Gastrointestinal and urological complications of deep infiltrating endometriosis : Literature review and a case report

Summary

Endometriosis is the presence of endometrial tissue outside the endometrial cavity. Deep infiltrating endometriosis (DIE) includes rectovaginal lesions as well as infiltrative disease to the bowel, urinary bladder, ureter and other rare locations.

Non gynecological complications of DIE can be divided into two major categories:
complications of the disease itself which include pelvic and abdominal pain, bowel stricture, cyclic rectal bleeding, dyschezia, chronic anemia, dysuria, hematuria, ureteral stenosis as well as loss of kidney function and complications of the treatment which include fistula formation, bladder void dysfunction and recurrent urinary tract infections. DIE has potential for malignant transformation in the affected organ.

DIE may be managed conservatively or surgically. However definitive treatment is surgical.

In the current work, literature review of gastrointestinal and urological complications of DIE is presented together with an exemplary case report of a patient managed at the clinical center for treatment of endometriosis in Znojmo Czech republic.

Key words:
deep infiltrating endometritis – pelvic pain – subfertility

Introduction

Endometriosis is defined as the presence of functional endometrial tissues outside the endometrial cavity. This clinical condition is found in 6%-10% of reproductive age women [1] and about 2.5% of postmenopausal women [2]. Typical locations for endometriotic lesions is in the pelvis involving the uterine wall (adenomyosis), ovaries, uterosacral ligaments, rectovaginal septum, rectosigmoid colon, urinary bladder and ureters. However, the presence of endometriosis has been reported in almost all organs in the body and rarely the condition appears in males [3].

Deep infiltrating endometriosis (DIE) is a form of endometriosis whereby the disease penetrates more the 5 mm beneath the peritoneum. These lesions are very active and associated with pelvic pain, dyspareunia and certain degree of dysfunction of the infiltrated organ.

Intestinal involvement is estimated to occur in 6%–35% of DIE patients [4]. Of these, 75%-90% are colorectal lesions known as Deep Infiltrating Colorectal Endometriosis (DICE) [5]. These may infiltrate the outer layers or penetrate deeper into the muscularia and mucosa.

It is estimated that 1% of endometriosis patients have urinary tract involvement [6] majority of which are located in the urinary bladder (80%-84%) [7]. Among DIE patients bladder and ureter involvements are approximated to be 12.4% and 4.4% respectively [8,9]. Histopathologically ureteral endometriosis can be intrinsic, when the wall of the ureter is infiltrated causing fibrosis and proliferation of its muscular layer, or extrinsic in which case the affected periureteric tissue compresses the ureter [10].

In the current work, literature review of gastrointestinal and urological complications of DIE are presented together with an exemplary case report of a patient managed at the clinical center for treatment of endometriosis in Znojmo Czech republic.

Pathogenesis of endometriosis

Many theories attempt to explain pathogenesis of endometriosis. However, none of these fully addresses all issues associated with development of endometriosis and hence pathogenesis of DIE and endometriosis at large remains elusive.

In transplantation theory retrograde menstruation through fallopian tubes is said to carry endometrial tissues into the abdominal cavity where they are seeded and proliferate to form endometriosis [11]. This theory, however, does not explain why endometriosis develops only in some women. Retrograde menstruation occurs in all reproductive age women, but endometriosis develops only in 6%-10% of them. One acceptable explanation to this is immune response dysfunction in those who develop endometriosis. Macrophage, natural killer cells and lymphocytes are capable of scavenging endometrial tissues contained in retrograde menstrual blood. Any defect in scavenging activity of endometrial tissues in retrograde menstrual blood may allow their seeding and proliferation to form endometriosis. Another shortcoming of this theory is that it does not explain the presence of deep endometriosis without surface peritoneal lesions. Additionally, the presence of endometriosis outside the abdominal cavity, where retrograde menstrual blood is anatomically barred from reach, remains unaddressed by this theory [12].

Lymphatic and vascular spread theory suggests the spread of endometrial tissues from the endometrial cavity by means of aberrant lymphatic and vascular spread. This theory explains the presence of endometriosis outside the abdominal cavity and isolated DIE nodules beneath the peritoneum and inside the cavitary organs without peritoneal involvement. Additionally, the propensity of spread of endometrial adenocarcinoma by lymphatic route highlights the ease of endometrial tissue spread by this method. However, this theory does not untangle the question of rare findings of endometriosis in males. Furthermore, despite the presence of case reports of lymphatic spread of endometriosis there is no satisfactory evidence from randomised studies to express its contribution in development of endometriosis [13].

