Endometriosis is the growth, infiltration, and recurrent bleeding of endometrial tissue (glandular and mesenchymal) in the uterine cavity outside of the overlying endometrium and myometrium, which can form nodules and masses and cause pain and infertility.
The characteristics are as follows.
1.Multiple cases in women of reproductive age, mainly causing pain and infertility;
2.The incidence has a significant upward trend;
3. The severity of symptoms and signs and disease are not proportional;
4. The lesions are widespread and varied in form;
5, very infiltrative, can form extensive, serious adhesions;
6, hormone-dependent, easy to recur.
The clinicopathological types of endometriosis are divided into 4 types.
1. peritoneal endometriosis PEM;
2. Ovarian endometriosis OEM;
3. deep infiltrative endometriosis DIE, including the uterosacral ligament, vaginal rectal fossa, rectocolonic wall, vaginal vault, etc;
4.OtEM of endometriosis in other areas, such as laughing digestive, urinary, respiratory, and scarring.
Peritoneal endometriosis Refers to various endometriotic lesions in the peritoneum of the pelvic abdomen, mainly including red lesions (early lesions), blue lesions (typical lesions), and white lesions (old lesions).
Ovarian-type endometriosis Those that form cysts become endometriotic cysts. There are two types depending on the size of the cyst and the degree of infiltration of the ectopic lesion.
In type I, the cysts are mostly less than 2 cm in diameter, and the cyst walls have adhesions and unclear levels, which are not easily peeled off by surgery.
Type II, subdivided into 3 types, A, B and C.
Type IIA: Endo-implantation foci superficially involve the ovarian cortex and do not reach the cyst wall, often combined with functional cysts, and are easy to peel off surgically.
IIB: The implantation foci of endometriosis have involved the coarctation cyst wall, but the boundary with the ovarian cortex is clear and easier to be peeled off surgically.
IIC: The ectopic implant foci have penetrated into the cyst wall and extended to the surrounding area. The cyst wall is densely adherent to the ovarian cortex with fibrosis or multiple compartments. The ovary is adherent to the pelvic lateral wall and is large and not easily detached surgically.
Deeply infiltrating endometriosis Refers to lesions infiltrating to a depth of ≥5 mm, commonly with the uterosacral ligament, the rectal fossa, the vaginal vault, and the vaginal rectal diaphragm. The invasion of the vaginal rectal diaphragm includes two conditions: one is pseudo-endometriosis of the vaginal rectal diaphragm, i.e., due to closure of the rectal fossa by adhesions, i.e., the lesion is located below the adhesions; the other is true endometriosis of the vaginal rectal diaphragm, i.e., the lesion is located extraperitoneally, within the vaginal rectal diaphragm, with no obvious anatomic abnormalities in the utero-rectal fossa.
Other sites of endometriosis include gastrointestinal, urinary, respiratory, and scarring, as well as rare, distant endometriosis.
Pathogenesis of endometriosis
1. Not yet fully understood The leading theory is the Sampson’s retrograde blood flow implantation, epithelial metaplasia of the corpora cavernosa, and the induction theory.
The role of endometrium The endometrium needs to undergo the process of adhesion, invasion and angiogenesis outside the uterine cavity to be able to implant, grow and develop lesions, and the qualities of in situ endometrium may play a decisive role.
3, the role of immune function and hormones, etc. In the completion of the above process, the collective systemic and local immune status and function, hormones, cytokines and enzymes play an important role in ectopic endometrium.
4.Ectopic ectopic disease has family aggregation.
5, the role of external environmental pollution such as dioxin dioxin may have some influence.
Clinical manifestations and auxiliary examination methods
1, pain 70%-80% of patients have varying degrees of pelvic pain, which is not exactly parallel to the degree of lesion. Dysmenorrhea: typically secondary and progressively increasing; non-menstrual abdominal pain: chronic pelvic pain; painful intercourse as well as painful defecation; rupture of ovarian endometriosis cysts may cause acute abdominal pain.
2. Infertility About 50% of patients are combined with infertility.
3.Menstrual abnormalities.
4.Pelvic mass.
5.Specific sites of endoheterosis Various symptoms often have cyclic changes and can be combined with clinical manifestations of pelvic endoheterosis.
1.Endoheterosis of the digestive tract, with symptoms such as increased frequency of stool or constipation, blood in stool, and painful defecation.
2.Urinary tract endoheterosis, frequent urination, painful urination, hematuria and back pain, even causing urinary system obstruction and renal dysfunction.
