Depth of Intestinal Wall Infiltration and Clinical Presentation of Deep Infiltrating Endometriosis: Evaluation of 553 Consecutive Cases

Abstract

Introduction:

Intestinal involvement in endometriosis was first described by Sampson in 1922. The reported incidence ranges between 3% and 37% in patients diagnosed with endometriosis. In literature, there are few studies that correlate the severity of endometriosis (in terms of intestinal infiltration) and its clinical presentation. The aim of this study was to review the correlation between the severity of symptoms, the depth of intestinal wall infiltration, and lymph node involvement in our tertiary referral center.

Materials and Methods:

We retrospectively analyzed 553 patients who had undergone intestinal resection for deep infiltrating endometriosis at our institution (Sacro Cuore Negrar Hospital) between 2004 and 2009. Based on intestinal wall infiltration, we divided patients into three groups (Group A: intestinal infiltration that reaches the muscle layer, Group B: infiltration to the submucosa, and Group C: endometriosis reaches the mucosa). Symptoms, intestinal stenosis, and positive lymph nodes were compared in the three groups with the chi-square test.

Results:

No statistical correlation was found between symptoms and the intestinal wall infiltrations. The three groups were also compared on the basis of positive visceral lymph nodes and we did find a statistical difference (P = .05) in the lymph node count in the two main groups.

Conclusion:

There seems to be no statistically significant difference in symptoms between patients with different degrees of infiltration. Although visceral lymph node involvement has been occasionally described in literature, we found that it is related to submucosal infiltration.

Introduction

Intestinal involvement in endometriosis was first described by Sampson in 1922.¹ The reported incidence ranges between 3% and 37% in patients diagnosed with endometriosis. It can affect any part of the gastrointestinal tract, from the first jejunal loop to the anal canal, but the sites most often affected are the sigmoid colon and rectum.^2,3 Patients with endometriosis may present with a wide range of symptoms characterized mainly by dysmenorrhea, dyspareunia, and pelvic pain. Endometriosis with intestinal localization is associated with characteristic symptoms, including pain on defecation, diarrhea, constipation, rectal bleeding, abdominal and pelvic swelling, and pain.^4,5 At diagnosis, 80% of patients present with the classic triad of symptoms: dysmenorrhea, dyspareunia, and pain on defecation.⁶ More rarely, the disease can lead to intestinal obstruction. The etiopathogenesis of the pain remains a matter of debate. The degree of pain and severity of disease do not show a linear relationship; in fact, symptoms can be more significant in cases of mild endometriosis compared with more severe cases with wider extension. Studies estimate that 5% of patients with extensive disease have no pain.^7,8

In literature, there are few studies that correlate the severity of endometriosis (in terms of intestinal infiltration) and its clinical presentation. The aim of this study is primarily to evaluate the possible correlation between symptoms (in terms of pelvic pain, dysmenorrhea, dyspareunia, dysuria, and pain on defecation) and the depth of intestinal wall infiltration in 553 patients who underwent intestinal segmental resection for deep infiltrating endometriosis (DIE) between 2004 and 2009. Second, we wanted to evaluate the presence of lymph node metastases and the presence of stenosis in the preoperative barium enema in the same patients.

Materials and Methods

Specimens from 553 patients who underwent laparoscopic intestinal segmental resection for DIE at the Sacro Cuore Don Calabria Hospital of Negrar (VR), Italy, between 2004 and 2009 were retrospectively evaluated.

The main inclusion criteria were rectosigmoid endometriosis; presence of symptoms: pelvic pain, dysuria, dyspareunia, dysmenorrhea, and pain on defecation; stenosis at the preoperative barium enema; laparoscopic segmental intestinal resection; and complete removal of macroscopic disease; the exclusion criteria were history of inflammatory chronic bowel disease and intestinal tumors. The indication for surgery was given by the presence of stenosis at the preoperative barium enema (significant stenosis was defined as > or equal to 30%) in association with symptoms in 322 patients (60%), while 231 patients (40%) had the presence of symptoms with a negative preoperative barium enema or a nonsignificant stenosis (defined as < than 30%) less than one-third of the rectal circumference.

