| Adenomyosis is a benign gynecological disease.The clinical symptoms include abnormal uterine bleeding and various pain symptoms mainly including dysmenorrhea.Among them,dysmenorrhea severely affects the quality of life and mental health of patients.Talan et al.reported patients suffering with adenomyosis have a higher risk of depression.Clinically,patients often seek treatment because of severe dysmenorrhea.Relieving symptoms and improving fertility are the goals of adenomyosis treatment.For patients with dysmenorrhea,the treatment methods include drugs and surgery,and drug treatment has problems such as tolerability,side effects and cost.For patients who are refractory or unable to tolerate drug treatment,the gold standard of treatment is hysterectomy.However,many patients desire to reserve fertility or are contraindicated for hysterectomy,then uterine preservation procedures can be offered,in which excision of the lesions can obtain the best relief of dysmenorrhea.However,any conservative surgery has a risk of recurrence.Adenomyosis can be classified into two categories:diffuse adenomyosis and focal adenomyosis(mainly adenomyoma).At present,lesion excision,while uterus is reserved,is mainly used for the adenomyoma in which the lesion is localized in the uterine wall and can be completely removed.However,for diffuse adenomyosis,it is difficult to completely remove the lesion due to unclear lesion boundaries,and the risk of postoperative recurrence of the lesion and dysmenorrhea is higher.Gonadotropin-releasing hormone agonists(GnRH-a)and Mirena-based postoperative adjuvant therapy can reduce recurrence,but there are many side effects and high costs for postoperative drugs.At present,excision of the lesion and keep the uterus in patients with diffuse adenomyosis has gained more and more recognition.Early identification of high-risk patients with postoperative dysmenorrhea persists or relapses is helpful for performing targeted adjuvant therapy after surgery to enhance the effect of surgical treatment,delay recurrence and avoid excessive treatment.The risk factors for recurrence of dysmenorrhea in patients with adenomyosis after surgery to preserve the uterus are not yet clear.Because adenomyosis is an estrogen-dependent disease,factors related to estrogen exposure such as younger age are considered to be risk factors for recurrence of dysmenorrhea after conservative surgery,while postoperative pregnancy and postoperative adjuvant drugs treatment are protective factors for adenomyosis.Other factors related to postoperative dysmenorrhea have not yet reached consensus.Some studies have found that body mass index(BMI)is a prognostic factor for recurrence of dysmenorrhea after high-intensity focused ultrasound ablation.The higher the BMI,the higher the risk of recurrence.Some studies have shown that large uterine volume may be a risk factor for recurrence after laparoscopic adenomyoma resection,but it is not relevant to dysmenorrhea recurrence after uterine artery embolization.The serum CA125 level of patients is generally used for the monitoring of the efficacy and recurrence of adenomyosis after treatment,but it is not clear whether it is related to postoperative dysmenorrhea.Therefore,the factors related to the recurrence of adenomyosis after conservative surgery need further exploration,but there are few studies on the factors affecting the persistence or recurrence of dysmenorrhea after excision of diffuse adenomyosis.In addition,excision of diffuse adenomyosis is often performed with open surgery.In recent years,laparoscopic resection of the diffuse lesions is also used in clinical practice.However,there are fewer studies compare the two surgical methods(open surgery and laparoscopic surgery)about the impact on postoperative persistence or recurrence of dysmenorrhea after excision of diffuse adenomyosis.Therefore,this study hopes to investigate the clinical features,surgical methods and their correlation with dysmenorrhea persistence or recurrence after excision of diffuse adenomyosis in order to find the clinical risk factors for postoperative dysmenorrhea persistence or recurrence,thus guiding the clinical recognition of high-risk patients for further management.However,the value of having only a limited number of clinical indicators as predictors for postoperative dysmenorrhea persistence or recurrence may be limited.The lesion specimens can be obtained after surgery.If an effective biomarker can be found,it will provide greater value in judging the prognosis of postoperative dysmenorrhea,and it may also help uncover pathogenesis of the development and progression of adenomyosis.Currently,research on molecular markers that can indicate the severity and prognosis of adenomyosis has progressed slowly.There are no valuable pathological biomarkers for clinical use.Studies have shown that the abnormal expression and function of estrogen receptor(ER)and progesterone receptor(PR)in adenomyosis foci may be involved in the pathogenesis of adenomyosis,and may be related to dysmenorrhea.However,there has been no study to investigate