3.Respiratory tract endoheterosis, menstrual hemoptysis and pneumothorax.
4, scar endoheterosis: nodules at incision scars after surgery such as abdominal wall cesarean section, which increase in size and pain during menstruation; nodules at perineal incision or wound scars, which increase in size and pain during menstruation.
6. Gynecological examination The uterus is often posterior and poorly mobile in typical cases. Tender nodules in the uterosacral ligament, rectal fossa of the uterus or posterior vault. There may be cystic inactive adnexal masses at the same time.
7.Blood CA125 test CA125 level is mostly mild to moderately elevated.
8.Imaging Ultrasound scan is mainly meaningful for the diagnosis of ovarian endometriosis cysts. The typical ultrasound image is an anechoic mass in the adnexal region with a strong light spot inside. MRI is meaningful for the diagnosis and evaluation of ovarian endometriosis cysts, extra-pelvic endometriosis and deep infiltrative lesions.
9.Other If necessary, other auxiliary examinations are feasible, such as IVP, cystoscopy, colonoscopy, etc.
Diagnosis of endoheterosis
1.Symptoms: pain (dysmenorrhea, CPP, painful intercourse, etc.), infertility.
2.Gynecological and auxiliary examinations: pelvic examination reveals endoheterozygous lesions, imaging reveals endoheterozygous lesions, and serum CA125 level is mildly or moderately elevated.
3.Laparoscopic examination: laparoscopy is the common method for diagnosing endoheterosis at present. The basis of diagnosis is mainly based on the morphology of the lesions under laparoscopy, but it is difficult to confirm all of them by pathology.
Clinical staging of endoheterosis
Currently, the commonly used staging method for endoheterosis is the American Fertility Society’s 1985 revised endoheterosis staging (r-AFS) method, which is mainly scored based on the size and depth of the peritoneal or ovarian lesion, the extent of adhesions between the ovary and the fallopian tube and the degree of adhesions, and the degree of closure of the rectal hollow of the uterus. The specific staging table will not be written, read the book.
Treatment of endometriosis
The goals of treatment are to reduce and eliminate lesions, relieve and relieve pain, improve and promote fertility, and reduce and avoid recurrence. The main factors to be considered in treatment are age, fertility requirements, severity of symptoms, extent of lesions, history of previous treatment, and the patient’s wishes. Treatment measures should be standardized and individualized. The treatment of pelvic pain, infertility and pelvic masses should be treated separately. Treatment methods can be divided into surgical, pharmacological, interventional and assisted reproductive treatment.
(i) Surgical treatment
1. Purpose of surgery: The purpose of surgery is to remove the lesion and restore the anatomy.
2.Surgical classification: Surgery for endometriosis is divided into different procedures according to the following.
(1) conservative surgery: to preserve the patient’s reproductive function, to remove as much as possible the lesions visible to the naked eye and the ovarian endometriosis cysts, and to separate the pelvic adhesions. It is suitable for those who are young or need to preserve their reproductive function.
(2) Semi-radical surgery: Removal of the uterus and lesions but preservation of the ovaries, mainly for those who have no reproductive requirements but wish to preserve the secretory function of the ovaries.
(3) Radical surgery: Removal of the whole uterus + both adnexa and all the lesions visible to the naked eye. It is suitable for those who are older, have no fertility requirements, have severe symptoms or have failed to respond to multiple treatments.
(4) Adjunctive surgery: such as uterine nerve removal and presacral nerve resection, for those with pain in the midline.
3. Pre-surgical preparation: The most important element of pre-surgical preparation is to accurately assess the severity of the condition, to adequately communicate with the patient or family, and to obtain understanding and informed consent. In addition, the risk of surgery, the possibility of surgical injury, especially urinary system and intestinal injury, and the possibility of laparoscopic surgery to open surgery should be evaluated; for deep infiltrative endometriosis, especially if the lesion involves the vaginal rectal area, adequate intestinal preparation should be done;
For those who have obvious infiltrative lesions in the parametrium, the ureter and growth should be checked for abnormalities before surgery, and the assistance of urology as well as general surgery is needed if necessary.
4. Key points of surgical implementation: firstly, pelvic adhesions should be separated to restore anatomy; to try to remove or destroy peritoneal type endometriosis lesions for the purpose of reduction; for smaller as well as more superficial lesions, cautery or vaporization can be performed; for deep infiltrating lesions, excision should be performed.
