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 endometriosis, 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 characteristics 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 endometriosis, 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.

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.

Polymorphisms of TNF-alpha (- 308), IL-1beta (+ 3954) and IL1-Ra (VNTR) are associated to severe stage of endometriosis in Mexican women: a case control study.

BACKGROUND: Endometriosis is an estrogen-dependent and chronic inflammatory disease affecting up to 10% of women. It is the result of a combined interaction of genetic, epigenetic, environmental, lifestyle, reproductive and local inflammatory factors. In this study, we investigated whether single nucleotide polymorphisms (SNPs) mapping to TNF-alpha (TNF, rs1800629) and IL-1beta (IL1B, rs1143634) and variable number tandem repeat polymorphism mapping to IL1-Ra (IL1RN intron 2, rs2234663) genetic loci are associated with risk for endometriosis in a Mexican mestizo population. METHODS: This study included 183 women with confirmed endometriosis (ENDO) diagnosed after surgical laparoscopy and 186 women with satisfied parity and without endometriosis as controls (CTR). PCR/RFLP technique was used for genotyping SNPs (rs1800629 and rs1143634); PCR for genotyping rs2234663. RESULTS: We found no statistical differences in age between groups nor among stages of endometriosis and the CTR group. We observed no difference in genotype and allele frequencies, nor carriage rate between groups in none of the three studied polymorphisms. The prevalence of TNF*2-allele heterozygotes (p = 0.025; OR 3.8), TNF*2-allele (p = 0.029; OR 3.4), IL1B*2-allele heterozygotes (p = 0.044; OR 2.69) and its carriage rate (p = 0.041; OR 2.64) in endometriosis stage IV was higher than the CTR group. Surprisingly, the carriage rate of IL1RN*2-allele (ENDO: p = 0.0004; OR 0.4; stage I: p = 0.002, OR 0.38; stage II: p = 0.002, OR 0.35; stage III: p = 0.003, OR 0.33), as well as the IL1RN*2-allele frequencies (ENDO: p = 0.0008, OR 0.55; I: p = 0.037, OR 0.60; II: p = 0.002, OR 0.41; III: p = 0.003, OR 0.38) were lower than the CTR group. Women with endometriosis stage IV (severe) had frequencies more alike to the CTR group in the IL1RN*2 allele frequency (31.2% vs. 27.2%) and carriage rate (37.5% vs. 41.9%). CONCLUSION: Although these polymorphisms are not associated with the risk of endometriosis, Mexican mestizo women with severe stage of endometriosis have higher frequencies of TNF*2-, IL1B*2- and IL1RN*2-alleles, which may explain a possible correlation with disease severity rather than predisposition or risk.

Expression of Membrane Progesterone Receptors in Eutopic and Ectopic Endometrium of Women with Endometriosis.

Endometriosis is one of the most frequent gynecological diseases in reproductive age women, but its etiology is not completely understood. Endometriosis is characterized by progesterone resistance, which has been explained in part by a decrease in the expression of the intracellular progesterone receptor in the ectopic endometrium. Progesterone action is also mediated by nongenomic mechanisms via membrane progesterone receptors (mPRs) that belong to the class II members of the progesterone and adipoQ receptor (PAQR) family. The aim of the present study was to evaluate the expression at mRNA and protein levels of mPR members in the eutopic and ectopic endometrium of women with endometriosis. Total RNA and total protein were isolated from control endometrium (17 samples), eutopic endometrium (17 samples), and ectopic endometrium (9 samples). The expression of PAQR7 (mPRα), PAQR8 (mPRß), and PAQR6 (mPRδ) at mRNA and protein levels was evaluated by RT-qPCR and Western blot, whereas PAQR5 (mPRγ) gene expression was evaluated by RT-qPCR. Statistical analysis between comparable groups was performed using one-way ANOVA followed by Tukey's multiple comparisons test with a confidence interval of 95 %. The analysis of gene expression showed that PAQR7 and PAQR5 expression was lower in both eutopic and ectopic endometrium as compared to the endometrium of women without endometriosis, whereas the expression of PAQR8 and PAQR6 was only reduced in eutopic endometrium. Furthermore, mPRα and mPRß protein content was decreased in the ectopic endometrium of women with endometriosis. Our results demonstrate a decrease in the expression and protein content of mPRs in eutopic and ectopic endometrium of patients with endometriosis, which could contribute to the progesterone resistance observed in patients with this disease.