the relationship between the expression of ER and PR in lesions and dysmenorrhea after excision of diffuse adenomyosis lesions,nor has it been studied to compare the expression difference of ER and PR in lesions with diffuse and localized growth patterns.It has been reported that the number of macrophages in the adenomyosis lesions increases and is related to the degree of dysmenorrhea.However,previous studies marked macrophages with the pan-macrophage biomarker CD68,while macrophages include both M1 and M2 types.Among them,M2 macrophages have anti-inflammatory effects and can promote tumor growth and angiogenesis,and their specific biomarkers are CD 163.In endometriosis,M1 macrophages kill the lesion,while CD 163-positive(CD163[+])M2 macrophages enhance the proliferation of ectopic endometrial stromal cells and the growth of the lesion.Tumor-associated macrophages(TAMs)exist in a variety of tumor microenvironments,which can inhibit inflammation and promote tumor growth,angiogenesis,immunosuppression and matrix remodeling,and are considered to be M2 macrophages.Studies have shown that CD163(+)TAMs are associated with poor prognosis of various malignant tumors.However,there has been no report on the infiltration and clinical significance of CD163(+)M2 macrophages in adenomyosis lesions and their relationship with postoperative prognosis.Therefore,in addition to the analysis of relevant clinical factors,this study also explored the differences about CD 163(+)macrophage infiltration,ER and PR expression in diffuse and localized adenomyosis lesions,and analyzed their relationship with the persistence or recurrence of dysmenorrhea after the excision of diffuse adenomyosis lesions,in order to find valuable biomarkers for judgment prognosis of postoperative of dysmenorrhea.Part I Analysis of related clinical factors of postoperativedysmenorrhea after excision of diffuse adenomyosisObjective:To investigate the clinical features of diffuse adenomyosis and its relationship with postoperative persistent or recurrence of dysmenorrhea after excision of diffuse adenomyosis in order to find out the clinical risk factors for postoperative dysmenorrhea.Methods:The clinical data,operation status and postoperative treatment of patients with dysmenorrhea who underwent excision of lesions for diffuse adenomyosis from January 2013 to January 2016 in our hospital was retrospectively collected.All the patients was histopathologically proven adenomyosis.The surgical methods included laparoscopic surgery and open surgery.The status of postoperative dysmenorrhea was obtained by telephone follow-up.The follow-up time was 2?5 years.Logistic regression analysis was used to analyze the relevant clinical factors of postoperative dysmenorrhea persistence or recurrence.Results:1.The median follow-up time for the 45 patients with diffuse adenomyosis with dysmenorrhea was 43 months(ranging from 24 months to 59 months).Dysmenorrhea was relieved in 42 cases after excision of diffuse adenomyosis.Excision of diffuse adenomyosis(including laparoscopic surgery and laparotomy)had an effective rate of 93.3%(42/45)in the treatment of dysmenorrhea.There was no significant difference in the efficacy of laparoscopic surgery and laparotomy on dysmenorrhea(p>0.05).Surgery had no effect on dysmenorrhea,that is,postoperative dysmenorrhea persists,in 3 cases.2.Among patients with relief of dysmenorrhea after surgery,the 2-year and 5-year cumulative recurrence-free survival were 81.0%and 78.1%respectively.Up to the follow-up deadline,dysmenorrhea recurred on 9 patients,and the median time to dysmenorrhea recurrence was 16 months(ranging from 11 months to 36 months).88.9%(8/9)dysmenorrhea recurrence occurred within 2 years after surgery.Postoperative dysmenorrhea persistence or recurrence rate was 26.7%(12/45).3.Comparing to patients with dysmenorrhea without recurrence,patients with persistent dysmenorrhea or recurrence had higher rates of high preoperative serum CA125 levels(CA125>129 U/mL)(66.7%vs.30.3%,p = 0.041),lower preoperative dysmenorrhea scores(6.5012.43 vs.7.94±1.78,p = 0.036),higher rates of laparoscopic surgery(66.7%vs.30.3%,p = 0.041)and fewer intraoperative penetration of uterine cavities(50.0%vs.81.8%,p = 0.033).However,there was no significant difference in the mean age,BMI,gravidity and parity,preoperative serum CA199 levels,preoperative dysmenorrhea duration,lesions extent,rate of combined endometriosis and the use of postoperative adjuvant drugs treatment between the two groups(p>0.05).4.Spearman correlation analysis showed that the level of CA125,the surgical methods,whether the uterine cavity was penetrated intraoperatively and preoperative dysmenorrhea duration were related to postoperative dysmenorrhea persistence or recurrence(p<0.05).5.Logistic multivariate regression analysis showed that high preoperative CA125 levels(>129 U/mL)and laparoscopic surgery were independent risk factors for persistent or recurrent dysmenorrhea after excision of diffuse adenomyosis,compared with low preoperative serum CA125 levels(<129 U/mL)and laparotomy(p = 