The nano-revolution in the diagnosis and treatment of endometriosis.

Endometriosis is a painful gynecological disease with a high prevalence, affecting millions of women worldwide. Innovative, non-invasive treatments, and new patient follow-up strategies are needed to deal with the harmful social and economic effects. In this scenario, considering the recent, very promising results already reported in the literature, a commitment to new research in the field of nanomedicine is urgently needed. Study findings clearly show the potential of this approach in both the diagnostic and therapeutic phases of endometriosis. Here, we offer a brief review of the recent exciting and effective applications of nanomedicine in both the diagnosis and therapy of endometriosis. Special emphasis will be placed on the emerging theranostic application of nanoproducts, and the combination of phototherapy and nanotechnology as new therapeutic modalities for endometriosis. The review will also provide interested readers with a guide to the selection process and parameters to consider when designing research into this type of approach.

Fertility in patients with untreated rectosigmoid endometriosis.

RESEARCH QUESTION: Several studies have investigated reproductive outcomes following surgical treatment of colorectal endometriosis, mainly segmental colorectal resection. This study examines pregnancy and live birth rates of women with rectosigmoid endometriosis not treated by surgery. DESIGN: A retrospective analysis of data collected between May 2009 and January 2020 related to 215 women affected by rectosigmoid endometriosis wishing to conceive. Patients had a diagnosis of rectosigmoid endometriosis by transvaginal ultrasonography and magnetic resonance imaging enema. Patients with estimated bowel stenosis >70% at computed tomographic colonography and/or subocclusive/occlusive symptoms were excluded. RESULTS: During the median length of follow-up of 31 months (range 13-63 months), the total pregnancy and live birth rates of the study population were 47.9% and 45.1%, respectively. Sixty-two women had a live birth after natural conception (28.8%; 95% confidence interval [CI] 22.8-35.6%) with a median time required to conceive of 10 months (range 2-34 months). Eighty-three women underwent infertility treatments (38.6%, 95% CI 32.1-45.5%); among these, 68 patients underwent IVF either directly (n = 51) or after intrauterine insemination (IUI) failure (n = 17). Time to conception was significantly higher in women having conceived by IVF than in those having conceived naturally (P < 0.001) or by IUI (P = 0.006). In patients undergoing IVF cycles, a worsening of some pain and intestinal symptoms was observed. CONCLUSIONS: At median follow-up of 31 months, women with rectosigmoid endometriosis have a 48% pregnancy rate. However, these patients must be referred to centres specialized in managing endometriosis to properly assess symptoms and degree of bowel stenosis.

Other imaging techniques: Double-contrast barium enema, endoscopic ultrasonography, multidetector CT enema, and computed tomography colonoscopy.

Double-contrast barium enema (DCBE), transrectal endoscopic ultrasonography (REU), multidetector computerized tomography enema (MDCT-e), and computed tomography colonoscopy (CTC) have been successfully used for the diagnosis of bowel endometriosis. DCBE provides a complete overview of the entire colon and allows detecting cecal nodules. The accuracy of DCBE is operator dependent and, thus, it may have low specificity. It does not allow identifying the cause of the mass effect. DCBE requires the administration of barium and exposure to radiation. REU precisely estimates the distance between the rectosigmoid nodule and the anal verge. However, it allows investigating only the distal part of rectosigmoid, it misses anterior pelvic lesions, and it has poor sensitivity for the diagnosis of endometriomas. MDCT-e is accurate and reproducible in diagnosing intestinal endometriosis and in assessing its characteristics: the largest diameter of the nodule, the distance between the distal part of the nodule and the anal verge, and depth of infiltration of endometriosis in the intestinal wall. MDCT-e requires the administration of iodinated contrast medium (CM) and the exposure to radiations. CTC has good performance in the diagnosis of rectosigmoid endometriosis. It allows estimating the degree of intestinal stenosis CTC, and the distance between the intestinal endometriotic nodule and the anal verge. It requires exposure to radiations, and it may require the administration of an iodinated CM.

Magnetic Resonance Rectal Enema Versus Computed Tomographic Colonography in the Diagnosis of Rectosigmoid Endometriosis.