For each patient, we collected the following data: demographic data, presence of preoperative symptoms (collected on a 0–10 [visual analog scale (VAS)]), nodule localization, depth of the intestinal wall infiltration, presence of positive lymph node for endometriosis, length of the specimen, extent and degree of the stenosis at the barium enema, type of intestinal resection performed, level of the anastomosis, operative time, intraoperative blood loss, execution of a colpotomy, postoperative data such as postoperative fever, use of antibiotics, days before discharge, days before opening the bowel, and surgical complications.

All patients underwent clinical examination to determine the presence of symptoms and to prescribe any further investigation. Symptom assessment was done using the VAS; pain was considered acceptable with VAS >5. On the basis of clinical and instrumental data, indication for surgery was given.

Operative technique

All surgical procedures were conducted laparoscopically with a standardized and well-defined technique that we previously described.⁹ The aim of the surgical procedure was the removal of all macroscopically visible and palpable endometriotic lesions. The first surgical period belongs to the gynecologists who provide a complete eradication of pelvic endometriosis. Second, general surgeons treated the intestinal segmental resection. In all patients, end-to-end colorectal anastomosis was performed. The level of end-to-end anastomosis was defined according to the distance from the anal verge as high (>8 cm), low (>5 cm and <8 cm), or ultralow (<5 cm). Pneumatic intraoperative test of the anastomosis was performed in all patients. In patients presenting ultralow anastomosis, a positive pneumatic test was performed, or in patients who underwent ureteral reimplantation, a temporary ileostomy was performed.

Histological evaluation

All surgical specimens were studied with the same protocol. On fresh tissue, we described the length of the surgical specimen, the number, size and macroscopic features, and the degree of stenosis of lesions. We also look for endometriotic secondary foci in lymph nodes. Surgical specimens were fixed in 10% buffered formalin for 12 hours. One day after surgery, the blocks were cut and macroscopic features were described. Each block was processed with standard paraffin technique and routinely stained with hematoxylin and eosin.

Statistical analysis

We divided patients into three groups based on intestinal wall infiltration: Group A: patients with an intestinal infiltration that reaches the muscle layer, Group B: infiltration to the submucosa, and Group C: endometriosis reaches the mucosa.

Gastrointestinal and gynecological symptoms as pelvic pain, dysmenorrhea, dyspareunia, dysuria, and pain on defecation were compared in the three groups with the chi-square test. The three groups were further divided according to two criteria: presence of stenosis at the barium enema and presence of lymph node endometriosis, these were than related to the presence of symptoms: pelvic pain and pain on defecation, dysmenorrhea, dyspareunia, and dysuria.

Results

Five hundred fifty-three patients underwent rectal or sigmoid laparoscopic segmental resection. No conversion to laparotomy was reported. Patients were divided into three groups on the basis of intestinal wall infiltration: Group A (243 patients) had muscle layer infiltration, Group B (265 patients) had submucosa infiltration, and Group C (45 patients) had mucosa infiltration (Table 1).

Table 1.

Baseline of Patients' Symptoms

	Group A/243 Pts	Group B/265 Pts	Group C/45 Pts	P value
Mean age (years)	33.6 (range 22–51)	32.6 (range 22–47)	32.9 (range 23–47)	—
Pelvic pain	131 (53.9%)	141 (53.2%)	20 (44.4%)	NS
Dyspareunia	141 (58%)	159 (60%)	28 (62.2%)	NS
Dysuria	45 (18.5%)	41 (15.4%)	3 (6.6%)	NS
Pain on defecation	149 (61.3%)	178 (67.1%)	26 (57.7%)	NS
Dysmenorrhea	204 (83.4)	237 (89.4%)	39 (95.8%)	NS
Stenosis >30% at BA	137 (58.7%)	180 (69.7%)	35 (77.7%)	NS

Group A, muscle layer infiltration; Group B, submucosa infiltration; Group C, mucosa infiltration; PTS, patients; BA, barium enema; NS, not significant.