Metaplasia theory proposes the presence of pluripotent coelomic tissues which can undergo metaplastic transformation to tissues histologically similar to eutopic endometrium. This hypothesis explains how endometriosis may happen in premenarchial and postmenopausal women as well as in males [14]. More research is needed to reveal contribution of this method in endometriosis development.

Biological factors induction theory suggests that biological factors such as hormones may induce tissue differentiation into endometrial tissues [15]. Development of endometriosis has been shown to be supported by oestrogen [16]. The presence of aromatase in endometriotic tissues enables them to convert ovarian and adrenal gland derived androgens into oestrogen. This intrinsic endometriotic oestrogen together with extrinsic oestrogen from the ovaries and adipose tissue support proliferation of endometriotic lesions. Although these biological factors are present in most women, endometriosis develops only in some of them, indicating that this theory alone does not suffice to explain development of endometriosis.

Endometriosis has been identified in scars after Caesarean section and other gynecologic surgeries [17,18]. These lesions are believed to develop from exposed eutopic endometrium during the procedures.

After reviewing the available literature. The author of this work is of idea that endometriosis is a multifactorial disease which develops when genetically predisposed individuals are subjected to a set of environmental factors.

Risk factors

Risk factors for DIE include family history, anatomical genital tract defects which block normal passage of menstrual blood, nulliparity especially when associated with sterility, Chronic or recurrent pelvic infections, environmental toxins and reproductive age. Excessive alcohol consumption and lack of physical activities are probable risk factors that require more scientific evidence [19,20].

Complications

Gastrointestinal complications

Gastrointestinal deep endometrisis may cause a wide range of symptoms such as dyschezia, diarrhoea, rectal bleeding and chronic abdominal pain. These symptoms may mimick irritable bowel disease and hence delay diagnosis. It is therefore prudent to consider bowel DIE in the differential diagnosis of episodic abdominal pain in reproductive age females especially when subfertility coexists.

Pain caused by DIE may largerly interfere with daily activities and compromise quality of life of the patient [21]. As a result there is economic impact due to absenteeism at work or school. For these reasons, DIE patients require adequate definitive treatment, preferbly surgically. Although DIE may develop in any part of GIT, the rectum, rectosigmoid colon and appendix are the most frequent locations [22]. DIE of the bowel may affect only the out layers or penetrate though the muscularis into the mucosa.

Bowel perforation is a rare complication of bowel endometriosis. It may present as asymptomatic or tender pelvic mass, mostly in the left iliac fossa. Careful history taking is key to indication of appropriate imaging and laboratory diagnostic methods that distinguish this rare condition from irritable bowel disease, bowel malignancy, diverticulitis or pylonephritis [23]. In the search for this literature review, most of the found cases of bowel perforation due to DIE were reported in pregnant women in the third trimester.

Serosal involvement of DIE results into formation of adhesions to the neighbouring intraabdominal structures. These may be extensive enough to cause bowel obstruction or change in bowel habits. Additionally adhesions hamper laparoscopic diagnosis or surgical intervention.

Among significant scientific findings about DIE is its potential for malignant transformation, in which case the most common histologic type is endometroid adenocarcinoma and rarely stromal sarcoma [24]. Similar to its effects on eutopic endometrium, hormone replacement therapy is also associated with development of malignancy in DIE lesions. These findings put DIE at a juction between benign and malignant diseases.

Ingrowth of DIE may be large enough to cause obstruction of the bowel lumen [25]. This may be associated with pain, dyschezia and change in bowel habits or it may be clinically silent until constipation ensues. For this reason, high suspiscion for DIE may enable early diagnosis and treatment to obviate debilitating outcomes.

Due to its location in the small pelvis, surgical treatment of DIE is technically limited by small space and poor visibility in the setting of anatomical alterations due to multiple organ involvement. Consequently, surgical treatment carries considerable risk of complications which must be discussed in detail with the patient prior to the surgery. Although these complications are discussed in this section, it should be noted that they overlap with complications of surgical treatment of DIE in the urinary tract or other organs in the small pelvis.

