Colorectal endometriosis. A proposal of complementary classification and surgical management in stages

Objective: To organize the experience and international knowledge in the surgical management and staging of colorectal endo- metriosis, with a management proposal in stages. Method: An extensive non-systematic review of the literature was carried to organize the disease in stages (limited, intermediate and advanced) according to a scoring system, which considers the charac- teristics of the endometrioma, the personal history and surgical findings. We tested the proposed staging in a retrospective group of patients. Results: From January 2017 to April 2023, we collected 19 patients with a confirmed diagnosis of colorectal endo- metriosis, treated laparoscopically, by the same group of surgeons, in whom we found a strong correlation between the stage of the disease and the presence of complications that required reinterventions. Conclusions: We suggest a sequence of colorectal surgical management in stages according to the staging of the disease and we hope that this work will be followed by joint efforts to test it prospectively in order to compare results between hospital centers and make planned decisions.

Colorectal endometriosis. Intestinal endometriosis. Deep endometriosis. Resumen Objetivo: Organizar la experiencia y el conocimiento internacional en el manejo quirúrgico y la estadificación de la endometriosis colorrectal, con una propuesta de manejo por etapas. Método: Se realizó una revisión amplia no sistemática de la literatura para organizar la enfermedad en etapas (limitada, intermedia y avanzada) de acuerdo con un sistema de puntuación que considera las características del endometrioma, los antecedentes personales y los hallazgos en la cirugía. La estatificación propuesta se probó en un grupo retrospectivo de pacientes. Resultados: De enero de 2017 a abril de 2023 recopilamos 19 pacientes con diagnóstico confirmado de endometriosis colorrectal, tratadas por vía laparoscópica, por el mismo grupo de cirujanos, en las que encontramos una fuerte correlación entre el estadio de la enfermedad y la presencia de complicaciones que requirieron reintervenciones. Conclusiones: Sugerimos una secuencia de manejo quirúrgico colorrectal en etapas de acuerdo con la estadificación de la enfermedad y esperamos que el presente trabajo sea seguido de esfuerzos compartidos por probarla de manera prospectiva para poder comparar resultados entre centros hospitalarios y tomar decisiones planificadas. Palabras clave : Endometriosis colorrectal. Endometriosis intestinal. Endometriosis profunda. ORIGINAL ARTICLE Cir Cir (Eng). 2024;92(1):103-109 Contents available at PubMed www.cirugiaycirujanos.com *Correspondence: Armando Cepeda-Silva E-mail: [email protected] 2444-0507/© 2023 Academia Mexicana de Cirugía. Published by Permanyer. This is an open access article under the terms of the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Date of reception: 12-05-2023 Date of acceptance: 12-08-2023 DOI: 10.24875/CIRUE.M23000598 CIRUGIA Y CIRUJANOS (ENG) Cirugía y Cirujanos (Eng). 2024;92(1) 104

Endometriosis is a chronic inflammatory disease caused by endometrial tissue growing outside the uterus. It is estimated to affect 2% to 10% of the fe - male population overall, rising up to 50% in women with infertility, affecting, at least, 190 million reproduc - tive-age women and some beyond menopause 1. A prevalence of 8% to 12% has been estimated for colorectal endometriosis, with almost 90% of all intes - tinal lesions being found in the rectum and sigmoid colon2. The main symptoms of endometriosis include chron - ic pelvic pain related to the menstrual cycle and infer - tility. When the condition affects the intestines, additional symptoms such as abdominal bloating, changes to bowel habits (constipation or diarrhea), passage of mucus with bowel movements, rectal bleeding, urgency to defecate, and feeling of incom - plete evacuation may occur, often worsening with the menstrual cycle. Additionally, endometriotic nodules can cause narrowing of the intestinal lumen leading to obstructive symptoms, and eventually to reduced quality of life affecting not only women with endome - triosis but also their partners and families 3,4. Medical treatment of deep endometriosis involving the colorectum is an option for many women, with symptomatic relief probabilities ranging from 70% to 80%5 and increased overall pregnancy rates from 42% up to 80% 3. However, there is a group of