Pilot study of treatment of patients with deep infiltrative endometriosis with methotrexate carried in lipid nanoparticles.

OBJECTIVE: Previously, lipid nanoparticles (LDE) injected in women with endometriosis were shown to concentrate in the lesions. Here, the safety and feasibility of LDE carrying methotrexate (MTX) to treat deep infiltrating endometriosis was tested. DESIGN: Prospective pilot study. SETTING: Perola Byington Hospital Reference for Women's Health. SUBJECTS: Eleven volunteers (aged 30-47 years, BMI 26.15 ± 6.50 kg/m2) with endometriosis with visual analog scale pelvic pain scores (VAS) > 7 and rectosigmoid lesions were enrolled in the study. INTERVENTION: Three patients were treated with LDE-MTX at single intravenous 25 mg/m2 dose of MTX and eight patients with two 25 mg/m2 doses with 1-week interval. MAIN OUTCOME MEASURES: Clinical complaints, blood count, and biochemistry were analyzed before treatment and on days 90, 120, and 180 after LDE-MTX administration. Endometriotic lesions were evaluated by pelvic and transvaginal ultrasound (TVUS) before treatment and on days 30 and 180 after LDE-MTX administration. RESULTS: No clinical complaints related with LDE-MTX treatment were reported by the patients, and no hematologic, renal, or hepatic toxicities were observed in the laboratorial exams. FSH, LH, TSH, free T4, anti-Müllerian hormone, and prolactin levels were also within normal ranges during the observation period. Scores for deep dyspareunia (p < 0.001), chronic pelvic pain (p = 0.008), and dyschezia (p = 0.025) were improved over the 180-day observation period. There was a non-significant trend for reduction of VAS scores for dysmenorrhea. Bowel lesions by TVUS were unchanged. No clear differences between the two dose levels in therapeutic responses were observed. CONCLUSION: Results support the safety and feasibility of using LDE-MTX in women with deep infiltrating endometriosis as a novel and promising therapy for the disease. More prolonged treatment schemes should be tested in future placebo-controlled studies aiming to establish the usefulness of this novel nanomedicine approach.

Preoperative Ultrasound Scoring of Endometriosis by AAGL 2021 Endometriosis Classification Is Concordant with Laparoscopic Surgical Findings and Distinguishes Early from Advanced Stages.

STUDY OBJECTIVE: To compare the accuracy of preoperative ultrasound (US) in predicting the laparoscopically defined 2021 American Association of Gynecologic Laparoscopists (AAGL) Endometriosis Staging. DESIGN: Retrospective multicenter study of patients treated at 3 specialized endometriosis centers. SETTING: Three specialized endometriosis surgical centers in São Paulo (Brazil), Barcelona (Spain), and Avellino (Italy) participated. PATIENTS: A total of 878 patients aged 15 to 45 years with no history of pelvic malignancy underwent laparoscopic (LPS) treatment for suspected endometriosis. INTERVENTIONS: Retrospective review of preoperative transvaginal and transabdominal US (index test) assessed for endometriosis at all sites used in the 2021 AAGL Endometriosis Classification and classified patients into AAGL-US stages 1 to 4. Results were compared with reference-standard LPS (AAGL-LPS) staging. MEASUREMENTS AND MAIN RESULTS: The AAGL-US and AAGL-LPS stage were concordant in 586 cases (66.7%) (weighted kappa [WK] 0.759; intraclass correlation = 0.906), with the highest agreement observed in patients with no endometriosis (n = 70, 75.3% concordance), AAGL-LPS stage 1 (104, 50.7%) and stage 4 disease (358, 88.2%). Endometriosis was most accurately diagnosed in the rectum/sigmoid colon (WK 0.862), bladder (WK 0.911), and ovaries (WK 0.835/0.795 for right/left, respectively) and least accurately diagnosed at superficial peritoneal (WK 0.442), tubal (WK 0.391/0.363 for right/left, respectively), and retrocervical/uterosacral ligament (WK 0.656) sites. CONCLUSION: Sonographic estimation of the 2021 AAGL Endometriosis Staging is greatest in AAGL-LPS stages 1 and 4 and among patients with no endometriosis. US best identifies endometriosis of the ovaries, bladder, and bowel but is more limited for the tubes and superficial peritoneum.

Systematic evaluation of endometriosis by transvaginal ultrasound can accurately replace diagnostic laparoscopy, mainly for deep and ovarian endometriosis.