In Group A, the barium enema showed in 96 (39.5%) cases, a stenosis at the sigmoid; in 69 (28.3%), at the rectal-sigmoid junction; and in 68 (27.9%), a rectal stenosis. In the second group, 103 (38.8%) patients had a sigmoid stenosis, 83 (31,3%) a stenosis at the rectal-sigmoid junction, while 68 (25.6%) cases showed a rectal localization. In the third group, the barium enema showed a stenosis in the sigmoid in 21 (46.6%) cases, a rectal-sigmoid junction stenosis in 10 (22.2%) cases, and a rectal stenosis in 13 (28.8%) patients (Table 2).

Table 2.

Level of Stenosis in Each Group After Barium Enema

	Pts (%) Group A	Pts (%) Group B	Pts (%) Group C	P value
Sigmoid	96 (39.5)	103 (38.8)	21 (46.6)	NS
Rectal–Sigmoid junction	69 (28.3)	83 (31.3)	10 (22.2)	NS
Rectal	68 (27.9)	68 (25.6)	13 (28.8)	NS

Group A, muscle layer infiltration; Group B, submucosa infiltration; Group C, mucosa infiltration; Pts, patients; NS, not significant.

We compared symptoms reported from the patients (pelvic pain, dyspareunia, dysmenorrhea, pain on defecation, and pelvic pain) with intestinal wall infiltration in the three groups, and no statistically significant differences were reported (Table 3).

Table 3.

Statistical Analysis Considering Symptoms Compared with Layer Infiltration in the Three Groups

	Group A–Group B	Group A–Group C	Group B–Group C	P value
Dyspareunia	0.41255	0.65649	0.99581	NS
Dysmenorrhea	0.61285	0.46091	0.29294	NS
Pelvic pain	0.94172	0.15046	0.15939	NS
Pain on defecation	0.64447	0.60053	0.78204	NS

Group A, muscle layer infiltration; Group B, submucosa infiltration; Group C, mucosa infiltration; NS, not significant.

Histological evaluation

The 553 specimens were studied with the same protocol. Mean length of the specimen was 9.4 cm (range 3–32 cm) in Group A, 10.4 cm (range 3–32 cm) in Group B, and 11.3 cm (range 5–24 cm) in Group C. In Group A, one single lesion was identified in 185 cases, 2 lesions were identified in 35 cases, and 3 lesions in one case. In the same group, mean length of the stenosis was 2.7 cm (range 0.5–15 cm). In Group B, 209 patients had one nodule, 31 cases showed 2 nodules, while 3 cases had 3. Mean length of the stenosis in this group was 2.7 cm (range 0.7–9.5 cm). In Group C, 31 specimens showed one lesion, 5 had 2, while 9 had 3 lesions. Mean length of the stenosis was 3.3 cm (range 2–10 cm). Positive lymph nodes were found in 59 patients (24.2%) in Group A, in 96 (36.2%) patients in Group B, and in 18 patients (40.0%) in Group C. As shown in Table 4, even though no difference in terms of enema results was reported in the three groups, patients with submucosal infiltration showed pathological lymph nodes with high frequency than the muscular layer infiltration group (Group B vs. Group A, P = .05)

Table 4.

Histological Evaluation

	Group A/243 Pts	Group B/265 Pts	Group C/45 Pts	P value
Mean length (cm)	9.4 (range 2–32)	10.4 (range 2–32)	11.3 (range 5–54)	NS
Stenosis mean length (cm)	2.7 (range 0.5–15)	2.7 (range 0.7–9.5)	3.3 (range 2–10)	NS
Positive lymph node	59 (24.2%)	96 (36.2%)	18 (40%)	0.05 (B vs. A)

Values shown in bold denote statistical significance.