OBJECTIVES: Rectosigmoid involvement by endometriosis causes intestinal symptoms such as constipation, diarrhea, and dyschezia. A precise diagnosis about the presence, location, and extent of bowel implants is required to plan the most appropriate treatment. The aim of the study was to compare the accuracy of magnetic resonance with distension of the rectosigmoid (MR-e) with computed colonography (CTC) for diagnosing rectosigmoid endometriosis. METHODS: This study was based on the retrospective analysis of a prospectively collected database of patients with suspicion of rectosigmoid endometriosis who underwent both MR-e and CTC, and subsequently were treated by laparoscopy. The findings of imaging techniques were compared with surgical and histological results. RESULTS: Of 90 women included in the study, 44 (48.9%) had rectosigmoid nodules and underwent bowel surgery. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the diagnosis of rectosigmoid endometriosis were 88.6%, 93.5%, 92.9%, 89.6%, and 91.1% for CTC, and 93.2%, 97.9%, 97.6%, 93.8%, and 95.6% for MR-e. There was no significant difference in the accuracy of both radiologic examinations for diagnosing rectosigmoid endometriosis (P = 0.344). However, MR-e was more accurate than CTC in estimating the largest diameter of the main rectosigmoid nodule (P < 0.001). The pain perceived by the patients was significantly lower during MR-e than during CTC (P < 0.001). CONCLUSIONS: MR-e and CTC have similar diagnostic performance for the diagnosis of rectosigmoid involvement of endometriosis. However, MR-e is more accurate in the estimation of the largest diameter of main rectosigmoid nodule and more tolerated than CTC.

Magnetic Resonance Enema in Rectosigmoid Endometriosis.

Intestinal endometriosis occurs in 4% to 37% of women with deep endometriosis (DE). Noninvasive diagnosis of presence and characteristics of rectosigmoid endometriosis permits the best counseling of patients and ensures best therapeutic planning. Magnetic resonance enema (MR-e) is accurate in diagnosing DE. After colon cleansing, rectal distention and opacification improves the performance of MR-e in diagnosing rectosigmoid endometriosis. MR imaging cannot optimally assess the depth of penetration of endometriosis in the intestinal wall. There is a need for multicentric studies with a larger sample size to evaluate reproducibility of MR-e in diagnosis of rectosigmoid endometriosis for less experienced radiologists.

Does Bowel Preparation Improve the Performance of Rectal Water Contrast Transvaginal Ultrasonography in Diagnosing Rectosigmoid Endometriosis?

OBJECTIVES: The primary objective of the study was to compare the performance of the rectal water transvaginal ultrasonography (RWC-TVS) with and without bowel preparation (BP) in diagnosing rectosigmoid endometriosis. The secondary objectives were to compare the performance of the 2 exams in estimating infiltration of the mucosa, length of the largest rectosigmoid nodules, distance of the nodules from the anal verge, and presence of multifocal disease. METHODS: This prospective study included patients with pain symptoms and intestinal complaints suggestive of endometriosis. Patients underwent RWC-TVS with and without BP within an interval of 1 week to 2 months. Two independent and blinded gynecologists performed the exams. The results of the 2 exams were compared with surgical and histologic findings. RESULTS: A total of 155 patients were included in the study; 92 patients had rectosigmoid endometriosis. There was no significant difference in the performance of RWC-TVS with or without BP in diagnosing rectosigmoid endometriosis (P = .727). There was no significant difference in the performance of RWC-TVS with or without BP in diagnosing infiltration of the mucosa (P = .424) and multifocal disease (P = .688), in estimating the main diameter of the largest nodule (P = .644) and the distance between the more distal rectosigmoid nodule and the anal verge (P = .090). The patients similarly tolerated the 2 exams (P = .799). CONCLUSIONS: Bowel preparation does not improve the performance of RWC-TVS in diagnosing rectosigmoid endometriosis and in assessing the characteristics of these nodules.

Bendamustine and rituximab combination is safe and effective as salvage regimen in Waldenström macroglobulinemia.