(1) Endo-ovarian cysts: the endo-ovarian cysts should be removed by separating the adhesions with the surrounding area, aspirating the fibrous tissue ring around the cystic rupture, and stripping the cystic wall intact to protect the normal ovarian tissue as much as possible; hysteroscopy and tubal lavage can be performed at the same time in cases of combined infertility.
(2) Deep infiltrative endoheterosis: it is difficult to deal with. If the lesion does not invade the rectum or colon wall, try to remove the lesion; if there is intestinal wall infiltration but no intestinal stenosis, it is generally not recommended to remove the intestinal wall or intestinal segment, and it is appropriate to reduce the lesion; if the lesion is large and causes intestinal stenosis or even intestinal obstruction, perform intestinal segment resection and anastomosis as appropriate.
(3) Endocystic ectasia: Depending on the size of the lesion of endocystic ectasia, resection of the lesion or partial cystectomy of the bladder wall is performed.
(4) Endoureteral heterogeneity: depending on the lesion and the degree of ureteral obstruction, perform adhesiolysis or partial ureteral resection and anastomosis.
(5) Scar endoheteropathy: surgical treatment is the main treatment, because drug treatment is mostly insensitive. For endometriosis lesions that are difficult to be removed cleanly by surgery, or when there is a possibility of damaging important organ tissues, drugs such as GnRH-a can be used for 3-6 months before surgery. When separating adhesions, removing the uterus, dealing with the uterine vessels as well as ligaments, attention should be paid to the anatomical relationships around the ureter, and if necessary, a ureteral catheter should be placed preoperatively as an indication. In addition, postoperative patients may be treated with anti-adhesion preparations.
(ii) Pharmacological treatment
The aim of pharmacological treatment is to inhibit ovarian function, stop the progression of endometriosis, reduce the activity of endometriotic lesions as well as reduce the formation of adhesions. The selection of drugs should be informed by.
(1) Drug therapy is recommended for cases with a basic diagnosis and long-term “experimental treatment” is not recommended;
(2) There are no standardized protocols for drug therapy;
(3) The efficacy of various regimens is basically the same, but the side effects are different;
(4) The patient’s wishes and financial ability should be considered.
The four main types of drugs available for the treatment of endometriosis are oral contraceptives, highly effective progestins, androgen derivatives, and GnRH-a. Commonly used medication regimens, mechanisms of action and side effects are as follows.
1.Oral contraceptive pills: continuous or cyclic administration for a total of 6 months, which can inhibit ovulation; less side effects, but may have gastrointestinal symptoms or abnormal liver function, etc.
2.High-efficiency progestin: 20-30mg/d of medroxyprogesterone acetate, divided into 2-3 oral doses, for 6 months. Medroxyprogesterone acetate can cause meconium-like changes in endothelial tissue, eventually leading to endothelial atrophy, and at the same time can negatively feedback inhibit hypothalamic-pituitary-ovarian axis. Side effects include breakthrough bleeding, breast pain, weight gain, gastrointestinal symptoms, and abnormal liver function.
3.Androgen derivatives: The androgen derivatives used for the treatment of endometriosis are.
(1) Danazol: 600-800mg/d, divided into 2-3 oral doses for 6 months. Danazol inhibits the mid-menstrual luteinizing hormone (LH) peak, thereby inhibiting ovulation; it also inhibits a variety of enzymes involved in steroid synthesis and increases the level of free testosterone in the blood. The side effects are mainly masculine manifestations, such as increased hair, mood changes, and thickening of the voice; in addition, it may also affect lipoprotein metabolism, cause liver function damage, and weight gain.
(2) Pregnatrienone: 2.5mg orally 2-3 times/week for 6 months. Pregnant trienone can antagonize progesterone and estrogen, reduce the level of sex hormone binding protein, and increase the level of free testosterone in blood. The side effects are mainly anti-estrogen and androgen-like effects, basically the same as Danazol, but less severe.
4.GnRH-a: According to different dosage forms, it is divided into subcutaneous injection and intramuscular injection, once a month for 3-6 months. The side effects are mainly menopausal symptoms caused by hypoestrogenemia, such as hot flashes, vaginal dryness, decreased libido, insomnia and depression, etc. Long-term application can cause bone loss.
The theoretical basis of the GnRH-a+Add-back regimen is based on the “estrogen window dose theory”, which states that different tissues have different sensitivities to estrogen, and that the estrogen level in the body should be maintained in a range that does not stimulate the growth of ectopic endometrium without causing menopausal symptoms and bone loss (estradiol levels between The Add-back regimen includes
(1) Combined estrogen and progestin regimen: combined estrogen 0.3-0.625mg/d (or Tegretol 1-2mg) + medroxyprogesterone acetate 2-4mg/d.