patients who will require surgical management, including those who have not responded favorably to medical manage - ment, those with contraindications or intolerance to hormonal therapy, those with intestinal obstructive symptoms, and couples seeking natural conception or preferring surgery 6. Two distinct approaches have been described in the management of colorectal endometriosis, with differ - ent rates of complications, long-term side effects, and recurrences: – A radical approach with segmental colorectal re - section and anastomosis. – A more conservative approach involving local transmural and non-transmural resections, with reconstructions using manual or mechanical sutures5,6. The balance between the conservative or the radical approach regarding complications and recurrence rates has led to a debate among different surgical schools, with no current consensus on the standard surgical technique 5. We believe that the problem arises when discussing colorectal endometriosis as a uniform condition with - out recognizing the significant differences in treating limited vs advanced disease. Currently, there is no standardized classification to design staged therapies that can be compared among different working groups regarding cure outcomes, morbidity/mortality, and recurrence. Therefore, we decided to develop a staging classifi - cation for colorectal endometriosis, considering the cu - mulative global experience in its management, including the treating surgeon’s criteria for choosing the extent and type of surgery, associated complications, disease recurrence rates, and need for reinterventions. We ret - rospectively tested this classification on a group of patients treated at Instituto Nacional de Perinatología, Mexico City, Mexico from 2017 through 2023.

The group of authors, including 6 national and 1 international member of various backgrounds (gyne - cologists, urogynecologists, reproductive biologists, colorectal surgeons, and general surgeons), all expe - rienced in advanced pelvic surgery, both laparoscopic and open, worked collaboratively, both in-person and online, to conduct a non-systematic review of the lit - erature. This review included the clinical practice guidelines from the European Society of Human Re - production and Embryology (ESHRE) 7, the German guidelines from 2014 8, and meta-analyses, random - ized and non-randomized controlled clinical trials, pro - spective and retrospective studies since 2006 through 2022. Overall, these sources included a total of 16 846 patients, aiming to review the factors involved in the surgeons’ decisions when treating patients with colorectal endometriosis, the factors associated with intra- and postoperative complications, and the factors associated with disease recurrence. Once these factors were identified, they were grouped into categories, being the most relevant those associated with tumor characteristics (T), with the patients’ medical history (H) and with surgical fac - tors (S), creating the acronym THS. After defining the categories, they were categorized into 3 groups, being the first one the best clinical- surgical scenario and the third one being the worst scenario and defining an intermediate group in terms of technical difficulty, complications, and recurrences. A. Cepeda-Silva et al. Colorectal endometriosis. Treatment 105 Each group was assigned a numerical parameter representing it, allowing for proper differentiation of each group. This resulted in defining an unclassifiable stage due to lack of data, an initial stage or THS 1, an intermediate stage of evolution or THS 2, and an advanced stage of the disease or THS 3. Due to the nature of the disease and the difficulties in diagnosis, an initial preoperative classification (for surgical planning purposes) will be performed, which will be complemented with intraoperative findings and defined postoperatively with histopathological results (both with prognostic purposes). The version thus obtained is retrospectively eval - uated using data from electronic health records from a group of consecutive patients treated at In - stituto Nacional de Perinatología from January 2017 through April 2023 (including the years of the CO - VID-19 pandemic, which limited non-emergency surgeries due to hospital restructuring), with a con - firmed histopathological diagnosis of colorectal endometriosis. Based on the findings made, the group provides recommendations for the staged surgical treatment of patients with colorectal endometriosis.