Group A, muscle layer infiltration; Group B, submucosa infiltration; Group C, mucosa infiltration; PTS, patients; NS, not significant.

Discussion

Intestinal endometriosis has been described for the first time by Sampson in 1922.¹ Nowadays, it reaches an incidence between 3% and 37% of all patients with endometriosis. In most cases, infiltration can reach not only the muscular and submucosal layer of the intestinal wall but it can also reach the mucosa.^8,10 Patients with endometriosis present with different clinical complaints at various stages of disease. The majority of those with bowel involvement develop a variety of GI (gastrointestinal) complaints, including constipation, diarrhea, abdominal bloating, tenesmus, lower abdominal pain, and occasionally rectal bleeding. Symptoms usually occur cyclically at or about the time of menstruation. At the time of the diagnosis, 80% of patients present with the classic triad of symptoms: dysmenorrhea, dyspareunia, and pain on defecation.⁶ Cases of mild endometriosis have more significant symptomatology if compared with cases with a more aggressive infiltration. Some authors^7,8 pointed out that about 5% of patients with an extensive disease do not present any pain-related symptoms. In literature, there are few studies that try to find a correlation between symptoms and infiltration with lack of evidence of this relationship; despite this, we are convinced that a multicenter study with a huge number of patients may prove this interesting hypothesis.

In the population examined, we evaluated the possible correlation between the degree of intestinal infiltration and symptoms. This comparison revealed no statistically significant differences. This result deserves some considerations. First of all, our histological evaluation data included only the degree of infiltration of the wall, and we did not study the infiltration of nervous tissue. In addition, we had no data on the use by patients of analgesic drugs pre- and postoperatively and it may be considered that preoperative anamnestic interview of the patients has not been performed by the same surgeon. These results may suggest an accurate clinical investigation, intestinal symptoms may hide a bowel infiltration that could change the surgery program; although these are not enough to rely on for decision-making, surgeons should keep them in mind and perform an accurate preoperative study. The microscopic persistence of disease would be theoretically responsible for reduced effectiveness of surgery on health status, but there is no evidence that endometriotic residual lesions can develop and become symptomatic. The hypothetical recurrences could be caused by new endometriotic lesions. Moreover, medical therapy after surgery can arrest the possible progression of endometriosis.

Furthermore, our results confirm the findings of Fauconnier and Bazot^11,12 that exclude a linear correlation between the degree of infiltration and perceived pain. With regard to the other characteristic symptoms, some authors demonstrate correlation between seat of infiltration and symptoms. Fauconnier and collegues¹¹ indicate that dysmenorrhea increases in cases of involvement of rectouterine excavation, dyspareunia is related to infiltration of the uterosacral ligament, pain on defecation during the menstrual cycle occurs more frequently with vaginal involvement, and urinary symptoms with bladder infiltration. Although this is the only study that points to this correlation, there are many studies about reducing the symptoms in patients undergoing respective surgery for deep endometriosis.¹³ Several authors agree that laparoscopic bowel resection is feasible and can be performed safely when needed.⁵ However, a debate exists regarding the extent of intestinal wall resection necessary to adequately treat the disease. Remorgida et al.¹⁴ demonstrated that in subjects with true bowel endometriosis (penetrating beyond the serosa layer), surgical removal of lesions is associated with a significant improvement of gastrointestinal symptoms at 1 year. Fedele et al.¹⁵ reported a total recurrence of pain symptoms at 36 months in 28% of women with posterior deep endometriosis; however, women who underwent bowel resection had fewer clinical or sonographic recurrences and reoperations. Serracchioli and coauthors, in their recent study,¹⁶ showed that after 3 years of follow-up, qualitative changes in the severity of symptoms after surgery demonstrated that specific bowel symptoms (pain on defecation, pain on bowel movement, and low back pain) were improved in 20 of the 22 women studied. Constipation and diarrhea disappeared or improved in all women, and these results were maintained during the follow-up period. Transient intestinal symptoms such as mildly irregular bowel habit have been reported by other authors^17,18 after colorectal resection. All women with rectal bleeding observed a complete resolution of their symptoms after surgery. With regard to nonspecific bowel symptoms, Serracchioli et al.¹⁶ showed that dysmenorrhea and dyspareunia showed postoperative improvement in 18 of 21 and 14 of 18 affected women, respectively. Noncyclical pelvic pain was the only symptom that showed nonimprovement and a high recurrence rate (nearly half of the affected women) after 3 years. One of the hypotheses that may explain the persistence of noncyclical pelvic pain is the presence of adhesions. There appears to be sufficient evidence to suggest that adhesions have a contributory role in the persistence of noncyclical pelvic pain. Bowel resection is likely to add to pre-existing adhesions from endometriosis or from previous surgery performed for endometriosis.