Cervical ectopic pregnancy: A case series and literature review

Objective: To describe a case series of nine patients diagnosed with cervical ectopic pregnancy. Design: Descriptive retrospective study of the clinical records of nine consecutive cases of women diagnosed with cervical pregnancy attended at the Instituto Nacional de Perinatología, Mexico City. Results: 448 ectopic pregnancies were attended from January 2011 through June 2018. They represented 2.2% of all pregnancies during the period studied. Of these, nine were cervical pregnancies (2% of all ectopic pregnancies). Five of these patients were admitted because of vaginal bleeding. All nine patients were diagnosed with cervical pregnancy by ultrasonography. Eight patients were initially offered pharmacological treatment with resolution of the ectopic pregnancy confirmed by hCG in two patients. Six patients required surgical intervention, and fertility was preserved in five cases. Conclusions: Cervical ectopic pregnancy is a risk factor for extreme maternal morbidity. It can present as an unexpected massive hemorrhage that commonly leads to hysterectomy and even death. Nowadays, there is no universal algorithm for treatment as it is performed in a regional and non-standardized manner, and in many cases, fertility preservation is not contemplated. Prospective studies are needed to issue recommendations on the management of these patients.

Objetivo. Describir una serie de casos de nueve pacientes con diagnóstico de embarazo ectópico cervical atendidas. Metodología. Estudio retrospectivo descriptivo, con revisión del expediente clínico de nueve casos consecutivos de mujeres con diagnóstico de embarazo ectópico cervical entre enero 2011 y junio 2018, en el Instituto Nacional de Perinatología de Ciudad de México. Resultados. Se halló un total de 448 embarazos ectópicos, que representaron 2,2% del total de embarazos, de los cuales, 9 (2% de los ectópicos) resultaron cervicales. Clínicamente, 5 pacientes presentaron sangrado transvaginal, 3 cursaron con dolor cólico y 2 estuvieron asintomáticas. La edad gestacional promedio fue 7,5 semanas. El diagnóstico de embarazo cervical fue mediante ultrasonografía de segunda dimensión. Con respecto al tratamiento, a 8 de las 9 pacientes se les ofreció inicialmente tratamiento farmacológico; solamente dos de las pacientes mostraron resolución de la hCG (gonadotropina coriónica humana) con la terapia farmacológica; el resto requirió alguna intervención quirúrgica. Se logró tratamiento preservador de la fertilidad en 5 pacientes. Conclusiones. El embarazo ectópico cervical es un factor de riesgo de morbilidad materna extrema. Puede presentarse con hemorragia masiva inesperada, que comúnmente conduce a la histerectomía e incluso a la muerte. Actualmente no existe un algoritmo universal de tratamiento; se realiza de forma regional y no estandarizada y, en muchos casos, no se contempla la preservación de la fertilidad. Se requiere estudios prospectivos para poder emitir una recomendación sobre el manejo de este grupo de pacientes.

Increased systemic and peritoneal oxidative stress biomarkers in endometriosis are not related to retrograde menstruation.

Objetives: The goal of this study was to determine if systemic and peritoneal oxidative stress biomarkers are related to each other and to retrograde menstruation in endometriosis. Methods: Plasma and peritoneal fluid oxidative stress biomarkers and hemoglobin and erythrocytes in peritoneal fluid as retrograde menstruation indicators, were measured in 28 patients with endometriosis and 23 without endometriosis. Results: In the peritoneal fluid, carbonyls and lipohydroperoxides, indicative of protein and lipid oxidative damage, were higher in endometriosis group (21%, p = 0.016 and 46%, p = 0.009, respectively). However, these biomarkers were not different in the blood plasma of both groups, and only protein dityrosine, was increased in the plasma of endometriosis group (31%, p = 0.04). The peritoneal fluid hemoglobin content was not higher in the endometriosis group, nor related to carbonyls and lipohydroperoxides. Additionally, the peritoneal fluid oxidative biomarkers were not correlated with the blood plasma ones, and only malondialdehyde, and ischemia-modified albumin were almost two times higher in peritoneal fluid. Discussion: Our results show a peritoneal and systemic oxidative stress biomarkers increase in endometriosis, but not related to each other, and do not support the hypothesis of an increase in hemoglobin-iron supply towards the peritoneal cavity that causes oxidative damage.

Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis.

Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue (glands and stroma) outside the uterus, mainly in the peritoneal cavity, ovaries, and intestines. This condition shows estrogen dependency and progesterone resistance, and it has been associated with chronic inflammation, severe pain, and infertility, which negatively affect the quality of life in reproductive women. The molecular mechanisms involved in the pathogenesis of endometriosis are not completely understood; however, inflammation plays a key role in the pathophysiology of the disease, mainly by altering the function of immune cells (macrophages, natural killer, and T cells) and increasing levels of pro-inflammatory mediators in the peritoneal cavity, endometrium, and blood. These immune alterations inhibit apoptotic pathways and promote adhesion and proliferation of endometriotic cells, as well as angiogenesis and neurogenesis in endometriotic lesions. It has been demonstrated that hormonal alterations in endometriosis are related to the inflammatory unbalance in this disease. Particularly, steroid hormones (mainly estradiol) promote the expression and release of pro-inflammatory factors. Excessive inflammation in endometriosis contributes to changes of hormonal regulation by modulating sex steroid receptors expression and increasing aromatase activity. In addition, dysregulation of the inflammasome pathway, mediated by an alteration of cellular responses to steroid hormones, participates in disease progression through preventing cell death, promoting adhesion, invasion, and cell proliferation. Furthermore, inflammation is involved in endometriosis-associated infertility, which alters endometrium receptivity by impairing biochemical responses and decidualization. The purpose of this review is to present current research about the role of inflammasome in the pathogenesis of endometriosis as well as the molecular role of sex hormones in the inflammatory responses in endometriosis.

[Future reproductive ability in post-treatment Asherman's syndrome patients]. / Futuro reproductivo en pacientes con síndrome de Asherman postratamiento.

BACKGROUND: Hysteroscopy is the best approach for the management of Asherman syndrome with reproductive purposes, since it allows a quick diagnosis and treatment of partial or total uterine adhesions. However, there are a few studies on the reproductive outcome in patients with Asherman's syndrome. OBJECTIVE: Evaluate the results of adherenciolisis hysteroscopy in women with Asherman's syndrome. PATIENTS AND METHODS: We performed a cohort study of thirty-nine patients diagnosed with Asherman's syndrome and who underwent surgical hysteroscopic adherenciolisis by bipolar energy through the period from 2006 to June 2011. RESULTS: Thirty-nine cases were reviewed. All patients restored their menstrual cycle in the course of the first three months after surgery. The pregnancy rate after hysteroscopic treatment was 71.7% (28/39), with a son living at home in 28.2% of the cases (11/39). There was no statistical difference to achieve term pregnancy based on a cut-off point at 35 years of age. A history of menstrual pattern before hysteroscopy was associated with perinatal success. All pregnancies were achieved spontaneously within the first year after the procedure. CONCLUSIONS: Spontaneous pregnancy is possible after hysteroscopic adherenciolisis in Asherman's Syndrome. It confirms the viability of using bipolar energy to restore the size and shape of the uterine cavity with minimal endometrial damage and with an exclusive reproductive purpose.

Quantitative and qualitative peritoneal immune profiles, T-cell apoptosis and oxidative stress-associated characteristics in women with minimal and mild endometriosis.

OBJECTIVES: To assess immunological variables, T-cell apoptosis and oxidative stress markers in the peripheral blood and peritoneal fluid of women with (WEN) and without (WWE) endometriosis. DESIGN: Observational and transverse case-control study. SETTING: National Institute of Perinatology, Mexico City, Mexico. POPULATION AND SAMPLE: Peripheral blood and peritoneal fluid obtained from 30 WWE and 32 WEN. METHODS: Blood was drawn before surgery and peritoneal fluid was collected during surgery but before any surgical procedure had been carried out. Flow cytometry, spectrophotometry, high-performance liquid chromatography and multiplex immunoassay analyses were performed. MAIN OUTCOME MEASURES Peripheral and peritoneal lymphocyte subpopulations (CD3(+), CD4(+) CD3(+), CD8(+) CD3(+), CD16(+) CD56(+), human leucocyte antigen-DR(+) CD3(+) and CD19(+)), intracellular CD4(+) CD3(+) and CD8(+) CD3(+) cytokine synthesis (interleukin-2 [IL-2] and interferon-γ [IFN-γ]), CD3(+) apoptosis, malondialdehyde and ascorbate concentrations and peritoneal cytokine concentrations. RESULTS: No differences were found in peripheral and peritoneal lymphocyte subsets between the groups. Peritoneal T lymphocytes from WEN produced less IL-2 and IFN-γ than those from WWE. Peritoneal malondialdehyde concentrations were higher and ascorbate concentrations were lower in WEN than in WWE. Higher peritoneal concentrations of pro-inflammatory cytokines (IL-1ß, tumour necrosis factor-α and IL-6) and chemokines (IL-10, IL-8, eotaxin, vascular endothelial growth factor, monocyte chemotactic protein-1 and regulated upon activation, normal T-cell expressed, and secreted) and lower concentrations of IFN-γ, IL-1 receptor antagonist and IL-15 were found in WEN. No statistical differences were found in IL-2, IL-4, IL-12 and IL-13 concentrations. CONCLUSION: The alterations observed in WEN were associated with a diminished peritoneal T helper type 1 immune response. Pro-inflammatory, chemotactic, angiogenic and oxidative stress markers were altered in the peritoneal milieu of WEN. These changes appeared to contribute to the peritoneal immune alterations found.