Pathophysiology and Clinical Implications of Ovarian Endometriomas.

Ovarian endometriomas affect many patients with endometriosis and have significant effects on quality of life, fertility, and risk of malignancy. Endometriomas range from small (1-3 cm), densely fibrotic cysts to large (20 cm or greater) cysts with varying degrees of fibrosis. Endometriomas are hypothesized to form from endometriotic invasion or metaplasia of functional cysts or alternatively from ovarian surface endometriosis that bleeds into the ovarian cortex. Different mechanisms of endometrioma formation may help explain the phenotypic variability observed among endometriomas. Laparoscopic surgery is the preferred first-line modality of diagnosis and treatment of endometriomas. Ovarian cystectomy is preferred over cyst ablation or sclerotherapy for enabling pathologic diagnosis, improving symptoms, preventing recurrence, and optimizing fertility outcomes. Cystectomy for small, densely adherent endometriomas is made challenging by dense fibrosis of the cyst capsule obliterating the plane with normal ovarian cortex, whereas cystectomy for large endometriomas can carry unique challenges as a result of adhesions between the cyst and pelvic structures. Preoperative and postoperative hormonal suppression can improve operative outcomes and decrease the risk of endometrioma recurrence. Whether the optimal management, fertility consequences, and malignant potential of endometriomas vary on the basis of size and phenotype remains to be fully explored.

Adnexal masses during pregnancy: diagnosis, treatment, and prognosis.

Adnexal masses are identified in pregnant patients at a rate of 2 to 20 in 1000, approximately 2 to 20 times more frequently than in the age-matched general population. The most common types of adnexal masses in pregnancy requiring surgical management are dermoid cysts (32%), endometriomas (15%), functional cysts (12%), serous cystadenomas (11%), and mucinous cystadenomas (8%). Approximately 2% of adnexal masses in pregnancy are malignant. Although most adnexal masses in pregnancy can be safely observed and approximately 70% spontaneously resolve, a minority of cases warrant surgical intervention because of symptoms, risk of torsion, or suspicion of malignancy. Ultrasound is the mainstay of evaluation of adnexal masses in pregnancy because of accuracy, safety, and availability. Several ultrasound mass scoring systems, including the Sassone, Lerner, International Ovarian Tumor Analysis Simple Rules, and International Ovarian Tumor Analysis Assessment of Different NEoplasias in the adneXa scoring systems have been validated specifically in pregnant populations. Decisions regarding expectant vs surgical management of adnexal masses in pregnancy must balance the risks of torsion or malignancy with the likelihood of spontaneous resolution and the risks of surgery. Laparoscopic surgery is preferred over open surgery when possible because of consistently demonstrated shorter hospital length of stay and less postoperative pain and some data demonstrating shorter operative time, lower blood loss, and lower risks of fetal loss, preterm birth, and low birthweight. The best practices for laparoscopic surgery during pregnancy include left lateral decubitus positioning after the first trimester of pregnancy, port placement with respect to uterine size and pathology location, insufflation pressure of less than 12 to 15 mm Hg, intraoperative maternal capnography, pre- and postoperative fetal heart rate and contraction monitoring, and appropriate mechanical and chemical thromboprophylaxes. Although planning surgery for the second trimester of pregnancy generally affords time for mass resolution while optimizing visualization with regards to uterine size and pathology location, necessary surgery should not be delayed because of gestational age. When performed at a facility with appropriate obstetrical, anesthetic, and neonatal support, adnexal surgery in pregnancy generally results in excellent outcomes for pregnant patients and fetuses.

Aberrant Endometrial DNA Methylome and Associated Gene Expression in Women with Endometriosis.