Hemoperitoneum requiring blood transfusion may result from injury to blood vessels during surgical treatment of DIE.

In case of bowel resection, anastomotic postoperative leakage may happen. This may be managed by resuture and protective colostomy or low rectal resection and coloanal anastomosis and temporary ileostomy. In some cases rectovaginal fistula complicates postoperative outcomes. This may be managed by loop ileostomy and bowel anastomosis resuture. Depending on the severity, permanent colostomy may be necessary.

Postoperative abscess formation and mechanical ileus my cause bowel obstruction. Additionally anastomotic stenosis may occur. This may be severe enough to require corrective resection and anastomosis.

Desctruction of vegetative nervous supply of the bladder during the surgery may lead to bladder void dysfunction (paralytic retention). It is also suggested that chronic bladder overstimulation yields chronic myogenic destruction with resultant urinary retention [26].

Urinary tract complications

Urinary retention may result from direct infiltration of autonomic nervous supply to the bladder [27]. Due to this recurrent urinary tract infections may occur.

Hematuria and consequent chronic anaemia may occur when DIE penetrates deeper into the muscularis layer of bladder or ureter [28].

Ureteral stricture caused by DIE may result into hydronephrosis and silent loss of renal function [29,30]. It is therefore imperative to properly and timely diagnose DIE so that this life threatening complication can be obviated. This may be achieved by including DIE in the differential diagnosis of unexplained urinary tract symptoms in reproductive aged female patients, especially when there is coexisting subfertility and dysmenorrhoea.

It is interesting to note that rarely, DIE may develop in the kidneys jeorpadising loss of their function [31].

Depending on the layers involved urinary tract DIE may be surgically managed by removal of the affected outer layers or resection of the affected part of the organ. It is therefore necessary to determine extent of invasion prior to the procedure so that appropriate consent may be obtained and technical arrangements for the surgery may be made.

Injury to adjacent organs including nerves and blood vessels is the commonest complication of surgical treatment of urinary tract DIE. Other complications of treatment are secondary stricture and abscess formation.

Diagnosis

Gastrointestinal and urological DIE may be suspected from carefully taken patient‘s history coupled with clinical examination. Diagnostic imaging technology such as ultrasound, magnetic resonance and computer tomography are useful in predicting location and size of the lesions.

Treatment

It is imperative that treatment strategy take into account reproductive plans of the patient. Owing to remarkable array of symptoms and patient expectations from therapy, choice of treatment method should be individualised.

Medical treatment of DIE may be used to halt disease progression, however on ceasessation of therapy the disease will continue to progress. Definitive treatment of DIE is therefore surgical, although neoadjuvant medical therapy may be used to limit disease progression prior to surgical intervention. For this purpose GnRH analogue, progestogens, combined oral contraceptives or antiprogestogens may be used.

Surgical removal of outer serosal layer is sufficient when only outer layers are involved. In case of stricture or inner layers involvement, resection of the affected part of the organ may be necessary.

Patients who are planning to conceive may be advised to use assisted reproduction method especially if prior efforts to conceive naturally were unsucceful. Treatment with GnRH analogues for 3 months post surgery has been shown to improve pregnancy rates [32].

Case report

In the year 2009, a 26 years old woman presented to our department with chief complains of unsuccessful efforts to conceive for longer that 1 year, dysmenorrhoea, oligomenotrrhoea and chronic pelvic pain. After complete examination laparoscopy was indicated and performed. During the procedure peritoneal changes suggestive of endometriosis were visualised. Ablation of the visible foci was performed and biopsy for histopathology taken. This confirmed the diagnosis of endometriosis.

GnRH were prescribed for 6 months and secondlook laparoscopy was perfomed seven months after the first surgery. In the second look laparoscopy there was marked improvement visually. The patient was advised to use assisted reproductive method, in vitro fertilisation (IVF), which was done successfully. Subsequently, she delivered a baby boy in January 2012.

In December 2013 the patient reported recurrence of pelvic pain and dysmenorrhoea. She had no gross hematuria, fever or lower urinary tract symptoms. Her stool was normal.