0.016).Conclusions:For patients with diffuse adenomyosis who have symptoms of dysmenorrhea,resection of the lesions has a satisfactory therapeutic effect on dysmenorrhea.Laparoscopic surgery and high preoperative serum CA125 levels are independent risk factors for persistent dysmenorrhea or recurrence after excision of diffuse adenomyosis.Part ? Expression of CD163,ER and PR in adenomyosis foci andtheir relationship with dysmenorrhea after excision of diffuseadenomyosis Objective:To investigate the infiltration and clinical significance of CD163(+)macrophages in adenomyosis foci,and to compare the differences about the infiltration of CD163(+)macrophages and the expression of ER and PR between the diffuse and localized adenomyosis lesions,and to analyze the relationship between the infiltration of CD163(+)macrophages,the expression of ER,the expression of PR in foci and persistence or recurrence of dysmenorrhea after excision of diffuse adenomyosis.Methods:Thirty-two patients with uterine adenomyoma with focal lesions and thirty-four patients with diffuse adenomyosis were studied,whose paraffin-embedded specimens after resection of lesions were obtained for sectioning and immunohistochemistry staining for CD 163,ER and PR.The general clinical data of the patients were collected and patients with diffuse adenomyosis was followed up by telephone for postoperative dysmenorrhea status.The clinical significance of infiltration of CD163(+)macrophages in adenomyosis lesions was analyzed.The differences of the infiltration of CD 163(+)macrophage,the expression of ER and PR between diffuse adenomyosis and localized adenomyosis,as well as their association with dysmenorrhea persistence or recurrence after excision of diffuse adenomyosis were analyzed.Results:1.CD 163(+)macrophages are scattered in stroma surrounding the ectopic endometrium.The mean age at surgery,BMI,and peripheral blood mononuclear cell count were not different when infiltration of CD163(+)macrophages in adenomyosis foci was different.However,patients with high infiltration of CD163(+)macrophages in foci stroma had higher preoperative serum CA125 levels(p = 0.001),more severe dysmenorrhea(p<0.001),lower percentage of peripheral blood mononuclear cell(p =0.020),and the proportion of diffuse adenomyosis was also higher(94.1%vs.5.9%,p<0.001).Spearman correlation analysis showed that the degree of CD 163(?)macrophages infiltration in the stroma of adenomyosis foci was positively correlated with the diffuse growth of the lesions,serum CA125 levels,dysmenorrhea,and was negatively correlated with the percentage of peripheral blood mononuclear cells(p<0.05).2.ER and PR were mainly expressed in the nucleus of glandular epithelial cells and the stroma cells of the adenomyosis lesions,and the expression level in the glandular epithelial cells was higher than that in the stroma cells(p<0.05).Diffusely growing lesions had higher levels of PR expression in stroma cells compared to locally growing lesions(p<0.05),whereas there was no significant difference in the ER expression levels in both glandular epithelial cells and stroma cells,and PR expression levels in glandular epithelial cells(p>0.05).3.Among the patients with diffuse adenomyosis,there were 30 cases with premenstrual dysmenorrhea before surgery,who were enrolled for analysis of relevant pathological factors of dysmenorrhea persistence or recurrence after excision of diffuse adenomyosis.Among them,9 cases went through persistent or recurrent dysmenorrhea.In the adenomyosis lesions of patients with postoperative persistent or recurrent dysmenorrhea,the expression levels of ER in glandular epithelial cells and stromal cells were higher than those without postoperative dysmenorrhea persistence or recurrence(3.05±0.44 vs.2.69±0.40,p = 0.038;2.66±0.37 vs.2.36±0.35,p= 0.041),while the infiltration of CD 163(+)macrophages in the foci stroma,the expression of PR in glandular epithelial cells and stroma cells in the lesions were not statistically different between the two groups(p>0.05).The spearman coefficients of correlation between the infiltration of CD163(+)macrophages in foci stroma,the expression level of ER and PR in glandular epithelium and stroma cells of adenomyosis foci and persistent or recurrent dysmenorrhea after excision of diffuse adenomyosis was not statistically significant(p>0.05).Conclusions:The infiltration of CD 163(+)macrophages and the PR expression level of stroma cells were higher in diffusely growing adenomyosis foci than that of localized adenomyosis foci.The expression levels of ER in glandular epithelial cells and stromal cells of ectopic endometrium of patients with persistent dysmenorrhea after excision of diffuse adenomyosis were higher than that of patients without postoperative dysmenorrhea recurrence,and the infiltration of CD 163(+)macrophages and the PR expression levels in both glandular epithelial cells and stromal cells of adenomyosis foci were not associated with persistent or recurrent dysmenorrhea after excision of diffuse adenomyosis. |
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