STUDY QUESTION: What is the sensitivity and the specificity of preoperative transvaginal ultrasound with bowel preparation (TVUS-BP) compared to diagnostic laparoscopy (DL) for the identification of ovarian and deep sites of endometriosis? SUMMARY ANSWER: DL was able to detect retrocervical, ovarian, and bladder endometriosis with similar sensitivity and specificity as TVUS-BP, whereas for vaginal and rectosigmoid endometriosis, DL had lower sensitivity and specificity than TVUS-BP. WHAT IS KNOWN ALREADY: TVUS-BP is a non-invasive examination with good accuracy for diagnosing ovarian and deep endometriosis. DL is expensive and can lead to surgical complications. STUDY DESIGN, SIZE, DURATION: This prospective study included a total of 120 consecutive patients who underwent surgery for suspected endometriosis with preoperative imaging (TVUS-BP), including a video of the laparoscopic procedure, between March 2017 and September 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two radiologists performed preoperative TVUS-BP using the same protocol for diagnosing endometriosis. Two surgeons, who were blinded to the results of the preoperative imaging and clinical data, reviewed the surgical videos from the entry of the abdominal cavity until the surgeon finalized a complete and systematic review prior to beginning any dissection (considered as a DL). A data sheet was used by surgeons and radiologists to record the sites and size of disease involvement, the American Society for Reproductive Medicine (ASRM) stage, and the Enzian score. The surgical visualization of endometriosis lesions that were confirmed by histological analysis was the gold standard. MAIN RESULTS AND THE ROLE OF CHANCE: DL was able to detect retrocervical, ovarian, and bladder endometriosis with similar sensitivity and specificity as TVUS-BP. DL was not able to detect vaginal endometriosis (sensitivity and specificity 0%): this is compared to a sensitivity and specificity of 85.7% and 99.1%, respectively with the utilization of a preoperative TVUS-BP. In addition, DL was notably poor at detecting rectosigmoid endometriosis, with a sensitivity of 3.7-5.6%, and this compares to 96.3% sensitivity with utilization of a preoperative TVUS (P < 0.001). For the ASRM stage, TVUS-BP results were highly correlated with the degree of endometriosis and pouch of Douglas (POD) obliteration (weighted Kappa of 0.867 and 0.985, respectively). For the Enzian score, there was a substantial correlation between TVUSP-BP and DL for compartment A (weighted Kappa = 0.827), compartment B (weighted Kappa = 0.670), and compartment C (weighted kappa = 0.814). LIMITATIONS, REASONS FOR CAUTION: The number of participants included may be a limitation in this study and, as the evaluators were blinded to the physical exam, the DL accuracy could be underestimated. As biopsies of pelvic organs were obtained only if there was a suspicion of endometriosis, the gold standard was not always applicable. This aspect could underestimate the prevalence of lesions and overestimate the sensitivity and the specificity of both the TVUS-BP and the DL. WIDER IMPLICATIONS OF THE FINDINGS: Preoperative TVUS-BP was accurate in identifying all sites of ovarian and deep endometriosis that were evaluated. It had significantly higher sensitivity than DL in detecting rectosigmoid endometriosis and predicting intraoperative ASRM staging and the Enzian score. These results suggest that TVUS-BP can replace DL for the diagnosis and treatment planning for patients with ovarian and deep endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no source of funding or conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Role of Imaging Tools for the Diagnosis of Borderline Ovarian Tumors: A Systematic Review and Meta-Analysis.

Borderline ovarian tumors (BOTs) have a low malignant potential and occur most often in young women. Its preoperative diagnosis can improve surgical strategy and reproductive approach. This study systematically reviews the literature for the accuracy of transvaginal ultrasound (TVUS), magnetic resonance (MRI), and computed tomography (CT) in the diagnostic of BOTs. We conducted a search in PubMed/Medline of articles in English from the last 5 years and included 14 studies for systematic review, 9 of them in the meta-analysis. The pooled sensibility and specificity was respectively 77.0% and 83.0% for TVUS (5 studies) and 85% and 74% for MRI (4 studies) in differentiating benign from malignant BOTs. CT and positron emission tomography (PET)-CT techniques were heterogeneous between studies, so a meta-analysis was not performed for the 4 studies on CT and PET-CT. However, these 4 studies have also shown a high accuracy in differentiating BOTs from malignant ovarian cancers.

Appendiceal Nodules in the Setting of Endometriosis Can Be Carcinoid Tumors.