On physical examination tender mass about 4 cm wide was palpable per rectum in the rectovaginal septum. Rectoscopic examination was performed and penetrating lesion in the rectum was confirmed.

Laboratory findings were unremarkable.

Laparoscopically assisted surgical intervention was indicated. Intraoperative findings were adhesions in the ileocaecal region, endometrioma in the rectovaginal excation, infiltrates of endometriosis on the appendix, soft enlarged uterus suggestive of adenomyosis, left ovarium sarrounded by compact infiltrates of endometriosis which extend to the rectum and encapsulate the left ureter causing stenosis of about 1 cm of its length by external compression (See figure 1). Peritoneum of rectovaginal excavation was found with Allen-Masters syndrome. Peritoneum of the vesicovaginal excavation was smooth without focal changes. In the American Fertility Society classification the findings fall into stage IV (AFS IV).

The procedure started with adhesiolysis follwed by appendectomy. Then Deperitonisation of the cul de sac was performed coupled with bilateral ureterolysis (See figure 2 and figure 5). Due to the presence of infiltrates around the left ovarium, left sided adnexectomia was performed. Then the rectum was released with meticulous attention to spare the pelvic nervous supply. Treitz ligament and paracolic peritoneum were dissected up to the lienal flexture. Minilaparotomy was performed to enable the surgeon to perform extracorporeal resection of the rectum with end to end anastomosis accroding to Hartman procedure (see figure 3 and 4).

Total time for the surgery was 300 minutes.

Examination of the resected segment revieled infiltration of endometrioma into the lumen reducing its crosssectional area into half (figure 6). Histopathology confirmed endometriosis.

One week after the procedure the patient developed fever. Laboratory examination revealed elevated inflamatory markers. Ultrasound was suggestive of fluid accumulation in the cul de sac. Diagnostic laparotomy was performed in which abscess of cul de sac was identified. The abscess was incised and drained and the patient put under antibiotic therapy for 14 days. She was later discharged in good condition.

On outpatient follow up the patient reported remarkable improvement and absence of pelvic pain. At the moment of preparation of this work, she was not planning pregnancy, hence combined oral contraceptives were prescribed.

Discussion and conclusion

DIE of gastrointestinal and urinary tract may compromise quality of life of the affeced patient. Furthermore, some of its forms are life threatening as may cause loss of kidney fuction or malignant transformation.

Due to non gynecological location of a gynecological disease, these patients are likely to report their initial complaints to other specialists than gynecologists. The diagnosis and treatment of DIE may be missed or delayed if these specialist do not include DIE in the differential diagnosis. It is therefor prudent to include DIE in the differential diagnosis of cyclic or non cyclic pelvic and abdominal pain especially in reproductive age women with primary infertility.

In the presented case, ureteral stenosis could not be suspected from presenting clinical features. However, as it seen in figure 1 below, if left untreated stenosis could progress to cause left sided loss of renal function. Similary, the patient did not have dyschezia or constipation but progression of invasion could eventually lead to total obstruction presenting as surgical emergency. In this situation, radical surgical treatment was inevitable to obviate debilitating outcomes.

Initial surgical ablation followed by GnRH analogue treatment led into successful IVF treatment in the presented case. This is in the line with suggestions from literature [32].

Recurrence in our case occured two years after delivery. Although this case alone is not sufficient to suggest good practice. It can generally be suggested that DIE patients be followed up for a period of about two years after surgical treatment so that recurrence can be timely diagnosed and long term complications of surgery be ruled out.

In the management of DIE in these non gynecological locations, cooperation with abdominal surgeons, urologists, intensive care physicians and psychologists is inevitable. Therefore, to optimise the outcome of treatment, accurate clinical and radiological estimation of the extent of the disease should be performed prior to the surgery. This will enable arrangements to ensure presence of the needed consultants as well as obtaining patients consent for the procedure. Regular availability of DIE surgery consultants may be more reliable in specialised centers. It is therefore convinient to centralise DIE management in specialised centers which have appropriate expertise and facilities.

Doručeno do redakce dne 19. 8. 2014

Přijato po recenzi dne 10. 9. 2014

MUDr. Kondo Imani H.

zemarcopolo@yahoo.co.uk

Gynekologicko-porodnické oddělení, Nemocnice Znojmo

www.nemzn.cz