Endometriosis is an estrogen-dependent, progesterone-resistant disorder largely derived from retrograde transplantation of menstrual tissue/cells into the pelvis, eliciting an inflammatory response, pelvic pain, and infertility. Eutopic endometrium (within the uterus), giving rise to pelvic disease, displays cycle-dependent transcriptomic, proteomic, and signaling abnormalities, and although its DNA methylation profiles dynamically change across the cycle in healthy women, studies in endometriosis are limited. Herein, we investigated the DNA methylome and associated gene expression in three phases of the cycle in eutopic endometrium of women with severe endometriosis versus controls, matched for ethnicity, medications, smoking, and no recent contraceptive steroid use. Genome-wide DNA methylation and gene expression were coassessed in each sample. Cycle phase was determined by histology, serum hormone levels, and unsupervised principal component and hierarchical cluster analyses of microarray data. Altered endometrial DNA methylation in endometriosis was most prominent in the midsecretory phase (peak progesterone), with disruption of the normal pattern of cycle-dependent DNA methylation changes, including a bias toward methylation of CpG islands, suggesting wide-range abnormalities of the chromatin remodeling machinery in endometriosis. DNA methylation changes were associated with altered gene expression relevant to endometrial function/dysfunction, including cell proliferation, inflammation/immune response, angiogenesis, and steroid hormone response. The data provide insight into epigenetic reprogramming and steroid hormone actions in endometrium contributing to the pathogenesis and pathophysiology of endometriosis.

Control-matched surgical evaluation of endometriosis progression after IVF: a retrospective cohort study.

BACKGROUND: The aim of this study was to examine the surgical findings at repeated surgeries for endometriosis and to compare disease progression in patients after IVF to those without interval fertility treatments. METHODS: A retrospective case-control study set at the referral center for gynecologic endoscopy at Stanford University. Women who had two surgeries for treatment of symptomatic endometriosis since 1997 were searched in the database. Twenty-one women were identified who underwent IVF treatment between the two procedures (IVF group), and compared to 36 women who did not receive any fertility treatment (controls). The main outcomes were time to recurrence and surgical findings including rASRM score. The presence and size of endometrioma, rectovaginal and para-rectal spaces location of endometriosis were also compared between the two surgical procedures. RESULTS: Demographics in the two groups were similar. The change in rASRM score between surgeries was not significantly different (P=0.80) between the two groups. There was no difference between the two groups in the size and number of pathology proven endometriomas as well as no difference in the presence of rectovaginal and pararectal endometriosis. CONCLUSIONS: No significant difference was found in the two groups, suggesting that IVF treatment does not lead to an accelerated progression of endometriosis in patients with recurrence.

Robotic-assisted laparoscopy vs conventional laparoscopy for the treatment of advanced stage endometriosis.

STUDY OBJECTIVE: To compare robotic-assisted laparoscopy with conventional laparoscopy for treatment of advanced stage endometriosis insofar as operative time, estimated blood loss, complication rate, and length of hospital stay. STUDY DESIGN: Retrospective cohort study (Canadian Task Force classification II2). All procedures were performed by one surgeon between January 2004 and July 2012. Data was collected via chart review. SETTING: Tertiary referral center for treatment of endometriosis. PATIENTS: Four hundred twenty women with advanced endometriosis. INTERVENTIONS: Fertility-sparing surgery to treat advanced endometriosis, either via conventional or robotic-assisted laparoscopy. MEASUREMENTS AND MAIN RESULTS: Patient demographic data, operative time, estimated blood loss, complication rate, and length of hospital stay were compared between the 2 groups. Two hundred seventy-three patients underwent conventional laparoscopy and 147 patients underwent robotic-assisted laparoscopy for fertility-sparing treatment of advanced stage endometriosis. Patients in both groups had similar characteristics insofar as age, body mass index, and previous abdominal surgeries. There were no significant differences in blood loss or complication rate between the 2 groups. Mean operative time in the conventional laparoscopy group was 135 minutes (range, 115-156 minutes), and in the robotic-assisted laparoscopy group was 196 minutes (range, 185-209 minutes), with a mean difference in operative time of 61 minutes (p < .001). Length of hospital stay was also significantly increased in the robotic-assisted laparoscopy group. Most patients who underwent conventional laparoscopy were discharged to home on the day of surgery. Of 273 patients in the conventional laparoscopy group, only 63 remained in the hospital overnight, and all 147 patients in the robotic-assisted laparoscopy group were discharged on postoperative day 1. CONCLUSION: Conventional laparoscopy and robotic-assisted laparoscopy are excellent methods for treatment of advanced stages of endometriosis. However, use of the robotic platform may increase operative time and might also be associated with longer hospital stay.