Characteristics to be assessed by the surgeon for surgical decision-making in patients with colorectal endometriosis After reviewing the literature on factors impacting the surgeon’s decision-making on the surgical treat - ment of patients with colorectal endometriosis, factors associated with intra- and postoperative complica - tions, and factors associated with disease recurrence, we stay with the following elements as the character - istics that should be evaluated: those that are endo - metrioma-dependent, those dependent on the patients’ past medical history, and those dependent on surgery (Table 1): – Tumor or endometrioma: size, number, location, depth of invasion of colorectal wall, and presence or absence of intestinal lumen obstruction. – Patient history: age, body mass index, thrombo - embolic risk, and health status. – Surgery: previous surgeries for endometriosis, type of current surgery, intraoperative bleeding, and histopathological examination of resected material. Table 1. Characteristics to be evaluated by the surgeon for surgical decision-making in a patient with colorectal endometriosis Tumor (characteristics of colorectal endometrioma) Size Number Location Depth of invasion Intestinal lumen obstruction

Age BMI Caprini (thromboembolic risk classification) ASA (American Society of Anesthesiologists) health status classification Surgery History of previous surgeries for endometriosis Type of surgery performed in the current procedure Intraoperative bleeding Histopathological resection ASA: American Society of Anesthesiologists; BMI: body mass index. Once the characteristics to be considered by the surgeon in decision-making were defined and grouped, a table was created to score their importance in 3 categories, from 0 to 3, based on the importance of each characteristic and its specific weight in decision- making process ( Table 2). Regarding the characteristics of the endometrioma or tumor, we considered as the most favorable scenarios the presence of only 1 lesion, size < 3 cm, location above the rectum, depth of invasion not exceeding the serosa, and no evidence of colorectal lumen obstruction. Conversely, the least favorable characteristics include endometrioma or tumor size > 3 cm, presence of 3 or more lesions, lower rectum location, involving the full thickness of the wall, and causing some form of colorectal lumen obstruction. Regarding the patient’s past medical history, the most favorable scenarios are said to be age younger than 40 years, a body mass index (BMI) under 34, low-to-moderate thromboembolic risk, and a healthy- to-stable and controlled comorbidity status (American Society of Anesthesiologists [ASA] I-II). Conversely, the least favorable scenarios include age older than Cirugía y Cirujanos (Eng). 2024;92(1) 106 Table 2. Auxiliary table for scoring characteristics based on their importance for decision-making in the treatment of a patient with colorectal endometriosis Item 0 points 1 point 3 points Tumor Size: 3 cm Number: 1 Number: 2 Number: > 3 Location: above rectum Location: rectosigmoid junction Location: lower rectum Depth: serosal Depth: muscular Depth: full thickness Obstruction: no No scoring Intestinal lumen obstruction: yes History Age: 40 No scoring BMI: 35 Caprini: low, medium Caprini: high or very high ASA: I-II ASA: > III Surgery Previous surgeries for endometriosis: no Previous surgeries for endometriosis: yes No scoring Current surgery: nodules resection Current surgery: includes hysterectomy Current surgery: includes urinary tract opening or extrapelvic involvement Hemorrhage: 500 mL Pathology: complete resection Pathology: residual endometriosis No scoring ASA: American Society of Anesthesiologists; BMI: body mass index. 