These data support the feasibility of colorectal resection for deep infiltrating endometriosis, although this surgery may be associated with major complications. For this reason, it is mandatory to perform it when indicated with accurate preoperative counseling. Therefore, preoperative radiologic and endoscopic examinations that can show stenosis of the intestinal lumen or extrinsic compression of the bowel wall, infiltrating endometriotic lesions, or cases of multifocal disease are mandatory in symptomatic women.

Indications for colorectal resection, in these cases, are controversial because there is no standard approach to the patient with endometriosis. Our study suggests that intestinal surgery may be proposed in all cases with evidence or suspicion of stenosis of the lumen or when there is sonographic suspicion of intestinal endometriotic lesions larger than 2 cm. Indeed, even though we found no statistically significant differences between clinical intestinal wall infiltration and clinical presentation in this study, indications for surgery should be based on patient's symptoms and widely discussed with every patient.

In literature, there are reports of lymph node localization of deep endometriosis disease. For these reasons, we tried to evaluate lymph node involvement in our baseline, distinguishing the three groups. We reported higher incidence of positive lymph nodes in the group with infiltration of the submucosa compared with the one with infiltration limited to the muscle (P = .05). The significance of this finding may be better evaluated: Is it a sign of a more aggressive disease or just a different lymphatic drainage? The evaluation at follow-up in these patients, looking for a possible increase in the incidence rate of recurrent disease, will be crucial.

Our study has several limitations. Our center is a tertiary referral center for endometriosis; therefore, our patients may not be representative of the population as a whole. The retrospective nature of this study limited our ability to control for confounding factors and thus limited our ability to reliably predict those factors that lead to recurrence. All the presenting symptoms in our study were self-reported. Our study was limited to patients with proven bowel endometriosis, so we were not able to determine how valuable GI symptoms may be in predicting the presence of bowel endometriosis. To determine the predictive nature of gastrointestinal symptoms and adequately compare disc excision with segmental bowel resection for treatment of bowel endometriosis, further prospective controlled trials are warranted.

Conclusions

A study of the correlation between the degree of tissue infiltration, the clinical presentation, and the involvement of nervous and lymphatic tissues, as well as a careful study of the molecular mediators and receptors involved in endometriosis, is needed to understand the pathological processes that subtend the disease to a create an effective therapeutic regimen.

An effort should also be made in the standardization of pre- and postoperative study through the use of appropriate score for pain, quality of life, extent of symptoms, and patient satisfaction.

Footnotes

Acknowledgments

R.R. was responsible for manuscript writing, study design, data collection, and interpretation; L.G. was responsible for editing and drafting the manuscript; P.A. and Z.G. were responsible for study design and performed the specimen analyses; C.M and R.G. performed the surgery and were responsible for data interpretation; and R.L. and G.I. performed the statistical analysis and literature review.

Disclosure Statement

No competing financial interests exist.

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