When will video-assisted and robotic-assisted endoscopy replace almost all open surgeries?

This article traces the development of laparoscopy, and establishment resistance to its emergence as the technique to replace almost all laparotomies.

Increased mitogen-activated protein kinase kinase/extracellularly regulated kinase activity in human endometrial stromal fibroblasts of women with endometriosis reduces 3',5'-cyclic adenosine 5'-monophosphate inhibition of cyclin D1.

Endometriosis is characterized by endometrial tissue growth outside the uterus, due primarily to survival, proliferation, and neoangiogenesis of eutopic endometrial cells and fragments refluxed into the peritoneal cavity during menses. Although various signaling molecules, including cAMP, regulate endometrial proliferation, survival, and embryonic receptivity in endometrium of women without endometriosis, the exact molecular signaling pathways in endometrium of women with disease remain unclear. Given the persistence of a proliferative profile and differential expression of genes associated with the MAPK signaling cascade in early secretory endometrium of women with endometriosis, we hypothesized that ERK1/2 activity influences cAMP regulation of the cell cycle. Here, we demonstrate that 8-Br-cAMP inhibits bromodeoxyuridine incorporation and cyclin D1 (CCND1) expression in cultured human endometrial stromal fibroblasts (hESF) from women without but not with endometriosis. Incubation with serum-containing or serum-free medium resulted in higher phospho-ERK1/2 levels in hESF of women with vs. without disease, independent of 8-Br-cAMP treatment. The MAPK kinase-1/2 inhibitor, U0126, fully restored cAMP down-regulation of CCND1, but not cAMP up-regulation of IGFBP1, in hESF of women with vs. without endometriosis. Immunohistochemistry demonstrated the highest phospho-ERK1/2 in the late-secretory epithelial and stromal cells in women without disease, in contrast to intense immunostaining in early-secretory epithelial and stromal cells in those with disease. These findings suggest that increased activation of ERK1/2 in endometrial cells from women with endometriosis may be responsible for persistent proliferative changes in secretory-phase endometrium.

Infertility treatment: the viability of the laparoscopic view.

Assisted reproductive technology (ART) and laparoscopy are not mutually exclusive, but coexisting and potentially complimentary treatments. For disease conditions contributing to infertility in addition to other concomitant or potential morbidity, laparoscopy represents a more comprehensive approach.

Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.

The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.

Laparoscopic repair of gastric perforation secondary to umbilical trocar insertion.

A postmenopausal woman was scheduled to undergo laparoscopic treatment of an 8-cm simple ovarian cyst. During abdominal entry, umbilical trocar insertion caused a gastric perforation that was diagnosed immediately and repaired laparoscopically. Following completion of the procedure, the patient was observed for 24 hours with a nasogastric tube in place and was discharged to home on the second postoperative day without further complications. The possibility of gastric distension and perforation is almost always present during laparoscopic abdominal entry. When perforation occurs, repair can be accomplished safely by laparoscopy.

Fertility considerations in laparoscopic treatment of infiltrative bowel endometriosis.

OBJECTIVE: The purpose of this study was to examine our experience with laparoscopic and laparoscopically assisted management of bowel endometriosis and to recommend treatment approaches, considering patient goals for both pain mitigation or fertility, or both. METHODS: The medical records of 187 women treated laparoscopically for intestinal endometriosis were reviewed retrospectively for presenting symptoms, methods of surgical treatment, complications, and efficacy of treating pain and infertility. The extent of resection was determined by the severity of the endometriotic lesion, tempered by the patient's fertility goals. RESULTS: The most common patient complaint preceding surgery was pelvic pain. In addition, 58 (31%) patients experienced impaired fertility. Of the patients available for long-term follow-up, 152 (85%) reported complete or significant long-term pain relief. Complete pain relief in the immediate postoperative period was significantly more likely with partial bowel resection compared with shaving only, 92% vs 80%, respectively, P<0.04. The least invasive procedure, shaving, was associated with a significantly lower complication rate, 6%, compared with 23% for disc excision (P<0.007) and 38% for segmental resection (P<0.001), and higher pregnancy rates. The incidence of pregnancy in patients with a history of infertility was 34% during the follow-up period.