40 years, BMI > 35, high-to-very high thromboembolic risk, and ASA > III health status. The patient’s pats medical history was scored from 0 to 1 point as it was considered by the surgeons to be of lesser importance in intraoperative decision-making vs tumor characteristics or surgical factors. Regarding surgical factors, the most favorable scenario is when the patient has no history of previous surgeries for endometriosis, only undergoing resection of endometriotic nodules in the current surgery, with intraoperative bleeding of < 500 mL, and pathology reporting complete resection of the endometrioma margins. In contrast, the least favorable scenario includes a history of previous surgeries for endometriosis, current surgery involving opening the genital or urinary tracts or with extrapelvic involvement, intraoperative bleeding > 500 mL, and residual endometriosis on the histopathological examination. Having defined the importance of these characteristics and grouped them for scoring, patients were categorized into 4 stages. The first stage including those for whom sufficient information was not available for classification, while the remaining stages include those with limited, intermediate, and advanced disease ( Table 3). Retrospective assessment of patients treated with a confirmed diagnosis of colorectal endometriosis From January 2017 through April 2023, we collected data from 19 patients diagnosed with colorectal endometriosis, treated laparoscopically by the same group of lead surgeons ( Table 4). According to the Enzian classification, 17 of our patients were considered to have C1 colorectal involvement, 1 patient had C2 involvement, and another one, C3 involvement. When categorized based on the THS system, patients fell into THS 1 (8 patients), THS 2 (6 patients), and THS 3 (5 patients) (Table 5). Table 3. Stage categorization of patients with colorectal endometriosis Stage Meaning Score U Unclassifiable Missing data for classification purposes THS 1 Limited 0-2 THS 2 Intermediate 3-4 THS 3 Advanced > 5 A. Cepeda-Silva et al. Colorectal endometriosis. Treatment 107 Table 4. Retrospective evaluation of patients treated at Instituto Nacional de Perinatología with a confirmed diagnosis of colorectal endometriosis Patient THS score THS stage Enzian classification* Surgical management Complications and observations 1 4 2 C1 LNTR No 2 4 2 C1 LNTR No 3 4 2 C1 LNTR No 4 1 1 C1 LNTR No 5 6 3 C1 SRA No 6 4 2 C1 LNTR No 7 0 1 C1 LNTR No 8 8 3 C1 LNTR Yes† 9 4 2 C1 LNTR No 10 4 2 C1 LNTR No 11 2 1 C1 LNTR No 12 5 3 C1 LNTR Yes‡ 13 4 2 C1 LNTR No 14 4 2 C1 LNTR No 15 1 1 C2 LNTR Yes§ 16 12 3 C3 SRA Yes¶ 17 2 1 C1 LNTR No 18 6 3 C1 LNTR Yes** 19 2 1 C1 LNTR No LNTR: local non-transmural resection; SRA: segmental resection with anastomosis. *Only Enzian stage is considered for colorectal involvement. †Intestinal perforation as a complication not detected intraoperatively, requiring intestinal resection and emergency stoma in a 2nd surgical act. ‡Surgical wound infection. Six colorectal nodules, each 1 cm in size, were resected during a 6-hour surgery. §Surgical drainage of pelvic hematoma via laparoscopy. ¶3rd degree burn due to equipment use, requiring escharotomy and double interpositional flap. **Intraoperative hemorrhage (1800 mL) and 6-hour surgical time. Regarding the type of surgical management used, 17 patients underwent local non-transmural resection (LNTR), and 2 patients underwent segmental resec - tion with colo-colo segmental resection with anasto - mosis (SRA) without protective stoma. We encountered complications in 5 patients, ac - counting for 26% of the sample, with 74% of the pa - tients progressing uneventfully. Among patients treated with SRA, 1 progressed un - eventfully, while another one suffered a third-degree burn due to equipment use, which required escharoto - my and a double interpositional flap in a 2nd surgical act. Among the patients operated on with LNTR, we had 4 cases with complications: 1 had an intraoperative undetected intestinal perforation, which required intes - tinal resection and emergency stoma in a 2 nd surgical act, 1 had a surgical wound infection, 1 required surgi - cal laparoscopial drainage of a pelvic hematoma, and finally, 1 experienced intraoperative bleeding (1800 mL) and a 6-hour surgical procedural time. Four out of the 5 patients with complications had advanced colorectal disease with THS 3, which ac - counted for 80% of the sample. Additionally, we ob - served that a THS 3 level positively correlated with the presence or absence of surgical complications, 80% and 93% sensitivity and specificity rates, respec - tively ( Table 6).

