition, considering that the recurrence rate of AWE is related to the follow-up time, patients who had undergone surgery 12 months earlier were selected to monitor for disease recurrence. The exclusion of some patients with incomplete medical records from this study may also have potentially affected the reliability of the findings.In this study, 501 patients with AWE were all secondary to cesarean section, missing cases secondary to other patients with a history of abdominal surgery or spontaneous AWE, and some patients with recurrence lacked histological evidence of recurrence of endometriosis.

The number of cesarean section is an independent risk factor for postoperative recurrence; compared with superficial lesions, the cumulative recurrence rate of deep lesions is higher. Therefore, for patients with multiple cesarean section history and deep lesions, personalized diagnosis and treatment, regular follow-up, to reduce recurrence, reduce the psychological and physiological burden of patients, improve the quality of life of patients.