INTRODUCTION: Endometriosis is occasionally found in the appendix, particularly in severe forms of deep infiltrating disease. Carcinoid tumor is the most common neoplasm of the appendix and may be overlooked or misdiagnosed when there are multiple endometriosis lesions in the pelvis. CASE DESCRIPTION: We describe two cases of carcinoid tumor diagnosed in patients who underwent surgery to treat endometriosis, in whom the diagnosis of appendiceal endometriosis was presumed. DISCUSSION: In the context of endometriosis, surgery is indicated when the appendix is affected. Despite the more likely diagnosis of appendiceal endometriosis, carcinoid tumors cannot be ruled out by imaging examinations.

Transvaginal ultrasonography with bowel preparation is able to predict the number of lesions and rectosigmoid layers affected in cases of deep endometriosis, defining surgical strategy.

BACKGROUND: Successful surgical treatment of deep bowel endometriosis depends on obtaining detailed information about the lesions, prior to the procedure. The objective of this study was to determine the capability of transvaginal ultrasonography with bowel preparation (TVUS-BP) to predict the presence of one or more rectosigmoid nodules and the deepest bowel layer affected by the disease. METHODS: A prospective study of 194 patients with clinical and TVUS-BP suspected deep endometriosis submitted to videolaparoscopy. Image data were compared with surgical and histological results. RESULTS: With respect to bowel nodule detection and presence of at least two rectosigmoid lesions, TVUS-BP had a sensitivity of 97 and 81%, specificity 100 and 99%, positive predictive value (PPV) 100 and 93% and negative predictive value (NPV) 98 and 96%, respectively. Regarding diagnosis of infiltration of the submucosal/mucosal layer, TVUS-BP had a sensitivity of 83%, specificity 94%, PPV 77%, NPV 96%. CONCLUSIONS: These findings show that TVUS-BP is an adequate exam for evaluating the presence of one or more rectosigmoid nodules and the deepest layer affected in deep infiltrating bowel endometriosis, confirming the importance of this technique for defining the most appropriate surgical strategy to be implemented.

Transvaginal ultrasound for diagnosis of deeply infiltrating endometriosis.

Deeply infiltrating endometriosis is the clinical form of the disease that is generally associated with conditions of more intense pain and may require more complex surgical management, consequently resulting in greater risks to the patient. In recent years, various investigators have confirmed the usefulness of methods such as magnetic resonance imaging (MRI), transrectal ultrasound and transvaginal ultrasound (TVUS) for the diagnosis of deep endometriotic lesions. The objectives of the present study are to describe the method used to perform TVUS for the detection of deeply infiltrating endometriosis, and to discuss the clinical benefits that the data obtained may offer clinicians providing care for patients suspected of having this type of endometriosis.

Epigastric pain relating to menses can be a symptom of bowel endometriosis.

CONTEXT AND OBJECTIVE: Endometriosis is a common affliction that may affect the intestinal tract. The objective of this case report was to describe an unusual clinical presentation of this form of the disease. CASE REPORT: The patient was a 35-year-old woman with epigastric pain that only occurred during menstruation, who had a history of bladder endometriosis. Endoscopy of the upper digestive tract showed normal results. Transvaginal ultrasound and nuclear magnetic resonance of the pelvis showed a lesion involving the ileocecal junction and appendix, measuring 30 x 22/x/13/mm, that was suggestive of endometriosis. The patient underwent laparoscopic resection of the bowel segment affected by the disease, followed by anastomosis of the ileum and ascending colon for immediate restoration of intestinal transit. Histological analysis confirmed the diagnosis of endometriosis. CONCLUSIONS: In young women, recurrent epigastric pain should be evaluated with regard to its relationship to menstruation, particularly if there is a history of endometriosis, since this may be a clinical sign that the disease is affecting the intestinal transit.

Epigastric pain relating to menses can be a symptom of bowel endometriosis / Dor epigástrica relacionada ao período menstrual pode ser um sinal de endometriose intestinal

CONTEXT AND OBJECTIVE: Endometriosis is a common affliction that may affect the intestinal tract. The objective of this case report was to describe an unusual clinical presentation of this form of the disease. CASE REPORT: The patient was a 35-year-old woman with epigastric pain that only occurred during menstruation, who had a history of bladder endometriosis. Endoscopy of the upper digestive tract showed normal results. Transvaginal ultrasound and nuclear magnetic resonance of the pelvis showed a lesion involving the ileocecal junction and appendix, measuring 30 x 22/x/13/mm, that was suggestive of endometriosis. The patient underwent laparoscopic resection of the bowel segment affected by the disease, followed by anastomosis of the ileum and ascending colon for immediate restoration of intestinal transit. Histological analysis confirmed the diagnosis of endometriosis. CONCLUSIONS: In young women, recurrent epigastric pain should be evaluated with regard to its relationship to menstruation, particularly if there is a history of endometriosis, since this may be a clinical sign that the disease is affecting the intestinal transit.