(2) Tibolone: 1.25mg/d. GnRH-a has been applied for more than 3 months, and the Add-back regimen is mostly advocated. Depending on the severity of symptoms, it can also be started in the 2nd month of medication, and the treatment dose should be individualized, and estrogen levels should be monitored when available.
(iii) Treatment of dysmenorrhea and infertility
1. Treatment of dysmenorrhea: for those with combined pelvic nodes or adnexal masses, surgery is preferred; for those without pelvic nodes or adnexal masses, drug therapy is preferred; for those for whom drug therapy is ineffective, surgery can be considered.
Commonly used drugs for the treatment of dysmenorrhea include.
(1) First-line medication: non-steroidal anti-inflammatory drugs or oral contraceptives can be used. Oral contraceptives can be used cyclically or continuously, and those who are effective can continue to use them, and those who are ineffective can switch to second-line drugs.
(2) Second-line drugs: Progestins, androgen derivatives and GnRH-a can be used, among which GnRH-a+Add-back regimen is preferred, which can effectively control the adverse effects of its long-term use. If second-line medications are ineffective, surgical treatment is considered.
(3) Pre-operative medication: for those who have heavy lesions and it is estimated that surgery is difficult to remove completely or surgery is likely to damage important organs, preoperative medication can be used briefly for 3 months to reduce the difficulty of surgery.
(4) Post-operative medication: according to the specific situation, if the lesion is mild or the surgical resection is complete, no medication can be temporarily used; if the pelvic lesion is serious or the lesion cannot be completely removed, medication can be used for 3-6 months depending on the presence of painful symptoms.
2. Treatment of infertility: for patients with endometriosis who have been examined comprehensively, other infertility factors have been ruled out, and drug treatment alone is ineffective, laparoscopy is feasible to assess the type and stage of endometriosis lesions; for young patients with mild or moderate endometriosis, natural conception is expected for six months after surgery, and fertility guidance is given; for those with high-risk factors (age ≥ 35 years, adhesions in the fallopian tubes with low functional score, infertility time ≥ 3 years) 3 years, especially depending on primary infertility, moderate or severe endometriosis with pelvic adhesions, and incomplete excision of the lesion), assisted reproductive techniques should be actively used to help conception.
Laparoscopic conservative surgery for infertility treatment should be performed to remove the lesions as thoroughly as possible, separate the adhesions and restore anatomy; attention should be paid to protecting normal ovarian tissues when removing endoheterocysts; intraoperative tubal lavage should be performed at the same time to understand the patency of the fallopian tubes, and hysteroscopy should be performed to understand the uterine cavity. Assisted reproductive techniques for treating infertility mainly include controlled ultra-ovulation and/or artificial insemination, in vitro fertilization-embryo transfer, etc., which should be selected according to the specific conditions of the patient.
(1) Controlled superovulation and/or artificial insemination are mainly used for patients with mild or moderate endometriosis, male factor (mild oligospermia, weak sperm, etc.), cervical factor, and patients with unexplained infertility. The single-cycle pregnancy rate of artificial insemination is about 15%, and if pregnancy is not successful after 3-4 treatments, the mode of pregnancy assistance should be adjusted.
(2) IVF-ET is mainly used for infertility patients with severe endometriosis or failure of other treatments (including natural conception, ovulation induction, artificial insemination, surgical treatment, etc.), long duration of disease, and advanced age. Pre-treatment with GnRH-a for 2-3 months prior to IVF-ET is recommended to help improve the success rate of assisted conception. The duration of dosing is adjusted according to the severity of the patient’s endometriosis and ovarian reserve.
Hormone therapy in patients with endometriosis
Hormone therapy can be administered to patients with endometriosis after menopause or radical surgery to improve their quality of life. Hormone therapy should be individualized according to the patient’s symptoms. Even if the uterus has been removed, if there are residual lesions of endometriosis, it is recommended to apply progestin along with estrogen therapy.
Recurrence of endometriosis
The recurrence of endoheterosis is defined as the reduction or disappearance of lesions and the remission of symptoms after surgery and standardized drug treatment, and the recurrence of clinical symptoms and their return to the pre-treatment level or aggravation, or the recurrence of endoheterosis lesions. The principles of treatment for recurrence of endoheterosis basically follow the principles of primary treatment, but should be individualized.