According to the European Society for Medical Oncology and National Comprehensive Cancer Network guidelines on Waldenström macroglobulinemia, bendamustine (B) may be considered a suitable therapeutic option. To address the role of B in combination with rituximab (BR), we analyzed the outcome of 71 patients with relapsed/refractory disease, median age 72 years, treated with R 375 mg/m(2) day 1 and B days 1 and 2 (dosage ranging from 50 to 90 mg/m(2)). Patients had previously received a median number of 2 lines of treatment (range 1-5). Overall and major response rates were 80.2% and 74.6%. Major toxicity was grade 3/4 neutropenia occurring in 13% of courses. There was no significant association between baseline features or patients' characteristics and response achievement. Median progression-free survival was not reached after a median follow-up of 19 months (range 3-54). None of the patients developed aggressive lymphoma or secondary myelodysplastic syndrome/acute myeloid leukemia. BR was found to be an active and well-tolerated salvage regimen leading to rapid disease control.

Triptorelin for the treatment of endometriosis.

INTRODUCTION: Over the past 30 years, gonadotropin-releasing hormone agonists (GnRH-a) have been used to induce a hypoestrogenic status in women with endometriosis with the aim to cause an improvement in pain symptoms similar to that observed after menopause. Triptorelin is one of the most commonly used GnRH-a. AREAS COVERED: This review offers an explanation of the mechanism of action, of the pharmacokinetics and pharmacodynamics of triptorelin and gives the readers a complete overview of the studies on the clinical efficacy, tolerability and safety of this agent in patients with endometriosis. EXPERT OPINION: The studies reviewed in the current manuscript demonstrate the efficacy of triptorelin in improving pain symptoms caused by endometriosis. Further, this effect is confirmed by the reduction in the volume of the endometriotic nodules during treatment. Future research should evaluate whether the pre-operative administration of triptorelin prior to surgical excision of endometriomas may be useful in preserving the ovarian reserve.

Multidetector computerized tomography enema versus magnetic resonance enema in the diagnosis of rectosigmoid endometriosis.

PURPOSE: To compare the accuracy of multidetector computerized tomography enema (MDCT-e) and magnetic resonance enema (MRI-e) in determining the presence of sigmoid and rectal endometriotic nodules. MATERIALS AND METHODS: 260 women (32.6 ± 4.3 years) with symptoms suggestive of rectosigmoid endometriosis underwent MDCT-e and MRI-e prior to laparoscopy. After retrograde colonic distention and injection of intravenous contrast medium, patients were scanned on a 64-row MDCT scanner. MRI-e was performed on a 1.5T magnet using an 8 channels phased array coil; intestinal distention was achieved by introducing in the rectum 250-300 ml of ultrasonographic gel diluted with saline solution. Radiological findings were compared with surgical and histological results. RESULTS: 176 women had rectosigmoid endometriosis at surgery. There was no significant difference in the accuracy of MDCT-e (98.5%) and MRI-e (96.9%) in the diagnosis of sigmoid and rectal endometriosis (p=0.248). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of MDCT-e and MRI-e were respectively 98.3%, 98.8%, 99.4%, 96.5%, 81.59, 0.02 and 97.2%, 96.4%, 98.3%, 94.1%, 26.89, 0.03. CONCLUSIONS: Both MDCT-e and MRI-e are accurate in the diagnosis of rectal and sigmoid endometriosis.

Sorafenib for ovarian cancer.

INTRODUCTION: Sorafenib is an unselective inhibitor of multiple kinases which has demonstrated clinical advantage in renal cancer and hepatocellular carcinoma. It inhibits tumor proliferation by targeting receptor accessory factor (Raf) kinase isoforms, inhibiting receptor tyrosine kinases of a variety of pro-angiogenic factors and of several receptor tyrosine kinases involved in neovascularization and tumor development. AREAS COVERED: This review offers an explanation of the mechanism of action and of the pharmacokinetics of sorafenib, and gives readers a complete overview of Phase I and II studies on the clinical efficacy, tolerability and safety of this agent in the setting of ovarian cancer (OC) treatment. EXPERT OPINION: The available results from the studies which investigated the use of sorafenib for OC treatment demonstrated poor clinical benefit either as single agent or in combination therapy. The most promising results have been achieved combining sorafenib with bevacizumab, although overlapping and cumulative toxicities should be taken in consideration. Research should focus its attention to the development of reliable predictive biomarkers to assess response and direct therapy in order to allow patient selection and improving treatment schedules maximizing the clinical benefit and simultaneously minimizing the toxicity related to the chemotherapy. Further studies are needed to evaluate the role of sorafenib in the primary treatment of OC.