Synchronous rectovaginal, urinary bladder, and pulmonary endometriosis.

BACKGROUND: Extragenital endometriosis is an uncommon condition that can affect almost any organ system and tissue in the human body. Disease involving multiple distant sites is extremely uncommon. METHODS: We report a rare case of synchronous rectovaginal, urinary bladder, and pulmonary endometriosis. We performed a Medline literature search using keywords "endom etriosis," "recto vaginal," "pulmonary," "bladder," "ureteral," "bowel," "extrapelvic," and "extragenital" and were unable to find any prior case reports of such findings. A 31-year-old female presented with catamenial dysuria of 1-year duration, pleurisy associated with spontaneous pneumothoraces of 7 months' duration and a long-standing history of pelvic pain. A multispecialty team with experience in endoscopic techniques was assembled, consisting of a thoracic, a urologic, and a gynecologic surgeon. Video-assisted thoracoscopic surgery with fulguration of all visible pleural endometriosis and pleurodesis was performed, followed by laparoscopic segmental bladder wall endometrioma excision and resection of rectovaginal endometriosis. Twelve months after surgery and without additional hormonal treatment, the patient is symptom free. CONCLUSION: Extragenital endometriosis may coexist in multiple sites. A high index of suspicion aids in the diagnosis. A multidisciplinary approach in a tertiary center, followed by appropriate surgical eradication of visible disease, can successfully treat endometriosis even in such extreme cases.

A porcine model for endolaparoscopic abdominal aortic repair and endoscopic training.

OBJECTIVES: The goals of this laboratory model were to evaluate the performance of the surgical team and endolaparoscopic techniques in the porcine model of infrarenal abdominal aortic repair. METHODS: Twenty-four pigs underwent full endolaparoscopic aorto-aortic graft implantation with voice-activated computerized robotics. The first group of 10 pigs (acute) was sacrificed while under anesthesia at 0.5 hours (5 animals) and 2 hours (5 animals). The second group of 14 pigs (survival) were recovered from anesthesia and maintained for 7 hours (5 pigs) and 7 days (9 pigs) prior to sacrifice. Survival animals were observed for evidence of hind limb dysfunction. All grafts were visually inspected at autopsy. RESULTS: All animals survived the operation. All grafts were successfully implanted, and all were patent with intact anastomoses at autopsy. Mean aortic clamp time for each group was as follows: acute, 92.9 +/- 28.04 minutes; survival, 59.6 +/- 13.8 minutes; P=0.0008. Total operative time for each group was as follows: acute, 179 +/- 39.6 minutes; survival, 164.6 +/- 48 minutes; P=0.44 ns. Estimated blood loss for each group was as follows: acute, 214 -/+ 437.8 mL; survival 169.2 +/- 271 mL; P=0.76 ns. from respiratory arrest; 1 animal suffered motor sensory dysfunction of the hind limbs (spinal cord ischemia); significant bleeding occurred in 6 of 24 pigs; 8 of the 9 seven-day survivors required minimal pain medication and had normal hind limb function. CONCLUSIONS: The reduction in aortic clamp time, total operative time, and blood loss as the study progressed indicate the feasibility of this surgical protocol and the maturation of the learning process, which is paramount in prevention of 2 main sources of morbidity: bleeding and spinal cord ischemia. The reduction in aortic clamp time between the acute and survival groups was dramatic and statistically significant. An intensive formal training program combining dry and live surgical laboratories is deemed essential for the development of endoscopic skill sets necessary for this challenging procedure.