Endometriosis is a condition estimated to affect 190 million reproductive-aged women worldwide, with Cirugía y Cirujanos (Eng). 2024;92(1) 108 a prevalence of colorectal involvement of 8% up to 12%, accounting for approximately 19 million women in this age group 2. Colorectal complications in patients with endometriosis are challenging for the medical team, requiring the availability of special resources including human expertise (experienced pelvic surgeon, urologist, and general or colorectal surgeon) and material resources (advanced laparoscopic equipment and instrumentation with intestinal endographe). Therefore, preoperative management planning is crucial, based on the patient’s clinical presentation, including bimanual, rectal, and speculum examination, supported by diagnostic aids such as transvaginal ultrasound and occasionally magnetic resonance imaging with rectal and vaginal contrast 9. Currently, the most widely used classification for endometriosis is the Enzian classification, which specifically considers only the size of the lesion (C1 = 1 cm, C2 = 1-2 cm, and C3 > 3 cm) 10. However, upon analyzing the international literature for this study on 16 846 patients, we found that the surgical management decision-making process for the surgeon involves other factors besides the size of the nodule, such as the number and depth of lesions, the presence or absence of intestinal lumen obstruction, the opening of genital, urinary, and digestive tracts in the same surgical act, intraoperative blood loss, history of previous surgeries for endometriosis, the patient’s overall health status, specific surgical risk, and the possibility of clinically relevant disease recurrence. Therefore, we decided to include these factors in a classification system we coined THS (tumor or endometrioma characteristics, the patients’ medical history and observations during surgery) We categorized our patients into 3 stages of disease (limited, intermediate, and advanced) and tested the staging classification in a group of patients retrospectively treated at Instituto Nacional Perinatología from January 2017 through April 2023. We found a strong correlation within our group between high THS scale values (advanced colorectal endometriotic disease) and the presence of complications requiring subsequent surgical management. Based on this correlation, we suggest a staged surgical management scheme: – For all stages: • Management in centers experienced in the management of endometriosis. • Preoperative definition of Enzian and THS stage as accurately as possible based on experience and available institutional resources (physical and bimanual vaginal examination with speculoscopy and transvaginal ultrasound, supplemented, if necessary, with magnetic resonance imaging with rectal and vaginal contrast). • Appropriate informed consent. Do not operate if the patient does not agree and is not aware of the benefits and risks of the procedure, or if the risks due to comorbidities outweigh the expected benefits. • Availability of complete human team (gynecological, general, urological, and colorectal surgeons) and technical equipment to address unforeseen events (staplers, blood products, etc.) • Preoperative intestinal preparation. – THS 1 stage (limited): local non-transmural extirpations or resections. – THS 2 stage (intermediate): transmural discoid resection. No more than 2 in segments < 10 cm. – THS 3 stage (advanced): segmental colon resection with anastomosis, preferably without a stoma. We believe that the present study contributes to a staged surgical management plan for patients with colorectal endometriosis, in addition to serving as a basis for comparing results between centers and opening new avenues for prospective research. Table 5. Distribution of patients based on colorectal endometriosis damage Enzian THS Stage Patients Stage Patients C1 17 1 8 C2 1 2 6 C3 1 3 5 Table 6. 2 × 2 table for the sensitivity and specificity of THS 3 and surgical complications Current complication Absent complication Present THS 3 4 1 Abent THS 3 1 13 Sensitivity: 80%. Specificity: 93%. A. Cepeda-Silva et al. Colorectal endometriosis. Treatment 109