Bowel endometriosis: presentation, diagnosis, and treatment.

UNLABELLED: Bowel endometriosis opens a new frontier for the gynecologist, as it forces the understanding of a new anatomy, a new physiology, and a new pathology. Although some women with bowel endometriosis may be asymptomatic, the majority of them develop a variety of gastrointestinal complains. No clear guideline exists for the evaluation of patients with suspected bowel endometriosis. Given the fact that, besides rectal nodules, bowel endometriosis can not be diagnosed by physical examination, imaging techniques should be used. Several techniques have been proposed for the diagnosis of bowel endometriosis including double-contrast barium enema, transvaginal ultrasonography, rectal endoscopic ultrasonography, magnetic resonance imaging, and multislice computed tomography enteroclysis. Medical management of bowel endometriosis is currently speculative; expectant management should be carefully balanced with the severity of symptoms and the feasibility of prolonged follow-up. Several studies demonstrated an improvement in quality of life after extensive surgical excision of the disease. Bowel endometriotic nodules can be removed by various techniques: mucosal skinning, nodulectomy, full thickness disc resection, and segmental resection. Although the indications for colorectal resection are controversial, recent data suggest that aggressive surgery improves symptoms and quality of life. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe the varied appearance of bowel endometriosis, recall that it is difficult to diagnose preoperatively, and explain that surgical treatment offers the best treatment in symptomatic patients through a variety of surgical techniques which is best accomplished with a team approach.

Bowel endometriosis: CT-enteroclysis.

Although several radiological techniques have been used for the diagnosis of bowel endometriosis, no gold standard is currently established. We used multislice computerized tomography (CT) combined with the distention of the colon by rectal enteroclysis (MSCTe) for the diagnosis of bowel endometriosis. Following bowel preparation, pharmacological hypotonicity, retrograde colonic distention by water enteroclysis, and intravenous injection of iodinated contrast medium, a single volumetric acquisition of the abdomen is performed. MSCTe findings suggestive of bowel endometriosis are the presence of solid nodules with positive enhancement, contiguous or penetrating the colonic wall. When endometriotic lesions are detected, the degree of infiltration of the intestinal wall can be estimated; however, the depth infiltrated by nodules reaching the submucosa may be underestimated. MSCTe is well tolerated by the patients. The strength of MSCT consists in the high spatial resolution; volumetric data acquired by using thin slices provide isotropic voxels and multiplanar reconstructions have a quality comparable with that of the original axial scans. The potential of MSCTe for the diagnosis of bowel endometriosis relies on the fact that the serosal, muscular, and mucosal layers of the bowel wall can be evaluated.

Multislice CT enteroclysis in the diagnosis of bowel endometriosis.

This prospective study aims to evaluate the efficacy of multislice computed tomography combined with colon distension by water enteroclysis (MSCTe) in determining the presence and depth of bowel endometriotic lesions. Ninety-eight women with symptoms suggestive of colorectal endometriosis underwent MSCTe; locations, number of nodule/s, size of the nodule/s and depth of bowel wall infiltration were determined. Independently from the findings of MSCTe, all women underwent laparoscopy. MSCTe findings were compared with surgical and histological results. Abnormal findings suggestive of bowel endometriotic nodules were detected by MSCTe in 75 of the 76 patients with bowel endometriosis. MSCTe identified 110 (94.8%) of the 116 bowel endometriotic nodules removed at surgery; 6 nodules missed at MSCTe were located on the rectum. MSCTe correctly determined the degree of infiltration of the bowel wall in all of the 34 serosal bowel nodules identified at MSCTe. In six nodules reaching the submucosa, the depth of infiltration was underestimated by MSCTe. MSCTe had a sensitivity of 98.7%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 95.7% in identifying women with bowel endometriosis. MSCTe is effective in determining the presence and depth of bowel endometriotic lesions.