Surgery or ultrasound-guided puncture can be performed for endoheterozygous cysts, and medication is given after surgery. If recurrence occurs after medication for dysmenorrhea, surgery should be performed; if recurrence occurs after surgery, medication can be used first and if it is still ineffective, surgery should be considered; if the patient is older, has no fertility requirements and has heavy symptoms, radical surgery can be considered. Infertile patients with combined ovarian endometriosis cysts can be treated surgically or by ultrasound-guided puncture, and given GnRH-a for 3 months after surgery, followed by IVF-ET; those without combined ovarian endometriosis cysts can be given GnRH-a for 3 months followed by IVF-ET.
Malignant transformation of endometriosis
The incidence of malignant changes in endometriosis is about 1%. Malignancy should be alerted in the presence of.
(1) Cysts >10 cm in diameter or significantly enlarged in a short period of time;
(2) Recurrence after menopause;
(3) Altered pain rhythm, solid or papillary structure of the mass, color Doppler ultrasound shows abundant blood flow to the lesion and low resistance index;
(4) Significant elevation of serum CA125 (>200 KU/L).
The diagnostic criteria of atypical endograft showed that.
(1) Cancerous tissue and endoheterozygous tissue coexist in the same lesion site;
(2) Histological correlation between the two, similar to endometrial mesenchyme and glands, or the presence of old bleeding;
(3) The presence of other primary tumors is excluded, or the cancerous tissue occurs in the endometriosis lesion and does not metastasize from other sites;
(4) There is morphologic evidence of migration of the endoheteropathic lesion to the malignant lesion, or the benign endoheteropathic lesion is infiltrated with malignant tumor tissue. Atypical endoheterosis is an atypical or nuclear heterogeneous change in the histopathologically diagnosed ectopic endothelial glandular epithelium that does not break through the basement membrane; its histopathological manifestations are deep or lightly stained, pale nuclei of ectopic endothelial glandular epithelial cells with moderate or severe heterogeneity, increased nuclear/stromal ratio, and dense, compound or clustered cell protrusions. Atypical endoheterosis is considered a precancerous or junctional tumor state.
The site of endometriosis malignancy is mainly in the ovary and, less frequently, in other sites such as the vaginal rectal diaphragm, abdomen or perineal incision. The treatment of endometriosis malignant lesions follows the principles of ovarian cancer treatment.
Adenomyosis of the uterus
Interstitial endometrial glands exist within the myometrium of the uterus, which under the influence of hormones undergoes hemorrhage and myofibrous connective tissue hyperplasia, forming diffuse lesions or limited lesions, which may also form adenomyoma.
1, etiology: At present, the etiology of uterine adenomyosis is unclear, mainly endometrial invasion theory, others include vascular, lymphatic dissemination, epithelial metaplasia and hormonal influence.
2.Clinical manifestations.
(1) Dysmenorrhea: more than half of the patients have secondary dysmenorrhea, and it is progressively aggravated;
(2) Menstrual abnormalities: it can be manifested as excessive menstruation, prolonged menstruation and irregular bleeding;
(3) Infertility;
(4) Uterine enlargement: the uterus is mostly uniformly enlarged and spherical, but it can also be raised unevenly and hard.
3.Diagnosis: Preliminary diagnosis can be made based on symptoms, pelvic examination and the following auxiliary examinations.
(1) Ultrasound scan shows an enlarged uterus with thickened muscular layer, more pronounced posterior wall and anterior shift of the endometrial line. The lesion is isoechoic enhanced with punctate hypoechogenicity seen in between, and there is no obvious boundary between the lesion and the surrounding area.
(2) MRI shows the presence of poorly defined lesions with low signal intensity in the uterus. T2 enhancement images may have lesions with high signal intensity and a widened endometrium-myometrium binding area >12 mm.
(3) Serum CA125 levels may be elevated in most cases.
(4) Pathological diagnosis is the gold standard of uterine adenomyosis.
4.Treatment.
(1) Expectant treatment: asymptomatic, no fertility requirements can be observed regularly.
(2) Surgical treatment: It is the main treatment method, of which hysterectomy is the radical surgery. For young people who need to preserve function, focal resection or wedge hysterectomy can be performed, as well as adjuvant uterine nerve removal, presacral nerve resection or uterine artery blocking. For those who do not require fertility with increased menstrual flow, endometrial removal can be performed.
(3) Drug therapy: Same as endometriosis.
(4) Interventional treatment.
(5) Adjuvant fertility treatment: infertile patients can be treated with GnRH-a for 3-6 months and then assisted conception treatment. For those with limited lesions or adenomyosis, surgery + GnRH-a treatment can be performed first and then assisted conception treatment.