Colorectal endometriosis is a common condition that requires a planned and comprehensive approach to reduce complications from overtreatment or subop - timal management, which should be based on a good preoperative diagnosis including comprehensive physical examination, bimanual examination, digital rectal examination, and speculoscopy, complemented by transvaginal ultrasound and sometimes magnetic resonance imaging with rectal and vaginal contrast. Currently, the most widely used classifications for endometriosis, such as Enzian, especially for colorectal involvement, only consider the size of the nodule, which we believe to be insufficient for surgical decision- making. Therefore, we propose a classification that considers a more comprehensive approach based on the patient’s history, nodule characteristics, and intraoperative conditions. In our patients, advanced endometriotic disease de - termined by THS classification positively correlated with the presence of complications, so we consider the pres- ent staged classification for colorectal endometriosis an approach to achieve disease staging by organizing the international experience already available in the man - agement of these patients, allowing us to define stage- based treatments and compare results between hospitals. Due to its limitations, this study should pave the way for prospective studies that, with appropriate statisti - cal analysis, should allow us to refine the scale and increase its utility, to offer patients the best option for personalized surgical management and perform planned interventions with a multidisciplinary team in a single procedure. Acknowledgments The authors would like to thank Dr. Ana Cristina Artea- ga Gómez, Dr. Minerva Guedea Téllez, and Brenda Sán- chez Ramírez for their help reviewing the text, Dr. Myrna Souraye Godínez Enríquez for her support and advice in initiating the project, and Dr. Luis Hernández López for his support in making this work possible. Funding None declared. Conflicts of interest None declared. Ethical disclosures Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this study. Confidentiality of data. The authors declare that they have followed the protocols of their work center on the publication of patient data. Right to privacy and informed consent. The au - thors have obtained approval from the Ethics Commit - tee for analysis and publication of routinely acquired clinical data and informed consent was not required for this retrospective observational study. Use of artificial intelligence for generating text. The authors declare that they have not used any type of generative artificial intelligence for the writing of this manuscript, nor for the creation of images, graphics, tables, or their corresponding captions.

1. Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L. ESHRE Guideline: endometriosis. Hum Reprod Open. 2022;2022:hoac009. 2. Mabrouk M, Raimondo D, Altieri M, Arena A, Del Forno S, Moro E, et al. Surgical, clinical, and functional outcomes in patients with rectosigmoid endometriosis in the gray zone: 13-year long-term follow-up. J Minim Invasive Gynecol. 2019;26:1110-6. 3. Hudelist G, Aas-Eng MK, Birsan T, Berger F, Sevelda U, Kirchner L, et al. Pain and fertility outcomes of nerve-sparing, full-thickness disk or segmental bowel resection for deep infiltrating endometriosis — a pros - pective cohort study. Acta Obstet Gynecol Scand. 2018;97:1438-46. 4. Ferrero S, Stabilini C, Barra F, Clarizia R, Roviglione G, Ceccaroni M. Bowel resection for intestinal endometriosis. Best Pract Res Clin Obstet Gynaecol. 2021;71:114-28. 5. Bafort C, Van Elst B, Neutens S, Meuleman C, Annouschka D, Hoore A. Outcome after surgery for deep endometriosis infiltrating the rectum. Fertil Steril. 2020;113:1319-27. 6. Vercellini P, Sergenti G, Buggio L, Frattaruolo MP, Dridi D, Berlanda N. Advances in the medical management of bowel endometriosis. Best Pract Res Clin Obstet Gynaecol. 2021;71:78-99. 7. Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022: hoac009. 8. Ulrich U, Buchweitz O, Greb R, Keckstein J, von Leffern I, Oppelt P, et al. National German guideline (S2k): Guideline for the diagnosis and treatment of endometriosis: Long version - AWMF registry no. 015-045. Geburtshilfe Frauenheilkd. 2014;74:1104-18. 9. Silveira da Cunha Araújo R, Abdalla Ayroza Ribeiro HS, Sekula VG, da Costa Porto BT, Ayroza Galvão Ribeiro PA. Long-term outco - mes on quality of life in women submitted to laparoscopic treat - ment for bowel endometriosis. J Minim Invasive Gynecol. 2014;21: 682-8. 10. Keckstein J, Saridogan E, Ulrich UA, Sillem M, Oppelt P, Schweppe KW, et al. The #Enzian classification: a comprehensive non‐invasive and surgical description system for endometriosis. Acta Obstet Gynecol Scand. 2021;100:1165-75.