CONTEXTO E OBJETIVO: A endometriose é uma doença freqüente que pode acometer o trato intestinal. O objetivo deste relato de caso é descrever forma pouco usual de apresentação clínica. RELATO DE CASO: Paciente de 35 anos tinha queixa de dor em região epigástrica somente durante o período menstrual e antecedente de endometriose vesical. Endoscopia digestiva alta era normal, e ultra-sonografia transvaginal e ressonância nuclear magnética da pelve demonstravam lesão em transição íleo-ceco-apendicular de 30 x 22 x 13 mm sugestiva de endometriose. A paciente foi submetida a ressecção laparoscópica do segmento intestinal afetado pela doença com imediata reconstrução do trânsito intestinal através da confecção de anastomose íleo-cólon ascendente. A análise histológica confirmou o diagnóstico de endometriose. CONCLUSÕES: Dor epigástrica recorrente deve ser caracterizada quanto à sua relação com o período menstrual em mulheres jovens, especialmente se houver antecedente de endometriose, pois pode ser um sinal clínico da doença acometendo o trato intestinal.

Comparison between clinical examination, transvaginal sonography and magnetic resonance imaging for the diagnosis of deep endometriosis.

BACKGROUND: Deeply infiltrating endometriosis affecting the retrocervical region and the rectosigmoid generally requires surgical treatment. Clinical examination, transvaginal ultrasonography (TVUS) and pelvic magnetic resonance imaging (MRI) are useful in the preoperative diagnosis of the involvement of these sites. The objective of this study was to evaluate the capacity of digital vaginal examination, TVUS and MRI to diagnose rectosigmoid and retrocervical involvement. METHODS: A total of 104 patients with clinically suspected endometriosis were submitted to clinical examination, pelvic MRI and TVUS until 3 months prior to videolaparoscopy and the findings of these methods were matched with histopathological confirmation of endometriosis. RESULTS: Endometriosis was histologically confirmed in 98 of 104 (94.2%) patients. With respect to the rectosigmoid and retrocervical sites, respectively, digital vaginal examination had a sensitivity of 72 and 68%, specificity of 54 and 46%, positive predictive value (PPV) of 63 and 45%, negative predictive value (NPV) of 64 and 69% and accuracy of 63 and 55%. For TVUS, sensitivity was 98 and 95%, specificity 100 and 98%, PPV 100 and 98%, NPV 98 and 97% and accuracy 99 and 97%. MRI had a sensitivity of 83 and 76%, specificity of 98 and 68%, PPV of 98 and 61%, NPV of 85 and 81% and accuracy of 90 and 71%. CONCLUSIONS: TVUS had better sensitivity, specificity, PPV, NPV and accuracy in cases of deep retrocervical and rectosigmoid endometriosis when compared with MRI and digital vaginal examination, confirming that it is an important preoperative examination for the definition of surgical strategies.

Estudo comparativo entre a acurácia da ultra-sonografia intra-retal e a do toque retal no estadiamento do câncer do reto / Comparative study of the accuracy of intrarectal ultrasound and rectal examination in the staging of rectal cancer

O tratamento adequado do câncer retal requer conhecimento preciso da extensäo local e sistêmica da doença. O toque retal, único método utilizado para avaliar localmente estes tumores até recentemente, tem boa precisäo em mäos experientes, porém limita-se a variaçöes individuais, bem como dificilmente define o acometimento dos linfonodos. A tomografia computadorizada, introduzida no início da década de 80, tem-se mostrado confiável apenas para o estadiamento dos tumores avançados do reto; näo demonstra as lesöes menores que um centímetro e nem a presença de linfonodos pequenos, além de apresentar dificuldades operacionais e custo alto. Já a ultra-sonografia intra-retal (USIR) tem sido descrita como método confiável para a avaliaçäo dos tumores retais. Na tentativa de elucidar a validade da utilizaçäo deste método, comparando-o ao toque retal, foi realizado trabalho prospectivo, o qual incluiu 52 indivíduos: 42 eram portadores de câncer do terço médio ou distal do reto e 10 näo tinham afecçäo retal. O aparelho utilizado foi da marca Aloka, modelo 650. Todos os indivíduos foram previamente submetidos ao exame de toque retal, cujos achados foram confrontados com aqueles da ultra-sonografia...